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Background: The latest review of studies on multimorbidity patterns showed high heterogeneity in the methodology for identifying groups of multimorbid conditions. However, it is unclear how analytical methods used influence the identified multimorbidity patterns., Methods: We undertook a systematic review of analytical methods used to identify multimorbidity patterns in PubMed and EMBASE from their inception to January 2017. We conducted a comparison analysis to assess the effect the analytical methods had on the multimorbidity patterns identified, using the Australian National Health Survey (NHS) 2007-08 data., Results: We identified 13 194 studies and excluded 13 091 based on titles/abstracts. From the full-text reviews of the 103 remaining publications, we identified 41 studies that used five different analytical methods to identify multimorbid conditions in the studies. Thirty-seven studies (90%) adopted either the factor-analysis or hierarchical-clustering methods, but heterogeneity arises for the use of different proximity measures within each method to form clusters. Our comparison analysis showed the variation in identified groups of multimorbid conditions when applying the methods to the same NHS data. We extracted main similarities among the groupings obtained by the five methods: (i) cardiovascular and metabolic diseases, (ii) mental health problems and (iii) allergic diseases., Conclusion: We showed the extent of effects for heterogeneous analytical methods on identification of multimorbidity patterns. However, more work is needed to guide investigators for choosing the best analytical method to improve the validity and generalizability of findings. Investigators should also attempt to compare results obtained by various methods for a consensus grouping of multimorbid conditions.

Consuming a healthy diet characterised by a variety of nutritious foods is essential for promoting and maintaining health and wellbeing, yet the diets of Australian children continue to fall well short of national healthy eating recommendations. This research endeavours to identify patterns of dietary intake in Australian children at three and five years of age and investigate associations between early childhood dietary patterns and socio-economic and demographic indicators and Body Mass Index (BMI), as well as identify changes in children's dietary patterns over time. Cross-sectional dietary patterns were derived for 1565 and 631 children aged three and five years, respectively using Latent Class Analysis (LCA), with changes over time analysed with Latent Transition Analysis (LTA). Demographic variables of interest included child sex, parental age, family status, and use of childcare services and socio-economic variables included education, income and employment status. Three patterns of dietary intake were identified at three years (Highly Unhealthy, Healthier and Moderately Unhealthy) and two patterns at five years (Unhealthy and Healthier). Children with younger mothers, working mothers, fathers with a higher BMI and living in a two-carer household were more likely to have unhealthy eating patterns at three years, and children with working mothers and living in a two-carer household were more likely to have unhealthy patterns of dietary intake at five years. Approximately one eighth of the sample transitioned from the healthier to unhealthy pattern of dietary intake from three to five years. The quality of Australian children's diets appears to be declining through the early childhood years, continuing to highlight the importance of nutrition policies and interventions targeted towards the early years of life., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Geographical disparity in colorectal cancer (CRC) survival rates may be partly due to aging populations and disadvantage in more remote locations; factors that also impact the incidence and outcomes of other chronic health conditions. The current study investigates whether geographic disparity exists amongst previously diagnosed health conditions in CRC patients above and beyond age and area-level disadvantage and whether this disparity is linked to geographic disparity in CRC survival. Methods: Data regarding previously diagnosed health conditions were collected via computer-assisted telephone interviews with a cross-sectional sample of n = 1,966 Australian CRC patients between 2003 and 2004. Ten-year survival outcomes were acquired in December 2014 from cancer registry data. Multivariate logistic regressions were applied to test associations between previously diagnosed health conditions and survival rates in rural, regional, and metropolitan areas. Results: Results suggest that only few geographical disparities exist in previously diagnosed health conditions for CRC patients and these were largely explained by socio-economic status and age. Living in an inner regional area was associated with cardio-vascular conditions, one or more respiratory diseases, and multiple respiratory diagnoses. Higher occurrences of these conditions did not explain lower CRC-specific 10 years survival rates in inner regional Australia. Conclusion: It is unlikely that health disparities in terms of previously diagnosed conditions account for poorer CRC survival in regional and remote areas. Interventions to improve the health of regional CRC patients may need to target issues unique to socio-economic disadvantage and older age.

Thyroid cancer is rapidly increasing in incidence worldwide. Although most thyroid cancer can be cured with surgery, radioactive iodine, and/or chemotherapy, thyroid cancers still recur and may become chemoresistant. Autophagy is a complex self-degradative process that plays a dual role in cancer development and progression. In this study, we found that miR-125b was downregulated in tissue samples of thyroid cancer as well as in thyroid cancer cell lines, and the expression of Foxp3 was upregulated. Further, we demonstrated that miR-125b could directly act on Foxp3 by binding to its 3' UTR and inhibit the expression of Foxp3. A negative relationship between miR-125b and Foxp3 was thus revealed. Overexpression of miR-125b markedly sensitized thyroid cancer cells to cisplatin treatment by inducing autophagy through an Atg7 pathway in vitro and in vivo. Taken together, our findings demonstrate a novel mechanism by which miR-125b has the potential to negatively regulate Foxp3 to promote autophagy and enhance the efficacy of cisplatin in thyroid cancer. miR-125 may be of therapeutic significance in thyroid cancer., (Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Protein glycosylation is post-translational modification (PTM) which is important for pharmacokinetics and immunogenicity of recombinant glycoprotein therapeutics. As a result of variations in monosaccharide composition, glycosidic linkages and glycan branching, glycosylation introduces considerable complexity and heterogeneity to therapeutics. The host cell line used to produce the glycoprotein has a strong influence on the glycosylation because different host systems may express varying repertoire of glycosylation enzymes and transporters that contributes to specificity and heterogeneity in glycosylation profiles. In this review, we discuss the types of host cell lines currently used for recombinant therapeutic production, their glycosylation potential and the resultant impact on glycoprotein properties. In addition, we compare the reported glycosylation profiles of four recombinant glycoproteins: immunoglobulin G (IgG), coagulation factor VII (FVII), erythropoietin (EPO) and alpha-1 antitrypsin (A1AT) produced in different mammalian cells to establish the influence of mammalian host cell lines on glycosylation.

Background: Few randomised controlled trials (RCTs) have evaluated the different recalling approaches for enhancing adherence to faecal immunochemical test (FIT)-based screening., Aim: The authors evaluated the effectiveness of two telecommunication strategies on improving adherence to yearly FIT screening., Design and Setting: A randomised, parallel group trial was performed in a primary care screening practice., Method: The authors recruited 629 asymptomatic individuals aged 40-70 years with a negative FIT in 2015 to a population-based screening programme. On participation, they were invited to repeat their second round of FIT in 2016, 12 months after the first test. Each participant was randomly assigned to either interactive telephone reminder ( n = 207), short message service reminder (SMS, n = 212), or control, where no additional interventions were delivered after the findings of their first FIT was communicated to the participants ( n = 210). Reminders in the intervention groups were delivered 1 month before subjects' expected return. Additional telephone reminders were delivered 2 months after the expected return date to all subjects who defaulted specimen return. The outcomes included rates of FIT collection and specimen return up to 6 months after their expected return., Results: At 6 months, the cumulative FIT collection rate was 95.1%, 90.4%, and 86.5%, respectively, for the telephone, SMS, and control groups ( P = 0.010). The corresponding specimen return rate was 94.1%, 90.0%, and 86.0% ( P = 0.022). When compared with the control, only subjects in the telephone group were significantly more likely to collect FIT tubes (adjusted odds ratio [AOR] 3.18, 95% confidence interval [CI] = 1.50 to 6.75, P = 0.003) and return completed specimens (AOR = 2.73, 95% CI = 1.35 to 5.53, P = 0.005)., Conclusion: Interactive telephone reminders are effective at securing previously screened subjects to repeat screening 1 year after a negative finding., (© British Journal of General Practice 2018.)

