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Proximal femoral deformities can occur in children as sequelae of several disorders such as hip joint infection or avascular necrosis of the femoral head. Early surgical correction of deformities promises a good result; however, limited exposure of the surgical field often creates difficulties for surgeons. Application of a rapid prototyping model for proximal femoral corrective osteotomy in children serves not only as a guide for surgical planning but also as a communication tool between physicians and patients. [ABSTRACT FROM AUTHOR]

Cell sampling is a key step performed regularly throughout the cell manufacturing process to gather cell samples for cell growth, progress, and characteristics analysis. While the current method of sampling by pipetting in a biosafety cabinet is commonly used, it is labour-intensive and susceptible to contamination risks. We have developed Device for Automated Aseptic Sampling (DAAS), to enable automated, small volume (0.02-1.00 mL) aseptic sampling with minimal dead volume primarily for cell and gene therapy manufacturing. The aim of DAAS is to enable an accurate and consistent sampling process, with minimal contamination risks and interruption to the cells in culture. DAAS can potentially interface with other automated solutions to enable automated and streamlined cell manufacturing workflow and reduce overall manufacturing costs. DAAS has been verified as an aseptic sampling solution via repeated microbial ingression tests. It has also been tested for achieving comparable cell density and viability compared to manual pipetting, with negligible cross-sample carryover when used to sample Jurkat cells of different cell concentrations. The application of using DAAS to sample cell periodically and monitor cell growth and viability continuously for prolonged cell culture was successfully demonstrated with Jurkat cell culture in a static culture flask and donor T cell culture in an automated bioreactor system over a culture duration of 10 days in a Biosafety Level-2 laboratory. Overall, DAAS presents great potential as an automated and aseptic sampling solution, offering cell and gene therapy manufacturers easier and more frequent access to cell samples with minimal interruptions to the cell culture. This enables close monitoring of cell culture and a more automated, connected and cost-effect cell and gene therapy manufacturing process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dan, Ying Ying, Prabhu, bin Abdul Rahim and Jia Sheng.)

Background: Personality traits have been proposed as risk factors for depressive symptoms. However, the neural mechanism behind these relationships is unclear. This study examined the possible mediating effect of resting-state functional connectivity networks on these relationships., Methods: Data from 153 healthy Germans were obtained from the MPI-Leipzig Mind-Brain-Body: Neuroanatomy & Connectivity Protocol database. Network-based statistics were used to identify significant functional connectivity networks that were positively and negatively associated with the personality traits of neuroticism, conscientiousness, and extraversion, with and without demographical covariates. Mediation analyses were performed for each personality trait and depressive symptoms with the significant positive and negative network strengths of the respective personality traits as mediators., Results: Neuroticism, conscientiousness, and extraversion were significantly correlated with depressive symptoms. Network-based statistics identified patterns of functional connectivity that were significantly associated with neuroticism and conscientiousness. After controlling for demographical covariates, significant conscientiousness-associated and extraversion-associated networks emerged. Mediation analysis concluded that only the neuroticism-positive network mediated the effect of neuroticism on depressive symptoms. When age and sex were controlled, the extraversion-positive network completely mediated the effect of extraversion on depressive symptoms., Conclusions: These findings revealed that patterns of intrinsic functional networks predict personality traits and suggest that the relationship between personality traits and depressive symptoms may in part be due to their common patterns of intrinsic functional networks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Despite ongoing improvements to regimens preventing allograft rejection, most cardiac and other organ grafts eventually succumb to chronic vasculopathy, interstitial fibrosis, or endothelial changes, and eventually graft failure. The events leading to chronic rejection are still poorly understood and the gut microbiota is a known driving force in immune dysfunction. We previously showed that gut microbiota dysbiosis profoundly influences the outcome of vascularized cardiac allografts and subsequently identified biomarker species associated with these differential graft outcomes., Methods: In this study, we further detailed the multifaceted immunomodulatory properties of protolerogenic and proinflammatory bacterial species over time, using our clinically relevant model of allogenic heart transplantation., Results: In addition to tracing longitudinal changes in the recipient gut microbiome over time, we observed that Bifidobacterium pseudolongum induced an early anti-inflammatory phenotype within 7 d, whereas Desulfovibrio desulfuricans resulted in a proinflammatory phenotype, defined by alterations in leukocyte distribution and lymph node (LN) structure. Indeed, in vitro results showed that B pseudolongum and D desulfuricans acted directly on primary innate immune cells. However, by 40 d after treatment, these 2 bacterial strains were associated with mixed effects in their impact on LN architecture and immune cell composition and loss of colonization within gut microbiota, despite protection of allografts from inflammation with B pseudolongum treatment., Conclusions: These dynamic effects suggest a critical role for early microbiota-triggered immunologic events such as innate immune cell engagement, T-cell differentiation, and LN architectural changes in the subsequent modulation of protolerant versus proinflammatory immune responses in organ transplant recipients., Competing Interests: This work was supported by the National Institute of Health (NIH), National Heart, Lung, and Blood Institute award R01HL148672 (J.S.B./B.M.), U01AI170050 (B.M./J.S.B.), and National Institute of Allergy and Infectious Diseases training grant T32AI95190-10 (S.J.G.). An earlier version of this article has been released as a preprint on bioRxiv ( https://doi.org/10.1101/2022.10.13.511915 ). E.F.M. contributed to this work as an employee of the University of Maryland School of Medicine. The views expressed in this article are his own and do not necessarily represent the views of the NIH or the US Government. The other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background : Maximizing survival for patients with primary cutaneous melanomas (melanomas) depends on an early diagnosis and appropriate management. Several new drugs have been shown to improve survival in high-risk melanoma patients. Despite well-documented guidelines, many patients do not receive optimal management, particularly when considering patient age. Objective : to provide an update on melanoma management from the time of the decision to biopsy a suspicious skin lesion. Methods : We reviewed melanoma-management research published between 2018 and 2023 and identified where such findings impact and update the management of confirmed melanomas. Pubmed, Google Scholar, Ovid and Cochrane Library were used as search tools. Results : We identified 81 publications since 2017 that have changed melanoma management; 11 in 2018, 12 in 2019, 10 in 2020, 12 in 2021, 17 in 2022 and 18 in 2023. Discussion : Delayed or inaccurate diagnosis is more likely to occur when a partial shave or punch biopsy is used to obtain the histopathology. Wherever feasible, a local excision with a narrow margin should be the biopsy method of choice for a suspected melanoma. The Breslow thickness of the melanoma remains the single most important predictor of outcome, followed by patient age and then ulceration. The BAUSSS biomarker, (Breslow thickness, Age, Ulceration, Subtype, Sex and Site) provides a more accurate method of determining mortality risk than older currently employed approaches, including sentinel lymph node biopsy. Patients with metastatic melanomas and/or nodal disease should be considered for adjuvant drug therapy (ADT). Further, high-risk melanoma patients are increasingly considered for ADT, even without disease spread. Invasive melanomas less than 1 mm thick are usually managed with a radial excision margin of 10 mms of normal skin. If the thickness is 1 to 2 mm, select a radial margin of 10 to 20 mm. When the Breslow thickness is over 2 mm, a 20 mm clinical margin is usually undertaken. In situ melanomas are usually managed with a 5 to 10 mm margin or Mohs margin control surgery. Such wide excisions around a given melanoma is the only surgery that can be regarded as therapeutic and required. Patients who have had one melanoma are at increased risk of another melanoma. Ideal ongoing management includes regular lifelong skin checks. Total body photography should be considered if the patient has many naevi, especially when atypical/dysplastic naevi are identified. Targeted approaches to improve occupational or lifestyle exposure to ultraviolet light are important. Management also needs to include the consideration of vitamin D supplementary therapy.

