On the necessity of different statistical treatment for Illumina BeadChip and Affymetrix GeneChip data and its significance for biological interpretation

<p>Abstract</p> <p>Background</p> <p>The original spotted array technology with competitive hybridization of two experimental samples and measuring relative expression levels is increasingly displaced by more accurate platforms that allow determining absolute expression values for a single sample (for example, Affymetrix GeneChip and Illumina BeadChip). Unfortunately, cross-platform comparisons show a disappointingly low concordance between lists of regulated genes between the latter two platforms.</p> <p>Results</p> <p>Whereas expression values determined with a single Affymetrix GeneChip represent single measurements, the expression results obtained with Illumina BeadChip are essentially statistical means from several dozens of identical probes. In the case of multiple technical replicates, the data require, therefore, different stistical treatment depending on the platform. The key is the computation of the squared standard deviation within replicates in the case of the Illumina data as weighted mean of the square of the standard deviations of the individual experiments. With an Illumina spike experiment, we demonstrate dramatically improved significance of spiked genes over all relevant concentration ranges. The re-evaluation of two published Illumina datasets (membrane type-1 matrix metalloproteinase expression in mammary epithelial cells by Golubkov et al. Cancer Research (2006) 66, 10460; spermatogenesis in normal and teratozoospermic men, Platts et al. Human Molecular Genetics (2007) 16, 763) significantly identified more biologically relevant genes as transcriptionally regulated targets and, thus, additional biological pathways involved.</p> <p>Conclusion</p> <p>The results in this work show that it is important to process Illumina BeadChip data in a modified statistical procedure and to compute the standard deviation in experiments with technical replicates from the standard errors of individual BeadChips. This change leads also to an improved concordance with Affymetrix GeneChip results as the spermatogenesis dataset re-evaluation demonstrates.</p> <p>Reviewers</p> <p>This article was reviewed by I. King Jordan, Mark J. Dunning and Shamil Sunyaev.</p

Not all transmembrane helices are born equal: Towards the extension of the sequence homology concept to membrane proteins

<p/> <p>Background</p> <p>Sequence homology considerations widely used to transfer functional annotation to uncharacterized protein sequences require special precautions in the case of non-globular sequence segments including membrane-spanning stretches composed of non-polar residues. Simple, quantitative criteria are desirable for identifying transmembrane helices (TMs) that must be included into or should be excluded from start sequence segments in similarity searches aimed at finding distant homologues.</p> <p>Results</p> <p>We found that there are two types of TMs in membrane-associated proteins. On the one hand, there are so-called simple TMs with elevated hydrophobicity, low sequence complexity and extraordinary enrichment in long aliphatic residues. They merely serve as membrane-anchoring device. In contrast, so-called complex TMs have lower hydrophobicity, higher sequence complexity and some functional residues. These TMs have additional roles besides membrane anchoring such as intra-membrane complex formation, ligand binding or a catalytic role. Simple and complex TMs can occur both in single- and multi-membrane-spanning proteins essentially in any type of topology. Whereas simple TMs have the potential to confuse searches for sequence homologues and to generate unrelated hits with seemingly convincing statistical significance, complex TMs contain essential evolutionary information.</p> <p>Conclusion</p> <p>For extending the homology concept onto membrane proteins, we provide a necessary quantitative criterion to distinguish simple TMs (and a sufficient criterion for complex TMs) in query sequences prior to their usage in homology searches based on assessment of hydrophobicity and sequence complexity of the TM sequence segments.</p> <p>Reviewers</p> <p>This article was reviewed by Shamil Sunyaev, L. Aravind and Arcady Mushegian.</p

