Causal associations between gut microbiota with intervertebral disk degeneration, low back pain, and sciatica: a Mendelian randomization study.

PURPOSE: Although studies have suggested that gut microbiota may be associated with intervertebral disk disease, their causal relationship is unclear. This study aimed to investigate the causal relationship between the gut microbiota and its metabolic pathways with the risk of intervertebral disk degeneration (IVDD), low back pain (LBP), and sciatica. METHODS: Genetic variation data for 211 gut microbiota taxa at the phylum to genus level were obtained from the MiBioGen consortium. Genetic variation data for 105 taxa at the species level and 205 metabolic pathways were obtained from the Dutch Microbiome Project. Genetic variation data for disease outcomes were obtained from the FinnGen consortium. The causal relationships between the gut microbiota and its metabolic pathways and the risk of IVDD, LBP, and sciatica were evaluated via Mendelian randomization (MR). The robustness of the results was assessed through sensitivity analysis. RESULTS: Inverse variance weighting identified 46 taxa and 33 metabolic pathways that were causally related to IVDD, LBP, and sciatica. After correction by weighted median and MR-PRESSO, 15 taxa and nine pathways remained stable. After FDR correction, only the effect of the genus_Eubacterium coprostanoligenes group on IVDD remained stable. Sensitivity analyses showed no evidence of horizontal pleiotropy, heterogeneity, or reverse causation. CONCLUSION: Some microbial taxa and their metabolic pathways are causally related to IVDD, LBP, and sciatica and may serve as potential intervention targets. This study provides new insights into the mechanisms of gut microbiota-mediated development of intervertebral disk disease.

The complexities of decision-making in food waste valorization: A critical review.

The efficient utilization of food waste (FW) resources through Food Waste Valorization (FWV) has received increasing attention in recent years. Various decision-making studies have been undertaken to facilitate FWV implementation, such as the studies on decision-making framework and FWV technology assessment. Food waste hierarchy is a widely discussed framework in FW management, but it was found too simplified and does not always contribute positively to environmental sustainability. Moreover, decision-making studies in FWV often focus on specific aspects of the food system and employ distinctive decision-making approaches, making it difficult to compare the results from different studies. Therefore, our literature review is conducted to provide a comprehensive understanding of FWV decision-making. This study identifies what decisions are needed, and three levels of decisions are revealed: system-level, FW stream-level, and FWV option-level. The assessment approaches and criteria used to support decision-making in FWV are also collected and analyzed. Building upon these findings, an hourglass model is synthesized to provide a holistic illustration of decision-making in FWV. This study untangles the complexities of FWV decision-making and sheds light on the limitations of current studies. We anticipate this study will make more people realize that FWV is a multidisciplinary issue and requires the collective participation of researchers, practitioners, policymakers, and consumers. Such collective engagement is essential to effectively address practical challenges and propel the transition of the current food system toward a more resource-efficient paradigm.

Schisandrol A, a bioactive constituent from Schisandrae Chinensis Fructus, alleviates drug-induced liver injury by autophagy activation via exosomes.

OBJECTIVE: To investigate the bioactive compounds of Schisandrae Chinensis Fructus (SCF) and their mechanisms of action in the treatment of drug-induced liver injury (DILI), specifically Acetaminophen (APAP)-induced DILI. METHOD: Chemical components in SCF were identified using the UPLC-Q-TOF-MS method. Active components were then screened using HotMap, combined with SCF efficacy results concerning the prevention and treatment of drug-induced liver injury. Its direct target was elucidated using a comprehensive chemical-pharmacodynamic-exosome approach. RESULT: We identified Schisandrol A, is a lignan component, as a key active compound that improved the symptoms DILI in mouse liver tissue; specifically, reducing oxidative stress and thereby the inflammatory response. To further understand the biological function of miRNAs in mouse liver exosomes, we used TargetScan (v5.0) and Miranda (v3.3a) to predict the target genes of MicroRNAs (miRNAs), where changes in the expression of mmu-let-7 family miRNAs were closely related to autophagy. This revealed differential miRNA target genes that were involved in 20 Kyoto Encyclopedia of Genes and Genomes pathways, including glycerol phosphate metabolism, inositol phosphate metabolism, phospholipase D signaling pathway, Rap1 signaling pathway, and Ras signaling pathway. CONCLUSION: Schisandrol A alleviated the symptoms of DILI in mice by inhibiting oxidative stress and inflammation, whereas, it alleviated DILI by activating autophagy in the exosomes.

