Risk factors for falls in patients with total hip arthroplasty and total knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: Falls are common after total hip arthroplasty (THA) and total knee arthroplasty (TKA). While previous studies have investigated various risk factors for falls in patients following THA and TKA, no systematic reviews have summarized these risk factors. Therefore, the current systematic review aimed to summarize evidence regarding risk factors for falls in patients after THA and/or TKA. METHODS: MEDLINE, EMBASE, CINAHL, SPORTDiscus, and Physiotherapy Evidence Database (from inception to June 30, 2018) were searched. The methodological quality and quality of evidence of the included studies were assessed by two independent reviewers. Relevant data regarding participants' characteristics, study design, follow-up time points, and identified risk factors were extracted. Meta-analyses and narrative syntheses were performed. RESULTS: Twelve studies with a total of 1,292,689 participants were included. Twenty-nine identified risk factors for post-THA/TKA falls were classified into either inpatient or post-discharge risk factors. Key risk factors for both post-THA and/or post-TKA inpatient falls that showed moderate level of evidence included: postoperative complications or comorbidities and revision THA/TKA. Likewise, risk factors for post-discharge falls after THA and/or TKA that demonstrated moderate level of evidence included: medications, psychiatric diseases, living alone, prior history of TKA, falls history and female gender. The quality of the included studies varied and sample sizes were not justified. CONCLUSIONS: This review summarized both non-modifiable and modifiable risk factors for post-THA/TKA falls. Our findings highlight the importance of developing strategies to lower the falls risk among patients following THA/TKA.

Feasibility and safety of extended adjuvant temozolomide beyond six cycles for patients with glioblastoma.

INTRODUCTION: Temozolomide is the first chemotherapeutic agent proven effective for patients with newly diagnosed glioblastoma. The drug is well tolerated for its low toxicity. The current standard practice is concomitant chemoradiotherapy for 6 weeks followed by 6 cycles of adjuvant temozolomide. Some Caucasian studies have suggested that patients might benefit from extended adjuvant cycles of temozolomide (>6 cycles) to lengthen both progression-free survival and overall survival. In the present study, we compared differences in survival and toxicity profile between patients who received conventional 6-cycle temozolomide and those who received more than 6 cycles of temozolomide. METHODS: Patients with newly diagnosed glioblastoma without progressive disease and completed concomitant chemoradiotherapy during a 4-year period were studied. Progression-free survival was compared using Kaplan-Meier survival curves. t Test, U test, and correlation were chosen accordingly to examine the impact of age, extent of resection, MGMT promoter methylation status and adjuvant cycles on progression-free survival. For factors with a P value of <0.05 in univariate analyses, Cox regression hazard model was adopted to determine the strongest factors related to progression-free survival. RESULTS: The median progression-free survival was 17.0 months for patients who received 6 cycles of temozolomide (n=7) and 43.4 months for those who received more than 6 cycles (n=7) [P=0.007, log-rank test]. Two patients in the former group and one in the latter group encountered grade 1 toxicity and recovered following dose adjustment. Cycles of adjuvant temozolomide were correlated with progression-free survival (P=0.016, hazard ratio=0.68). CONCLUSION: Extended cycles of temozolomide are safe and feasible for Chinese patients with disease responsive to temozolomide.

Frameless stereotactic radiosurgery for brain metastases: a review of outcomes and prognostic scores evaluation.

