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Esther TL Lau,1,2 Shirin H Tan,2,3 Yasmin J Antwertinger,1 Tony Hall,1 Lisa M Nissen1,21School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD, Australia; 2School of Pharmacy, University of Queensland, Brisbane, QLD, Australia; 3Clinical Research Center, Sarawak General Hospital, Kuching, Sarawak, MalaysiaBackground: People living with persistent pain in Australia often cannot access adequate care to manage their pain. Therefore, as the most accessible healthcare professionals, community pharmacists have an important role to play in helping to improve patient outcomes. Hence, it is important to investigate patient needs and expectations in terms of counseling interactions with pharmacists, along with pharmacists’ approach to counseling interactions with these patients.Method: The nature of patient–pharmacist counseling interactions was explored with seven patients (one focus group), and 10 practicing pharmacists (two focus groups, three semi-structured interviews). The themes identified informed the development of an online survey that was advertised online to patients and pharmacists across Australia.Results: A total of 95 patients and 208 pharmacists completed the survey. Overall, more than half of patients (77/95) were satisfied with the care provided by their pharmacist, but only a third (71/205) of pharmacists were satisfied with the care they provided to patients. The majority of patients (67/94) reported that pharmacists provided good information about medications. This aligned with pharmacists’ responses, as most reported focusing on medication side effects (118/188) and instructions for taking pain medication (93/183) during patient interactions. However, when asked about empathy and rapport from pharmacists, only half to two-thirds (48–61/95) of patients expressed positive views. Overall, half of the patients (39/75) wanted a caring, empathetic, respectful, and private conversation with the pharmacist, and nearly half (40/89) perceived the pharmacist’s role as providing (new) information on alternative pharmacological and non-pharmacological therapies, including general advice on pain management.Conclusion: There was a disparity in the nature of the interaction and information that patients wanted from pharmacists, compared to what was provided by pharmacists. Training and education may help pharmacists to better engage in patient-centered care when interacting with people living with persistent pain, thereby improving health outcomes for these patients.Keywords: persistent, chronic, pain, pharmacist, counseling

Aida Sefidani Forough,1 Esther TL Lau,1 Kathryn J Steadman,1,2 Julie AY Cichero,1,2 Greg J Kyle,1 Jose Manuel Serrano Santos,1 Lisa M Nissen1 1School of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia; 2School of Pharmacy, University of Queensland, Brisbane, QLD, Australia Abstract: Solid oral dosage forms such as tablets and capsules are generally the preferred method of drug delivery due to their convenience, cost, and acceptability. However, for many people, it can be a challenge to swallow solid oral medications, even those with healthy swallowing function. This review describes current strategies available to facilitate medication administration to otherwise healthy people with pill-swallowing difficulties. In general, restoring and maintaining the ability to swallow pills whole should ideally be the first choice in managing people with pill-swallowing difficulties. A number of strategies can potentially make it easier to swallow pills whole. These include postural adjustments, using pill-swallowing aids, and teaching pill-swallowing techniques. Where these are not successful or appropriate, then other approaches have to be considered using alternative formulations/routes of administration or deprescribing. If there is no other option, and it is not directly contraindicated for each specific medication dosage form, pills may be modified and mixed in foods and drinks to aid swallowing. In conclusion, people with pill-swallowing difficulties can benefit from a number of strategies designed to facilitate swallowing medications. However, these strategies should be further evaluated with regard to the evidence relating to both their efficacy and safety. Keywords: swallowing difficulties, pill swallowing, medication administration, oral dosage forms, tablets, capsules

A convertible bond is a corporate bond that offers the holders the right but not the obligation to convert the bond at any time to a specific number of shares of the issuer's corporation or receive the par at maturity. The conversion right gives the holder the possibility to benefit from future capital appreciation in the company's equity, while the fixed income component provides a return floor. Like usual corporate bonds, the bond issuer pays regular discrete coupon payments to the holders. Since the bondholders have the conversion right as an incentive, they may accept a lower coupon rate in the bond. In essence, the bond issuer shorts a conversion option to the holders.

To determine whether amnio-polymerase chain reaction (amnio-PCR) can replace conventional cytogenetic study for confirming the karyotype of fetuses in women with positive biochemical screening for fetal Down syndrome. To check the accuracy of this technique in our laboratory, we first compared the amnio-PCR results with those of conventional cytogenetic study in 235 patients referred from June 1999 to December 2001 for prenatal diagnosis in a referral center in Hong Kong. We then reviewed the results of 1526 amniotic fluid cultures performed for positive fetal Down syndrome screening between January 1997 and December 2001 and classified them as detectable or not detectable by amnio-PCR, using the assumption that we had replaced conventional cytogenetic study with amnio-PCR. The 235 amnio-PCR results were all informative, without a false-positive or false-negative result. Of the 1526 cases with positive fetal Down syndrome screening and no ultrasound abnormalities, only two cases of sex chromosome abnormalities and two cases of marker chromosomes would have been missed if conventional cytogenetic study had been replaced by amnio-PCR.Amnio-PCR can be an alternative to conventional cytogenetic study for women with positive biochemical screening for fetal Down syndrome and no demonstrable fetal structural abnormality. [ABSTRACT FROM AUTHOR]

Thi-My-Uyen Nguyen,1 Esther TL Lau,1,3 Kathryn J Steadman,1 Julie AY Cichero,1 Kaeleen Dingle,2 Lisa M Nissen1,3 1School of Pharmacy, University of Queensland, Brisbane, QLD, Australia; 2School of Public Health, Queensland University of Technology, Brisbane, QLD, Australia; 3School of Clinical Sciences, Queensland University of Technology, Brisbane, QLD, Australia Background: People often modify oral solid dosage forms when they experience difficulty swallowing them. Modifying dosage forms may cause adverse effects to the patient, and the person undertaking the modification. Pharmacists are often the first point of contact for people in the general community seeking advice regarding medications. Nurses are at the forefront of administering medications to patients and are likely to be most directly affected by a patient’s swallowing ability, while general practitioners (GPs) are expected to consider swallowing abilities when prescribing medications. Objective: To compare the perspectives and experiences of GPs, pharmacists, and nurses regarding medication dosage form modification and their knowledge of medication modification. Method: Questionnaires tailored to each profession were posted to 630 GPs, and links to an online version were distributed to 2,090 pharmacists and 505 nurses. Results: When compared to pharmacists and GPs, nurses perceived that a greater proportion of the general community modified solid dosage forms. Pharmacists and GPs were most likely to consider allergies and medical history when deciding whether to prescribe or dispense a medicine, while nurses’ priorities were allergies and swallowing problems when administering medications. While nurses were more likely to ask their patients about their ability to swallow medications, most health professionals reported that patients “rarely” or “never” volunteered information about swallowing difficulties. The majority of health professionals would advise a patient to crush or split noncoated non-sustained-release tablets, and would consult colleagues or reference sources for sustained-release or coated tablets. Health professionals appeared to rely heavily upon the suffix attached to medication names (which suggest modified release properties) to identify potential problems associated with modifying medications. Conclusion: The different professional roles and responsibilities of GPs, pharmacists, and nurses are associated with different perspectives of, and experiences with, people modifying medications in the general community and knowledge about consequences of medication modification. Keywords: crushing tablets, opening capsules, dosage form modification, health professional