Bifidobacterium is a widely distributed commensal bacterial genus that displays beneficial pro-homeostatic and anti-inflammatory immunomodulatory properties. Depletion or absence of Bifidobacterium in humans and model organisms is associated with autoimmune responses and impaired immune homeostasis. At the cellular level, Bifidobacterium upregulates suppressive regulatory T cells, maintains intestinal barrier function, modulates dendritic cell and macrophage activity, and dampens intestinal Th2 and Th17 programs. While there has been a large volume of literature characterizing the probiotic properties of various Bifidobacterial species, the likely multifactorial mechanisms underlying these effects remain elusive, in particular, its immune tolerogenic effect. However, recent work has shed light on Bifidobacterium surface structural polysaccharide and protein elements, as well as its metabolic products, as commensal mediators of immune homeostasis. This review aims to discuss several mechanisms Bifidobacterium utilizes for immune modulation as well as their indirect impact on the regulation of gut microbiome structure and function, from structural molecules to produced metabolites. These mechanisms are pertinent to an increasingly networked understanding of immune tolerance and homeostasis in health and disease.

Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Adenosine triphosphate-binding cassette (ABC) transporters, such as multidrug resistance protein 1 (MRP1), protect against cellular toxicity by exporting xenobiotic compounds across the plasma membrane. However, constitutive MRP1 function hinders drug delivery across the blood-brain barrier, and MRP1 overexpression in certain cancers leads to acquired multidrug resistance and chemotherapy failure. Small-molecule inhibitors have the potential to block substrate transport, but few show specificity for MRP1. Here we identify a macrocyclic peptide, named CPI1, which inhibits MRP1 with nanomolar potency but shows minimal inhibition of a related multidrug transporter P-glycoprotein. A cryoelectron microscopy (cryo-EM) structure at 3.27 Å resolution shows that CPI1 binds MRP1 at the same location as the physiological substrate leukotriene C4 (LTC 4 ). Residues that interact with both ligands contain large, flexible sidechains that can form a variety of interactions, revealing how MRP1 recognizes multiple structurally unrelated molecules. CPI1 binding prevents the conformational changes necessary for adenosine triphosphate (ATP) hydrolysis and substrate transport, suggesting it may have potential as a therapeutic candidate.

Glycerol-3-phosphate acyltransferase (GPAT)1 is a mitochondrial outer membrane protein that catalyzes the first step of de novo glycerolipid biosynthesis. Hepatic expression of GPAT1 is linked to liver fat accumulation and the severity of nonalcoholic fatty liver diseases. Here we present the cryo-EM structures of human GPAT1 in substrate analog-bound and product-bound states. The structures reveal an N-terminal acyltransferase domain that harbors important catalytic motifs and a tightly associated C-terminal domain that is critical for proper protein folding. Unexpectedly, GPAT1 has no transmembrane regions as previously proposed but instead associates with the membrane via an amphipathic surface patch and an N-terminal loop-helix region that contains a mitochondrial-targeting signal. Combined structural, computational and functional studies uncover a hydrophobic pathway within GPAT1 for lipid trafficking. The results presented herein lay a framework for rational inhibitor development for GPAT1., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: This systematic review and meta-analysis aim to synthesize the extant literature reporting the effects of COVID-19 pandemic based on the pooled prevalence of depression among affected populations in Asia Pacific, as well as its risk factors., Method: A systematic review and meta-analysis approach was adopted as per the PRISMA guidelines, targeting articles published in PubMed, Google Scholar and Scopus from January 2021 to March 30, 2021. The screening resulted in 82 papers., Results: The overall pooled depression prevalence among 201,953 respondents was 34% (95%CI, 29-38, 99.7%), with no significant differences observed between the cohorts, timelines, and regions (p > 0.05). Dominant risk factors found were fear of COVID-19 infection (13%), gender (i.e., females; 12%) and deterioration of underlying medical conditions (8.3%), regardless of the sub-groups. Specifically, fear of COVID-19 infection was the most reported risk factor among general population (k = 14) and healthcare workers (k = 8). Gender (k = 7) and increased workload (k = 7) were reported among healthcare workers whereas education disruption among students (k = 7)., Limitation: The review is limited to articles published in three electronic databases. Conclusion The pandemic has caused depression among the populations across Asia Pacific, specifically among the general population, healthcare workers and students. Immediate attention and interventions from the concerned authorities are needed in addressing this issue., (Copyright © 2021 Elsevier B.V. All rights reserved.)

With the record surge of positive cases in Southeast Asia, there is a need to examine the adverse mental effects of COVID-19 among the under-researched countries. This study aims to synthesize the extant literature reporting the effects of COVID-19 pandemic on the psychological outcomes of people in Southeast Asia, and its risk factors. A scoping review was adopted targeting articles published in PubMed, Google Scholar and Scopus from January 2020 to March 30, 2021. Articles were screened using predetermined eligibility criteria, resulting in 26 papers. Elevated prevalence of adverse mental effects was noted in most of the countries as the pandemic progressed over time, with Malaysia and Philippines reporting higher prevalence rates. Mental decline was found to be more profound among the general population compared to healthcare workers and students. Dominant risk factors reported were age (younger), sex (females), education (higher), low coping skill and social/family support, and poor reliability in COVID-19 related information. Adverse mental effects were noted among population, healthcare workers and students in most of the Southeast Asian countries. Intervention and prevention efforts should be based at community-level and prioritize young adults, females, and individuals with dire financial constraints., Competing Interests: Conflict of InterestThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

Mounting evidence suggests that, in parallel with well-defined changes in language, primary progressive aphasia (PPA) syndromes display co-occurring social cognitive impairments. Here, we explored multidimensional profiles of carer-rated social communication using the La Trobe Communication Questionnaire (LCQ) in 11 semantic dementia (SD), 12 logopenic progressive aphasia (LPA) and 9 progressive non-fluent aphasia (PNFA) cases and contrasted their performance with 19 Alzheimer's disease (AD) cases, 26 behavioural variant frontotemporal dementia (bvFTD) cases and 31 healthy older controls. Relative to the controls, the majority of patient groups displayed significant overall social communication difficulties, with common and unique profiles of impairment evident on the LCQ subscales. Correlation analyses revealed a differential impact of social communication disturbances on functional outcomes in patient and carer well-being, most pronounced for SD and bvFTD. Finally, voxel-based morphometry analyses based on a structural brain MRI pointed to the degradation of a distributed brain network in mediating social communication dysfunction in dementia. Our findings suggest that social communication difficulties are an important feature of PPA, with significant implications for patient function and carer well-being. The origins of these changes are likely to be multifactorial, reflecting the breakdown of fronto-thalamic brain circuits specialised in the integration of complex information.