INTRODUCTION: Stereotactic brain radiosurgery provides good local control in patients with limited brain metastases. A newly developed frameless system allows pain-free treatment. We reviewed the effectiveness of this frameless stereotactic brain radiosurgery and identified prognostic factors that may aid better patient selection. METHODS: Medical records of patients with brain metastases treated with linear accelerator-based frameless stereotactic brain radiosurgery between January 2010 and July 2015 in a university affiliated hospital in Hong Kong were reviewed. Outcomes including local and distant brain control rate, progression-free survival, and overall survival were analysed. Prognostic factors were identified by univariable and multivariable analyses. Association of outcomes with four common prognostic scores was performed. RESULTS: In this study, 64 patients with 94 lesions were treated with a median dose of 18 Gy (range, 12-22 Gy) in a single fraction. The median follow-up was 11.5 months. One-year actuarial local and distant brain control rates were 72% and 71%, respectively. The median overall survival was 13.0 months. On multivariable analysis, Karnofsky performance status score (>50 vs ≤50) and number of lesions (1-2 vs ≥3) were found to associate significantly with distinct brain progression-free survival (P=0.022, hazard ratio=0.20, 95% confidence interval 0.05-0.80 and P=0.003, hazard ratio=0.31, 95% confidence interval 0.14-0.68, respectively). Overall survival was associated significantly with Basic Score for Brain Metastases (P=0.031), Score Index for Radiosurgery in Brain Metastases (P=0.007), and Graded Prognostic Assessment (P=0.003). Improvement in overall survival was observed in all groups of different prognostic scores. CONCLUSION: Frameless stereotactic brain radiosurgery is effective in patients with oligo-metastases of brain and should be increasingly considered in patients with favourable prognostic scoring.

Ten-year review of survival and management of malignant glioma in Hong Kong.

INTRODUCTION: Surgical resection used to be the mainstay of treatment for glioma. In the last decade, however, opinion has changed about the goal of surgical resection in treating glioma. Ample evidence shows that maximum safe resection in glioblastoma improves survival. Neurosurgeons have therefore revised their objective of surgery from diagnostic biopsy or limited debulking to maximum safe resection. Given these changes in the management of glioma, we compared the survival of local Chinese patients with glioblastoma multiforme over a period of 10 years. METHODS: We retrospectively reviewed the data of the brain tumour registry of the CUHK Otto Wong Brain Tumour Centre in Hong Kong. Data of patients with glioblastoma multiforme were reviewed for two periods, during 1 January 2003 to 31 December 2005 and 1 January 2010 to 31 December 2012. Overall survival during these two periods of time was assessed by Kaplan-Meier survival estimates. Risk factors including age, type and extent of resection, use of chemotherapy, and methylation status of O6-methylguanine-DNA methyltransferase were also assessed. RESULTS: There were 26 patients with glioblastoma multiforme with a mean age of 52.2 years during 2003 to 2005, and 42 patients with a mean age of 55.1 years during 2010 to 2012. The mean overall survival during these two periods was 7.4 months and 12.7 months, respectively (P<0.001). The proportion of patients who underwent surgical resection was similar: 69.2% in 2003 to 2005 versus 78.6% in 2010 to 2012 (P=0.404). There was a higher proportion of patients in whom surgery achieved total removal in 2010 to 2012 than in 2003 to 2005 (35.7% and 7.7%, respectively; P=0.015). During 2010 to 2012, patients who were given concomitant chemoradiotherapy showed definitively longer survival than those who were not (17.9 months vs 4.5 months; P=0.001). The proportion of patients who survived 2 years after surgery increased from 11.5% in 2003 to 2005 to 21.4% in 2010 to 2012. CONCLUSIONS: Hong Kong has made substantial improvements in the management of glioblastoma multiforme over the last decade with corresponding improved survival outcomes. The combination of an aggressive surgical strategy and concomitant chemoradiotherapy are probably the driving force for the improvement.

Ultrasound-guided plugged percutaneous biopsy of solid organs in patients with bleeding tendencies.