Nutrient leaching and volatilization cause environmental pollution, thus the pursuit of developing controlled-release fertilizer formulation is necessary. Biochar-based fertilizer exhibits slow-release characteristic, however the nutrient release mechanism needs to be improved. To overcome this limitation, the approach of applying encapsulation technology with biochar-based fertilizer has been implemented in this study. Black peppercorn waste was used to synthesize urea-impregnated biochar (UIB). Central composite design was used to investigate the effects of pyrolysis temperature, residence time and urea:biochar ratio on nitrogen content of UIB. The optimum condition to synthesize UIB was at 400 °C pyrolysis temperature, 120 min residence time and 0.6:1 urea:biochar ratio, which resulted in 16.07% nitrogen content. The tapioca starch/palm oil (PO) biofilm formulated using 8 g of tapioca starch and 0.12 µL of PO was coated on the UIB to produce encapsulated urea-impregnated biochar (EUIB). The UIB and EUIB pellets achieved complete release of nitrogen in water after 90 min and 330 min, respectively. The nutrient release mechanism of UIB and EUIB was best described by the Higuchi model and Korsmeyer-Peppas model, respectively. The improvement of water retention ratio of UIB and EUIB pellets was more significant in sandy-textural soil as compared to clayey-textural soil. The EUIB derived from peppercorn waste has the potential to be utilized as a sustainable controlled-release fertilizer for agriculture., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ivy Ai Wei Tan reports financial support was provided by Malaysia Ministry of Higher Education., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Competing Interests: Intérêts concurrents: Rose Yeung a reçu une subvention de recherche du Fonds albertain Novo Nordisk pour le diabète (Fondation de l’Hôpital universitaire, société Novo Nordisk et ministère du Développement économique et du Commerce de l’Alberta). Rose Yeung est directrice médicale du Bureau de l’éducation permanente et du Programme de formation médicale de l’Université de l’Alberta; ce programme est subventionné par le gouvernement de l’Alberta. Darren Lau a reçu des honoraires du Collège des médecins de famille de l’Alberta. Aucun autre intérêt concurrent n’a été déclaré.

Objective: There is a lack of literature on indirect decompression in uniportal endoscopic posterolateral transforaminal lumbar interbody fusion (EPTLIF). Our aim is to evaluate the dimensions of the spinal canal and contralateral foramen before and after EPTLIF., Methods: This is a retrospective study of patients who underwent EPTLIF in a tertiary spine centre over a 2-year period. The cross-sectional area of the spinal canal and the contralateral foramen at the level of fusion were measured on magnetic resonance imaging scan at 1-day postoperation and at the final follow-up. Patients were grouped according to the decompression performed as per the clinician's judgement., Results: One hundred fifty-two levels of fusion were performed in 120 patients. There was a statistically significant clinical improvement in visual analogue scale and Oswestry Disability Index scores postoperation. The measurements of the spinal canal area were 106.0 mm2, 138.8 mm2, and 195.5 mm2; while contralateral foraminal area were 73.2 mm2, 104.4 mm2, and 120.7 mm2 at preoperation, 1-day postoperation, and at the final follow-up, respectively (p < 0.001). For the subgroup analyses, spinal canal area measurements for the bilateral decompression cohort (n = 35) were 57.0 mm2, 123.9 mm2, and 191.8 mm2; for the ipsilateral decompression cohort (n = 42) were 89.3 mm2, 128.9 mm2, 183.3 mm2; and for the cohort without any decompression and only cage inserted (n = 75) were 138.3 mm2, 151.2 mm2, and 204.1 mm2 (p < 0.001). Contralateral foraminal area measurements were 73.3 mm2, 106.4 mm2 and 120.4 mm2 in the bilateral decompression cohort; 69.5 mm2, 99.0 mm2, 116.9 mm2 in the ipsilateral decompression cohort; and 75.1 mm2, 106.5 mm2, 122.9 mm2 in the cohort without any decompression (p < 0.001)., Conclusion: Indirect decompression of both the spinal canal and the contralateral foramen can be achieved via EPTLIF. Decompression on an asymptomatic contralateral side is not necessary.

Objectives: NHS England has set itself a target of net zero emissions by 2050. Therefore, to address this gap in the literature, this study aimed to explore engagement with NHS policy on carbon reduction (including awareness of the Sustainable Development Unit [SDU] and the Coalition for Sustainable Pharmaceuticals and Medical Devices [CSPM]) in NHS hospital pharmacists in England., Methods: Semi-structured interviews were conducted with 23 pharmacists working in six NHS England hospitals across all hierarchical levels. Four interview questions elicited Yes/No responses and one generated qualitative data which were analysed by two methods - Leximancer and manual coding., Key Findings: Only five (5/23; 21.74%) had heard of the SDU and none knew its purpose. Those who did not wish to learn more about the SDU could not see its relevance to their clinical practice. Barriers identified to the inclusion of sustainability considerations in clinical decision-making were lack of knowledge of the environmental risk profiles for treatment options, lack of quality environmental evidence incorporated into clinical guidelines and lack of time to research for themselves. Many participants did not believe that environmental considerations were part of their job., Conclusions: For NHS England to successfully deliver on its target of net zero emissions by 2050, immediate action is required from all hospital staff, clinicians included. The challenge for the NHS will be engaging pharmacists and other clinicians with sustainable clinical practice and working with clinicians to reduce identified barriers. As these data were collected in 2016, further research is warranted to determine if pharmacists' attitudes towards sustainable practice are changing., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Design: A radiographic comparative study., Objective: To investigate the influence of radiographic lower limb-spinal length proportion on sagittal radiographic parameters., Summary of Background Data: Although lordotic realignment of the lumbar spine is a well-established surgical strategy, its ideal target has not been fully understood. The widely used pelvic incidence-lumbar lordosis discrepancy (PI-LL) method to guide lordotic restoration of the lumber spine in the standing posture, may be further refined using the novel, radiographic lower limb-spinal length proportion parameter in selected subjects., Methods: A 100 healthy subjects were imaged in the standing posture using EOS imaging to obtain whole-body lateral radiographs for the measurement of sagittal radiographic parameters. Univariate analyses were performed to compare radiographic parameters between groups with different radiographic lower limb-spinal length proportion. Multivariate analyses were performed to identify the associations between lower limb-spinal length proportions and other radiographic parameters., Results: Regardless of lower limb-spinal length proportion (mean = 1.4), global lumbar angle (GLA) differed from spinal lordosis (SL), with the absolute means of SL and GLA larger and smaller than pelvic incidence (PI) respectively. Univariate analysis showed that patients with proportionately larger lower limb-spinal length proportion are more likely to have larger mean T1-slope, global thoracic angle (GTA), spinal kyphosis (SK), GLA, and SL. Multivariate analysis showed that a larger lower limb length-spinal length proportion is predictive of larger GLA is less than -47.69° (Odds Ratio (OR) 2.660, P = 0.026), and larger T1-slope of more than 18.84° (OR 3.695, P = 0.012)., Conclusion: Larger radiographic lower limb-spinal length proportion results in naturally accentuated spinal curves. These patients balance with a larger lumbar lordosis that is closer to the PI and a higher T1-slope which should be considered for spinal realignment. SL differs from GLA and should be separately assessed.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Pharmaceuticals and their packaging have a significant negative impact on the environment providing a very strong argument for action on the part of pharmacists and pharmacy technicians to engage with pro-environmental behaviours (PEBs) in their workplaces. The aims of this research were therefore to investigate in hospital pharmacists and pharmacy technicians, 1) factors affecting engagement with workplace PEBs, and 2) determine if legislated carbon reduction targets in the UK influenced workplace PEBs in the UK compared with Australia which does not have legislated carbon reduction targets. The environmentally responsible disposal of pharmaceutical waste was the PEB of interest in this study. A mixed methods research design was utilised and a conceptual model (key variables: environmental attitude, concern, and knowledge, and organisational factors) was developed to identify factors influencing workplace PEBs. Participants were from five hospitals in Queensland, Australia and five NHS hospitals in England, UK. There was no statistically significant difference in environmental attitude or concern between the two groups-most had a mid-environmental attitude score and low levels of environmental concern. Participants lacked knowledge of the issue and the link between the environment and public health. Both Australian and UK participants reported recycling packaging waste was not a priority in the hospital pharmacy workplace (even in hospitals with recycling capability) as hospitals focused on compliance with clinical (contaminated) and confidential waste streams. Environmental attitude, knowledge, and concern therefore appeared to be weak influences on intention to perform workplace PEBs with workplace social norms (compliance due to audits) appearing to be a significant mediator of action. The key difference between the cohorts was that UK pharmacists felt waste was not in the scope of their role, and therefore not their responsibility. This study identified that legislated carbon reduction targets did not influence hospital pharmacy workplace PEBs-neither cohort reported engaging significantly in workplace PEBs. UK Government and NHS sustainability policy did not appear to have disseminated to pharmacy department level of UK public hospitals to any great extent., Competing Interests: The authors have declared that no competing interests exist.