Non-invasive prenatal test findings in 41,819 pregnant women: results from a clinical laboratory in southern China.

BACKGROUND: This paper evaluated the clinical utility of massively parallel sequencing-based non-invasive prenatal testing (NIPT) for detecting trisomy 21 (T21), T18, T13, sex chromosome aneuploidies (SCA), and rare chromosome aneuploidies (RCA) among the data collected by a clinical laboratory in southern China. METHODS: In a 3-year period between January 2017 and December 2019, over 40,000 pregnant women underwent NIPT clinical screening test for fetal T21, T18, T13, SCA, and RCA in our laboratory. NIPT samples were processed using the NextSeq CN500 platform. The positive results were confirmed by karyotyping, and chromosomal microarray analysis (CMA) or copy number variants (CNV) sequencing. Details of the pregnancy outcomes were collected via telephone interview. RESULTS: NIPT results were available for 41,819 cases; 691 positive cases were reported. The overall sensitivity for detection of T21, T18, T13, SCA, and RCA was 99.21, 100.00, 100.00, 98.55, and 100.00%, and the specificity was 99.95, 99.94, 99.98, 99.69, and 99.92%, respectively. The positive predictive values (PPVs) for detection of T21, T18, T13, SCA, and RCA were 85.62, 45.24, 40.00, 34.17, and 13.51%, respectively, and those for detection of 45,X, 47,XXY, 47,XXX, 47,XYY, and 46,XY(delX) 20.00, 59.18, 28.95, 61.54, and 25.00%, respectively. Regarding pregnancy outcomes, 92.38% of the pregnancies with confirmed aneuploidies were terminated, and 91.20% of those identified as having a false-positive result were carried to term. Among 252 unconfirmed cases, 24.60% of the pregnancies were terminated and 38.10% carried to term, while 37.30% declined interview. CONCLUSIONS: NIPT is widely used to screen fetal aneuploidies based on its high sensitivity and specificity. However, in this study, the PPVs of NIPT in terms of detecting T18, T13, XO, XXX and RCA were < 50%. In addition, more than one-third of NIPT-positive women did not accept invasive prenatal diagnosis. Confirmatory diagnosis is strongly recommended for women with positive NIPT outcomes before any further decision is made.

Potential reuse of domestic organic residues as soil organic amendment in the current waste management system in Australia, China, and The Netherlands.

Soil organic carbon (SOC) is essential for most soil functions. Changes in land use from natural land to cropland disrupt long-established SOC balances and reduce SOC levels. The intensive use of chemical fertilisers in modern agriculture accelerates the rate of SOC depletion. Domestic organic residues (DOR) are a valuable source of SOC replenishment with high carbon content. However, there is still a lack of knowledge and data regarding whether and to what extent DOR can contribute to replenishing SOC. This paper aims to unpack the potential of DOR as a SOC source. Total SOC demand and annual SOC loss are defined and calculated. The carbon flow within different DOR management systems is investigated in three countries (China, Australia, and The Netherlands). The results show that the total SOC demand is too large to be fulfilled by DOR in a short time. However, DOR still has a high potential as a source of SOC as it can mitigate the annual SOC loss by up to 100%. Achieving this 100% mitigation requires a shift to more circular management of DOR, in particular, more composting, and direct land application instead of landfilling and incineration (Australia and China), or a higher rate of source separation of DOR (The Netherlands). These findings form the basis for future research on DOR recycling as a SOC source.

Mathematically formulated key performance indicators for design and evaluation of treatment trains for resource recovery from urban wastewater.