OBJECTIVE: To establish and verify the utility of plugging biopsy tracts, using a combination of Gelfoam slurry and torpedo in the prevention of post-biopsy bleeding in patients at high risk of post-procedure haemorrhage following ultrasound-guided percutaneous biopsy of solid organs. DESIGN: Case series. SETTING: Radiology Department of a regional hospital in Hong Kong. PATIENTS: In our unit, all patients considered to be at high risk of post-biopsy haemorrhage of a solid organ underwent ultrasound-guided plugged percutaneous biopsy from year 2005 to 2012. INTERVENTIONS: All the included patients had undergone real-time ultrasound-guided biopsy of solid organs (liver in 10 and spleen in one patient). In all cases, a combination of a coaxial introducer needle and Temno needle were used. After adequate specimens were obtained, Gelfoam slurry (for distal embolisation) followed by Gelfoam torpedo (for proximal embolisation) were used to plug the biopsy tract. MAIN OUTCOME MEASURES: Technical success, any post-biopsy haemorrhage treated by transfusion or other intervention, and plugging-related complications were reviewed for each patient. RESULTS: Technical success was achieved in all patients and none experienced post-biopsy haemorrhage treated by blood transfusion or any other intervention. CONCLUSION: Plugging of the biopsy tract with Gelfoam slurry followed by Gelfoam torpedo is a direct and simple procedure that can safely and effectively prevent haemorrhage in patients at high risk of post-biopsy haemorrhage.

Acute appendicitis complicating Amyand's hernia: imaging features and literature review.

Acute appendicitis complicating Amyand's hernia is an extremely rare condition, in which the appendix herniates into the inguinal sac and, subsequently, gets inflamed. The condition is difficult to diagnose clinically. Imaging is valuable for its diagnosis and detection of the associated complications. In this article, we will discuss the imaging features of acute appendicitis complicating Amyand's hernia and the results of a literature review on the condition.

An evolutionarily conserved nested gene pair - Mab21 and Lrba/Nbea in metazoan.

The embedding of one gene in another as a nested gene pair is a unique phenomenon of gene clustering in the metazoan genome. A gene-centric paralogous genomic sequence comparison strategy was used in this study to align these paralogous nested pairs, Mab21l2-Lrba and Mab21l1-Nbea, to identify the associated paralogous non-coding elements (pNEs) they shared. A majority of these pNEs in the Mab21l2-Lrba locus display tissue-specific enhancer activities recapitulating the expression profiles of Mab21l2 and Mab21l1. Since these enhancers are spread into the introns of Lrba, dissociation of the two genes will likely disrupt the function of at least one of them. Phylogenetic analysis of this complex locus in different species suggests that Mab21 was probably locked in the Lrba/Nbea intron in the ancestral metazoan species, in which the cis-elements uncovered in this study may act as a selective force to prevent the dissociation of this gene pair in vertebrates.

Modulatory effects of ayahuasca on personality structure in a traditional framework.

Ayahuasca is a psychoactive plant brew containing dimethyltryptamine (DMT) and monoamine oxidase inhibitors (MAOIs). It originates from the Amazon basin, where it is used primarily for ceremonial purposes. Ayahuasca tourists are now entering certain communities seeking alternative physical or psychological healing, as well as spiritual growth. RATIONALE: Recent evidence has shown that the similar acting psychedelic compound, psilocybin, facilitated long-term increases in trait openness following a single administration. OBJECTIVES: This paper assesses the impact of ayahuasca on personality in a traditional framework catering for ayahuasca tourists. METHOD: Within a mixed design, we examined the effect of ayahuasca on participants' personality (measured by the NEO Personality Inventory 3 questionnaire) across time (pre- to post-ayahuasca administration, and 6-month follow-up), relative to a comparison group (who did not ingest ayahuasca). RESULTS: The results demonstrated significant increases in agreeableness pre- and post-ayahuasca administration and significant reductions in neuroticism in 24 participants, relative to the comparison group. Both of these changes were sustained at 6-month follow-up, and trait level increases were also observed in openness at this stage. Additionally, greater perceived mystical experience (measured using the Mystical Experience Questionnaire 30) was associated with increased reductions in neuroticism. CONCLUSIONS: These findings, which indicate a positive mediating effect of ayahuasca on personality, support the growing literature suggesting potential therapeutic avenues for serotonergic psychedelics.

Community Priority setting for Fetal Alcohol Spectrum Disorder Research in Australia.