Study Design: A retrospective, radiographic comparative study conducted in a single academic institution., Objective: This study aims to compare fulcrum extension with conventional extension imaging to determine maximum "hip lordosis" (HL), an important novel patient-specific parameter in spinal realignment surgery, as well as understand the extension capabilities of the lower lumbar spine, which together, are key contributors to whole-body balancing., Summary of Background Data: Recent literature recognizes the hip as an important contributor to whole-body lordosis beyond a compensator for spinal imbalance., Methods: Patients >45 years' old with mechanical low back pain due to degenerative spinal conditions were included and grouped based on the imaging performed-fulcrum or conventional extension. All imaging was performed using EOS under standardized instructions and visual aids. Radiographic parameters include global lumbar angle (GLA), inflexion-S1 (Inf-S1) angle, segmental lumbar angles, pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), femoral alignment angle (FAA), HL and spinocoxa angle (SCA). Unpaired t test was used to compare between radiographic parameters., Results: One hundred patients (40 males and 60 females, mean age 63.0 years) underwent either fulcrum or conventional extension EOS® imaging. Both groups had comparable baseline radiographic parameters. Fulcrum extension gave a larger mean GLA (-60.7° vs. -48.5°, P = 0.001), Inf-S1 angle (-58.8° vs. -48.8°, P = 0.003), SCA (-36.5° vs. -24.8°, P < 0.001), L4/5 and L5/S1 lordosis (-20.7° vs. -17.7°, P = 0.041, and -22.3° vs. -17.1°, P = 0.018, respectively), compared to conventional extension. PI, SS, PT, FAA, and HL were similar between both extension postures., Conclusion: Fulcrum extension, compared to conventional extension, is better at generating lordosis in the lower lumbar spine, thus improving preoperative assessment of stiffness or instability of the lumbar spine. Both extension methods were equally effective at determining the patient-specific maximum HL to assess the flexibility and compensation occurring at the hip, potentially guiding surgical management of patients with degenerative spines.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: In Australia, polypharmacy and medication-related problems are prevalent in the community. Therefore, medicines safety initiatives such as the Home Medicines Review (HMR) service are critical to health care provision. While the evidence continues to expand around HMR service, little is known of accredited pharmacists' experiences of HMR time investment., Objective: This study aimed to explore accredited pharmacists' experiences of HMR practice regarding time investment in the study's defined HMR Stages: 1 (initial paper-based assessment and review), 2 (in-home patient-accredited pharmacist consultation), and 3 (HMR report collation, generation, completion, and provision to the patient's General Practitioner, including any liaison time)., Methods: An electronic survey was developed and piloted by a panel of reviewers. Convenience sampling was used to distribute the final anonymous survey nationally via professional pharmacy organisations. Data were analyzed for frequency distributions and a chi-square test of independence was performed to evaluate any association between demographic variables relating to HMR time investment., Results: There was a total of 255 survey respondents, representing approximately 10% of national accredited pharmacist membership. The majority were experienced accredited pharmacists who had completed >100 HMRs (73%), were female (71%), and aged >40 years (60%). Regarding time investment for a typical instance of HMR, most spent: <30 minutes performing Stage 1 (46.7%), and 30-60 minutes performing Stage 2 (70.2%). In Stage 3, 40.0% invested 1-2 hours, and 27.1% invested 2-3 hours in HMR report collation and completion. Quantitative analysis revealed statistically significant (p=0.03) gender findings where females performed longer patient consultations than males (Stage 2). More HMR career experience resulted in statistically significant (p=0.01) less time performing Stage 1 (initial paper-based assessment and review); with a trend to less time performing Stage 3 (HMR report writing)., Conclusions: Accredited pharmacists invest significant time in performing comprehensive HMRs, especially during in-home patient consultations and during HMR report collation and completion. Their significant HMR time investment as medicines experts provides insight for program and workforce considerations and warrants further research to better understand their work processes for optimizing medicines use and improving health., Competing Interests: CONFLICT OF INTEREST None., (Copyright: © The Authors.)

Study Design: A cross-sectional study on a randomly selected prospective cohort of patients presenting to a single tertiary spine center., Objective: The aim of this study was to describe the clinical and radiographic parameters of patients with S- and C-shaped thoracolumbar sagittal spinal profiles, and to identify predictors of these profiles in a natural, relaxed sitting posture., Summary of Background Data: Sagittal realignment in adult spinal deformity surgery has to consider the sitting profile to minimize the risks of junctional failure. Persistence of an S-shaped sagittal profile in the natural, relaxed sitting posture may reflect a lesser need to accommodate for this posture during surgical realignment., Methods: Consecutive patients with low back pain underwent whole body anteroposterior and lateral radiographs in both standing and sitting. Baseline clinical data of patients and radiographic parameters of both standing and sitting sagittal profiles were compared using χ, unpaired t tests, and Wilcoxon rank-sum test. Subsequently, using stepwise multivariate logistic regression analysis, predictors of S-shaped curves were identified while adjusting for confounders., Results: Of the 120 patients included, 54.2% had S-shaped curves when sitting. The most common diagnoses were lumbar spondylosis (26.7%) and degenerative spondylolisthesis (26.7%). When comparing between patients with S- and C-shaped spines in the sitting posture, only diagnoses of degenerative spondylolisthesis (odds ratio [OR], 5.44; P = 0.01) and degenerative scoliosis (OR, 2.00; P = 0.039), and pelvic incidence (PI) >52.5° (OR, 5.48; P = 0.008), were predictive of an S-shaped sitting sagittal spinal alignment on multivariate analysis., Conclusion: Stiffer lumbar curves (eg, patients with degenerative spondylolisthesis and degenerative scoliosis) or those who have a predilection for an S-shaped standing sagittal profile when sitting (eg, high PI) may be more amenable to fusion in accordance with previously studied sagittal realignment targets. In contrast, more flexible curves may benefit from less aggressive lordotic realignment to prevent potential junctional failures., Level of Evidence: 3.