While urban wastewater infrastructure is aging and no longer adequate, climate change and sustainability are urging the transition from pollution management to resource recovery. Lacking evidence-based quantitative evaluation of the potential benefits and consequences of resource recovery from wastewater hinders the negotiation amongst stakeholders and slows down the transition. This study proposes mathematical formulations for technical, environmental, economic, and social key performance indicators (KPIs) that can be used to quantify the benefits and the risks of resource recovery. The proposed formulations are derived from the literature and validated with stakeholders. Each KPI is mathematically formulated at treatment train level by considering: (1) the characteristics of individual unit processes (UPs) in the treatment train (TT), (2) the context in which the TT is installed, and (3) the resources to be recovered. The mathematical formulations of the KPIs proposed in this study enable a transparent, consistent and informative evaluation of existing treatment trains, as well as support the (computer aided) design of new ones. This could aid the transition from urban wastewater treatment to resource recovery from urban wastewater.

A conceptual framework for a multi-criteria decision support tool to select technologies for resource recovery from urban wastewater.

In the context of circular economy, wastewater can be used to address some of the 21st century's challenges regarding the transition to renewable resources for water, energy, and nutrients. Despite all the research, development, and experience with resource recovery from urban wastewater, its implementation is still limited. The transition from treatment to resource recovery is complex due to the difficulty of selecting unit processes from a large number of candidate processes considering the operational limitations of each process, and sustainability objectives. Presently, a multi-criteria decision support tool that deals with the difficulty of unit process selection for resource recovery from wastewater has not been developed. Therefore, this paper presents the conceptual framework of a decision support tool to find the optimum treatment train consisting of compatible unit processes which can recover water, energy and/or nutrients from a specified influent composition. The framework presents the relationship between the user input, the knowledge library of technologies and a weighted multi-objective nonlinear programming model to aid process selection. The model presented here shows, not only how the processes are selected, but also the four-dimensional sustainability impact of the generated treatment train while considering the weight provided by the user. Thus, this study presents a reproducible framework which can support private and public decision-makers in transparent evidence-based decision making and eventually the systematic implementation of resource recovery from urban wastewater.

The relationship between substrate topography and stem cell differentiation in the musculoskeletal system.

It is well known that biomaterial topography can exert a profound influence on various cellular functions such as migration, polarization, and adhesion. With the development and refinement of manufacturing technology, much research has recently been focused on substrate topography-induced cell differentiation, particularly in the field of tissue engineering. Even without biological and chemical stimuli, the differentiation of stem cells can also be initiated by various biomaterials with different topographic features. However, the underlying mechanisms of this biological phenomenon remain elusive. During the past few decades, many researchers have demonstrated that cells can sense the topography of materials through the assembly and polymerization of membrane proteins. Following the activation of RHO, TGF-b or FAK signaling pathways, cells can be induced into various differentiation states. But these signaling pathways often coincide with canonical mechanical transduction pathways, and no firm conclusion has been reached among researchers in this field on topography-specific signaling pathways. On the other hand, some substrate topographies are reported to have the ability to inhibit differentiation and maintain the 'stemness' of stem cells. In this review, we will summarize the role of topography in musculoskeletal system regeneration and explore possible topography-related signaling pathways involved in cell differentiation.

Proton pump inhibitors reduce breast cancer risk in gastric ulcer patients: A population-based cohort study.

We aim to evaluate breast cancer risk relating to PPIs usage in women with peptic ulcer. From 2000 to 2013, incidence rates of breast cancer were compared between the two cohorts (with or without PPIs). Each study cohort consisted of 4838 women. The incidence density rate of breast cancer in the PPI cohort was 0.29 that in the comparison cohort (10.0 vs 31.6 per 10 000 person-years), with an adjusted HR (hazard ratio) of 0.32 (95% CI = 0.20-0.49) for the PPI cohort. In conclusion, the medication of PPIs is associated with reduced breast cancer risk for women with gastric ulcer.

Adverse respiratory events with sevoflurane compared with desflurane in ambulatory surgery: A systematic review and meta-analysis.