Purpose of Review: The microbiota plays an important role in health and disease. During organ transplantation, perturbations in microbiota influence transplant outcome. We review recent advances in characterizing microbiota and studies on regulation of intestinal epithelial barrier function and mucosal and systemic immunity by microbiota and their metabolites. We discuss implications of these interactions on transplant outcomes., Recent Findings: Metagenomic approaches have helped the research community identify beneficial and harmful organisms. Microbiota regulates intestinal epithelial functions. Signals released by epithelial cells or microbiota trigger pro-inflammatory or anti-inflammatory effects on innate and adaptive immune cells, influencing the structure and function of the immune system. Assessment and manipulation of microbiota can be used for biomarkers for diagnosis, prognosis, and therapy., Summary: The bidirectional dialogue between the microbiota and immune system is a major influence on immunity. It can be targeted for biomarkers or therapy. Recent studies highlight a close association of transplant outcomes with microbiota, suggesting exciting potential avenues for management of host physiology and organ transplantation., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling side effect of various chemotherapeutic agents, including oxaliplatin. It is highly prevalent amongst cancer patients, causing sensory abnormalities and pain. Unfortunately, as the underlying mechanisms remain poorly understood, effective therapeutics are lacking. Neuro-immune interactions have been highlighted as potential contributors to the development and maintenance of CIPN, however, whether this is the case in oxaliplatin-induced peripheral neuropathy (OIPN) is yet to be fully established. Methods: In this study we used flow cytometry to examine the peripheral immune response of male C57BL/6 mice following both single and repeated oxaliplatin administration. In animals exposed to repeated dosing, we also undertook mechanical and thermal behavioural assays to investigate how oxaliplatin alters phenotype, and conducted RT-qPCR experiments on bone marrow derived macrophages in order to further inspect the effects of oxaliplatin on immune cells. Results: In contrast to other reports, we failed to observe substantial changes in overall leukocyte, lymphocyte or myeloid cell numbers in dorsal root ganglia, sciatic nerves or inguinal lymph nodes. We did however note subtle, tissue-dependant alterations in several myeloid subpopulations following repeated dosing. These included a significant reduction in MHCII antigen presenting cells in the sciatic nerve and an increase in infiltrating cell types into the inguinal lymph nodes. Though repeated oxaliplatin administration had a systemic effect, we were unable to detect a pain-like behavioural phenotype in response to either cold or mechanical stimuli. Consequently, we cannot comment on whether the observed myeloid changes are associated with OIPN. Conclusions: Our discussion puts these results into the wider context of the field, advocating for greater transparency in reporting, alignment in experimental design and the introduction of more clinically relevant models. Only through joint concerted effort can we hope to increase our understanding of the underlying mechanisms of CIPN, including any immune contributions., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Hore ZL et al.)

Cooperative social behaviour in humans hinges upon our unique ability to make appropriate moral decisions in accordance with our ethical values. The complexity of the neurocognitive mechanisms underlying moral reasoning is revealed when this capacity breaks down. Patients with the behavioural variant of frontotemporal dementia (bvFTD) display striking moral transgressions in the context of atrophy to frontotemporal regions supporting affective and social conceptual processing. Developmental studies have highlighted the importance of social knowledge to moral decision making in children, yet the role of social knowledge in relation to moral reasoning impairments in neurodegeneration has largely been overlooked. Here, we sought to examine the role of affective and social conceptual processes in personal moral reasoning in bvFTD, and their relationship to the integrity and structural connectivity of frontotemporal brain regions. Personal moral reasoning across varying degrees of conflict was assessed in 26 bvFTD patients and compared with demographically matched Alzheimer's disease patients (n = 14), and healthy older adults (n = 22). Following each moral decision, we directly probed participants' subjective emotional experience as an index of their affective response, while social norm knowledge was assessed via an independent task. While groups did not differ significantly in terms of their moral decisions, bvFTD patients reported feeling 'better' about their decisions than healthy control subjects. In other words, although bvFTD patients could adjudicate between different courses of action in the moral scenarios, their affective responses to these decisions were highly irregular. This blunted emotional reaction was exclusive to the personal high-conflict condition, with 61.5% of bvFTD patients reporting feeling 'extremely good' about their decisions, and was correlated with reduced knowledge of socially acceptable behaviour. Voxel-based morphometry analyses revealed a distributed network of frontal, subcortical, and lateral temporal grey matter regions involved in the attenuated affective response to moral conflict in bvFTD. Crucially, diffusion-tensor imaging implicated the uncinate fasciculus as the pathway by which social conceptual knowledge may influence emotional reactions to personal high-conflict moral dilemmas in bvFTD. Our findings suggest that altered moral behaviour in bvFTD reflects the dynamic interplay between degraded social conceptual knowledge and blunted affective responsiveness, attributable to atrophy of, and impaired information transfer between, frontal and temporal cortices. Delineating the mechanisms of impaired morality in bvFTD provides crucial clinical information for understanding and treating this challenging symptom, which may help pave the way for targeted behavioural interventions., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Logopenic progressive aphasia is a neurodegenerative syndrome characterized by sentence repetition and naming difficulties arising from left-lateralized temporoparietal atrophy. Clinical descriptions of logopenic progressive aphasia largely concentrate on profiling language deficits, however, accumulating evidence points to the presence of cognitive deficits even on tasks with minimal language demands. Although non-linguistic cognitive deficits in logopenic progressive aphasia are thought to scale with disease severity, patients at discrete stages of language dysfunction display overlapping cognitive profiles, suggesting individual-level variation in cognitive performance, independent of primary language dysfunction. To address this issue, we used principal component analysis to decompose the individual-level variation in cognitive performance in 43 well-characterized logopenic progressive aphasia patients who underwent multi-domain neuropsychological assessments and structural neuroimaging. The principal component analysis solution revealed the presence of two, statistically independent factors, providing stable and clinically intuitive explanations for the majority of variance in cognitive performance in the syndrome. Factor 1 reflected 'speech production and verbal memory' deficits which typify logopenic progressive aphasia. Systematic variations were also confirmed on a second, orthogonal factor mainly comprising visuospatial and executive processes. Adopting a case-comparison approach, we further demonstrate that pairs of patients with comparable Factor 1 scores, regardless of their severity, diverge considerably on visuo-executive test performance, underscoring the inter-individual variability in cognitive profiles in comparably 'logopenic' patients. Whole-brain voxel-based morphometry analyses revealed that speech production and verbal memory factor scores correlated with left middle frontal gyrus, while visuospatial and executive factor scores were associated with grey matter intensity of right-lateralized temporoparietal, middle frontal regions and their underlying white matter connectivity. Importantly, logopenic progressive aphasia patients with poorer visuospatial and executive factor scores demonstrated greater right-lateralized temporoparietal and frontal atrophy. Our findings demonstrate the inherent variation in cognitive performance at an individual- and group-level in logopenic progressive aphasia, suggesting the presence of a genuine co-occurring cognitive impairment that is statistically independent of language function and disease severity., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Vibrio cholerae , the causative agent of the infectious disease, cholera, is commonly found in brackish waters and infects human hosts via the fecal-oral route. V. cholerae is a master of stress resistance as V. cholerae's dynamic lifestyle across different physical environments constantly exposes it to diverse stressful circumstances. Specifically, V. cholerae has dedicated genetic regulatory networks to sense different environmental cues and respond to these signals. With frequent outbreaks costing a tremendous amount of lives and increased global water temperatures providing more suitable aquatic habitats for V. cholerae , cholera pandemics remain a probable catastrophic threat to humanity. Understanding how V. cholerae copes with different environmental stresses broadens our repertoire of measures against infectious diseases and expands our general knowledge of prokaryotic stress responses. In this review, we summarize the regulatory mechanisms of how V. cholerae fights against stresses in vivo and in vitro., Competing Interests: Conflicts of interest: The authors reported no conflicts of interest., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)