Black pepper production in Malaysia was restricted by various diseases. Hazardous chemical products appear to be the best solution to control diseases in black pepper cultivation. However, persistence of chemical residues in peppercorns could affect the quality of exports and consumptions. Application of fertilizers is crucial to sustain pepper growth and high yield. But, continuous use of chemical fertilizers could affect the soil ecosystem and eventually restrict nutrient uptake by pepper roots. Therefore, we propose biological approaches as an alternative solution instead of chemical products to sustain pepper cultivation in Malaysia. In this study, we have isolated a total of seven indigenous rhizobacteria antagonistic to soil-borne Fusarium solani, the causal fungus of slow decline, the most serious debilitating disease of black pepper in Malaysia. The isolated bacteria were identified as Bacillus subtilis, Bacillus siamensis, Brevibacillus gelatini, Pseudomonas geniculata, Pseudomonas beteli, Burkholderia ubonensis and Burkholderia territorii. These bacteria were effective in production of antifungal siderophore with the amount of 53.4 %-73.5 % per 0.5 mL of cell-free supernatants. The bacteria also produced appreciable amount of chitinase with chitinolytic index was ranged from 1.19 to 1.76. The bacteria have shown phosphate solubilizing index within 1.61 to 2.01. They were also efficient in ACC deaminase (0.52 mM-0.62 mM) and ammonia (60.3 mM-75.3 mM) production. The isolated antagonists were efficacious in stimulation of black pepper plant growth and root development through IAA (10.5 μg/mL-42.6 μg/mL) secretion. In conclusion, the isolated rhizobacteria are potent to be developed not only as biocontrol agents to minimize the utilization of hazardous chemicals in black pepper disease management, but also developed as bio-fertilizers to improve black pepper plant growth due to their capabilities in plant growth-promotion., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Black pepper is an important commodity crop in Malaysia that generates millions of annual revenue for the country. However, black pepper yield is affected by slow decline disease caused by a soil-borne fungus Fusarium solani. RNA sequencing transcriptomics approach has been employed in this study to explore the differential gene expression in susceptible Piper nigrum L. and resistant Piper colubrinum Link. Gene expression comparative analysis of the two pepper species has yielded 2,361 differentially expressed genes (DEGs). Among them, higher expression of 1,426 DEGs was detected in resistant plant. These DEGs practically demonstrated the major branches of plant-pathogen interaction pathway (Path: ko04626). We selected five groups of defence-related DEGs for downstream qRT-PCR analysis. Cf-9, the gene responsible for recognizing fungal avirulence protein activity was found inexpressible in susceptible plant. However, this gene exhibited promising expression in resistant plant. Inactivation of Cf-9 could be the factor that causes susceptible plant fail in recognition of F. solani and subsequently delay activation of adaptive response to fungal invasion. This vital study advance the understanding of pepper plant defence in response to F. solani and aid in identifying potential solution to manage slow decline disease in black pepper cultivation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Black pepper ( Piper nigrum ) is a vital spice crop with uses ranging from culinary to pharmacological applications. However, limited genetic information has constrained the understanding of the molecular regulation of flower and fruit development in black pepper. In this study, a comparison among three different black pepper varieties, Semengok Aman (SA), Kuching (KC), and Semengok 1 (S1), with varying fruit characteristics was used to provide insight on the genetic regulation of flower and fruit development. Next-generation sequencing (NGS) technology was used to determine the flower and fruit transcriptomes by sequencing on an Illumina HiSeq 2500 platform followed by de novo assembly using SOAPdenovo-Trans. The high-quality assembly of 66,906 of unigenes included 64.4% of gene sequences (43,115) with similarity to one or more protein sequences from the GenBank database. Annotation with Blast2Go assigned 37,377 genes to one or more Gene Ontology terms. Of these genes, 5,874 genes were further associated with the biological pathways recorded in the KEGG database. Comparison of flower and fruit transcriptome data from the three different black pepper varieties revealed a large number of DEGs between flower and fruit of the SA variety. Gene Ontology (GO) enrichment analysis further supports functions of DEGs between flower and fruit in the categories of carbohydrate metabolic processes, embryo development, and DNA metabolic processes while the DEGs in fruit relate to biosynthetic process, secondary metabolic process, and catabolic process. The enrichment of DEGs in KEGG pathways was also investigated, and a large number of genes were found to belong to the nucleotide metabolism and carbohydrate metabolism categories. Gene expression profiling of flower formation-related genes reveals that other than regulating the flowering in black pepper, the flowering genes might also be implicated in the fruit development process. Transcriptional analysis of sugar transporter and carbohydrate metabolism genes in different fruit varieties suggested that the carbohydrate metabolism in black pepper fruit is developmentally regulated, and some genes might serve as potential genes for future crop quality improvement. Study on the piperine-related gene expression analysis suggested that lysine-derived products might present in all stages of fruit development, but the transportation was only active at the early stage of fruit development. These results indicate several candidate genes related to the development of flower and fruit in black pepper and provide a resource for future functional analysis and potentially for future crop improvement., Competing Interests: The authors confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2020 Choy Yuen Khew et al.)

Black pepper (Piper nigrum L.) is one of the most popular and oldest spices in the world with culinary uses and various pharmacological properties. In order to satisfy the growing worldwide demand for black pepper, improved productivity of pepper is highly desirable. A primary constraint in black pepper production is the non-synchronous nature of flower development and non-uniform fruit ripening within a spike. The uneven ripening of pepper berries results in a high labour requirement for selective harvesting contributes to low productivity and affects the quality of the pepper products. In Malaysia, there are a few recommended varieties for black pepper planting, each having some limitations in addition to the useful characteristics. Therefore, a comparative study of different black pepper varieties will provide a better understanding of the mechanisms regulates fruit development and ripening. Plant hormones are known to influence the fruit development process and their roles in black pepper flower and fruit development were inferred based on the probe-based gene expression analysis and the quantification of the multiple plant hormones using high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). In this study, jasmonic acid and salicylic acid were found to play roles in flowering and fruit setting, whereas auxin, gibberellin and cytokinins are important for fruit growth. Abscisic acid has positive role in fruit maturation and ripening in the development process. Distinct pattern of plant hormones related gene expression profiles with the hormones accumulation profiles suggested a complex network of regulation is involved in the signaling process and crosstalk between plant hormones was another layer of regulation in the black pepper fruit development mechanisms. The current study provides clues to help in elucidating the timing of the action of each specific plant hormone during fruit development and ripening which could be applied to enhance our ability to control the ripening process, leading to improving procedures for the production and post-harvest handling of pepper fruits.

Background: A comparative survey from patients and radiographers of the new slump sitting flexion posture and the conventional standing forward bending posture. This study was performed to compare the technical and logistical aspects of the slump sitting versus the forward bending posture. Slump sitting flexes the lumbar spine more than the forward bending and increases the diagnosis rate of sagittal spinal instability up to 40% depending on the diagnostic criteria used. This should not come at the expense of patient safety and comfort nor burden the radiographers., Methods: Sixty patients were recruited from a single tertiary spine centre. Patients were block randomised into two groups with either the forward bending or the slump sitting being performed first. Feedback was obtained through self-administered questionnaires from patients regarding perceived safety, convenience and comfort, plus from radiographers regarding the imaging process, proxy measures of radiographer ability and scan difficulty., Results: There was no significant difference between the baseline characteristics in both groups. Majority (63%) of patients preferred slump sitting and felt that forward bending caused pain (P=0.025). Overall, slump sitting was equivalent in comfort, perceived safety and ease to forward bending. Despite requiring more logistics (P=0.031), more effort to set up (P=0.002) and explain (P=0.012), the majority of radiographers (83%) preferred slump sitting. This method was felt to be less dangerous (P=0.015) and easier to maintain (P<0.001)., Conclusions: This study showed that the superiority of slump sitting in allowing more lumbar flexion compared to the forward bending comes with patient safety or comfort. The technical demands of the learning curve can be offset with training. As such, slump sitting flexion views should be adopted as the standardized method for assessing spinal instability., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Purpose: Evidence guiding the use of CT and MRI scans in blunt trauma patients who are obtunded remains controversial. This study aims to determine and predict if computed tomography (CT) scans alone can be performed without risking oversight of substantial injuries found on follow-up magnetic resonance imaging (MRI)., Methods: This is a retrospective cohort study of 63 blunt trauma patients with a Glasgow Coma Scale of < 8. Data were collated from electronic medical records and included patient demographics, premorbid mobility, mechanism of injury, suspected level of injury and neurological examination findings. Patients were urgently evaluated using CT scans, followed by non-contrast MRI scans within 48 h of admission. The accuracy of CT scan was evaluated using MRI as a reference. Adjusted multivariable analysis was also performed to identify predictors for findings detected on MRI but not on CT., Results: The mean age of patients was 42.3 years and 90.5% were males. CT scans had a high specificity of 100% and sensitivity of 87.2%. Predictors of MRI abnormalities include females, patients with relatively milder mechanisms of injury, patients with suspected thoracic spine injury, and CT scan findings of facet dislocation and intracranial haemorrhage. There was no predictor for spinal cord oedema., Conclusions: MRI should be performed in the presence of the aforementioned predictive factors and in the presence of neurological deficits. Otherwise, patients can be treated medically without the fear of missing a substantial cervical injury.

Purpose: To describe normal variations in sagittal spinal radiographic parameters over an interval period and establish physiological norms and guidelines for which these images should be interpreted., Methods: Data were prospectively collected from a continuous series of adult patients with first-episode mild low back pain presenting to a single institution. The sagittal parameters of two serial radiographic images taken 6-months apart were obtained with the EOS ® slot scanner. Measured parameters include CL, TK, TL, LL, PI, PT, SS, and end and apical vertebrae. Chi-squared test and Wilcoxon Signed Rank test were used to compare categorical and continuous variables, respectively., Results: Sixty patients with a total of 120 whole-body sagittal X-rays were analysed. Mean age was 52.1 years (SD 21.2). Mean interval between the first and second X-rays was 126.2 days (SD 47.2). Small variations (< 1°) occur for all except PT (1.2°), CL (1.2°), and SVA (2.9 cm). Pelvic tilt showed significant difference between two images (p = 0.035). Subgroup analysis based on the time interval between X-rays, and between the first and second X-rays, did not show significant differences. Consistent findings were found for end and apical vertebrae of the thoracic and lumbar spine between the first and second X-rays for sagittal curve shapes., Conclusions: Radiographic sagittal parameters vary between serial images and reflect dynamism in spinal balancing. SVA and PT are predisposed to the widest variation. SVA has the largest variation between individuals of low pelvic tilt. Therefore, interpretation of these parameters should be patient specific and relies on trends rather than a one-time assessment.