Background: Massive occurrences of interstitial loss of heterozygosity (LOH) likely resulting from gene conversions were found by us in different cancers as a type of single-nucleotide variations (SNVs), comparable in abundance to the commonly investigated gain of heterozygosity (GOH) type of SNVs, raising the question of the relationships between these two opposing types of cancer mutations., Methods: In the present study, SNVs in 12 tetra sample and 17 trio sample sets from four cancer types along with copy number variations (CNVs) were analyzed by AluScan sequencing, comparing tumor with white blood cells as well as tissues vicinal to the tumor. Four published "nontumor"-tumor metastasis trios and 246 pan-cancer pairs analyzed by whole-genome sequencing (WGS) and 67 trios by whole-exome sequencing (WES) were also examined., Results: Widespread GOHs enriched with CG-to-TG changes and associated with nearby CNVs and LOHs enriched with TG-to-CG changes were observed. Occurrences of GOH were 1.9-fold higher than LOH in "nontumor" tissues more than 2 cm away from the tumors, and a majority of these GOHs and LOHs were reversed in "paratumor" tissues within 2 cm of the tumors, forming forward-reverse mutation cycles where the revertant LOHs displayed strong lineage effects that pointed to a sequential instead of parallel development from "nontumor" to "paratumor" and onto tumor cells, which was also supported by the relative frequencies of 26 distinct classes of CNVs between these three types of cell populations., Conclusions: These findings suggest that developing cancer cells undergo sequential changes that enable the "nontumor" cells to acquire a wide range of forward mutations including ones that are essential for oncogenicity, followed by revertant mutations in the "paratumor" cells to avoid growth retardation by excessive mutation load. Such utilization of forward-reverse mutation cycles as an adaptive mechanism was also observed in cultured HeLa cells upon successive replatings. An understanding of forward-reverse mutation cycles in cancer development could provide a genomic basis for improved early diagnosis, staging, and treatment of cancers.

Interferon regulatory factor 9 (IRF9) is an integral transcription factor in mediating the type I interferon antiviral response, as part of the interferon-stimulated gene factor 3. However, the role of IRF9 in many important non-communicable diseases has just begun to emerge. The duality of IRF9's role in conferring protection but at the same time exacerbates diseases is certainly puzzling. The regulation of IRF9 during these conditions is not well understood. The high homology of IRF9 DNA-binding domain to other IRFs, as well as the recently resolved IRF9 IRF-associated domain structure can provide the necessary insights for progressive inroads on understanding the regulatory mechanism of IRF9. This review sought to outline the structural basis of IRF9 that guides its regulation and interaction in antiviral immunity and other diseases.

Background: Preventive chemotherapy is the current global control strategy for schistosomiasis. The WHO target coverage rate is at least 75% for school-aged children. In the Philippines, the reported national coverage rate (43.5%) is far below the WHO target. This study examined the factors associated with non-compliance to mass drug administration., Methods: A cross-sectional survey was conducted in 2015 among 2189 adults in the province of Northern Samar, the Philippines using a structured face-to-face survey questionnaire., Results: The overall rate of non-compliance to mass drug administration (MDA) in the last treatment round was 27%. Females (aOR = 1.67, P = 0.033) were more likely to be non-compliant. Respondents who believed that schistosomiasis was acquired by open defecation and poor sanitation (aOR = 1.41, P = 0.015), and by drinking unclean water (aOR = 2.09, P = 0.001) were more likely to refuse treatment. Uncertainties on whether schistosomiasis can be treated (aOR = 2.39, P = 0.033), their fear of adverse reactions to praziquantel (aOR = 1.94, P = 0.021), misconceptions about alternative forms of treatment (aOR = 1.45, P = 0.037), and that praziquantel is used for purposes other than deworming (aOR = 2.15, P = 0.021) were all associated with a higher odd of non-compliance. In contrary, being a farmer (aOR = 0.62, P =0.038), participation in past MDA (aOR = 0.30, P < 0.001), informed about impending MDA (aOR = 0.08, P < 0.001), and having heard of schistosomiasis (aOR = 0.22, P = 0.045) were all significantly associated with reduced non-compliance., Conclusions: To improve drug compliance for schistosomiasis there is an urgent need for intensive health education campaigns before conducting MDA that would not only provide disease specific information, but also deal with prevailing misconceptions about transmission, prevention, treatment, and drug side-effects.

Background: There are patients with recalcitrant psoriasiform plaques that do not fit into conventional categories of facial dermatoses. Our study aims to describe the clinicopathological characteristics of several patients with a unique presentation of persistent psoriasiform facial rashes., Methods: This retrospective cross-sectional study analyzed clinical and histological data of known cases of recalcitrant psoriasiform dermatosis of the face diagnosed at National Skin Centre, Singapore, over 10 years., Results: There were 8 Chinese patients with mean age at onset of 29 years. Majority had pink to pink-orange well-defined plaques with dry scale (n = 6, 75%), distributed mostly on the cheeks (100%) and chin (n = 7, 88%). Hyperkeratosis, parakeratosis, preserved granular layer and psoriasiform hyperplasia were showed in all biopsies. Other common findings included subtle subcorneal acantholysis, "checkerboard" alternating ortho-/parakeratosis, vacuolated keratinocytes and follicular plugging. All patients showed little treatment response. One patient eventually developed features of type II pityriasis rubra pilaris (PRP). Our study was limited by its small sample size and lack of a pre-existing diagnostic code., Conclusions: This recalcitrant psoriasiform facial dermatosis seems to be a distinct entity, with consistent and reproducible clinical features and a PRP-like histology, bearing some resemblance to the recently described condition-facial discoid dermatosis., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

While low back pain significantly impacts on an individual's well-being, our understanding of the role of well-being in the natural history of low back pain is limited. This cohort study aimed to investigate the association between psychological and general well-being and the development and progression of low back pain and disability in community-based women over a 2-year period. 506 women recruited from a research database were invited to participate. Overall psychological and general well-being and its subdomains were assessed at baseline using the Psychological General Well-Being Index (PGWB). The intensity of and degree of disability arising from low back pain were examined using the Chronic Pain Grade Questionnaire at baseline and at 2-year follow-up. Participants were categorized as having no, developing, resolving, or persistent high-intensity pain and disability. 444 participants (87.8%) completed the study. Women with persistent high-intensity pain had lower PGWB scores at baseline than those with no high-intensity pain at follow-up, after adjusting for confounders (M(SE) = 69.9(2.55) vs 80.1(2.63), p < 0.005). Furthermore, women with persistent high disability scores had lower well-being scores than those without persistent high disability scores (M(SE) = 69.1(3.49) vs. 81.2(0.802), p = 0.001). Moreover, lower scores in the well-being subdomains of general health and vitality were associated with persistent high pain intensity and disability (all p < 0.007). In summary, lower levels of general health and vitality were associated with persistent high-intensity low back pain and disability, suggesting that improving these aspects of well-being has the potential to reduce high levels of chronic low back pain and disability in community-based women., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: This paper examines the direct and intermediary relationships between life stress, stress appraisal, and resilience, and increased anxiety and depressive symptoms in Australian women after cancer treatment., Methods: Data examined from 278 women aged 18 years and older previously treated for breast, gynaecological, or blood cancer, participating in the Australian Women's Wellness after Cancer Program. Serial mediation models interrogated the effect of stressful life events (List of Threatening Experiences-Modified) mediated by appraisal and coping (Perceived Stress Scale and Connor-Davidson Resilience Scale), on symptoms of anxiety and depression (Zung Self-rating Anxiety Scale and Center for Epidemiologic Studies Depression Scale)., Results: Over one-quarter (30.2%) of participants reported 1 or more stressful life events, other than their cancer, in the previous 6 months. Results indicate that perceived stress fully mediated the relationships between life stress, anxiety (indirect effect = 0.09, Bias-corrected bootstrap 95% CI 0.02-0.18, Percent mediation = 0.51), and depressive symptoms (indirect effect = 0.11, Bias-corrected bootstrap 95% CI 0.02-0.23, Percent mediation = 0.71) and accounted for more than half of the relationship between predictor and outcome., Conclusions: Findings indicate that stress appraisal mediated the relationship between past life stressors and anxiety and depressive symptoms. This analysis also highlights the need to consider wellness within a broader care context to identify potentially vulnerable patients to possibly avert future health concerns., (Copyright © 2018 John Wiley & Sons, Ltd.)