The cognitive construct of prospective memory (PM) refers to the capacity to encode, retain and execute delayed intentions (e.g. to remember to buy milk on the way home). Although previous research suggests that PM performance is enhanced by healthy sleep, conclusions tend to be drawn based on designs featuring ecologically unnatural manipulations (e.g. total sleep deprivation). This study investigates whether a more common everyday experience (bedtime stress) affects next-day PM performance and, in so doing, also contributes to the heretofore inconsistent literature on stress and PM. Forty young adults received PM task instructions and were then assigned to either a stress condition (exposure to a laboratory-based stress-induction manipulation; n = 20, 9 women) or a non-stress condition (exposure to a non-stressful control manipulation; n = 20, 12 women). After completing the experimental manipulation, all participants had their objective sleep quality measured over a full night of polysomnographic monitoring. Upon awakening, they completed the PM task. Analyses detected significant between-group differences in terms of stress outcomes, sleep quality and PM performance: Participants exposed to the manipulation experienced heightened signs of stress (captured using a composite variable that included self-report, psychophysiological and endocrinological measures), had longer sleep latencies and poorer sleep depth and displayed significantly longer reaction times to PM cues. An interaction between experimental condition (being exposed to the stressor) and disrupted sleep (longer sleep latency) significantly predicted poorer next-day PM reaction time. We interpret these findings as indicating that bedtime stress, which leads to heightened presleep arousal, affects sleep processes and, consequently, the deployment of attentional resources during next-day execution of a delayed intention., (Copyright © 2020 Goldberg, Thomas and Lipinska.)

Chemokines are important protein-signaling molecules that regulate various immune responses by activating chemokine receptors which belong to the G protein-coupled receptor (GPCR) superfamily. Despite the substantial progression of our structural understanding of GPCR activation by small molecule and peptide agonists, the molecular mechanism of GPCR activation by protein agonists remains unclear. Here, we present a 3.3-Å cryo-electron microscopy structure of the human chemokine receptor CCR6 bound to its endogenous ligand CCL20 and an engineered Go. CCL20 binds in a shallow extracellular pocket, making limited contact with the core 7-transmembrane (TM) bundle. The structure suggests that this mode of binding induces allosterically a rearrangement of a noncanonical toggle switch and the opening of the intracellular crevice for G protein coupling. Our results demonstrate that GPCR activation by a protein agonist does not always require substantial interactions between ligand and the 7TM core region.

Background: Dental caries in primary teeth is a serious oral health concern among children. It can lead to detrimental impacts on a child's growth, development, and quality of life. Therefore, this cross-sectional study aimed to examine the prevalence of dental caries and its associations with nutritional status, sugar and second-hand smoke exposure among pre-schoolers., Methods: A total of 26 pre-schools in Seremban, Malaysia were randomly selected using the probability proportional to size sampling. Dental examination was performed by a dentist to record the number of decayed teeth (dt). Weight and height of the pre-schoolers were measured. The mother-administered questionnaire was used to gather information pertaining to the sociodemographic characteristics and second-hand smoke exposure. Total sugar exposure was calculated from a 3-day food record., Results: Among the 396 participating pre-schoolers, 63.4% of them had at least one untreated caries, with a mean ± SD dt score of 3.56 ± 4.57. Negative binomial regression analysis revealed that being a boy (adjusted mean ratio = 1.42, 95% CI = 0.005-0.698, p = 0.047), exposed to second-hand smoke (adjusted mean ratio = 1.67, 95% CI = 0.168-0.857, p = 0.004) and those who had more than 6 times of daily total sugar exposure (adjusted mean ratio = 1.93, 95% CI = 0.138-0.857, p = 0.013) were significantly associated with dental caries among pre-schoolers., Conclusion: A high prevalence of dental caries was reported in this study. This study highlights the need to reduce exposure to second-hand smoke and practice healthy eating behaviours in reducing the risk of dental caries among pre-schoolers.

ATP-binding cassette (ABC) transporters are molecular pumps ubiquitous across all kingdoms of life. While their structures have been widely reported, the kinetics governing their transport cycles remain largely unexplored. Multidrug resistance protein 1 (MRP1) is an ABC exporter that extrudes a variety of chemotherapeutic agents and native substrates. Previously, the structures of MRP1 were determined in an inward-facing (IF) or outward-facing (OF) conformation. Here, we used single-molecule fluorescence spectroscopy to track the conformational changes of bovine MRP1 (bMRP1) in real time. We also determined the structure of bMRP1 under active turnover conditions. Our results show that substrate stimulates ATP hydrolysis by accelerating the IF-to-OF transition. The rate-limiting step of the transport cycle is the dissociation of the nucleotide-binding-domain dimer, while ATP hydrolysis per se does not reset MRP1 to the resting state. The combination of structural and kinetic data illustrates how different conformations of MRP1 are temporally linked and how substrate and ATP alter protein dynamics to achieve active transport., Competing Interests: LW, ZJ, MW, JL, JC, SL No competing interests declared, (© 2020, Wang et al.)