Study Design: Comparative study of prospectively collected radiographic data., Objective: To predict physiological alignment of the cervical spine and study its morphology in different postures., Summary of Background Data: There is increasing evidence that normal cervical spinal alignment may vary from lordosis to neutral to kyphosis, or form S-shaped or reverse S-shaped curves., Methods: Standing, erect sitting, and natural sitting whole-spine radiographs were obtained from 26 consecutive patients without cervical spine pathology. Sagittal vertical axis (SVA), global cervical lordosis, lower cervical alignment C4-T1, C0-C2 angle, T1 slope, C0-C7 SVA and C2-7SVA, SVA, thoracic kyphosis, thoracolumbar junctional angle, lumbar lordosis, sacral slope, pelvic tilt, and pelvic incidence were measured. Statistical analysis was performed to elucidate differences in cervical alignment for all postures. Predictive values of T1 slope and SVA for cervical kyphosis were evaluated., Results: Most patients (73.0%) do not have lordotic cervical alignment (C2-C7) upon standing (mean -0.6, standard deviation 11.1°). Lordosis increases significantly when transitioning from standing to erect sitting, as well as from erect to natural sitting (mean -17.2, standard deviation 12.1°). Transition from standing to natural sitting also produces concomitant increases in SVA (-8.8-65.2 mm) and T1-slope (17.4°-30.2°). T1 slope and SVA measured during standing significantly predicts angular cervical spine alignment in the same position. SVA < 10 mm significantly predicts C4-C7 kyphosis (P < 0.001), and to a lesser extent, C2-C7 kyphosis (P = 0.02). T1 slope <20° is both predictive of C2-C7 and C4-7 kyphosis (P = 0.001 and P = 0.023, respectively). For global cervical Cobb angle, T1 slope seems to be a more significant predictor of kyphosis than SVA (odds ratio 17.33, P = 0.001 vs odds ratio 11.67, P = 0.02, respectively)., Conclusion: The cervical spine has variable normal morphology. Key determinants of its alignment include SVA and T1 slope. Lordotic correction of the cervical spine is not always physiological and thus correction targets should be individualized., Level of Evidence: 3.

Study Design: A cross-sectional study of prospectively collected data., Objective: To compare lumbar spine alignment in six common postures, and estimate loss in range of motion (ROM) relative to standing., Summary of Background Data: Ideal position for fusion of lumbar spine remains unknown. Although surgical fusion is necessary for deformity correction and symptom relief, the final position in which the vertebrae are immobilized should provide maximum residual function., Methods: Data were collected prospectively from 70 patients with low back pain recruited over a year. All subjects had x-rays performed in slump sitting, forward bending, supine, half squatting, standing, and backward bending postures. ROM quantified in terms of sagittal global and segmental Cobb angles was measured from L1 to S1. Loss of ROM relative to standing was calculated for each posture. Analysis of variance and unpaired t tests were used to identify differences in alignment between postures., Results: Slump sitting gives the greatest lumbar flexion followed by forward bending, and supine postures (P < 0.001). Backward bending produces greater lumbar extension than standing (P = 0.035). Half-squatting and standing postures were not significantly different (P = 0.938). For all postures, L4-5 and L5-S1 segments remained in lordosis, with L4-5 having greater ROM than L5-S1. L1-2 turns kyphotic in lying supine, L2-3 at forward bending, and L3-4 at slump sitting in the form of a "kyphosing cascade." Should the entire lumbar spine be fused in standing position from L1-S1, there would likely be a mean loss of 47.6° of lumbar flexion and 5.9° of lumbar extension., Conclusion: The present study demonstrates the extent of flexibility required of the lumbar spine in assuming various postures. It also enables comparison of the differences in degree of motion occurring in the lumbar spine, both across postures and across segments. Significant loss in ROM, particularly flexion, is anticipated with fusion modeled after the lordotic standing lumbar spine., Level of Evidence: 2.

Background Context: Adult spinal deformity correction sometimes involves long posterior pedicle screw constructs extending from the lumbosacral spine to the thoracic vertebra. As fusion obliterates motion and places supraphysiological stress on adjacent spinal segments, it is crucial to ascertain the ideal upper instrumented vertebra (UIV) to minimize risk of proximal junctional failure (PJF). The T10 vertebra is often chosen to allow bridging of the thoracolumbar junction into the immobile thoracic vertebrae on the basis that it is the lowest immobile thoracic vertebra strut by the rib cage., Purpose: This study aimed to characterize the range of motion (ROM) of each vertebral segment from T7 to S1 to determine if T10 is truly the lowest immobile thoracic vertebra., Study Design/setting: This is a prospective, comparative study., Patient Sample: Seventy-nine adults (mean age of 45.4 years) presenting with low back pain or lower limb radiculopathy or both, without previous spinal intervention, metastases, fractures, infection, or congenital deformities of the spine, were included in the study., Outcome Measures: A ROM >5° across two vertebral segments as determined by the Cobb method from radiographs., Methods: Lumbar flexion-extension and neutral erect radiographs were obtained in randomized order using a slot scanner. Segmental ROM was measured from T7-T8 to L5-S1 and analyzed for significant differences using t tests. Age, gender, radiographical indices such as standard spinopelvic parameters, sagittal vertical axis (SVA), C7-T12 SVA, T1 slope, thoracic kyphosis (TK), and lumbar lordosis (LL) were studied via multivariate analysis to identify predictive factors for >5° change in ROM at the various segmental levels. There were no sources of funding and no conflicts of interest associated with this study., Results: In the thoracolumbar spine, significant decreases in ROM when compared with the adjacent caudad segment occurs up to T9-T10, with mean total ROM of 1.98±1.47° (p<.001) seen in T9-T10, 2.19±1.67° (p<.001) in T10-T11, and 3.92±3.21°(p<.001) in T11-T12. The total ROM of T8-T9 (2.53±1.79°) was not significantly different from that of T9-T10 (p=.261). At the thoracolumbar junction, absence of scoliosis (OR 11.37, p=.020), high pelvic incidence (OR 1.14, p=.046), and low T1 slope (OR 1.45, p=.030) were predictive of ROM >5°., Conclusions: Lumbar spine flexion-extension ROM decreases as it approaches the thoracolumbar junction. T10 is indeed the lowest immobile thoracic vertebra strut by the rib cage, and the last significant decrease in ROM is observed at T9-T10, in relation to T10-T11. However, because this also implies that a UIV of T10 would mean there is only one level of fixation above the relatively mobile segment, while respecting other factors that influence UIV selection, we propose the T9 vertebra as a more ideal UIV to fulfill the biomechanical concept of bridge fixation. However, this decision should still be taken on a case-by-case basis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Review Question/objective: The objective of this review is to identify the experiences of nurses in administering oral medications to residents of aged care facilities with swallowing difficulties.More specifically, the review question is:What problems do nurses experience when administering oral medicines to people with swallowing difficulties living in aged care facilities?