Background: It is unclear whether recommended doses of intramuscular polyvalent immune globulin are optimal for both effectiveness and efficiency of disease prevention when administered post-exposure to measles and rubella., Methods: The peak concentration and decay of disease-specific antibodies after intramuscular dosing of polyvalent immune globulin in adults were modeled using published pharmacokinetic parameters and product disease-specific antibody concentrations. Models simulated dosing according to current Australian guidelines, then adjusted the dose in clinically relevant increments to estimate the optimal dose of disease-specific immunoglobulins for post-exposure prophylaxis of nonimmune individuals against measles and rubella. Optimal dosing assumed a target serum concentration of disease-specific antibodies of the correlate of protection plus a 10% margin of error at an incubation period., Results: Current Australian guidelines appeared to underdose a measles-naïve subpopulation. The optimal dose of measles-specific antibodies was 17.5 IU/kg assuming 75% bioavailability and 25.5 IU/kg assuming 50% bioavailability. Current Australian guidelines recommend 520 IU/kg rubella antibodies for an 80-kg individual. This model suggests that 13 IU/kg is more than sufficient., Conclusions: The recommended dose of intramuscular polyvalent immune globulin should be increased following measles exposure and decreased following rubella exposure for recommended subgroups. These models may be adapted for use internationally.

Purpose: As a core component of a new gynecologic cancer radiation program, we envisioned, structured, and implemented a novel Interventional Radiation Oncology (IRO) unit and magnetic resonance (MR)-brachytherapy environment in an existing MR simulator., Methods and Materials: We describe the external and internal processes required over a 6-8 month time frame to develop a clinical and research program for gynecologic brachytherapy and to successfully convert an MR simulator into an IRO unit., Results: Support of the institution and department resulted in conversion of an MR simulator to a procedural suite. Development of the MR gynecologic brachytherapy program required novel equipment, staffing, infrastructural development, and cooperative team development with anesthetists, nurses, therapists, physicists, and physicians to ensure a safe and functional environment. Creation of a separate IRO unit permitted a novel billing structure., Conclusions: The creation of an MR-brachytherapy environment in an MR simulator is feasible. Developing infrastructure includes several collaborative elements. Unique to the field of radiation oncology, formalizing the space as an Interventional Radiation Oncology unit permits a sustainable financial structure., (Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Importance: It is well established from different population-based studies that visual impairment is associated with increased mortality rate. However, to our knowledge, the association of visual impairment with increased mortality rate has not been reported among indigenous Australian individuals., Objective: To assess the association between visual impairment and 10-year mortality risk among the remote indigenous Australian population., Design, Setting, and Participants: Prospective cohort study recruiting indigenous Australian individuals from 30 remote communities located within the central Australian statistical local area over a 36-month period between July 2005 and June 2008. The data were analyzed in January 2017., Exposures: Visual acuity, slitlamp biomicroscopy, and fundus examination were performed on all patients at recruitment. Visual impairment was defined as a visual acuity of less than 6/12 in the better eye., Main Outcomes and Measures: Mortality rate and mortality cause were obtained at 10 years, and statistical analyses were performed. Hazard ratios for 10-year mortality with 95% confidence intervals are presented., Results: One thousand three hundred forty-seven patients were recruited from a total target population number of 2014. The mean (SD) age was 56 (11) years, and 62% were women. The total all-cause mortality was found to be 29.3% at 10 years. This varied from 21.1% among those without visual impairment to 48.5% among those with visual impairment. After adjustment for age, sex, and the presence of diabetes and hypertension, those with visual impairment were 40% more likely to die (hazard ratio, 1.40; 95% CI, 1.16-1.70; P = .001) during the 10-year follow-up period compared with those with normal vision., Conclusions and Relevance: Bilateral visual impairment among remote indigenous Australian individuals was associated with 40% higher 10-year mortality risk compared with those who were not visually impaired. Resource allocation toward improving visual acuity may therefore aid in closing the gap in mortality outcomes between indigenous and nonindigenous Australian individuals.

Background: Although anaerobic digestion for biogas production is used worldwide in treatment processes to recover energy from carbon-rich waste such as cellulosic biomass, the activities and interactions among the microbial populations that perform anaerobic digestion deserve further investigations, especially at the population genome level. To understand the cellulosic biomass-degrading potentials in two full-scale digesters, this study examined five methanogenic enrichment cultures derived from the digesters that anaerobically digested cellulose or xylan for more than 2 years under 35 or 55 °C conditions., Results: Metagenomics and metatranscriptomics were used to capture the active microbial populations in each enrichment culture and reconstruct their meta-metabolic network and ecological roles. 107 population genomes were reconstructed from the five enrichment cultures using a differential coverage binning approach, of which only a subset was highly transcribed in the metatranscriptomes. Phylogenetic and functional convergence of communities by enrichment condition and phase of fermentation was observed for the highly transcribed populations in the metatranscriptomes. In the 35 °C cultures grown on cellulose, Clostridium cellulolyticum -related and Ruminococcus -related bacteria were identified as major hydrolyzers and primary fermenters in the early growth phase, while Clostridium leptum -related bacteria were major secondary fermenters and potential fatty acid scavengers in the late growth phase. While the meta-metabolism and trophic roles of the cultures were similar, the bacterial populations performing each function were distinct between the enrichment conditions., Conclusions: Overall, a population genome-centric view of the meta-metabolism and functional roles of key active players in anaerobic digestion of cellulosic biomass was obtained. This study represents a major step forward towards understanding the microbial functions and interactions at population genome level during the microbial conversion of lignocellulosic biomass to methane. The knowledge of this study can facilitate development of potential biomarkers and rational design of the microbiome in anaerobic digesters.

