Summary What is known and objective Mucopolysaccharidoses (MPSs) are a group of rare inherited metabolic diseases caused by genetic defects in the production of lysosomal enzymes. MPSs are clinically heterogeneous and are characterized by progressive deterioration in visceral, skeletal and neurological functions. This article aims to review the classification and pathophysiology of MPSs and discuss current therapies and new targeted agents under development. Methods A Medline search through PubMed was performed for relevant articles and treatment guidelines on MPSs published in English for years 1970 to September of 2013 inclusive. The references listed in the identified articles, prescribing information of the drugs approved for the treatment of MPSs, as well as recent clinical trial information posted on Clinicaltrials.gov website, were reviewed. Results and discussion Until recently, supportive care was the only option available for the management of MPSs. In the early 2000s, enzyme replacement therapy (ERT) was approved by the United States Food and Drug Administration (FDA) for the treatment of MPS I, II and VI. Clinical trials of ERT showed substantial improvements in patients' somatic symptoms; however, no benefit was found in the neurological symptoms because the enzymes do not readily cross the blood–brain barrier (BBB). Haematopoietic stem cell transplantation (HSCT), another potentially curative treatment, is not routinely advocated in clinical practice due to its high risk profile and lack of evidence for efficacy, except in preserving cognition and prolonging survival in young patients with severe MPS I. In recent years, substrate reduction therapy (SRT) and gene therapy have been rapidly gaining greater recognition as potential therapeutic avenues. What is new and conclusion Enzyme replacement therapy (ERT) is effective for the treatment of many somatic symptoms, particularly walking ability and respiratory function, and remains the mainstay of MPS treatment. The usefulness of HSCT has not been established adequately for most MPSs. Although still under investigation, SRT and gene therapy are promising MPS treatments that may prevent the neurodegeneration not affected by ERT.

BackgroundAn optimal therapy for the treatment of pneumonia caused by drug-resistant Acinetobacter baumannii remains unclear. This study aims to compare various antimicrobial strategies and to determine the most effective therapy for pneumonia using a network meta-analysis.MethodsSystematic search and quality assessment were performed to select eligible studies reporting one of the following outcomes: all-cause mortality, clinical cure, and microbiological eradication. The primary outcome was all-cause mortality. A network meta-analysis was conducted with a Bayesian approach. Antimicrobial treatments were ranked based on surface under the cumulative ranking curve (SUCRA) value along with estimated median outcome rate and corresponding 95% credible intervals (CrIs). Two treatments were considered significantly different if a posterior probability of superiority (P) was greater than 97.5%.ResultsTwenty-three studies evaluating 15 antimicrobial treatments were included. Intravenous colistin monotherapy (IV COL) was selected as a common comparator, serving as a bridge for developing the network. Five treatments ranked higher than IV COL (SUCRA, 57.1%; median all-cause mortality 0.45, 95% CrI 0.41–0.48) for reducing all-cause mortality: sulbactam monotherapy (SUL, 100.0%; 0.18, 0.04–0.42), high-dose SUL (HD SUL, 85.7%; 0.31, 0.07–0.71), fosfomycin plus IV COL (FOS + IV COL, 78.6%; 0.34, 0.19–0.54), inhaled COL plus IV COL (IH COL + IV COL, 71.4%; 0.39, 0.32–0.46), and high-dose tigecycline (HD TIG, 71.4%; 0.39, 0.16–0.67). Those five treatments also ranked higher than IV COL (SUCRA, 45.5%) for improving clinical cure (72.7%, 72.7%, 63.6%, 81.8%, and 90.9%, respectively). Among the five treatments, SUL (P = 98.1%) and IH COL + IV COL (P = 99.9%) were significantly superior to IV COL for patient survival and clinical cure, respectively. In terms of microbiological eradication, FOS + IV COL (P = 99.8%) and SUL (P = 98.9%) were significantly superior to IV COL.ConclusionsThis Bayesian network meta-analysis demonstrated the comparative effectiveness of fifteen antimicrobial treatments for drug-resistant A. baumannii pneumonia in critically ill patients. For survival benefit, SUL appears to be the best treatment followed by HD SUL, FOS + IV COL, IH COL + IV COL, HD TIG, and IV COL therapy, in numerical order.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1916-6) contains supplementary material, which is available to authorized users.

The functional role of Langerhans cells (LCs) in ocular surface inflammation and nerve damage in dry eye (DE) disease has yet to be determined. This study was performed to investigate this relationship through both clinical study on DE patients and in vivo mouse models with induced DE disease. In a cross-sectional case-control study (54 eyes of DE patients; 34 eyes of control patients), average cell density, area, and process length of LCs were measured using confocal microscopy. Data were analyzed to determine whether changes in LCs are correlated with subbasal nerve plexus (SNP) parameters (nerve density, beading, and tortuosity). In DE patients, SNP density marginally decreased and nerve beading and tortuosity were significantly increased compared to the control group. The total number of LCs significantly increased in DE patients, and some LCs with elongated processes were found to be attached to nerve fibers. Interestingly, nerve loss and deformation were correlated with inactivation of LCs. In an in vivo experiment to elucidate the role of LCs in ocular surface inflammation and corneal nerve loss, we used a genetically modified mouse model (CD207-DTR) that reduced the population of CD207 (Langerin) expressing cells by injection of diphtheria toxin. In CD207-depleted mice with DE disease (CD207-dDTR+DE), corneal nerves in the central region were significantly decreased, an effect that was not observed in wild-type (WT)+DE mice. In CD207-dDTR+DE mice, infiltration of CD4+, CD19+, CD45+, and CD11b+ cells into the ocular surface was increased, as confirmed by flow cytometry. Increased IL-17 and IFN-γ mRNA levels, and decreased expression of neurotrophic factors and neurotransmitters, were also found in the CD207-dDTR+DE mice. These data support a functional role for LCs in negatively regulating ocular surface inflammation and exhibiting a neuroprotective function in DE disease.