Background Context: Flexion radiographs have been used to identify cases of spinal instability. However, current methods are not standardized and are not sufficiently sensitive or specific to identify instability., Purpose: This study aimed to introduce a new slump sitting method for performing lumbar spine flexion radiographs and comparison of the angular range of motions (ROMs) and displacements between the conventional method and this new method., Study Design: This study used is a prospective study on radiological evaluation of the lumbar spine flexion ROMs and displacements using dynamic radiographs., Patient Sample: Sixty patients were recruited from a single spine tertiary center., Outcome Measure: Angular and displacement measurements of lumbar spine flexion were carried out., Method: Participants were randomly allocated into two groups: those who did the new method first, followed by the conventional method versus those who did the conventional method first, followed by the new method. A comparison of the angular and displacement measurements of lumbar spine flexion between the conventional method and the new method was performed and tested for superiority and non-inferiority., Results: The measurements of global lumbar angular ROM were, on average, 17.3° larger (p<.0001) using the new slump sitting method compared with the conventional method. They were most significant at the levels of L3-L4, L4-L5, and L5-S1 (p<.0001, p<.0001 and p=.001, respectively). There was no significant difference between both methods when measuring lumbar displacements (p=.814)., Conclusion: The new method of slump sitting dynamic radiograph was shown to be superior to the conventional method in measuring the angular ROM and non-inferior to the conventional method in the measurement of displacement., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background Context: Sitting spinal alignment is increasingly recognized as a factor influencing strategy for deformity correction. Considering that most individuals sit for longer hours in a "slumped" rather than in an erect posture, greater understanding of the natural sitting posture is warranted., Purpose: This study aimed to investigate the differences in sagittal spinal alignment between two common sitting postures: a natural, patient-preferred posture; and an erect, investigator-controlled posture that is commonly used in alignment studies., Design/setting: This is a randomized, prospective study of 28 young, healthy patients seen in a tertiary hospital over a 6-month period., Patient Sample: Twenty-eight patients (24 men, 4 women), with a mean age of 24 years (range 19-38), were recruited for this study. All patients with first episode of lower back pain of less than 3 months' duration were included. The exclusion criteria consisted of previous spinal surgery, radicular symptoms, red flag symptoms, previous spinal trauma, obvious spinal deformity on forward bending test, significant personal or family history of malignancy, and current pregnancy., Outcome Measures: Radiographic measurements included sagittal vertical axis (SVA), lumbar lordosis (LL), thoracolumbar angle (TL), thoracic kyphosis (TK), and cervical lordosis (CL). Standard spinopelvic parameters (pelvic incidence, pelvic tilt [PT], and sacral slope) and sagittal apex and end vertebrae were also measured., Methods: Basic patient demographics (age, gender, ethnicity) were recorded. Lateral sitting whole spine radiographs were obtained using a slot scanner in the imposed erect and the natural sitting posture. Statistical analyses of the radiographical parameters were performed comparing the two sitting postures using chi-squared tests for categorical variables and paired t tests for continuous variables., Results: There was forward SVA shift between the two sitting postures by a mean of 2.9 cm (p<.001). There was a significant increase in CL by a mean of 11.62° (p<.001), and TL kyphosis by a mean of 11.48° (p<.001), as well as a loss of LL by a mean of 21.26° (p<.001). The mean PT increased by 17.68° (p<.001). The entire thoracic and lumbar spine has the tendency to form a single C-shaped curve with the apex moving to L1 (p=.002) vertebra in the majority of patients., Conclusions: In a natural sitting posture, the lumbar spine becomes kyphotic and contributes to a single C-shaped sagittal profile comprising the thoracic and the lumbar spine. This is associated with an increase in CL and PT, as well as a constant SVA. These findings lend insight into the body's natural way of energy conservation using the posterior ligamentous tension band while achieving sitting spinal sagittal balance. It also provides information on one of the possible causes of proximal junctional kyphosis or proximal junctional failure., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Chromosomal microarray offers superior sensitivity for identification of submicroscopic copy number variants (CNV) and it is advocated to be the first tier genetic testing for patients with autism spectrum disorder (ASD). In this regard, diagnostic yield of array comparative genomic hybridization (CGH) for ASD patients is determined in a cohort of Chinese patients in Hong Kong., Methods: A combined adult and paediatric cohort of 68 Chinese ASD patients (41 patients in adult group and 27 patients in paediatric group). The genomic DNA extracted from blood samples were analysed by array CGH using NimbleGen CGX-135K oligonucleotide array., Results: We identified 15 CNV and eight of them were clinically significant. The overall diagnostic yield was 11.8 %. Five clinically significant CNV were detected in the adult group and three were in the paediatric group, providing diagnostic yields of 12.2 and 11.1 % respectively. The most frequently detected CNV was 16p13.11 duplications which were present in 4 patients (5.9 % of the cohort)., Conclusions: In this study, a satisfactory diagnostic yield of array CGH was demonstrated in a Chinese ASD patient cohort which supported the clinical usefulness of array CGH as the first line testing of ASD in Hong Kong.

Objective: To assess the safety and efficacy of an early home-based walking program for first-time implantable cardioverter-defibrillator (ICD) recipients., Design: Pre-post intervention trial., Setting: Institutional and private practice., Participants: Cardiac patients (N=301) with an initial ICD implantation for primary or secondary prevention; able to read, speak, and write English; and having access to telephone., Interventions: Early home-based walking protocol implemented 1-month post-ICD implant. Exercise tolerance monitored by study nurses via telephone., Main Outcome Measures: Safety assessment was based on the frequency of ICD therapies and hospitalizations, and efficacy assessment was based on pedometer measures and self-report of ICD self-efficacy and physical activity., Results: ICD recipients were on average 64.1±11.9 years old, predominantly men, and white, with an ejection fraction of <35% and a mean Charlson comorbidity score of 2.3±1.5. Nineteen individuals (6.3%) received 28 ICD shocks; 15 (53.6%) were appropriate and 13 (46.4%) inappropriate. Antitachycardia pacing therapies were delivered 72 times in 18 individuals (6%), with 61 (84.7%) being appropriate and 11 (15.3%) inappropriate. Five ICD shocks (2 appropriate and 3 inappropriate) and 2 antitachycardia pacing therapies occurred during walking. Five participants (2%) were hospitalized for an ICD shock, none of which was associated with walking. Average steps per day increased by 806 over 3 months. Perceived exercise self-efficacy improved significantly as did weekly exercise. Predictors of receiving any ICD shock were younger age (P<.0001), moderate to severe renal disease (P=.001), and lymphoma (P=.024)., Conclusions: Early ambulation after an initial ICD was safe and effective, with few ICD shocks and improved efficacy., (Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

We here report an unusual case of Hb Bart's (γ4) disease. Thalassemia screening of a couple showed that the wife was an α(0)-thalassemia (α(0)-thal) carrier and her husband's mean corpuscular volume (MCV) was normal. Chorionic villus sampling (CVS) was performed at 13 weeks' gestation for positive Down syndrome screening and chromosomal study of the cultured CVS showed a normal karyotype. Ultrasound examination at 22 weeks' gestation showed fetal cardiomegaly and raised middle cerebral artery peak systolic velocity. Cordocentesis confirmed fetal anemia and showed Hb Bart's disease. Multiplex gap-polymerase chain reaction (gap-PCR) for α-thal deletions on DNA extracted from the CVS showed the presence of a homozygous α(0)-thal - -(SEA) (Southeast Asian) deletion. The husband was found to be a carrier of the α(+)-thal -α(3.7) (rightward) deletion. Non paternity was excluded by fluorescent PCR using short tandem repeat (STR) markers on chromosomes 13, 18 and 21. A de novo terminal deletion of chromosome 16 was excluded by array comparative genomic hybridization (aCGH). Detection of uniparental disomy (UPD), using STR markers on chromosome 16 showed maternal uniparental isodisomy from 16pter to 16p13.2, and uniparental heterodisomy from 16p13.13 to 16qter.