Background: To clarify the effect of induction chemotherapy (ICT) in patients with advanced pharyngeal and laryngeal squamous cell carcinoma (PLSCC) treated with concurrent chemoradiotherapy (CCRT)., Methods: Patients with treatment-naïve nonmetastatic advanced PLSCC were stratified according to disease stage (III or IV) and resectability before being randomized to either a ICT/CCRT or CCRT arm. A cisplatin/tegafur-uracil/leucovorin regimen was administered during ICT and CCRT. The primary end point was overall survival (OS)., Results: We enrolled 151 patients during December 2006 to February 2011. The median follow-up of surviving patients was 54.5 months. The ICT/CCRT arm included more patients with hypopharynx cancer (57.1% vs 40.5%, p = 0.09) and N2 or N3 diseases (85.7% vs 74.4%, p = 0.02). In the ICT/CCRT and CCRT arms, the 5-year OS was 48.1% and 53.2% (p = 0.45); progression-free survival (PFS) was 31.8% and 55.6% (p = 0.015); and locoregional control (LRC) was 37.7% and 56.2% (p = 0.026), respectively. The adverse events and compliance to radiotherapy were similar. However, the proportion of patients receiving a total dose of cisplatin during CCRT <150 mg/m 2 was higher in the ICT/CCRT arm (46.8% vs 16.2%; p = 0.000) and independently predicted poorer PFS and LRC in multivariate analysis., Conclusion: OS did not vary between the ICT/CCRT and CCRT arms. However, poorer compliance to CCRT and inferior LRC and PFS were observed in the ICT/CCRT arm. Optimizing the therapeutic ratio in both ICT and CCRT settings are necessary for developing a sequential strategy for patients with advanced-stage PLSCC., (Copyright © 2018 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Oligosaccharides are generally considered to be un-utilized for growth of mammalian cells because their permeability across the cell membrane is low. However, in our previous study, we discovered that CHO and HEK293 cells consume maltose in culture media without serum and glucose. This is interesting because the transporter for maltose in mammalian cells has not been discovered to-date, and the only animal disaccharide transporter that is recently discovered is a sucrose transporter. The application of oligosaccharides in mammalian cell-based biopharmaceutical manufacturing can be beneficial, because it can theoretically increase carbohydrate content of the culture medium and decrease lactate production. Here, we first determined that specific maltose consumption rate in CHO cells was similar to galactose and fructose at 0.257 ng/cell/day. We then demonstrated that CHO cells can be cultivated with reasonable cell growth using higher maltose concentrations. After which, we evaluated the use of maltose supplementation in the production of a recombinant monoclonal antibody in batch and fed-batch cultures, demonstrating improvements in recombinant monoclonal antibody titer of 15% and 23% respectively. Finally, glycosylation profiles of the antibodies were analyzed.

Objectives: Chronic low back pain (CLBP) is a major health issue, yet its underlying mechanisms remain unknown. Studies have demonstrated the importance of emotion and cognition in chronic pain; however, the relevant brain physiology in magnetic resonance imaging (MRI) studies are unclear in CLBP populations. Therefore, this review aimed to identify MRI brain changes and examine their potential relationship with emotional and cognitive processes in CLBP., Methods: A systematic search was conducted in 5 databases. Studies that recruited adult, CLBP populations, and used brain MRI protocols were included., Results: In total, 55 studies met the inclusion criteria. Of the structural MRI studies, 10 of 15 studies found decreased gray matter and 7 of 8 studies found white matter changes in CLBP groups compared with controls. Fourteen resting-state functional MRI studies all reported differences between CLBP and control groups in the default mode network. Interestingly, only 3 of 10 functional MRI studies observed significant differences during noxious stimulation between CLBP and control groups, whereas 13 of 16 studies observed significant brain activation differences in CLBP groups during various external tasks. Finally, there were 3 studies that observed a degree of recovery in functional connectivity following intervention., Discussion: The brain changes in CLBP groups were mainly observed in areas and networks important in emotion and cognition, rather than those typically associated with nociception. This supports the understanding that emotional and cognitive processes may be the core contributor to the CLBP experience; however, future studies need to explore these processes further.

Nitrification plays a crucial role in global nitrogen cycling and treatment processes. However, the relationships between the nitrifier guilds of ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) are still poorly understood, especially in freshwater habitats. This study examined the physiological interactions between the AOB and NOB present in a freshwater aquarium biofilter by culturing them, either together or separately, in a synthetic medium. Metagenomic and 16S rRNA gene sequencing revealed the presence and the draft genomes of Nitrosomonas -like AOB as well as Nitrobacter -like NOB in the cultures, including the first draft genome of Nitrobacter vulgaris . The nitrifiers exhibited different growth rates with different ammonium (NH 4 + ) or nitrite concentrations (50-1,500 μM) and the growth rates were elevated under a high bicarbonate (HCO 3 - ) concentration. The half-saturation constant ( K s for NH 4 + ), the maximum growth rate (μ max ), and the lag duration indicated a strong dependence on the synergistic relationships between the two guilds. Overall, the ecophysiological and metagenomic results in this study provided insights into the phylogeny of the key nitrifying players in a freshwater biofilter and showed that interactions between the two nitrifying guilds in a microbial community enhanced nitrification.

Background: The appropriate structure, scope and cost of government incentives in the private health insurance (PHI) market is a matter of ongoing debate., Objective: In order to inform policy decisions we designed a two-stage study to (1) model the uptake of PHI covering hospital treatment in Australia, and (2) identify the costs of various policy scenarios to the government., Methods: Using a microsimulation with a cost-benefit component, we modelled the insurance decisions made by individuals who collectively represented the Australian insurance population in the financial year 2014-15., Results: We found that the mean willingness to pay (WTP) for PHI ranged from A$446 to A$1237 per year depending on age and income. Our policy scenarios showed a considerable range of impacts on the government budget (from A$4 billion savings to A$6 billion expense) and PHI uptake (from 3.4 million fewer to 2.5 million more individuals insured), with cost-effectiveness ranging from -A$305 to A$22,624 per additional person insured, relative to the status quo., Conclusions: Based on the scenario results we recommend policy adjustments that either increase the PHI uptake at a small per-person cost to the public budget or substantially reduce government subsidisation of PHI at a relatively small loss in terms of persons insured.

Purpose: This study aims to study the impact of clinical factors on the lymph node sampling in a large cohort of patients with colorectal cancer., Methods: A colorectal cancer database of 2298 patients in Queensland, Australia, was established. Zero-inflated regression method was used to model positive lymph node counts given the number of lymph nodes examined, with patient's demographic and clinical factors as covariates in the model. Sensitivity and survival analyses were performed to illustrate the applicability of the recommendation of the minimum number of lymph nodes need to be pathologically examined., Results: Younger patients with a larger sized tumour located at the left colon or rectum require fewer lymph nodes to be pathologically examined. Overall, 45.9% of the patients require eight or nine lymph nodes and 31.5% needs ten or 11 lymph nodes to be harvested for pathological examination. A simple formula could be used to obtain the minimum number of lymph node sampling required in patients with colorectal cancer based on patients' age as well as site and dimension of the cancer., Conclusions: The findings provide practical information about that the minimum number of lymph nodes that could be harvested at the time of collection of lymph nodes for pathological examination for patients with colorectal cancer. The minimum number of lymph nodes harvested depends on demographic (age) and clinical (location and dimension of cancer) characteristics of the patients with colorectal cancer.

