The immediate effects of passive hip joint mobilization on hip abductor/external rotator muscle strength in patients with anterior knee pain and impaired hip function. A randomized, placebo-controlled crossover trial.

BACKGROUND: Anterior knee pain (AKP) is often associated with persistent hip muscle weakness and facilitatory interventions may be beneficial for managing patients with AKP (pwAKP). Physiotherapists often employ passive oscillatory hip joint mobilizations to increase hip muscle function. However, there is little information about their effectiveness and the mechanisms of action involved. OBJECTIVES: To investigate the immediate effects of passive hip joint mobilization on eccentric hip abductor/external rotator muscle strength in pwAKP with impaired hip function. DESIGN: A double-blinded, randomized, placebo-controlled crossover design. METHOD: Eighteen patients with AKP participated in two sessions of data collection with one week apart. They received passive hip joint mobilization or placebo mobilization in a randomized order. Eccentric hip muscle strength was measured immediately before and after each intervention using a portable hand-held dynamometer. RESULTS: An ANCOVA with the sequence of treatment condition as the independent variable, the within-subject post-treatment differences as the dependent variable and the within-subject pre-treatment differences as the covariate was conducted. Patients showed a significant mean increase in eccentric hip muscle strength of 7.73% (p = 0.001) for the mobilization condition, compared to a mean decrease of 4.22% for the placebo condition. Seventeen out of eighteen participants reported having no pain during any of the strength testing. CONCLUSION: These data suggest that passive hip joint mobilization has an immediate positive effect on eccentric hip abductor/external rotator muscle strength in pwAKP with impaired hip function, even in the absence of current pain

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Population Pharmacokinetics and Pharmacodynamics of Caspofungin in Pediatric Patients▿†

We describe the pharmacokinetics (PKs) of caspofungin, an echinocandin antifungal, administered once daily as a 1-hour intravenous infusion in children and adolescents (ages, 3 months to 17 years), based on pooled data from four prospective pediatric studies. Caspofungin dosing was body-surface-area (BSA) based (50 mg/m2 daily after 70 mg/m2 on day 1). The area under the concentration-time curve from time zero to 24 h (AUC0–24), the concentration at the end of infusion (1 h after the start of infusion; C1), and the trough concentration (24 h after the start of infusion; C24) were obtained for 32 pediatric patients with invasive candidiasis, 10 with invasive aspergillosis, and 82 in the setting of empirical therapy with fever and neutropenia. Exposures were modestly higher (93 to 134% for C1, 45 to 78% for C24, ∼40% for AUC0–24) in pediatric patients than in adults receiving the standard 50-mg daily dose. The potential for covariates (age, gender, weight, race, renal status, serum albumin level, and disease state) to alter PKs was evaluated with a multiple-linear-regression model. Weight and disease state had statistically significant (P < 0.05) yet small effects on caspofungin PKs in pediatric patients. Concomitant use of dexamethasone (a cytochrome p450 inducer) was associated with a statistically significant reduction (44%) in C24 in a limited number of patients (n = 4). Odds ratios were estimated for the association between log-transformed PKs and treatment outcome or adverse events. No PK parameter or hybrid parameter (AUC/MIC, C1/MIC, and C24/MIC) was significantly correlated with treatment outcome or adverse events in the setting of similar response levels as adults, which suggests that the concentrations examined fall within the therapeutic window for caspofungin in pediatric patients. These results support a 50-mg/m2 daily dosing regimen (after a 70-mg/m2 loading dose) in children ages 3 months to 17 years

Prevalence and risk factors of chlamydia infection in Hong Kong: A population-based geospatial household survey and testing

Background: Chlamydia causes infertility and increases risk of HIV infection, and population-based studies provide essential information for effective infection control and prevention. This study examined Chlamydia trachomatis prevalence and risk factors among a representative sample of 18-49-year-old residents in Hong Kong. Methods: Census boundary map of 412 constituency areas was used as primary sampling units to construct the sampling frame and, residential buildings and units were randomly selected using geospatial modelling. A questionnaire on sexual practice and health was conducted, and polymerase chain reaction was used to test the urine for genital chlamydial infection. Invitation letters were sent to the selected households and a team of interviewers were sent to recruit one subject per household. Prevalence data was weighted according to the 2011 census and risk factors identified through logistic regression. Results: Among 881 participants (response rate of 24.5%), the overall Chlamydia trachomatis prevalence was low at 1.4% (95%CI 0.8–2.5%) but sexually active young (18–26 years) women had relatively high prevalence (5.8%, 95%CI 1.7–18.2%) in Hong Kong. A unique U-shape disease burden was observed with peaks in younger and older (40–49 years) women. Amongst the sexually active women, the risk factors of Chlamydia trachomatis infection were: younger age (aOR = 25.4, 95% CI 2.81–230); living alone (aOR = 8.99, 95% CI 1.46–55.40); and, among all the sexually active participants, males (including the male partners of the female participants) who had travelled out of Hong Kong in the previous 12 months had higher risks of infection (aOR = 5.35; 95% CI 1.25–22.8). A core-peripheral geographical distribution of Chlamydia trachomatis prevalence was also observed. Conclusion: Young and older sexually active women in Hong Kong have high prevalence of chlamydia. Routine screening for sexually active women and young men should be considered. Further research on testing feasibility and linkage-to-care are urgently needed to control the infection.</p

Correction: Prevalence and risk factors of chlamydia infection in Hong Kong: A population-based geospatial household survey and testing.

[This corrects the article DOI: 10.1371/journal.pone.0172561.]