BACKGROUND: An increasing number of studies have concluded that the number of adverse events in the upper airway caused by desflurane does not differ significantly from the number of adverse events caused by sevoflurane. The advantages of desflurane in ambulatory surgery should be reassessed. OBJECTIVES: The aim of this study was to compare adverse respiratory events and recovery outcomes in patients undergoing desflurane or sevoflurane-based anaesthesia in ambulatory surgery. DESIGN: A systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: A systematic search for eligible RCTs in PubMed, Medline, Cochrane Central Register of Controlled Trials, ScienceDirect and Embase published up to June 2019. ELIGIBILITY CRITERIA: RCTs investigating the occurrence of adverse respiratory events, including airway irritation, stridor, coughing, respiratory distress and laryngospasm, emergence agitation, postoperative nausea and vomiting (PONV), time to eye opening and time to discharge from the operation room after desflurane or sevoflurane-based anaesthesia. RESULTS: Thirteen trials were included and analysed. A total of 634 patients were included in the desflurane group, and 633 patients in the sevoflurane group. The occurrence of respiratory complications was significantly higher with desflurane-based anaesthesia than with sevoflurane-based anaesthesia (Total n = 673, 20.0 vs. 12.8%, relative risk (RR) 1.59 (95% CI 1.15 to 2.20)) with low heterogeneity (I = 20%). There was no difference in the occurrence of emergence agitation (Total n = 626, 29.1 vs. 27.2%, RR 1.05 (95% CI 0.84 to 1.30)) or the incidence of PONV between the desflurane and sevoflurane groups (Total n = 989, 19.0 vs. 21.0%, RR 0.95 (95% CI 0.71 to 1.26)). Time to eye opening was significantly faster with desflurane than that with sevoflurane (Total n = 1072, mean difference = -3.32 min (95% CI -4.02 to -2.61)) with a substantial heterogeneity (I = 72.6%). There was no significant difference in the time to discharge from the operation room between the two groups (Total n = 1056, mean difference = -0.45 min (95% CI -5.89 to 4.99)). CONCLUSION: Despite recent reports that there is no significant difference in adverse respiratory events between desflurane and sevoflurane, a pooled analysis revealed that desflurane resulted in a higher rate than sevoflurane. Therefore, the consequences of desflurane should not be neglected and its airway irritant properties should be taken into account. TRIAL REGISTRATION: PROSPERO (CRD42019147939).

Concurrent use of methanol and ethanol for chain-elongating short chain fatty acids into caproate and isobutyrate.

Microbial chain elongation (MCE) is a bioprocess that could utilise a mixed-culture fermentation to valorise organic waste. MCE converting ethanol and short chain fatty acids (SCFA; derived from organic waste) to caproate has been studied extensively and implemented. Recent studies demonstrated the conversion of SCFAs and methanol or ethanol into isomerised fatty acids as novel products, which may expand the MCE application and market. Integrating caproate and isomerised fatty acid production in one reactor system is theoretically feasible given the employment of a mixed culture and may increase the economic competence of MCE; however, the feasibility of such has never been demonstrated. This study investigated the feasibility of using two electron donors, i.e. methanol and ethanol, for upgrading SCFAs into isobutyrate and caproate concurrently in MCE Results show that supplying methanol and ethanol in MCE simultaneously converted acetate and/or butyrate into caproate and isobutyrate, by a mixed-culture microbiome. The butyrate supplement stimulated the caproate production rate from 1.5 to 2.6 g/L.day and induced isobutyrate production (1.5 g/L.day). Further increasing ethanol feeding rate from 140 to 280 mmol carbon per litre per day enhanced the direct use of butyrate for caproate production, which improved the caproate production rate to 5.9 g/L.day. Overall, the integration of two electron donors, i.e. ethanol and methanol, in one chain-elongation reactor system for upgrading SCFAs was demonstrated. As such, MCE could be applied to valorise organic waste (water) streams into a wider variety of value-added biochemical.

Association of Scrub Typhus With the Risk of Autoimmune Diseases: A Population-Based Cohort Study.

Infection plays a major role in the development of autoimmune diseases. In this study, we investigated the relationship between scrub typhus and systemic autoimmune diseases. We enrolled 6,928 hospitalized patients with scrub typhus between 2000 and 2012 from the Taiwan National Health Insurance Research Database, and we compared them with 27,712 selected inpatients who had never been diagnosed with scrub typhus (1:4 ratio, matched by age, sex, and index year) in relation to the risk of developing autoimmune diseases. Cox proportional hazards regression analysis was used to analyze the risk of autoimmune diseases by sex, age, and comorbidities, with hazard ratios and 95% confidence intervals. The adjusted hazard ratio for autoimmune diseases for the scrub typhus group was 2.4 (95% confidence interval: 1.66, 3.48, P < 0.0001) compared with the control group. Subgroup analysis showed that women aged <40 years had a significant higher risk of autoimmune diseases. The risk was significantly higher within 3 years after scrub typhus infection. In conclusion, a higher risk of autoimmune diseases was found among the scrub typhus group, especially for female patients, those aged <40 years, and within the first 3 years after getting scrub typhus.