Novosti u artroskopskoj kirurgiji ručnog zgloba: od resekcije do rekonstrukcije

One of the major advances in wrist arthroscopy is the development of various therapeutic procedures since the 90’s. Therapeutic procedures are no longer restricted to resection. More specific repair procedures and functional reconstruction involving replenishment of tissue defect and augmentation of vital structures are seen with proven value. In particular, wrist arthroscopy performed under local anaesthetic setting without tourniquet and sedation markedly reduces the risk and cost. This article highlights the common indications and applications of wrist arthroscopy, with emphasis on the latest and significant innovations in reconstructive arthroscopic surgery in Hong Kong. On the resection aspect, common procedures include joint debridement, synovectomy, ganglionectomy, capsular release and osteotomies. Reparative surgery includes ligament repair, arthroscopic assisted reduction and fixation of fracture dislocation and chondroplasty for small chondral lesions. Reconstructive surgery embraces surgical solutions tackling on osseous, soft tissue and cartilage problems. Scaphoid nonunion can be treated by arthroscopic bone grafting and percutaneous fixation with union rate of over 90 %. Partial wrist fusion can be achieved arthroscopically to maximize motion and to enhance union by preserving soft tissue and vascularity. Arthroscopic assisted reconstruction of the radio-ulnar ligaments with tendon graft can be performed to treat chronic distal radioulnar joint instability through bone tunnels in sigmoid notch and ulnar fovea. In chronic scapholunate (SL) instability, the dorsal and palmar portion of the SL interosseous ligament is reconstituted anatomically through arthroscopically assisted reconstruction with tendon graft in a box-like structure. In cartilage reconstruction, post–traumatic chondral lesion can be treated with arthroscopic osteochondral transplant.Od uvođenja artroskopije ručnog zgloba 90-ih godina prošloga stoljeća počinje razvoj i uvođenje brojnih novih terapijskih postupaka. Zahvati više nisu ograničeni samo na resekcije, već se počinje s razvojem reparacijskih i funkcionalnih rekonstrukcija, kao što su popunjavanje defekata i augmentacija vitalnih struktura. Artroskopija ručnog zgloba izvedena u lokalnoj anesteziji i bez Torniquetove poveske značajno smanjuje i cijenu zahvata. U ovom radu istaknute su najčešće indikacije i primjena artroskopija ručnog zgloba s naglaskom na najnoviji zahvat artroskopske rekonstrukcije ručnog zgloba u Hong Kongu. Glede resekcija, najčešći zahvati uključuju debridman zgloba, sinovijektomiju, ganglionekotimiju, opuštanje zglobne čahure i oteotomiju. Reparativni zahvati uključuju rekonstrukcije ligamenata, artroskopski asistirane repozicije i fiksacije prijeloma i luksacija te hondroplastike. Rekonstruktivni zahvati obuhvaćaju zahvate na kostima, mekim tkivima i hrskavici. Nesraštanje skafoidne kosti može se liječiti artroskopski s koštanim presadcima i perkutanim fiksacijama, a uspješnost cijeljenja je veća od 90 %. Djelomične artrodeze mogu se provesti artroskopski kako bi se očuvala pokretljivost ostalih dijelova i pojačalo cijeljenje očuvanjem mekih tkiva i vaskularizacije. Artroskopski asistirana rekonstrukcija radioularnih ligamenata s tetivnim transplantatima može se izvoditi pri kroničnim nestabilnostima distalnog radioulnarnog zgloba. Pri kroničnoj skafolunatnoj nestabilnosti, dorzalni i palmarni dio SL ligamenta mogu se anatomski rekonstruirati tetivnim presadcima. Posttraumatska hrskavična oštećenja mogu se liječiti artroskopski primjenom koštano-hrskavičnih transplantata

Effectiveness of a technology-based injury prevention program for enhancing mothers’ knowledge of child safety: protocol for a randomized controlled trial

Background: Provision of anticipatory guidance for parents is recommended as an effective strategy to prevent injuries among young children. Technology-based anticipatory guidance has been suggested to reinforce the effectiveness of injury prevention and improve parents’ knowledge of child safety. Objective: This study aims to examine the effectiveness of a technology-based injury prevention program with parental anticipatory guidance for enhancing mothers’ knowledge of child safety. Methods: In this randomized controlled trial, 308 mothers will be recruited from the antenatal clinics and postnatal wards of two major public hospitals in Hong Kong. Participating mothers will be randomly assigned into intervention and control groups. Mothers in the intervention group will be given free access to a technology-based injury prevention program with anticipatory guidance, whereas mothers in the control group will be given a relevant booklet on parenting. The injury prevention program, available as a website or on a mobile app, includes behavioral components based on the Theory of Planned Behavior. The primary outcome measure will be the change in the mother’s knowledge of child safety. The secondary outcome measures will be age-appropriate domestic safety knowledge, attitudes, intentions, perceived behavioral control, and self-reported behavior related to home safety practice. We will also determine dose-response relationships between the outcome measures and the website and mobile app usage. Results: Enrolment of participants will begin in October 2016. Results are expected by June 2018. Conclusions: Parents will be able to easily access the domestic injury prevention website to find information regarding child injury prevention. It is anticipated that the technology-based intervention will help parents improve their knowledge of child safety and raise their awareness about the consequences of domestic injuries and the importance of prevention. Trial Registration: Clinicaltrials.gov Clinicaltrials.gov NCT02835768; http://clinicaltrials.gov/ct2/show/NCT02835768 (Archived by WebCite at http://www.webcitation/6lbXYM6b9)

A qualitative exploration of the healthcare challenges and pharmaceutical care needs of people with Parkinson's and their caregivers