Introduction: Autologous bone grafting has been accepted as the gold standard in the treatment of non-unions and in definitive filling of segmental bone defects. However, there have been well-recognised complications associated with their harvest. The Reamer Irrigator Aspirator (RIA) system is an alternative technique of autologous bone graft harvesting. Studies have been published in the Western population showing the efficacy and outcome of this technique. No prior studies were done in the Asian population, who has smaller average canals, different femoral geometry as compared to Caucasians and weaker bone density in both genders. We aim to present the findings and discuss its suitability in the Asian population when dealing with segmental bone loss and non-unions requiring reconstruction., Methods: We conducted a retrospective analysis of all trauma patients with segmental bone loss and non-unions treated with RIA bone grafting over a 4.5 year period. A total of 57 cases of RIA bone grafting were conducted on 53 patients. The amount of bone graft harvested, blood loss and post-operative pain were measured. Patients were followed up for union rate as well as complications of the procedure., Results: Union was achieved in 86.8% of patients. The mean time to union was 17.64 weeks. Seven patients did not achieve union after the first RIA surgery, in which six of seven were open fractures initially and six were smokers. One major intra-operative complication was recorded, that being a fractured femoral shaft due to thinning of the cortex by the RIA harvester. There were two patients who developed donor site superficial soft tissue infection that resolved after a course of antibiotics. There were no long-term complications seen in all patients., Conclusions: The safety and efficacy of RIA bone graft harvesting for the management of non-union in the Asian population is promising, with adequate graft quantities, high success and low complication rates that are comparable to the Caucasian population. The diameter of the medullary canal in our population is suitable for this procedure. We believe that RIA bone graft harvesting provides a reliable and safe alternative source of autologous bone grafts for bone grafting of non-union sites., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Relative to other animal taxa, ecotoxicological studies on amphibians are scarce, even though amphibians are experiencing global declines and pollution has been identified as an important threat. Agricultural lands provide important habitats for many amphibians, but often these lands are contaminated with pesticides. The authors determined the acute toxicity, in terms of 96-h median lethal concentrations, of the carbamate pesticide methomyl on larvae of 3 Asian amphibian species, the Asian common toad (Duttaphrynus melanostictus), the brown tree frog (Polypedates megacephalus), and the marbled pygmy frog (Microhyla pulchra), at 5 different temperatures (15 °C, 20 °C, 25 °C, 30 °C, and 35 °C) to examine the relationships between temperature and toxicity. Significant interspecific variation in methomyl sensitivity and 2 distinct patterns of temperature-dependent toxicity were found. Because high proportions of malformation among the surviving tadpoles were observed, a further test was carried out on the tree frog to determine effect concentrations using malformation as the endpoint. Concentrations as low as 1.4% of the corresponding 96-h median lethal concentrations at 25 °C were sufficient to cause malformation in 50% of the test population. As the toxicity of pesticides may be significantly amplified at higher temperatures, temperature effects should not be overlooked in ecotoxicological studies and derivation of safety limits in environmental risk assessment and management., (© 2015 SETAC.)

Objectives: To investigate the test-retest reliability of JTT in older patients with Parkinson's disease (PD); and to compare the Jebsen Taylor Hand Function Test (JTT) scores between PD and healthy subjects., Study Design: Cross-sectional comparative study., Methods: Fifteen PD and fifteen healthy subjects performed the JTT and the time taken to complete the JTT was recorded., Results: Test-retest reliabilities of JTT subtests and total score of both dominant and non-dominant hand were good to excellent (ICCs = 0.77-0.97) except J5 checkers which had moderate reliability. PD subjects required significantly longer time to finish subtests and the whole JTT (p < 0.05), except the subtest J1 writing of dominant hand that showed marginal significance (p = 0.059)., Conclusion: JTT is a reliable and easily available assessment tool for assessing the hand function of PD subjects. PD subjects took a longer time to complete the JTT, suggesting that they have deficits in gross and fine functional dexterity., (Copyright © 2015 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the clinical impact of chromosomal microarray (CMA) on the management of paediatric patients in Hong Kong., Methods: We performed NimbleGen 135k oligonucleotide array on 327 children with intellectual disability (ID)/developmental delay (DD), autism spectrum disorders (ASD), and/or multiple congenital anomalies (MCAs) in a university-affiliated paediatric unit from January 2011 to May 2013. The medical records of patients were reviewed in September 2013, focusing on the pathogenic/likely pathogenic CMA findings and their "clinical actionability" based on established criteria., Results: Thirty-seven patients were reported to have pathogenic/likely pathogenic results, while 40 had findings of unknown significance. This gives a detection rate of 11% for clinically significant (pathogenic/likely pathogenic) findings. The significant findings have prompted clinical actions in 28 out of 37 patients (75.7%), while the findings with unknown significance have led to further management recommendation in only 1 patient (p < 0.001). Nineteen out of the 28 management recommendations are "evidence-based" on either practice guidelines endorsed by a professional society (n = 9, Level 1) or peer-reviewed publications making medical management recommendation (n = 10, Level 2). CMA results impact medical management by precipitating referral to a specialist (n = 24); diagnostic testing (n = 25), surveillance of complications (n = 19), interventional procedure (n = 7), medication (n = 15) or lifestyle modification (n = 12)., Conclusion: The application of CMA in children with ID/DD, ASD, and/or MCAs in Hong Kong results in a diagnostic yield of ∼ 11% for pathogenic/likely pathogenic results. Importantly the yield for clinically actionable results is 8.6%. We advocate using diagnostic yield of clinically actionable results to evaluate CMA as it provides information of both clinical validity and clinical utility. Furthermore, it incorporates evidence-based medicine into the practice of genomic medicine. The same framework can be applied to other genomic testing strategies enabled by next-generation sequencing.

We report on a baby girl with multiple congenital abnormalities, including cleft palate, intrauterine growth restriction, and double outlet right ventricle (DORV) with ventricular septal defect. She had an unbalanced chromosome translocation t (X;15) resulting in monosomy 15pter → p10 and trisomy Xq13.1 → q28. All three copies of Xq encompass the XIST gene. It is known that X chromosome inactivation could spread to the autosome part of an unbalanced translocation involving chromosome X and an autosome. To confirm the spread of X chromosome inactivation on chromosome 15, we evaluate the methylation change by the HumanMethylation450 BeadChip, a whole genome DNA methylation micorarray that includes 15,259 probes spanning 717 genes on chromosome 15. Results showed there was gain in DNA methylation of more than 20% in 586 CpG sites spanning the long arm of chromosome 15. We further examined the hypermethylated CpG sites located in CpG-island promoter, because genes subjected to X chromosome inactivation will have an increase in DNA methylation level in this region. A total of 75 sites representing 24 genes were hypermethylated. Nearly all of these probes are located in region proximal to the breakpoint, from 15q11.2 to 15q21.3 (35Mb) suggesting that X inactivation was spread to the proximal region of 15q. Gain of DNA methylation, especially in the CpG-island promoter, can result in functional inactivation of genes, and therefore could potentially worsen the phenotype of our patient., (© 2014 Wiley Periodicals, Inc.)

22q11.2 deletion syndrome (22q11.2DS) is a multi-systemic disorder with high phenotypic variability. Under-diagnosis in adults is common and recognition of facial dysmorphic features can be affected by age and ethnicity. This study aims to determine the prevalence of undiagnosed 22q11.2DS in adult Chinese patients with conotruncal anomalies and to delineate their facial dysmorphisms and extra-cardiac manifestations. We recruited consecutively 156 patients with conotruncal anomalies in an adult congenital heart disease (CHD) clinic in Hong Kong and screened for 22q11.2DS using fluorescence-PCR and fluorescence in-situ hybridization. Assessment for dysmorphic features was performed by a cardiologist at initial screening and then by a clinical geneticist upon result disclosure. Clinical photographs were taken and childhood photographs collected. Eighteen patients (11.5%) were diagnosed with 22q11.2DS, translating into 1 previously unrecognized diagnosis of 22q11.2DS in every 10 adult patients with conotruncal anomalies. While dysmorphic features were detected by our clinical geneticist in all patients, only two-thirds were considered dysmorphic by our cardiologist upon first assessment. Evolution of facial dysmorphic features was noted with age. Extra-cardiac manifestations included velopharyngeal incompetence or cleft palate (44%), hypocalcemia (39%), neurodevelopmental anomalies (33%), thrombocytopenia (28%), psychiatric disorders (17%), epilepsy (17%) and hearing loss (17%). We conclude that under-diagnosis of 22q11.2DS in Chinese adults with conotruncal defects is common and facial dysmorphic features may not be reliably recognized in the setting of adult CHD clinic, referral for genetic evaluation and molecular testing for 22q11.2DS should be offered to patients with conotruncal defects., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Objective: To evaluate the effectiveness of whole-genome array comparative genomic hybridization (aCGH) in prenatal diagnosis in Hong Kong., Methods: Array CGH was performed on 220 samples recruited prospectively as the first-tier test study. In addition 150 prenatal samples with abnormal fetal ultrasound findings found to have normal karyotypes were analyzed as a 'further-test' study using NimbleGen CGX-135K oligonucleotide arrays., Results: Array CGH findings were concordant with conventional cytogenetic results with the exception of one case of triploidy. It was found in the first-tier test study that aCGH detected 20% (44/220) clinically significant copy number variants (CNV), of which 21 were common aneuploidies and 23 had other chromosomal imbalances. There were 3.2% (7/220) samples with CNVs detected by aCGH but not by conventional cytogenetics. In the 'further-test' study, the additional diagnostic yield of detecting chromosome imbalance was 6% (9/150). The overall detection for CNVs of unclear clinical significance was 2.7% (10/370) with 0.9% found to be de novo. Eleven loci of common CNVs were found in the local population., Conclusion: Whole-genome aCGH offered a higher resolution diagnostic capacity than conventional karyotyping for prenatal diagnosis either as a first-tier test or as a 'further-test' for pregnancies with fetal ultrasound anomalies. We propose replacing conventional cytogenetics with aCGH for all pregnancies undergoing invasive diagnostic procedures after excluding common aneuploidies and triploidies by quantitative fluorescent PCR. Conventional cytogenetics can be reserved for visualization of clinically significant CNVs.