The capacity to generate naturalistic three-dimensional and spatially coherent representations of the world, i.e., scene construction, is posited to lie at the heart of a wide range of complex cognitive endeavours. Clinical populations with selective damage to key nodes of a putative scene construction network of the brain have provided important insights regarding the contribution of medial temporal and prefrontal regions in this regard. Here, we explored the capacity for atemporal scene construction, and its associated neural substrates, in the behavioural-variant of frontotemporal dementia (bvFTD); a neurodegenerative brain disorder in which atrophy systematically erodes medial and lateral prefrontal cortices with variable medial temporal lobe involvement. Nineteen bvFTD patients were compared to 18 typical Alzheimer's Disease (AD), and 25 healthy older Control participants on a scene construction task. Relative to Controls, both patient groups displayed marked impairments in generating contextually detailed and spatially coherent scenes, with bvFTD indistinguishable from AD patients across the majority of task metrics. Voxel-based morphometry, based on structural brain MRI, revealed divergent neural substrates of scene construction performance in each patient group. Despite widespread medial and lateral prefrontal atrophy, the capacity to generate richly detailed and spatially coherent scenes in bvFTD was found to rely predominantly upon the integrity of right medial temporal structures, including the hippocampus and parahippocampal gyrus. Scene construction impairments in AD, by contrast, hinged upon the integrity of posterior parietal brain regions. Our findings in bvFTD resonate with a large body of work implicating the right hippocampus in the construction of spatially integrated scene imagery. How these impairments relate to changes in autobiographical memory and prospection in bvFTD will be an important question for future studies to address., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

An intriguing aspect of human cognition is the unique capacity to mentally retreat from our immediate surroundings to consider perspectives distinct from the here and now. Despite increasing interest in this phenomenon, relatively little is known regarding age-related changes in off-task, self-generated thought (often referred to as "mind-wandering"), particularly under conditions of low cognitive demand. While a number of studies have investigated the temporal orientation of mind-wandering with increasing age, findings have been largely inconsistent. Here, we explored the frequency, temporal focus, and self-referential/social content of spontaneous task-unrelated, perceptually decoupled thought in 30 young and 33 healthy older adults using the Shape Expectations task, a validated experimental paradigm in which discrete facets of inner mentation are quantified along a conceptual continuum using open-ended report. Participants also completed the daydreaming subscale of the Imaginal Process Inventory (IPI) as a trait measure of mind-wandering propensity. Significant group differences emerged on the Shape Expectations task, with reduced instances of mind-wandering in the context of elevated task-related thoughts relative to younger adults. In terms of temporal focus, a preponderance of present/atemporal off-task thoughts was evident irrespective of group; however, significantly higher levels of future-oriented thoughts were provided by younger adults, contrasting with significantly higher instances of retrospection in the older group. In addition, older adults displayed significantly fewer incidences of self-referential cognition relative to their younger counterparts. Our findings indicate a distinct attenuation of off-task, self-generated thought processes with increasing age, with evidence for a shift in temporal focus and self-referential quality, during periods of low cognitive demand.

Background: Frontotemporal dementia (FTD) is characterised by changes in behaviour including alterations in sexual function. While hypersexual behaviour is commonly thought to predominate, emerging evidence suggests that hyposexual behaviour is in fact most prevalent. The underlying mechanisms driving these behavioural changes remain unclear; however, likely reflect interactions between cognitive, emotional, reward processing and physiological functioning. We aimed to systematically quantify changes in sexual behaviour in behavioural variant FTD (bvFTD) and semantic dementia (SD) in contrast with Alzheimer's disease (AD) and to elucidate the neural correlates of these changes using whole-brain voxel-based morphometry., Methods: Carers of 62 dementia patients (30 bvFTD, 12 SD, 20 AD) were interviewed using the Sexual Behaviour and Intimacy Questionnaire, which assesses changes in sexual function. Voxel-based morphometry analysis of structural MRI brain scans was used to determine the association between changes in grey matter intensity and the presence of hyposexual, hypersexual, and inappropriate sexual behaviour across groups., Results: Widespread attenuation of sexual drive, intimacy and the display of affection were evident irrespective of dementia subtype. In contrast, hypersexual and inappropriate sexual behaviour was present in only a small proportion of patients. Neuroimaging analyses revealed an association between hyposexual behaviour and atrophy of the right supramarginal gyrus, middle frontal gyrus and thalamus, whilst hypersexual behaviour was associated with cerebellar atrophy., Conclusion: Counter to the prevailing view, younger-onset dementia syndromes predominantly display an attenuation in sexual drive. Changes in sexual function likely reflect the degeneration of cortical and subcortical neural circuits implicated in reward, autonomic function, empathy, and emotional processing.

Posterior Cortical Atrophy (PCA) is a rare neurodegenerative syndrome characterised by profound visuoperceptual processing disturbances, attributable to focal parieto-occipital cortical atrophy. Despite relative sparing of the medial temporal lobes, converging evidence reveals significant autobiographical memory impairments in this syndrome, underscoring the crucial role of visual imagery for episodic memory processes. The contribution of visual imagery to complex constructive endeavours, however, remains unclear. Here, we investigated the capacity for atemporal scene construction in 5 well-characterised cases of PCA and contrasted their performance with 10 typical amnestic Alzheimer's Disease (AD) and 10 healthy older Control participants. Behavioural data were analysed using case-Control statistics comparing each PCA patient's scene construction scores to the mean scores of AD and Control groups. In keeping with their clinical phenotype, PCA patients demonstrated significant visuoperceptual and episodic memory impairments on standard neuropsychological tasks. Scene construction performance was grossly impaired in PCA, at a level comparable to that observed in the AD group, manifesting in impoverished and spatially fragmented scenes. Structural neuroimaging confirmed prominent grey matter intensity decrease predominantly in posterior cortical regions in PCA, in the absence of frank hippocampal atrophy. Using an a priori motivated region-of-interest approach across all participants, scene construction performance was found to correlate with grey matter intensity in the left angular gyrus, right precuneus, and right hippocampus. This study is the first to reveal compromised scene construction capacity in PCA, extending our understanding of the cognitive profile of this rare syndrome and pointing towards the fundamental contribution of visual imagery to atemporal forms of imagination., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The multidrug resistance protein MRP1 is an ATP-driven pump that confers resistance to chemotherapy. Previously, we have shown that intracellular substrates are recruited to a bipartite binding site when the transporter rests in an inward-facing conformation. A key question remains: how are high-affinity substrates transferred across the membrane and released outside the cell? Using electron cryomicroscopy, we show here that ATP binding opens the transport pathway to the extracellular space and reconfigures the substrate-binding site such that it relinquishes its affinity for substrate. Thus, substrate is released prior to ATP hydrolysis. With this result, we now have a complete description of the conformational cycle that enables substrate transfer in a eukaryotic ABC exporter., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Membrane transporters move substrates across the membrane by alternating access of their binding sites between the opposite sides of the membrane. An emerging model of this process is the elevator mechanism, in which a substrate-binding transport domain moves a large distance across the membrane. This mechanism has been characterized by a transition between two states, but the conformational path that leads to the transition is not yet known, largely because the available structural information has been limited to the two end states. Here we present crystal structures of the inward-facing, intermediate, and outward-facing states of a concentrative nucleoside transporter from Neisseria wadsworthii. Notably, we determined the structures of multiple intermediate conformations, in which the transport domain is captured halfway through its elevator motion. Our structures present a trajectory of the conformational transition in the elevator model, revealing multiple intermediate steps and state-dependent conformational changes within the transport domain that are associated with the elevator-like motion.