Objectives: Schistosomiasis control is centred on preventive chemotherapy through mass drug administration (MDA). However, endemic countries continue to struggle to attain target coverage rates and patient compliance. In the Philippines, barangay health workers (BHWs) play a vital role in the coordination of MDA, acting as advocates, implementers, and educators. The aim of this study was to determine whether BHW knowledge and attitudes towards schistosomiasis and MDA is sufficient and correlated with resident knowledge and drug compliance., Methods: A cross-sectional survey was conducted in 2015 among 2186 residents and 224 BHWs in the province of Northern Samar, the Philippines using a structured survey questionnaire., Results: BHWs showed good familiarity on how schistosomiasis is acquired and diagnosed. Nevertheless, both BHWs and residents had poor awareness of the signs and symptoms of schistosomiasis, disease prevention, and treatment options. There was no correlation between the knowledge scores of the BHWs and the residents (r=0.080, p=0.722). Kruskal-Wallis analysis revealed significant differences in BHW knowledge scores between the low (3.29, 95% confidence interval 3.16-3.36), moderate (3.61, 95% confidence interval 3.49-3.69), and high (4.05, 95% confidence interval 3.77-4.13) compliance village groups (p=0.002), with the high compliance areas having the highest mean knowledge scores., Conclusions: This study highlights the importance of community health workers in obtaining the World Health Organization drug coverage rate of 75% and improving compliance with MDA in the community. Investing in the education of community health workers with appropriate disease-specific training is crucial if disease elimination is ultimately to be achieved., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Cutaneous plasmacytosis (CP) is a rare skin disorder characterized by multiple reddish brown nodules with polyclonal plasma cell proliferation. It has most often been reported to affect the trunk but is also known to affect the face and extremities in adults and is predominantly seen in Asians. The etiology is poorly understood, and there is no consensus on treatment methods., Methods: Five cases diagnosed to have CP were collated from our institution. Their clinicopathologic features and treatment outcomes were reviewed., Results: Four of the 5 patients presented with lesions that affected multiple sites of the body including the trunk, axillae, face, and limbs. The remaining patient had lesions localized to his axillae. The lesions were generally asymptomatic. All patients had hypergammaglobulinaemia but only one had a faint monoclonal band detected on immunofixation. Common findings in the biopsy results for all patients were perivascular plasma cell infiltrates without light chain restriction on kappa/lambda staining, as well as mast cell infiltrates. Partial remission of cutaneous lesions was observed in 3 of the patients, with 2 of them responding well to psoralen and ultraviolet A radiation therapy., Conclusion: CP presents with distinctive clinical features and characteristic histological features including polyclonal perivascular plasma cell infiltrates. The axilla seems to be a frequent and characteristic site of involvement and may be a useful clinical clue to the condition. In the management of patients with CP, it is important to exclude secondary causes of plasmacytic infiltrates. While there are no clearly established treatment modalities for CP, psoralen and ultraviolet A radiation therapy may be a viable option in view of the clinical improvement observed in our patients who received it.

Imatinib mesylate is a tyrosine kinase inhibitor used in the treatment of oncological conditions, including chronic myeloid leukemia and gastrointestinal stromal tumors. The most frequent dermatological side effect reported is pigmentary abnormalities. We report a case series of three Asian Chinese females with preexisting acquired dermal melanocytosis that progressed after initiation of imatinib treatment, and concurrently developed generalized hypopigmentation of the skin. All three patients had similar histological findings on skin biopsy. It is postulated that the KIT/SCF pathway has a central role in the pathogenetic mechanism. Therefore, it is important for physicians to be aware of this potential side effect of paradoxical pigmentation in patients treated with imatinib.

Background: To describe trajectories of health-related quality of life (QoL), life satisfaction, and psychological adjustment for men with prostate cancer over the medium to long term and identify predictors of poorer outcomes using growth mixture models., Methods: One-thousand sixty-four (82.4% response) men diagnosed with prostate cancer were recruited close to diagnosis and assessed over a 72-month (6-year) period with self-report assessment of health-related QoL, life satisfaction, cancer-related distress, and prostate specific antigen anxiety. Urinary, bowel, and sexual function were also assessed using validated questionnaires., Results: Poorer physical QOL was predicted by older age, lower education, lower income, comorbidities, and receiving hormone therapy. Lower life satisfaction was related to younger age, lower income, not being partnered, and comorbidities. Poorer psychological trajectories were predicted by younger age, lower income, comorbidities, and receiving radical prostatectomy or brachytherapy. Better urinary, bowel, and sexual function were related to better global outcomes over time. Anxiety about prostate specific antigen testing was rare., Conclusions: Distinct trajectories exist for medium- to long-term QoL, life satisfaction, and psychological adjustment after prostate cancer; with age and socioeconomic deprivation playing a differential role in men's survivorship profile and the impact of functional status on outcomes increasing over time. These results reinforce the need for an appraisal of men's life course in addition to treatment side effects when planning survivorship care after cancer., (© 2016 The Authors. Psycho-Oncology Published by John Wiley & Sons Ltd.)

Intestinal helminths are endemic throughout the Philippines; however, there is limited evidence with respect to their prevalence, intensity, and impact on children's nutritional status. A cross-sectional survey was carried out on 693 children from five rural villages in Northern Samar, the Philippines. Data on dietary intake, nutritional status, and intestinal parasites were collected. Infection with Schistosoma japonicum , Ascaris lumbricoides , Trichuris trichiura , and hookworm was evident in 20.1, 54.4, 71.4, and 25.3% of the children. The majority (84.7%) was infected with one or more helminth species, with about one-quarter of the sample (24.7%) infected with three or more. About half (49.2%, n = 341) of the children were stunted and 27.8% ( n = 193) were wasted. A lower prevalence of normal height-for-age (48.3%) appeared in those with polyparasitism, while the prevalence of stunted children increased with infection (46.7% monoparasitism and 51.7% polyparasitism). There was a decreasing trend between infection intensity and the mean values of HAZ and BAZ identified for T. trichiura or hookworm infections. Stunted children were more likely to be male (AOR = 1.58; 95% CI: 1.05⁻2.39; p = 0.028), older in age (10⁻14 years) (AOR = 1.93; 95% CI: 1.29⁻2.88; p = 0.001), and living in poorer households with palm leaves/nipa roof (AOR = 1.85; 95% CI: 1.14⁻3.01; p = 0.013). Intestinal parasitic treatment needs to be combined with nutrient supplements and health education in order to interrupt the parasite life cycle and achieve sustainable control., Competing Interests: The authors declare no conflict of interest.

While previous cross-sectional studies have found that negative beliefs about low back pain are associated with pain intensity, the relationship between back beliefs and persistent low back pain is not well understood. This cohort study aimed to examine the role of back beliefs in persistent low back pain in community-based individuals. A hundred and ninety-two participants from a previous musculoskeletal health study were invited to take part in a two-year follow-up study. Beliefs about back pain were assessed by the Back Beliefs Questionnaire (BBQ) at baseline and low back pain intensity was measured by the Chronic Pain Grade Questionnaire at baseline and follow-up. Of the 150 respondents (78.1%), 16 (10.7%) reported persistent high intensity low back pain, 12 (8.0%) developed high intensity low back pain, in 16 (10.7%) their high intensity low back pain resolved and 106 (70.7%) experienced no high intensity low back pain. While participants were generally positive about low back pain (BBQ mean (SD) = 30.2 (6.4)), those with persistent high intensity pain reported greater negativity (BBQ mean (SD) = 22.6 (4.9)). Negative beliefs about back pain were associated with persistent high intensity low back pain after adjusting for confounders (M (SE) = 23.5 (1.6) vs. >30.1 (1.7), p < .001). This study found negative back beliefs were associated with persistent high intensity low back pain over 2 years in community-based individuals. While further longitudinal studies are required, these findings suggest that targeting beliefs in programs designed to treat and prevent persistent high intensity low back pain may be important.