Thyroid cancer risk in women with infertility and association with fertility medications in Taiwan.

BACKGROUND: The current study evaluated whether the risk of developing thyroid cancer in Asian women was associated with infertility and the use of fertility drugs. METHODS: The authors conducted a large, retrospective cohort study using Taiwan's National Health Insurance Research Database. From the insurance claims data, a total of 13,356 women aged 20 to 49 years who were diagnosed with infertility from 2000 through 2013 were included in the infertile group, and 53,424 women without a history of infertility were selected as fertile comparisons and were frequency matched by age and year of diagnosis. Both groups were followed up to 2013 to calculate incident thyroid cancer. Poisson regression analysis was used to estimate the incidence rate ratio (IRR). RESULTS: The incidence of thyroid cancer was 1.9-fold greater in the infertile group compared with the comparison group (2.85 vs 1.53 per 10,000 person-years), with an adjusted IRR of 1.80 (95% confidence interval [95% CI], 1.70-1.92) for the infertile group. Higher cancer incidence was demonstrated for the infertile group after 7 years of follow-up, with an adjusted IRR of 4.39 (95% CI, 4.03-4.78) compared with the comparison group. Among infertile women, those who had taken the fertility drug clomiphene were found to have a reduced incidence of thyroid cancer compared with those who were treated without the drug (2.69 vs 3.42 per 10,000 person-years), with an adjusted IRR of 0.86 (95% CI, 0.75-0.99). However, the cancer incidence in infertile women being treated with clomiphene was nearly 6-fold greater than that in fertile women taking the drug. CONCLUSIONS: The results of the current study provide evidence that women with infertility are at an increased risk of developing thyroid cancer.

Association between depression risk and polycystic ovarian syndrome in young women: a retrospective nationwide population-based cohort study (1998-2013).

STUDY QUESTION: Is polycystic ovarian syndrome (PCOS) in women associated with the increasing incidence of depression in an East Asian population? SUMMARY ANSWER: Younger PCOS patients (aged 15-29 years), but not middle-aged patients, have an increased risk of depression in Taiwan. WHAT IS KNOWN ALREADY: During reproductive age, 6-10% of women have PCOS. Among them, ~40% experience depression, mostly at young ages. STUDY DESIGN, SIZE, DURATION: This is a retrospective population-based cohort study analysing depression risk in Taiwanese women using data from a nationwide database containing 1998-2013 data of nearly 1 million people. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included 15- to 50-year-old women newly diagnosed with PCOS during 1998-2013 from the Taiwan National Health Insurance Research Database as the PCOS cohort (n = 7684) and then randomly matched them 4 : 1 by sex, age and index year with women without PCOS as the comparison cohort (n = 30 736). We used multivariable Cox proportional hazard regression analysis to determine the association between PCOS and depression risk [hazard ratio (HR) with 95% confidence interval (CI)]. MAIN RESULTS AND THE ROLE OF CHANCE: The incidence of depression was higher in the PCOS group than in the comparison group (6.67 vs. 4.82 per 1000 person-years; adjusted HR = 1.28, 95% CI = 1.12-1.46). PCOS patients aged 15-29 years had a significantly higher depression risk (adjusted HR = 1.39, 95% CI = 1.18-1.65); no such significant association was noted among patients aged 30-39 years and 40-50 years. LIMITATIONS, REASONS FOR CAUTION: A history of malignancy, which may increase depression, could not be obtained for our study patients. Moreover, we could not obtain a family history of depression, a relevant risk factor for depression. Finally, the database has no records of body mass index, which may influence depression outcome. WIDER IMPLICATIONS OF THE FINDINGS: In Taiwan, younger PCOS patients (15-29 years), but not the middle-aged patients, have an increased risk of depression. Our findings provide vital information to patients, clinicians, the Taiwan Government and other developing Asian countries to improve the PCOS treatment strategies in the future. Routine screening for depression in PCOS patients may be implemented into the health practice. STUDY FUNDING/COMPETING INTEREST(S): This study was supported in part by the Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW108-TDU-B-212-133 004), China Medical University Hospital, Academia Sinica Stroke Biosignature Project (BM10701010021), MOST Clinical Trial Consortium for Stroke (MOST 107-2321-B-039 -004-), Tseng-Lien Lin Foundation, Taichung, Taiwan and Katsuzo and Kiyo Aoshima Memorial Funds, Japan. No competing interest existed. TRIAL REGISTRATION NUMBER: N/A.