Background: People with Parkinson's are at higher risk of healthcare and pharmaceutical care issues. Objective: To determine the healthcare challenges, pharmaceutical care needs, and perceived need of a pharmacist-run clinic by people with Parkinson’s and their caregivers. Setting: Malaysian Parkinson's Disease Association Method: A focus group discussion adopting a descriptive qualitative approach was conducted involving people with Parkinson's and their caregivers. A semi-structured interview guide was used to determine the challenges they faced with their medications and healthcare system, their pharmaceutical care needs, and their views on a pharmacist-run clinic. Data was thematically analysed. Main outcome measure: Healthcare challenges faced by people with Parkinson's and caregivers along with their pharmaceutical care needs and perceived need of a pharmacist-run clinic. Results: Nine people with Parkinson's and four caregivers participated. Six themes were developed: 1) "It's very personalised": the need for self-experimentation, 2) "Managing it is quite difficult": challenges with medication, 3) "The doctor has no time for you": challenges with healthcare providers, 4) "Nobody can do it except me": challenges faced by caregivers, 5) "It becomes a burden": impact on quality of life, and 6) "Lack of consistency could be counterproductive": views on pharmacist-run clinic. Conclusion: The provision of pharmaceutical care services by pharmacists could help overcome issues people with Parkinson's face, however there is a need for them to first see pharmacists in their expanded roles and change their limited perception of pharmacists. This can be achieved through integration of pharmacists within multidisciplinary teams in specialist clinics which they frequent

Association of maternal levothyroxine use during pregnancy with offspring birth and neurodevelopmental outcomes: a population-based cohort study

BACKGROUND: The influence of maternal levothyroxine treatment during pregnancy remains unclear. This study aimed to evaluate the associations of maternal levothyroxine treatment during pregnancy with the birth and neurodevelopmental outcomes in offspring. METHODS: This population-based cohort study was conducted among pregnant women using the Hong Kong Clinical Data Analysis and Reporting System. Mother-child pairs in Hong Kong from 2001 to 2015 were included and children were followed up till 2020. We defined the exposure group as mothers who were exposed to levothyroxine during pregnancy. Preterm birth and small for gestational age (SGA) were included as birth outcomes. Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) were included as neurodevelopmental outcomes. Odds ratios (OR) or hazard ratios (HRs) with a 95% confidence interval (CI) were evaluated to assess the association of gestational levothyroxine use with offspring birth and neurodevelopmental outcomes respectively, using propensity score fine-stratification weighting and a Cox proportional hazards regression model. RESULTS: Among 422,156 mother-child pairs, 2125 children were born from mothers exposed to levothyroxine during pregnancy. A significantly increased risk of preterm birth was observed in children with maternal levothyroxine exposure during pregnancy, when compared to mothers who had no history of thyroid-related diagnoses or prescriptions (weighted OR [wOR]: 1.22, 95% CI: 1.07, 1.39). Similarly, an increased risk of preterm birth was found among children of gestational levothyroxine users, when compared to children of mothers who had used levothyroxine before but stopped during pregnancy (wOR: 2.16, 95% CI: 1.09, 4.25). Sensitivity analysis, by excluding mothers exposed to psychotropic or antiepileptic medications before or during pregnancy, also indicated a similar increased risk of preterm birth regarding the gestational use of levothyroxine (wOR: 1.26, 95% CI: 1.10, 1.45). No significant association was observed for the risk of SGA, ADHD, and ASD. CONCLUSIONS: There is no evidence that gestational use of levothyroxine is associated with SGA, ADHD, or ASD in offspring. Gestational levothyroxine treatment is associated with a higher risk of preterm birth. Such risk might be confounded by the underlying maternal thyroid disease itself, however, we cannot completely exclude the possible effect of gestational L-T4 treatment on offspring preterm birth. Our findings provided support to the current guidelines on the cautious use of levothyroxine treatment during pregnancy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02586-9

Transmitted drug resistance in recently infected HIV-positive Individuals from four urban locations across Asia (2007–2010) – TASER-S

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Phylodynamics of HIV-1 Subtype B among the Men-Having-Sex-with-Men (MSM) Population in Hong Kong

The men-having-sex-with-men (MSM) population has become one of the major risk groups for HIV-1 infection in the Asia Pacific countries. Hong Kong is located in the centre of Asia and the transmission history of HIV-1 subtype B transmission among MSM remained unclear. The aim of this study was to investigate the transmission dynamics of HIV-1 subtype B virus in the Hong Kong MSM population. Samples of 125 HIV-1 subtype B infected MSM patients were recruited in this study. Through this study, the subtype B epidemic in the Hong Kong MSM population was identified spreading mainly among local Chinese who caught infection locally. On the other hand, HIV-1 subtype B infected Caucasian MSM caught infection mainly outside Hong Kong. The Bayesian phylogenetic analysis also indicated that 3 separate subtype B epidemics with divergence dates in the 1990s had occurred. The first and latest epidemics were comparatively small-scaled; spreading among the local Chinese MSM while sauna-visiting was found to be the major sex partner sourcing reservoir for the first subtype B epidemic. However, the second epidemic was spread in a large-scale among local Chinese MSM with a number of them having sourced their sex partners through the internet. The epidemic virus was estimated to have a divergence date in 1987 and the infected population in Hong Kong had a logistic growth throughout the past 20 years. Our study elucidated the evolutionary and demographic history of HIV-1 subtype B virus in Hong Kong MSM population. The understanding of transmission and growth model of the subtype B epidemic provides more information on the HIV-1 transmission among MSM population in other Asia Pacific high-income countries