The multidrug resistance protein MRP1 is an ATP-binding cassette (ABC) transporter that confers resistance to many anticancer drugs and plays a role in the disposition and efficacy of several opiates, antidepressants, statins, and antibiotics. In addition, MRP1 regulates redox homeostasis, inflammation, and hormone secretion. Using electron cryomicroscopy, we determined the molecular structures of bovine MRP1 in two conformations: an apo form at 3.5 Å without any added substrate and a complex form at 3.3 Å with one of its physiological substrates, leukotriene C 4 . These structures show that by forming a single bipartite binding site, MRP1 can recognize a spectrum of substrates with different chemical structures. We also observed large conformational changes induced by leukotriene C 4 , explaining how substrate binding primes the transporter for ATP hydrolysis. Structural comparison of MRP1 and P-glycoprotein advances our understanding of the common and unique properties of these two important molecules in multidrug resistance to chemotherapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Secondary active transporters are responsible for the cellular uptake of many biologically important molecules, including neurotransmitters, nutrients, and drugs. Because of their physiological and clinical importance, a method for assessing their transport activity in vitro is necessary to gain a better understanding of how these transporters function at the molecular level. In this chapter, we describe a protocol for reconstituting the concentrative nucleoside transporter from Vibrio cholerae into proteoliposomes. We then describe a radiolabeled substrate uptake assay that can be used to functionally characterize the transporter. These methods are relatively common and can be applied to other secondary active transporters, with or without some modification., (© 2015 Elsevier Inc. All rights reserved.)

Concentrative nucleoside transporters (CNTs) are responsible for cellular entry of nucleosides, which serve as precursors to nucleic acids and act as signaling molecules. CNTs also play a crucial role in the uptake of nucleoside-derived drugs, including anticancer and antiviral agents. Understanding how CNTs recognize and import their substrates could not only lead to a better understanding of nucleoside-related biological processes but also the design of nucleoside-derived drugs that can better reach their targets. Here, we present a combination of X-ray crystallographic and equilibrium-binding studies probing the molecular origins of nucleoside and nucleoside drug selectivity of a CNT from Vibrio cholerae. We then used this information in chemically modifying an anticancer drug so that it is better transported by and selective for a single human CNT subtype. This work provides proof of principle for utilizing transporter structural and functional information for the design of compounds that enter cells more efficiently and selectively., (Copyright © 2014, Johnson et al.)

Nucleosides are required for DNA and RNA synthesis, and the nucleoside adenosine has a function in a variety of signalling processes. Transport of nucleosides across cell membranes provides the major source of nucleosides in many cell types and is also responsible for the termination of adenosine signalling. As a result of their hydrophilic nature, nucleosides require a specialized class of integral membrane proteins, known as nucleoside transporters (NTs), for specific transport across cell membranes. In addition to nucleosides, NTs are important determinants for the transport of nucleoside-derived drugs across cell membranes. A wide range of nucleoside-derived drugs, including anticancer drugs (such as Ara-C and gemcitabine) and antiviral drugs (such as zidovudine and ribavirin), have been shown to depend, at least in part, on NTs for transport across cell membranes. Concentrative nucleoside transporters, members of the solute carrier transporter superfamily SLC28, use an ion gradient in the active transport of both nucleosides and nucleoside-derived drugs against their chemical gradients. The structural basis for selective ion-coupled nucleoside transport by concentrative nucleoside transporters is unknown. Here we present the crystal structure of a concentrative nucleoside transporter from Vibrio cholerae in complex with uridine at 2.4 Å. Our functional data show that, like its human orthologues, the transporter uses a sodium-ion gradient for nucleoside transport. The structure reveals the overall architecture of this class of transporter, unravels the molecular determinants for nucleoside and sodium binding, and provides a framework for understanding the mechanism of nucleoside and nucleoside drug transport across cell membranes.

Eighteen patients with proximal tibial shaft non-union and shortening were treated. In each patient, the non-union area was débrided, realigned and stabilised with an Ilizarov lengthening frame. The tibia was gradually lengthened by 1-1.5 mm per day. After achieving the desired length, external fixation was converted to an angled blade plate and packed with cancellous bone graft. Follow-up of 16 patients for a median of 2.4 (1.2-4.5) years revealed satisfactory outcomes in all. No wound infections were noted. The described technique has a high success rate, a short treatment course and reduces patient discomfort. This method may be considered preferential treatment for all patients with the specified indications.

Study Design: Retrospective review and post-test-only control group design., Objective: To study the incidence and associated factors of ring apophysis fracture in adolescent lumbar disc herniation and to evaluate the long-term morbidity of untreated apophyseal fracture., Summary of Background Data: Ring apophysis fracture is a feature in adolescent disc herniation, but the incidence and prognosis are unknown. It is still controversial whether to remove the apophyseal fragment at time of discectomy., Methods: We studied 96 adolescents (mean age, 14.7 years) with clinical diagnosis of disc herniation proved by computerized tomography (CT). In CT scan ring, apophyseal fracture is classified by the size (large/small) and the location (central/lateral). We used modified Oswestry classification in the nonoperative patients for pain and functional evaluation. Patients with and without apophyseal fracture were compared to define the significance of the lesion., Results: Twenty-seven of the 96 CT studies (28%) demonstrated apophyseal fractures. All but 2 were at the level of the herniated disc. Large-central fragments were the most common in 16 patients (48%), large-lateral fragments in 2, small-central fragments in 6, and small-lateral fragment in 6. Rate of surgery was significantly higher in the disc herniation patients with apophyseal fractures. Sixty-four nonoperative patients were evaluated 6.6 years (range, 2.3-14.3) after the CT study and questionnaires were completed in 54 patients (84%). Patients with large apophyseal fragments had more chance of chronic back pain and limitation of daily activities than the patients with small fragments and patients without apophyseal fracture., Conclusion: Apophyseal fracture is not uncommon in adolescent lumbar disc herniation. The surgical decision must depend on clinical symptoms instead of radiologic findings, but disc herniation with apophyseal fracture may exhibit more severe symptoms. Patients with large apophyseal fragments must be informed of a greater chance of chronic back pain later on. Small apophyseal fragments had no clinical significance.