Association of hysterectomy with bipolar disorder risk: A population-based cohort study.

BACKGROUND: Hormonal fluctuations may trigger the onset of bipolar disorder. We designed a longitudinal follow-up study to evaluate the association between hysterectomies and bipolar disorder risk. METHODS: We conducted a large retrospective cohort study using Taiwan's National Health Insurance Research Database. A total of 4,337 women aged 30 to 50 years who underwent the hysterectomy during 2000-2013 were selected and 17,348 patients without hysterectomy were selected for comparison (1:4 match). Poisson regression analysis was used to calculate the incidence rate ratio (IRR) and 95% confidence interval (CI). RESULTS: During the follow-up of 7.93 years, 20 participants with hysterectomy and 28 without hysterectomy developed bipolar disorder. Receiving hysterectomy was associated with the risk of developing bipolar disorder (adjusted IRR = 2.80; 95% CI = 2.54-3.09). Women with hysterectomy had a higher risk of bipolar disorder in follow-up durations of <1 year (adjusted IRR = 2.18 with 95% CI = 1.94-1.45) and ≥1 year (adjusted IRR = 2.85 with 95% CI = 2.58-3.15). Endometriosis and Premarin use increased bipolar disorder incidence in the hysterectomy group (adjusted IRR = 3.17 [95% CI = 2.83-3.56] and 4.22 [95% CI = 3.71-4.80], respectively). CONCLUSION: This study concluded that women with hysterectomy have an increased risk of bipolar disorder. Endometriosis and hormone therapy may add to the risk of bipolar disorder after hysterectomy. Knowledge about how surgical or natural hormonal withdrawal influences mood is fundamental and emphasizes the importance of coordinated psychiatric and gynecological care.

Incidence and risk of venous thromboembolism in patients following appendectomy: a nationwide cohort study.

Surgery may lead to poor blood flow and hypercoagulation. Few studies have investigated the incidence of venous thromboembolism (VTE) in Asian patients following appendectomy. We conducted a nationwide cohort study to investigate the risk of VTE in patients who underwent appendectomy compared with those who did not in Taiwan. We studied the entire hospitalized population in Taiwan from 2000 to 2012, with a follow-up period extending to the end of 2013. We identified patients who underwent appendectomy in Taiwan's National Health Insurance Research Database as the appendectomy cohort, and selected a nonappendectomy cohort from the general population that was 4:1 frequency-matched by age (5-year interval), sex, and index year for each appendectomy case. We used Cox models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for symptomatic VTE in the appendectomy cohort for comparison with the nonappendectomy cohort. The appendectomy cohort exhibited a higher incidence of symptomatic VTE than the nonappendectomy cohort (5.90 vs. 3.29 per 10,000 person-years). After adjustment for covariates, a 1.68-fold HR for symptomatic VTE was observed in the appendectomy cohort (95% CI 1.56-1.81). Compared with the nonappendectomy cohort, the patients who underwent open appendectomy had a 1.73-fold increased adjusted HR for symptomatic VTE (95% CI 1.61-1.87). Laparoscopic appendectomy was not significantly associated with symptomatic VTE. An 8.15-fold higher adjusted HR for VTE was observed in patients who underwent appendectomy within the first month after surgery compared with the nonappendectomy cohort. Open appendectomy carried an increased risk of symptomatic VTE. Laparoscopic appendectomy was not significantly associated with symptomatic VTE.

Association Between Alcoholic Cirrhosis and Hemorrhagic Stroke: A Nationwide Population-based Study.