Purpose: Stereotactic body radiation therapy (SBRT) allows for high radiation doses to be delivered to the pancreatic tumors with limited toxicity. Nevertheless, the respiratory motion of the pancreas introduces major uncertainty during SBRT. Ultrasound imaging is a non-ionizing, non-invasive, and real-time technique for intrafraction monitoring. A configuration is not available to place the ultrasound probe during pancreas SBRT for monitoring., Methods and Materials: An arm-bridge system was designed and built. A CT scan of the bridge-held ultrasound probe was acquired and fused to ten previously treated pancreatic SBRT patient CTs as virtual simulation CTs. Both step-and-shoot intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) planning were performed on virtual simulation CT. The accuracy of our tracking algorithm was evaluated by programmed motion phantom with simulated breath-hold 3D movement. An IRB-approved volunteer study was also performed to evaluate feasibility of system setup. Three healthy subjects underwent the same patient setup required for pancreas SBRT with active breath control (ABC). 4D ultrasound images were acquired for monitoring. Ten breath-hold cycles were monitored for both phantom and volunteers. For the phantom study, the target motion tracked by ultrasound was compared with motion tracked by the infrared camera. For the volunteer study, the reproducibility of ABC breath-hold was assessed., Results: The volunteer study results showed that the arm-bridge system allows placement of an ultrasound probe. The ultrasound monitoring showed less than 2 mm reproducibility of ABC breath-hold in healthy volunteers. The phantom monitoring accuracy is 0.14 ± 0.08 mm, 0.04 ± 0.1 mm, and 0.25 ± 0.09 mm in three directions. On dosimetry part, 100% of virtual simulation plans passed protocol criteria., Conclusions: Our ultrasound system can be potentially used for real-time monitoring during pancreas SBRT without compromising planning quality. The phantom study showed high monitoring accuracy of the system, and the volunteer study showed feasibility of the clinical workflow., (© 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Lupus erythematosus (LE) is an autoimmune disease which may initially present solely with lip lesions. Due to a wide spectrum of presentation, these features may initially be misdiagnosed as other oral diseases such as lichen planus, erythema multiforme (EM), and actinic cheilitis, leading to a delay in diagnosis and treatment. We discuss a case of severely crusted cheilitis which was initially diagnosed as EM, with subsequent development of subacute cutaneous LE, and progression to systemic LE. We will discuss the clinical and histological features of lupus cheilitis., Competing Interests: There are no conflicts of interest. What is new? This case demonstrates an unusual presentation of severely crusted cheilitis as a presenting feature of systemic lupus erythematosusWe point out important features to distinguish it from differentials of other causes of crusted cheilitis and stress re-evaluation of patients particularly if ANA titers are high

Postoperative chylous fistula after neck dissection is an uncommon complication associated with significant patient morbidity. Octreotide acetate is a somatostatin analogue established in the treatment of chylothorax; however, its utility in the management of cervical chylous fistulae has not been fully evaluated. The investigators hypothesized that chylous fistula can be managed by a combination of octreotide and peripheral total parenteral nutrition (TPN). A retrospective review of cases compiled at our institution from 2009 to 2015 was conducted. Ten patients, all men, were identified as having a postoperative chylous fistula after a neck dissection. All patients were treated with peripheral TPN and intravenous octreotide. Mean age of the patients was 63.0 years (range 49 to 82). Five (50.0%) had a neck dissection for the management of metastatic nasopharyngeal carcinoma and had previous neck irradiation. In 8 (80%) patients, chylous fistula occurred in the left neck. Seven (70.0%) of the leaks occurred within the first 2 postoperative days. Eight (80%) leaks were controlled using TPN and octreotide, with 2 (20%) patients requiring surgical intervention. No factors were significant in the successful conservative management of chylous fistulae. One patient with a chylous fistula of 1,800 ml/day was managed successfully without surgical intervention. The results of this case series suggest that chylous fistulae may be managed conservatively with octreotide and TPN. However, long-term evaluation is needed to define if and when surgical intervention is required for control.

Background: Despite the proven effectiveness of colorectal cancer (CRC) screening on reduction of CRC mortality, the uptake of CRC screening remains low. Participation rate is one of determinants for the success of organized population-based screening program. This review aims to identify those who are hard-to-reach, and summarize the strategies to increase their screening rate from individual, provider and system levels., Methods: A systematic search of electronic English databases was conducted on the factors and strategies of uptake in CRC screening for the hard-to-reach population up to May 2017., Discussion: The coverage rate and participation rate are two indexes to identify the hard-to-reach population in organized CRC screening program. However, the homeless, new immigrants, people with severe mental illness, the jail intimates, and people with characteristics including lower education levels and/or low socioeconomic status, living in rural/remote areas, without insurance, and racial minorities are usually recognized as hard-to-reach populations. For them, organized screening programs offer a better coverage, while novel invitation approaches for eligible individuals and multiple strategies from primary care physicians are still needed to enhance screening rates among subjects who are hard-to-reach. Suggestions implied the effectiveness of interventions at the system level, including linkages to general practice; use of decision making tools; enlisting supports from coalition; and the continuum from screening to diagnosis and treatment., Conclusion: Organized CRC screening offers a system access to approach the hard-to-reach populations. To increase their uptake, multiple and novel strategies from individual, provider and system levels should be applied. For policymakers, public healthcare providers and community stakeholders, it is a test to tailor their potential needs and increase their participation rates through continuous efforts to eliminate disparities and inequity in CRC screening service., Competing Interests: Conflict of Interest: The authors declare no conflict of interest in this research.

Background: Ovarian cancer is the leading cause of death among gynecologic diseases in Western countries. We have previously identified a miR-200-E-cadherin axis that plays an important role in ovarian inclusion cyst formation and tumor invasion. The purpose of this study was to determine if the miR-200 pathway is involved in the early stages of ovarian cancer pathogenesis by studying the expression levels of the pathway components in a panel of clinical ovarian tissues, and fallopian tube tissues harboring serous tubal intraepithelial carcinomas (STICs), a suggested precursor lesion for high-grade serous tumors., Methods: RNA prepared from ovarian and fallopian tube epithelial and stromal fibroblasts was subjected to quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) to determine the expression of miR-200 families, target and effector genes and analyzed for clinical association. The effects of exogenous miR-200 on marker expression in normal cells were determined by qRT-PCR and fluorescence imaging after transfection of miR-200 precursors., Results: Ovarian epithelial tumor cells showed concurrent up-regulation of miR-200, down-regulation of the four target genes (ZEB1, ZEB2, TGFβ1 and TGFβ2), and up-regulation of effector genes that were negatively regulated by the target genes. STIC tumor cells showed a similar trend of expression patterns, although the effects did not reach significance because of small sample sizes. Transfection of synthetic miR-200 precursors into normal ovarian surface epithelial (OSE) and fallopian tube epithelial (FTE) cells confirmed reduced expression of the target genes and elevated levels of the effector genes CDH1, CRB3 and EpCAM in both normal OSE and FTE cells. However, only FTE cells had a specific induction of CA125 after miR-200 precursor transfection., Conclusions: The activation of the miR-200 pathway may be an early event that renders the OSE and FTE cells more susceptible to oncogenic mutations and histologic differentiation. As high-grade serous ovarian carcinomas (HGSOC) usually express high levels of CA125, the induction of CA125 expression in FTE cells by miR-200 precursor transfection is consistent with the notion that HGSOC has an origin in the distal fallopian tube.