INTRODUCTION: Fetal Alcohol Spectrum Disorder (FASD) is a neurodevelopmental disorder caused by prenatal alcohol exposure (PAE). FASD research is a rapidly growing field that crosses multiple disciplines. To ensure research is relevant and meaningful for people living with FASD, their families, and the broader public there is a need to engage community members in setting priorities for research. OBJECTIVES: Our primary objective was to formally identify the views of people living with FASD, their parents/caregivers, service providers, and the general community on the research priorities for FASD and alcohol use in pregnancy in Australia. Our secondary objective was to provide an overview of current research in the highest priority areas identified. METHODS: The approach for this study involved two community surveys and a consensus workshop, followed by a rapid literature review. Survey responses (n = 146) were collected and grouped using qualitative thematic analysis. The themes identified were then ranked in a second survey (n = 45). The 22 highest ranked themes were considered in a workshop with 21 community members, and consensus on the top ten priority areas was sought. The priority areas were grouped into conceptually similar topics and rapid literature reviews were undertaken on each. RESULTS: A diverse range of priorities was identified within key areas of prevention, diagnosis, and therapy. On request from participants, separate priority lists were developed by Aboriginal and non-Aboriginal participants. CONCLUSION: There is need for a national network of researchers to take forward the research commenced by the Centre of Research Excellence, FASD Research Australia, in addressing community priorities. KEY WORDS: Community, priorities, FASD, rapid review, Australia.

MicroRNA-143 targets DNA methyltransferases 3A in colorectal cancer.

BACKGROUND: MicroRNAs (miRNAs) are 19-25-nucleotides regulatory non-protein-coding RNA molecules that regulate the expressions of a wide variety of genes, including some involved in cancer development. In this study, we investigated the possible role of miR-143 in colorectal cancer (CRC). METHODS: Expression levels of human mature miRNAs were examined using real-time PCR-based expression arrays on paired colorectal carcinomas and adjacent non-cancerous colonic tissues. The downregulation of miR-143 was further evaluated in colon cancer cell lines and in paired CRC and adjacent non-cancerous colonic tissues by qRT-PCR. Potential targets of miR-143 were defined. The functional effect of miR-143 and its targets was investigated in human colon cancer cell lines to confirm miRNA-target association. RESULTS: Both real-time PCR-based expression arrays and qRT-PCR showed that miR-143 was frequently downregulated in 87.5% (35 of 40) of colorectal carcinoma tissues compared with their adjacent non-cancerous colonic tissues. Using in silico predictions, DNA methyltranferase 3A (DNMT3A) was defined as a potential target of miR-143. Restoration of the miR-143 expression in colon cell lines decreased tumour cell growth and soft-agar colony formation, and downregulated the DNMT3A expression in both mRNA and protein levels. DNMT3A was shown to be a direct target of miR-143 by luciferase reporter assay. Furthermore, the miR-143 expression was observed to be inversely correlated with DNMT3A mRNA and protein expression in CRC tissues. CONCLUSION: Our findings suggest that miR-143 regulates DNMT3A in CRC. These findings elucidated a tumour-suppressive role of miR-143 in the epigenetic aberration of CRC, providing a potential development of miRNA-based targeted approaches for CRC therapy.

A novel sulfate reduction, autotrophic denitrification, nitrification integrated (SANI) process for saline wastewater treatment.

This paper reports on a lab-scale evaluation of a novel and integrated biological nitrogen removal process: the sulfate reduction, autotrophic denitrification and nitrification integrated (SANI) process that was recently proposed for saline sewage treatment. The process consisted of an up-flow anaerobic sludge bed (UASB) for sulfate reduction, an anoxic filter for autotrophic denitrification and an aerobic filter for nitrification. The experiments were conducted to evaluate the performance of the lab-scale SANI system with synthetic saline wastewater at various hydraulic retention times, nitrate concentrations, dissolved oxygen levels and recirculation ratios for over 500 days. The system successfully demonstrated 95% chemical oxygen demand (COD) and 74% nitrogen removal efficiency without excess sludge withdrawal throughout the 500 days of operation. The organic removal efficiency was dependent on the hydraulic retention time, up-flow velocity, and mixing conditions in the UASB. Maintaining a sufficient mixing condition in the UASB is important for achieving effective sulfate reduction. For a typical Hong Kong wastewater composition 80% of COD can be removed through sulfate reduction. A minimum sulfide sulfur to nitrate nitrogen ratio of 1.6 in the influent of the anoxic filter is necessary for achieving over 90% nitrate removal through autotrophic denitrifiers which forms the major contribution to the total nitrogen removal in the SANI system. Sulfur balance analyses confirmed that accumulation of elementary sulfur and loss of hydrogen sulfide in the system were negligible.