The Korean version of the COHIP was successfully developed. The internal reliability, retest reliability, face validity, discriminant validity, and convergent validity of the COHIP Korean version were confirmed.

The pathogenesis of immune-mediated lacrimal gland (LG) dysfunction in Sjögren's syndrome has been thoroughly studied. However, the majority of dry eye (DE) is not related to Sjögren type, and its pathophysiology remains unclear. The purpose of this study was to determine and investigate the protective mechanisms against DE stress in mice. DE induced prominent blood vessel loss without apoptosis or necrosis in the LG. Autophagic vacuoles, distressed mitochondria, and stressed endoplasmic reticulum were observed via electron microscopy. Immunoblotting confirmed the increase in autophagic markers. Glycolytic activities were enhanced with increasing levels of succinate and malate that, in turn, activated hypoxia-inducible factor (HIF)-1α. Interestingly, the areas of stable HIF-1α expression overlapped with COX-2 and MMP-9 upregulation in LGs of DE-induced mice. We generated HIF-1α conditional knockout (CKO) mice in which HIF-1α expression was lost in the LG. Surprisingly, normal LG polarities and morphologies were completely lost with DE induction, and tremendous acinar cell apoptosis was observed. Similar to Sjögren's syndrome, CD3+ and CD11b+ cells infiltrated HIF-1α CKO LGs. Our results show that DE induced the expression of HIF-1α that activated autophagy signals to prevent further acinar cell damage and to maintain normal LG function.

This study aimed to provide fundamental data to be utilized in preventing and treating musculoskeletal disorders and analyzing working postures commonly used during periodontal treatment. [Subjects] The subjects were three dental hygienists with work experience in dental clinics for more than 10 years. [Methods] For the analysis of working postures, we simulated the work posture of dental hygienists during the scaling procedures and oral radiographic imaging tasks. The subjects were recorded on video to precisely observe them while they were working. The captured working postures were assessed and analyzed using ergonomic assessment methods, the Rapid Entire Body Assessment, Rapid Upper Limb Assessment, and Strain index. [Results] No differences were exhibited in the intensities of manual scaling and ultrasonic scaling. Commonly, the shoulders and waist were found to be the most overburdened. According to the strain index, manual scaling and ultrasonic scaling working postures were identified to be most dangerous. [Conclusion] The work postures of dental hygienists during scaling are postures that are highly likely to generate work-related musculoskeletal disorders. Therefore, the development of therapeutic exercise programs easily performable in the workplace and daily life is thought to be crucial to prevent work-related musculoskeletal disorders.

Objectives To investigate registered nurses’ awareness and implementation of oral health care in patients who are hospitalized in general wards or intensive care units (ICUs) in South Korea. Methods This research was performed as a descriptive survey of 149 nurses working in nine general hospitals with at least 100 beds in major Korean cities. Results Approximately half (40.9%) of the survey respondents reported providing oral health care for hospitalized patients but that relevant protocols were not available at most hospitals or wards (89.5%). Nurses working in an ICU were significantly more likely to provide oral health care than those working in general wards (83.9% vs 15.1%; P < .001). Most respondents (83.2%) were aware of the importance of providing oral health care for hospitalized patients; however, the proportion considering that such care should be provided by dental hygienists was greater than that considering it should be provided by nurses (36.4% vs 26.0%; P < .001). Agreement that oral health care should be provided for hospitalized patients by dental hygienists was highest in nurses working in ICUs (53.3%; P < .001). Conclusions According to this survey, oral healthcare provision is generally low in hospitalized patients and differs between ICUs and general wards. Most respondents considered that dental hygienists should provide oral health care for hospitalized patients. There is an opportunity for nurses and dental hygienists to work collaboratively towards development of an evidence‐based protocol for oral health care in hospitalized patients.

Introduction The purpose of the present study was to investigate current sugar‐sweetened beverage consumption habits in Korean adolescents in conjunction with their demo‐socioeconomic characteristics, and to identify variables that affect such behaviours. Materials and methods The study was conducted via secondary analysis of data from the 2015 Youth Risk Behavior Web‐Based Survey (the 11th survey). The dependent variable in the current study was the combined consumption frequency of three types of sugar‐sweetened beverages (carbonated beverages, highly‐caffeinated beverages, sugary beverages), and demographic (gender, academic grade, residence), sociological (father's education level, mother's education level, having experienced depression within the last 12 months) and economic (subjective economic status, weekly allowance) factors constituted the independent variables. Results Our results showed that the amount of weekly allowance had the greatest impact on adolescents’ beverage consumption of more than seven times a week. Increases in experiencing a depressed mood and allowance were associated with an increased tendency to consume ≥ 7 sugar‐sweetened beverages per week. Conclusion The results of the current study suggest that families and society should work collectively to motivate adolescents to consciously choose and buy healthy snacks. Furthermore, society should reach a consensus and invest effort to resolve this issue continuously and gradually, such as by presenting a standard for consumption of sugar‐added drinks and implementing regulations to ban sales to adolescents.