Copy number gain of 17p13.3 has been shown to be associated with developmental delay/autism and Split-Hand-Foot malformation. We report a case of fetus with bilateral split-hand malformation detected on prenatal ultrasound. Array comparative genomic hybridization detected 2 maternally inherited copy number gains in the 17p13.3 region with one of them involving the BHLHA9 gene and part of the YWHAE gene. The mother is normal in intelligence with mild right foot anomaly only. Although the BHLHA9 copy gain is known to be associated with split-hand-foot malformation, the penetrance and expressivity is highly variable. More challenging is the effect of partial YWHAE copy number gain on neurodevelopment is inconclusive based on current literature. This case highlights the difficulties of prenatal genetic counseling in array comparative genomic hybridization findings in clinical situation with incomplete understanding of genotype-phenotype correlation., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Ecotoxicity tests are often conducted following standard methods, and thus carried out at a fixed water temperature under controlled laboratory conditions. Yet, toxicity of a chemical contaminant may vary in a temperature-dependent manner, depending on the physiology of the test organism and physicochemical properties of the chemical. Although an assessment factor of 10 (AF10) is commonly adopted to account for variability in toxicity data related to temperature in the development of water quality guidelines and/or ecological risk assessment, no one has ever rigorously assessed the appropriateness of AF10 to account for potential variation in temperature-dependent chemical toxicity to aquatic organisms. This study, therefore, aims to address this issue through a meta-analysis by comparing median lethal concentration data for nine chemicals (cadmium, copper, nickel, lead, silver, zinc, arsenic, selenium and DDT) on a range of freshwater ectothermic animal species at different temperatures, and to assess whether AF10 is under- or over-protective for tropical and temperate freshwater ecosystems. Our results reveal varying extents of interaction between temperature and different chemicals on organisms and the complexity of these interactions. Applying AF10 sufficiently protects 90% of the animal species tested over a range of temperatures for cadmium, copper, nickel, silver, zinc and DDT in the tropics, but it is insufficient to adequately encompass a larger temperature variation for most studied chemicals in temperate regions. It is therefore important to set specific AFs for different climatic zones in order to achieve the desired level of ecosystem protection.

The authors present 2 unusual cases of haemoglobin (Hb) Bart's hydrops fetalis and highlight the problem of a screening system for α-thalassaemia which focuses on maternal and paternal mean corpuscular volume (MCV) alone. Normal paternal MCV may not preclude fetal Hb Bart's disease because of the rare occurrence of maternal uniparental disomy or non-paternity. During a mid-trimester anomaly scan, with fetal cardiomegaly or hydrops in a woman with low MCV but normal paternal MCV, obstetricians should remain alert for fetal Hb Bart's disease. This is very important and relevant for national screening systems in South-East Asia, where a routine mid-trimester scan may not be available. A routine mid-trimester anomaly scan should therefore be implemented and in high prevalence areas, sonographers should be sensitive to the cardio-thoracic ratio even if screening shows that pregnancy is unlikely to be at risk., (© 2013 S. Karger AG, Basel.)

We report on a male infant with de novo unbalanced t(5;15) translocation resulting in a 17.23 Mb deletion within 15q11.2-q14 and a 25.12 kb deletion in 5pter. The 15q11.2-q14 deletion encompassed the 15q11.2-q13 Prader-Willi syndrome (PWS) critical region and the recently described 15q13.3 microdeletion syndrome region while the 5pter deletion contained no RefSeq genes. From our literature review, patients with similar deletions in chromosome 15q exhibit expanded phenotype of severe developmental delay, protracted feeding problem, absent speech, central visual impairment, congenital malformations and epilepsy in addition to those typical of PWS. The patient reported herein had previously unreported anomalies of mega cisterna magna, horseshoe kidney and the rare neonatal interstitial lung disease known as pulmonary interstitial glycogenosis. Precise breakpoint delineation by microarray is useful in patients with atypical PWS deletions to guide investigation and prognostication., (Copyright © 2013 Wiley Periodicals, Inc.)

Zein was investigated for use as an oral-drug delivery system by loading prednisolone into zein microparticles using coacervation. To investigate the adaptability of this method to other drugs, zein microparticles were loaded with hydrocortisone, which is structurally related to prednisolone; or mesalazine, which is structurally different having a smaller LogP and ionizable functional groups. Investigations into the in vitro digestibility, and the electrophoretic profile of zein, and zein microparticles were conducted to shed further insight on using this protein as a drug delivery system. Hydrocortisone loading into zein microparticles was comparable with that reported for prednisolone, but mesalazine loading was highly variable. Depending on the starting quantities of hydrocortisone and zein, the average amount of microparticles equivalent to 4 mg hydrocortisone, (a clinically used dose), ranged from 60-115 mg, which is realistic and practical for oral dosing. Comparatively, an average of 2.5 g of microparticles was required to deliver 250 mg of mesalazine (a clinically used dose), so alternate encapsulation methods that can produce higher and more precise mesalazine loading are required. In vitro protein digestibility revealed that zein microparticles were more resistant to digestion compared to the zein raw material, and that individual zein peptides are not preferentially coacervated into the microparticles. In combination, these results suggest that there is potential to formulate a delivery system based on zein microparticles made using specific subunits of zein that is more resistant to digestion as starting material, to deliver drugs to the lower gastrointestinal tract.

Fetal DNA is present in the plasma of pregnant women. Massively parallel sequencing of maternal plasma DNA has been used to detect fetal trisomies 21, 18, 13 and selected sex chromosomal aneuploidies noninvasively. Case reports describing the detection of fetal microdeletions from maternal plasma using massively parallel sequencing have been reported. However, these previous reports were either polymorphism-dependent or used statistical analyses which were confined to one or a small number of selected parts of the genome. In this report, we reported a procedure for performing noninvasive prenatal karyotyping at 3 Mb resolution across the whole genome through the massively parallel sequencing of maternal plasma DNA. This method has been used to analyze the plasma obtained from 6 cases. In three cases, fetal microdeletions have been detected successfully from maternal plasma. In two cases, fetal microduplications have been detected successfully from maternal plasma. In the remaining case, the plasma DNA sequencing result was consistent with the pregnant mother being a carrier of a microduplication. Simulation analyses were performed for determining the number of plasma DNA molecules that would need to be sequenced and aligned for enhancing the diagnostic resolution of noninvasive prenatal karyotyping to 2 Mb and 1 Mb. In conclusion, noninvasive prenatal molecular karyotyping from maternal plasma by massively parallel sequencing is feasible and would enhance the diagnostic spectrum of noninvasive prenatal testing.