Aim: This study aimed to determine how endometriosis affects the quality of life of partners of women who suffer from this disease and how it impacts their relationships, finances, mental states, and daily living., Methods: This was a questionnaire-based cohort study that took place at a large tertiary hospital gynecology unit, which covered two sites. Fifty-one partners of women who had surgically diagnosed endometriosis agreed to participate in the study and returned completed surveys., Results: Ninety-two percent (n = 46) of partners reported negative feelings about the diagnosis of endometriosis. Seventy percent (n = 35) reported that endometriosis affected their day-to-day life either moderately or severely. Over half (52%) also felt that their finances were affected. Only 34% (n = 17) of partners felt that health professionals had engaged them in decision-making processes and had been supportive of them. Eighty percent (n = 40) of partners reported that they had received no information about the impact of endometriosis on couples. Partners reported a significant affect on their sex life (74%) and their relationship as a whole (56%). Participants whose relationships had been affected by endometriosis had also more likely had their day-to-day life (P = 0.027), sex life (P = 0.001), and finances (P = 0.002) affected., Conclusion: Overall, our findings suggest that endometriosis can have a significant impact on partners with respect to day-to-day living, finances, sex lives, and relationships. Improvements can be made to engage partners in the treatment process, and to provide better education, support, and holistic management to women and families who suffer with endometriosis., (© 2017 Japan Society of Obstetrics and Gynecology.)

Introduction and Hypothesis: High levels of mental health dysfunction have been identified in women with genital tract fistula. The aim of this study was to use the General Health Questionnaire-28 (GHQ-28) to screen women in western Uganda with severe pelvic organ prolapse, chronic fourth-degree obstetric tear and genital tract fistula for risk of mental health dysfunction., Methods: Women undergoing surgery for severe pelvic organ prolapse, chronic fourth-degree obstetric tear, and genital tract fistula were interviewed using the GHQ-28 to screen for the risk of mental health dysfunction., Results: A total of 125 women completed the GHQ-28, including 22 with pelvic organ prolapse, 47 with fourth-degree obstetric tear, 21 with genital tract fistula, and 35 controls. Nearly all women with these serious gynaecological conditions were positive for the risk of mental health dysfunction. In the domain assessing symptoms of severe depression, women with fourth-degree obstetric tear and genital tract fistula scored higher than women with pelvic organ prolapse., Conclusions: A significant risk of mental health dysfunction was identified in women with severe pelvic organ prolapse and chronic fourth-degree obstetric tear. These rates are similar to the high rates of mental health dysfunction in women with genital tract fistula. Identification and management of mental health dysfunction in women with these conditions should be a priority.

Pseudoepitheliomatous keratotic and micaceous balanitis (PKMB) is an uncommon premalignant condition involving the glans penis. We report the case of an 86-year-old man who presented with phimosis and pain on retracting his foreskin. He had previously undergone circumcision, which revealed a hyperkeratotic plaque with thin mica-like scales involving his glans penis. Histology of the lesion showed hyperkeratosis, parakeratosis, epidermal acanthosis and papillomatosis with no evidence of dysplasia. Immunohistochemistry for human papillomavirus was negative. The patient was treated with topical 5-fluorouracil and liquid nitrogen with clinical improvement. He is now under long-term surveillance for verrucous carcinoma and squamous cell carcinoma., (© 2017 British Association of Dermatologists.)

Effective development of host cells for therapeutic protein production is hampered by the poor characterization of cellular transfection. Here, we employed a multi-omics-based systems biotechnology approach to elucidate the genotypic and phenotypic differences between a wild-type and recombinant antibody-producing Chinese hamster ovary (CHO) cell line. At the genomic level, we observed extensive rearrangements in specific targeted loci linked to transgene integration sites. Transcriptional re-wiring of DNA damage repair and cellular metabolism in the antibody producer, via changes in gene copy numbers, was also detected. Subsequent integration of transcriptomic data with a genome-scale metabolic model showed a substantial increase in energy metabolism in the antibody producer. Metabolomics, lipidomics, and glycomics analyses revealed an elevation in long-chain lipid species, potentially associated with protein transport and secretion requirements, and a surprising stability of N-glycosylation profiles between both cell lines. Overall, the proposed knowledge-based systems biotechnology framework can further accelerate mammalian cell-line engineering in a targeted manner., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The clinical differentiation between pigmented basal cell carcinoma (BCC) and other benign pigmented skin lesions can be challenging even with an additional dermoscopic evaluation, especially if the lesion is small. In vivo reflectance confocal microscopy (RCM) is an emerging, non-invasive imaging tool that allows near-microscopic evaluation of skin lesions. The features of RCM for pigmented BCC and seborrhoeic keratosis have previously been described. However, the use of RCM to differentiate between these clinically and dermoscopically challenging pigmented skin lesions among Asians has not yet been demonstrated., Objectives: We aimed to evaluate the usefulness of non-invasive RCM to differentiate between clinically and dermoscopically challenging pigmented skin lesions among Asians in a series of 11 lesions., Methods: Nine patients with 11 clinically and dermoscopically difficult to distinguish pigmented skin lesions were evaluated by RCM to differentiate between pigmented BCC and benign lesions. In all cases, a histological confirmation of the RCM diagnosis was obtained., Results: The clinical or dermoscopical characteristics were non-specific in all 10 cases. RCM detected features of pigmented BCC in nine patients and seborrhoeic keratosis in one patient. These were all confirmed by histological examination., Conclusions: This case series shows the value of non-invasive in vivo RCM imaging in the differentiation of malignant and benign pigmented lesions. Early diagnosis of small, pigmented BCC allows earlier excision with better prognosis. Future biopsies of benign lesions in cosmetic areas could also be avoided., (© 2015 The Australasian College of Dermatologists.)

Background: No studies to date have explored the association of vision with mortality in Indigenous Australians. We aimed to determine the 10-year all-cause mortality and its associations among Indigenous Australians living in Central Australia., Design: Prospective observational cohort study., Participants: A total of 1257 (93.0%) of 1347 patients from The Central Australian Ocular Health Study, over the age of 40 years, were available for follow-up during a 10-year period., Methods: All-cause mortality and its associations with visual acuity, age and gender were analysed., Main Outcome Measures: All-cause mortality., Results: All-cause mortality was 29.3% at the end of 10 years. Mortality increased as age of recruitment increased: 14.2% (40-49 years), 22.6% (50-59 years), 50.3% (60 years or older) (χ = 59.15; P < 0.00001). Gender was not associated with mortality as an unadjusted variable, but after adjustment with age and visual acuity, women were 17.0% less likely to die (t = 2.09; P = 0.037). Reduced visual acuity was associated with increased mortality rate (5% increased mortality per one line of reduced visual acuity; t = 4.74; P < 0.0001) after adjustment for age, sex, diabetes and hypertension., Conclusions: The 10-year all-cause mortality rate of Indigenous Australians over the age of 40 years and living in remote communities of Central Australia was 29.3%. This is more than double that of the Australian population as a whole. Mortality was significantly associated with visual acuity at recruitment. Further work designed to better understand this association is warranted and may help to reduce this disparity in the future., (© 2016 Royal Australian and New Zealand College of Ophthalmologists.)

Seasonal changes and climate have a significant impact on human health. Diseases influenced by temperature and climate conditions are likely to undergo dynamic pattern shifts with consequent impact on human health. A number of infectious and non-infectious ophthalmic diseases are influenced by temperature and seasonality. Awareness of this is important from public and global health perspective in addition to resource allocation strategies. We examine the evidence for a seasonal pattern to ophthalmic diseases and assess the possible impact of climate change., (© 2016 Royal Australian and New Zealand College of Ophthalmologists.)