Background/purpose: We questioned the principle of treatment of late lateral condylar fracture of a pediatric elbow. We report the results of treating this condition using a different approach., Methods: We treated six children with type 3 late lateral condylar fractures. The average age was 4.5 years old. The time delay from injury to surgery averaged at 3.8 months. All the displaced lateral condyles were Milch type 2 with significant rotation away from the trochlea. The articular anatomic reduction of the lateral condyles was achieved via ulnar osteotomy in all six cases. We fixed both the fracture and the osteotomy with Kirschner wires buried under the skin. No strenuous passive physical therapy was needed., Results: All lateral condylar fractures and ulnar osteotomies were united within 3 months. Five out of six children had regained full range of motion and symmetric carrying angles at the latest follow-up 2 to 11 years later. Complications included transient physeal change and lateral bump., Conclusion: Based on our results, we recommend olecranon osteotomy via a posterior approach as one of the options in treating late cases of type 3 lateral condylar fracture of the elbow with significant displacement in children.

Background: The excellent oral bioavailability and the Gram-positive antimicrobial spectrum make linezolid an attractive antibiotic for treatment of osteoarticular infections. The clinical efficacy of this drug has not been previously evaluated for Gram-positive osteoarticular infections in children., Methods: Between July 2003 and June 2006, 13 children who received a linezolid-containing regimen for osteoarticular infections were identified from a hospital pharmacy database. The medical records were reviewed and outcomes with regard to clinical efficacy and safety were analyzed., Results: Eight (61.5%) children were male. Ages ranged from 3 months to 14 years. Nine previously healthy children had acute hematogenous osteoarticular infections involving the pelvis (n = 1) or lower limbs (n = 8). The remaining 4 children had postoperative infections of sternal wounds (n = 2) and fractured lower limbs (n = 2). Causative pathogens included methicillin-resistant Staphylococcus aureus in 11 children, methicillin-susceptible S. aureus in one, and Enterococcus faecium and coagulase-negative staphylococci in one. Surgical debridement was attempted in 9 children and effective antistaphylococcal antibiotics were used in all 13 patients for a median duration of 23 days (range, 5-41 days) before the use of linezolid. Linezolid was administered orally to 10 children as step-down therapy and by the parenteral followed by oral route to 3 children who were intolerant of glycopeptide for a median duration of 20 days (range, 9-36 days). Eleven of the 13 children were cured after management. Two children developed anemia during linezolid therapy. There was no premature cessation of linezolid because of severe adverse effects., Conclusion: Linezolid appears to be useful and well tolerated in step-down therapy or compassionate use for pediatric Gram-positive orthopedic infections. A well-designed prospective comparative study is needed to confirm this observation.

Background/purpose: Early detection and treatment for developmental dysplasia of the hip (DDH) by screening in nursery has been recommended for several decades. With the recent survey of high prevalence of surgery for DDH in Taiwan, it has raised issues of the effectiveness of baby hip screening., Methods: National Health Insurance covers 97% of the 22 million population in Taiwan. From the databank, we retrieved children who were admitted from birth to 5 years of age, with the diagnosis of DDH (International Classification of Disease version 9 [ICD-9] code 754.3x) or had had one of the treatments for DDH (ICD-9 code 77.39, 79.75, 79.85, 88.32) between 1997 and 2004., Results: There were 1229 children undergoing surgeries for DDH in this study. A total of 1097 of them were female (89%). The mean age at the first surgery was 1.7 years. Major operation, open reduction with or without osteotomy, accounted for 85% of the cases. The number of children who were born between 1997 and 1999 and who had surgery for DDH were 160, 129 and 134, respectively. Incidences of surgery for DDH among these 3 cohort years were 0.49, 0.48 and 0.47 per thousand live births, respectively., Conclusion: The incidence of DDH in Taiwan was reported as 1.2 per thousand, so 40% of the DDH children underwent surgery. However, with 87% of surgeries occurring after walking age, it is reasonable to postulate that the screening program was not performed accurately or universally. The rate of major procedures in surgical cases of DDH is a better indicator for the effectiveness of mass screening.

Sixty-two reducible trigger thumbs in 50 children with age from 0 to 4 years (mean, 1 year 11 months) were reviewed to study the effect of splinting. Thirty-one thumbs in 24 children received splinting for a mean of 11.7 weeks. The other 31 thumbs in 26 children were only observed. The results were categorized as cured, improved, or nonimproved. Follow-up was conducted after a mean of 20 months (age, 43 months). Result in the splinted group showed cured in 12 thumbs, improved in 10 thumbs, and nonimproved in 9 thumbs, whereas in the observed group, result showed 4, 3, and 24, respectively. Splinting results in 71% trigger thumbs cured or improved that is better than observation alone. The subsequent surgical release for the nonimproved trigger thumbs after splinting still had excellent results. Because surgical release for trigger thumb is not urgent, we suggest extension splinting to be a treatment option before the elective surgery.

The present study tested progressive coxa vara by eccentric growth tethering that might be used to correct coxa valga in cerebral palsy. Eight young pigs received screw fixation at inferior portion of right femoral head at age 4 months and were killed at age 7.25 months for bilateral femurs for comparison. The neck-shaft angle at the tethered side was significantly less than that at the control side (129.8 vs. 138.3 degrees , P<0.05). Histological study showed bony bar formation. Eccentric growth tethering by one screw resulted in a reduction of neck-shaft angle by 8.5 degrees and shortening of femoral length by 4%.

Background: X-linked hypophosphatemic rickets (XLH) is an X-linked dominant disease characterized by renal phosphate wasting, hypophosphatemia, aberrant vitamin D metabolism, and defective bone mineralization. The disease is caused by mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X-chromosome) located at Xp22.1. To date, a variety of PHEX mutations have been identified in these patients., Methods: PCR and direct sequencing was performed for all exons and intron-exon boundaries of the PHEX gene in two XLH families., Results: Two novel mutations, including a missense mutation (L206W) in exon 5 and a frameshift mutation (nucleotide 1826&#95;1830delAAAAG, stop after codon 610) in exon 18 were discovered and the laboratory and radiographic findings for these patients analyzed., Conclusions: We found that PHEX gene mutations were responsible for XLH in these Taiwanese patients. Additional studies are needed to enhance understanding of the role of PHEX in XLH pathogenesis., (Copyright 2006 S. Karger AG, Basel)

Background: This retrospective study investigated the treatment of femoral shaft aseptic nonunions associated with broken distal locked screws and shortening., Methods: In this study, 11 femoral shaft aseptic nonunions associated with both broken distal locked screws and shortening in 11 consecutive adult patients were treated. All nonunions were associated with at least 1.5 cm (range, 1.5-3.5 cm) shortening. These nonunions were treated by removal of locked nails, one-stage femoral lengthening, static locked nail stabilization, and corticocancellous bone graft supplementation. Postoperatively, ambulation with protected weightbearing was encouraged as early as possible., Results: Ten nonunions were followed up for a median of 4.1 years (range, 1.8-5.5 years), and nine fractures healed at a median of 4 months (range, 3-6 months). The nonunion case had broken locked screws again at 5 months and was treated with exchange nailing. The fracture healed uneventfully at 4 months. No other complications occurred., Conclusions: The key to removal of broken screws is withdrawal of the nail slightly to release the incarcerated broken screw end. The screw end then is pushed out with a used Knowles' pin or a smaller screwdriver under image intensifier guidance. Concomitant one-stage femoral lengthening to treat nonunion with shortening has a high success rate.