A novel sludge minimized biological nitrogen removal process for saline sewage treatment.

This study reports a lab-scale evaluation of a new biological nitrogen removal process for saline sewage treatment, namely a SANI process (Sulfate reduction, Autotrophic denitrification and Nitrification Integrated process). The experimental system consisted of an up-flow anaerobic bed for sulfate reduction, an anoxic filter for autotrophic denitrification using dissolved sulfide produced in the up-flow anaerobic bed and an aerobic filter for nitrification. The system successfully operated for more than 180 days with an overall organic carbon removal efficiency of 95%, in which, 82% removal was contributed by the up-flow anaerobic bed operating at a HRT of 6 h, and 13% removal by the anoxic filter. An average COD removed /sulfate removed ratio was found to be 0.76 gCOD/gSO(4) or 2.28 COD/gSO(4)-S further confirming that the organic removal was mainly achieved by the sulfate reduction. In terms of nitrogen removal efficiency, the SANI system was found sensitive to the recirculation rate between the anoxic filter and the aerobic filter. A recirculation rate of 3Q was found to be optimal for achieving 74% of the total nitrogen removal. It was confirmed that the autotrophic denitrification was a major contributor to the total nitrogen removal in the SANI system. Sulfur balance analysis indicated that both the accumulation of elementary sulfur in the biomass and the loss of hydrogen sulfide were trivial. During the entire operation period (330 days to date), no sludge was wasted from any reactors in this system. This was further confirmed by the biomass balance simulation results that low biomass yields of sulfate reducing bacteria, autotrophic denitrifiers and nitrifiers contribute to the zero excess sludge discharge.

Riboregulator H19 induction of MDR1-associated drug resistance in human hepatocellular carcinoma cells.

Acquisition of drug resistance is one of the main obstacles encountered in cancer chemotherapy. Overexpression of multi-drug resistance 1 (MDR1) gene and its protein product P-glycoprotein, accompanied with a decrease in doxorubicin accumulation level, was observed in doxorubicin-resistant R-HepG2 cells, a subline derived by selection of human hepatocellular carcinoma HepG2 cells with doxorubicin. In addition, Northern-blot analysis revealed an eight fold upregulation of the imprinted H19 mRNA in R-HepG2 cells. H19 knockdown by transfection with antisense H19 oligonucleotides suppressed the MDR1/P-glycoprotein expression, increased the cellular doxorubicin accumulation level and sensitized doxorubicin toxicity in both HepG2 parent cells and R-HepG2 cells. Results from methylation-specific polymerase chain reaction analysis indicated that the MDR1 gene promoter was hypomethylated in R-HepG2 cells. Antisense H19 oligonucleotides transfection induced a marked increase in the percentage of MDR1 promoter methylation and decrease in MDR1 expression in R-HepG2 cells. Thus, the H19 gene is believed to induce P-glycoprotein expression and MDR1-associated drug resistance at least in liver cancer cells through regulation of MDR1 promoter methylation.

Palladium-catalyzed method for the synthesis of carbazoles via tandem C-H functionalization and C-N bond formation.

The development of a new method for the assembly of unsymmetrical carbazoles is reported. The strategy involves the selective intramolecular functionalization of an arene C-H bond and the formation of a new arene C-N bond. The substitution pattern of the carbazole product can be controlled by the design of the biaryl amide substrate, and the method is compatible with a variety of functional groups. The utility of the new protocol was demonstrated by the concise synthesis of three natural products from commercially available materials.