Background: Herbochip ® technology is a high throughput drug screening platform in a reverse screening manner, in which potential chemical leads in herbal extracts are immobilized and drug target proteins can be used as probes for screening process [BMC Complementary and Alternative Medicine (2015) 15:146]. While herbal medicines represent an ideal reservoir for drug screenings, here a molecular chaperone GRP78 is demonstrated to serve as a potential target for antiviral drug discovery., Methods: We cloned and expressed a truncated but fully functional form of human GRP78 (hGRP78 1-508 ) and used it as a probe for anti-HBV drug screening on herbochips. In vitro cytotoxicity and in vitro anti-HBV activity of the herbal extracts were evaluated by MTT and ELISA assays, respectively. Finally, anti-HBV activity was confirmed by in vivo assay using DHBV DNA levels in DHBV-infected ducklings as a model., Results: Primary screenings using GRP78 on 40 herbochips revealed 11 positives. Four of the positives, namely Dioscorea bulbifera , Lasiosphaera fenzlii , Paeonia suffruticosa and Polygonum cuspidatum were subjected to subsequent assays. None of the above extracts was cytotoxic to AML12 cells, but P. cuspidatum extract (PCE) was found to be cytotoxic to HepG2 2.2.15 cells. Both PCE and P. suffruticosa extract (PSE) suppressed secretion of HBsAg and HBeAg in HepG2 2.2.15 cells. The anti-HBV activity of PSE was further confirmed in vivo., Conclusion: We have demonstrated that GRP78 is a valid probe for anti-HBV drug screening on herbochips. We have also shown that PSE, while being non-cytotoxic, possesses in vitro and in vivo anti-HBV activities. Taken together, our data suggest that PSE may be a potential anti-HBV agent for therapeutic use.

Background: To critically evaluate the use of endoscopic nasopharyngectomy in the treatment of recurrent nasopharyngeal carcinoma (NPC) through a case series, systematic literature review, and pooled analysis., Methods: A case series of 18 patients combined with systematic literature review and pooled analysis of PubMed, Web of Science, and Scopus search, identifying 576 papers. After excluding 307 papers as search engine duplicates, only 16 of the remaining papers had adequate patient data to be included., Results: Our case series of 18 patients had a 2-year disease-free survival (DFS) and overall survival (OS) of 90.0% and 100%, respectively. The pooled analysis of 300 patients that had an endoscopic resection of recurrent NPC showed recurrence-free survival and overall survival were 85.8% and 82.9%, respectively. Most, 56.1%, were recurrent T1 lesions. Resection margins were negative in 90.2% of patients. Local recurrence occurred in 20.1% of patients. Major complications occurred in 13.6% of patients. The mean hospital stay was 5.8 days, the mean operating time was 228.3 minutes, and the mean operative blood loss was 163 mL., Conclusion: Endoscopic resection of recurrent NPC occurs with low surgical morbidity. However, further long-term evaluation with longer follow-up data is needed to evaluate if the survival data is comparable or better than open approaches., (© 2016 ARS-AAOA, LLC.)

Background: Metabolic syndrome (MetS) and its components increase the risk of developing cardiovascular diseases, type 2 diabetes, and all-cause mortality. Reports on the trends of MetS and its components in longitudinal studies are scarce, especially in low- and middle-income countries. This study was designed to investigate the prevalence and trends of MetS and its components in a cohort of Iranian adults from 2001 to 2013., Methods: Participants were followed up for 12 years in a longitudinal population-based study of 6500 adults aged 35 years and older in 2001. Participants were randomly selected from three provinces in central Iran. Sociodemographic characteristics, anthropometry, blood pressure, and various biochemical indices were collected in 2001, 2007, and 2013. Secular trend and age-adjusted trend of MetS and its components were calculated from 2001 to 2013., Results: The standardized prevalence of MetS, hypertension, low high-density lipoprotein cholesterol (HDL-C), abdominal obesity, and diabetes/impaired glucose tolerance (IGT) increased over the 12 years (6.9%, 5.5%, 12.0%, 2.3%, and 18.7%, respectively), while the prevalence of hypertriglyceridemia decreased by 15.5% during this period. The prevalence of MetS, low HDL-C, and abdominal obesity were higher in females than males in all three phases. Moreover, the increases in the prevalence of these metabolic abnormalities were higher in the rural population than in the urban population., Conclusions: The present study underscored the increasing trends in MetS and most of its risk factors, thus, to prevent an increase in the cardiovascular risk factors, there is a need to improve lifestyle by education, screening, and treatment of abnormalities.

Mammalian cells are generally considered to be unable to utilize polysaccharides for cell growth because the phospholipid bilayer in the cell membrane has very low permeability to sugars. With the recent discovery of the only known animal disaccharide transporter, a sucrose transporter, we considered the potential use of polysaccharides as energy source, because that can impact biopharmaceutical manufacturing by potentially increasing carbohydrate loading in the culture medium and decreasing lactate accumulation. In this study, we found that mammalian cells can utilize maltose for growth in the absence of glucose and successfully adapted CHO-K1, CHO-DG44 and HEK293 cells to grow in glucose-free, maltose-containing serum-free protein-free media. We then cultivated a non-adapted CHO-K1 producer cell line in media containing both glucose and maltose to show that the cells can utilize maltose in a biphasic manner, that maltose enters the cells, and that maltose utilization only took place in the presence of the cells. This is the first report of a protein-free mammalian cell culture using a disaccharide as energy source.

Background: The interspecies interactions in a biomethanation community play a vital role in substrate degradation and methane (CH 4 ) formation. However, the physiological and molecular mechanisms of interaction among the microbial members of this community remain poorly understood due to the lack of an experimentally tractable model system. In this study, we successfully established two coculture models combining the cellulose-degrading bacterium Clostridium cellulovorans 743B with Methanosarcina barkeri Fusaro or Methanosarcina mazei Gö1 for the direct conversion of cellulose to CH 4 ., Results: Physiological characterizations of these models revealed that the methanogens in both cocultures were able to efficiently utilize the products produced by C. cellulovorans during cellulose degradation. In particular, the simultaneous utilization of hydrogen, formate, and acetate for methanogenesis was observed in the C. cellulovorans - M. barkeri cocultures, whereas monocultures of M. barkeri were unable to grow with formate alone. Enhanced cellulose degradation was observed in both cocultures, and the CH 4 yield of the C. cellulovorans - M. barkeri cocultures (0.87 ± 0.02 mol CH 4 /mol glucose equivalent) was among the highest compared to other coculture studies. A metabolic shift in the fermentation pattern of C. cellulovorans was observed in both cocultures. The expression levels of genes in key pathways that are important to the regulation and metabolism of the interactions in cocultures were examined by reverse transcription-quantitative PCR, and the expression profiles largely matched the physiological observations., Conclusions: The physiological and molecular characteristics of the interactions of two CH 4 -producing cocultures are reported. Coculturing C. cellulovorans with M. barkeri or M. mazei not only enabled direct conversion of cellulose to CH 4 , but also stabilized pH for C. cellulovorans , resulting in a metabolic shift and enhanced cellulose degradation. This study deepens our understanding of interspecies interactions for CH 4 production from cellulose, providing useful insights for assembling consortia as inocula for industrial biomethanation processes.

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm that arises from clonal proliferation of hematopoietic stem cells and leads to progressive bone marrow (BM) fibrosis. While cellular mutations involved in the development of PMF have been heavily investigated, noteworthy is the important role the extracellular matrix (ECM) plays in the progression of BM fibrosis. This review surveys ECM proteins contributors of PMF, and highlights how better understanding of the control of the ECM within the BM niche may lead to combined therapeutic options in PMF.