We followed 12 patients with nailed femoral shaft fractures in which breakage of the static locked nail occurred during fracture treatment. Only two fractures united. The remaining ten fractures had to be treated with exchange nailing after a median of 10 (4-14) months. Nine fractures healed after a median of 5 (4-7) months and one was lost to follow-up. Although breakage of a proximal static reamed femoral locked nail may imitate the effect of dynamisation, the success rate is low. Early exchange nailing is a more successful option to achieve fracture union.

Background: The optimal treatment for femoral fractures in children is controversial. The purpose of this study was to compare the results of Rush pin fixation with those of conservative treatment, and to evaluate the sequels of growth plate injury by internal fixation., Methods: Eighteen femoral shaft fractures in 17 children who had concomitant head injury or multiple traumas were treated surgically. The mean age at operation was 9 years 3 months (range, 7 years 5 months to 11 years 1 month). One Rush pin was inserted from the tip of the greater trochanter, without reaming, to fix the fracture. Another 20 age-matched children treated by traction and casting were the control subjects., Results: All the fractures united without consequences. In addition to a decrease in hospital stay with the use of the Rush pin (10 days vs. 27 days, p<0.05), fewer leg length discrepancies (4.2 mm vs. 7.1 mm, p<0.05) were also noted, compared with conservative treatment. The growth of the proximal femur after Rush pin fixation was evaluated after an average of 59 months. No femur shortening, coxa valgus, or hip dysplasia was noted., Conclusions: Intramedullary Rush pin fixation for femoral shaft fracture in children older than 7 years is a simple and reliable alternative. One narrow and non-reaming pin inserted from greater trochanter did not demonstrate femoral growth inhibition.

This study describes a consecutive series of 11 children who received a microsurgical second toe-metatarsal bone transfer for reconstructing a hypoplastic thumb associated with radial club hand, between 1996 and 2000. The parents refused pollicization in all cases for aesthetic and cultural reasons. Surgery was intended to improve hand function and cosmetic appearance. The average patient age was 3 years, and the average follow-up period was 4 years. Average surgery time for the second toe-metatarsal bone transplantation was 8 hr. The primary success rate was 90.9 percent, with one patient requiring repeat surgery owing to venous occlusion. The surgical outcomes reveal a normal growth of the transferred toe, an acceptable range of motion, and satisfactory recovery of sensation. All children achieved both small and large grasp functions. The parents were satisfied with the reconstruction procedures. Based on the preliminary results, second toe-metatarsal bone transfer appears an acceptable alternative for reconstructing radial deficiency with hypoplastic thumb.

Leiomyomas rarely occur in the hand. To our knowledge, there have been no reports of a leiomyoma of the hand mimicking a pearl ganglion in the English literature. We report such a case with a leiomyoma of the right third finger in a 59-year-old woman. The tumor was excised together with the underlying sheet of tissue. The pathology revealed that the tumor was linked to the underlying structure of a vascular wall by a stalk of tumor tissue. This report serves to remind clinicians to include leiomyoma in the differential diagnosis when encountering a 'ganglion-like lesion'. Also, this report demonstrates the link between a leiomyoma and its underlying origin.

Objective: To assess the effectiveness of a one-stage lengthening using a locked nail technique for the treatment of distal femoral shaft nonunions associated with shortening., Design: Retrospective., Setting: University hospital., Patients and Methods: During a 6-year period, 36 distal femoral shaft nonunions associated with shortening (>1.5 cm) were treated by the one-stage lengthening technique. Indications for this technique were distal femoral shaft aseptic or quiescent infected nonunions, 1.5-5 cm shortening, and a fracture level suitable for the insertion of two distal locked screws. The surgical technique involved skeletal traction using the femoral condyle, local débridement, lengthening by

Background: The purpose of this study was to review surgery-proven lumbar disc herniation in adolescents with an emphasis on the distinguishing features., Methods: Twenty-eight adolescents between 14 and 18 years old had lumbar discectomy after conservative treatment for 9 months. Indications for surgery were intractable pain and failure of conservative treatment for more than 6 weeks. Lumbar spine apophyseal ring fracture was found in 10 of the 24 patients (42%) who had computed tomography studies. Seven patients had piecemeal excision of the fractured apophysis together with the discectomy., Results: All but three patients could raise their leg more than 70 degrees after the operation. The latest follow-up was conducted an average of 6.1 years after surgery. Good or excellent results were noted in 93% of the patients. Two patients had follow-up operations for recurrent disc herniation and wound infection., Conclusion: Apophyseal ring fracture was a feature in adolescent disc herniation that requires surgical intervention. Early computed tomography study is proposed to detect apophyseal ring lesion, which may lead to failure of conservative treatment. Excision of the fractured ring apophysis is suggested in addition to discectomy when the canal space is occupied.

This retrospective study analyzed the clinical, bacteriological, and radiological features of pediatric patients with acute hematogenous osteomyelitis and septic arthritis. Eighty-four patients with septic arthritis and 39 with acute hematogenous osteomyelitis were enrolled. Their age ranged from 13 days to 17 years. In patients with septic arthritis, the hip joint was the most often infected site. The tibia was the most often involved site in acute hematogenous osteomyelitis. A bacteriological diagnosis was established in 78 (63%) patients. Overall, methicillin-susceptible Staphylococcus aureus (36 cases) was the most common causative organism identified, followed by methicillin-resistant S. aureus (10 cases). The median duration of antibiotic therapy was 33 days. Serum bactericidal titers were obtained for 19 (15%) of the 123 patients. The median duration of hospitalization and antibiotic treatment was not significantly different between patients with and without serum bactericidal titer testing. More patients without serum bactericidal titer testing had symptom relapse which required re-admission for further treatment. In conclusion, the incidence of methicillin-resistant S. aureus as a cause of bone and joint infections has been increasing. Serum bactericidal titer is valuable for the management of patients receiving sequential therapy for acute hematogenous osteomyelitis and septic arthritis.