AIMS: This study investigated whether patients with alcoholic cirrhosis have a high risk of hemorrhagic stroke. METHODS: In this study, 17,094 patients diagnosed with cirrhosis between 2000 and 2010 were identified using the Taiwan National Health Insurance claims data. Identified patients were randomly selected and propensity score matched with individuals without cirrhosis according to age, sex, comorbidities and index year. RESULTS: The overall incidence rate of stroke was 4.41 and 12.1 per 1000 person-years in the chronic liver disease and cirrhosis (CLDC) with hepatitis B virus (HBV) or hepatitis C virus (HCV) cohort and the alcoholic CLDC cohort, respectively. The alcoholic CLDC cohort exhibited a 4.53-fold higher risk of hemorrhagic stroke (adjusted subhazard ratio [aSHR] = 4.53, 95% confidence interval [CI] = 3.05-6.71) than did the non-CLDC cohort, and the CLDC with HBV or HCV cohort exhibited a 1.40-fold higher risk of hemorrhagic stroke (aSHR = 1.40, 95% CI = 1.10-1.78) than did the non-CLDC cohort. The alcoholic CLDC cohort and the CLDC with HBV or HCV cohort showed an aSHR of 1.80 (95% CI = 1.36-2.40) and 0.95 (95% CI = 0.83-1.07) for ischemic stroke, respectively, compared with the non-CLDC cohort. CONCLUSION: Alcoholic patients with CLDC had a higher risk of hemorrhagic stroke compared with non-alcoholic patients with CLDC and patients without CLDC.

A Collagen and Silk Scaffold for Improved Healing of the Tendon and Bone Interface in a Rabbit Model.

BACKGROUND The study aimed to develop a novel orthopedic surgical scaffold made of collagen and silk to repair the tendon and bone interface, and to investigate its influence on tendon and bone healing in a rabbit model. MATERIAL AND METHODS Four types of surgical scaffold were prepared, including a random collagen scaffold (RCS), an aligned collagen scaffold (ACS), a random collagen scaffold combined with knitted silk (RCSS), and an aligned collagen scaffold combined with knitted silk (ACSS). Rabbit bone marrow stem cells (BMSCs) were cultured and seeded onto the RCS and ACS scaffold. The animal model included four-month-old female New Zealand White rabbits (N=20) that underwent drilling into the rotator cuff of the left supraspinatus muscle tendon, randomized into the ACSS and RCSS groups. RESULTS Rabbit BMSCs adhered to and proliferated on the RCS and ACS in vitro. Transcription levels of the COL I, COL III, and tenascin (TCN) genes were significantly increased in the ACS group compared with the RCS group. Transcription levels of COL I, runt-related transcription factor-2 (RUNX-2) and bone morphogenetic protein-2 (BMP-2) were significantly increased in the RCS group compared with the ACS group. RCSS and ACSS implanted in the rabbit models for eight weeks resulted in more regenerative tissue in the RCSS group compared with the ACSS group, with new cartilage at the tendon and bone interface at 12 weeks. CONCLUSIONS A collagen and silk scaffold improved healing of the tendon and bone interface in a rabbit model.

Small molecule therapeutics for inflammation-associated chronic musculoskeletal degenerative diseases: Past, present and future.

Inflammation-associated chronic musculoskeletal degenerative diseases (ICMDDs) like osteoarthritis and tendinopathy often results in morbidity and disability, with consequent heavy socio-economic burden. Current available therapies such as NSAIDs and glucocorticoid are palliative rather than disease-modifying. Insufficient systematic research data on disease molecular mechanism also makes it difficult to exploit valid therapeutic targets. Small molecules are designed to act on specific signaling pathways and/or mechanisms of cellular physiology and function, and have gradually shown potential for treating ICMDDs. In this review, we would examine and analyze recent developments in small molecule drugs for ICMDDs, suggest possible feasible improvements in treatment modalities, and discuss future research directions.

Efficacy of Laminoplasty in Patients with Cervical Kyphosis.

BACKGROUND The efficacy of laminoplasty in patients with cervical kyphosis is controversial. The purpose of this study was to investigate the impact of the initial pathogenesis on the clinical outcomes of laminoplasty in patients with cervical kyphosis. MATERIAL AND METHODS A total of 137 patients with cervical spondylotic myelopathy (CSM) or ossification of the posterior longitudinal ligament (OPLL) underwent laminoplasty from April 2013 to May 2015. The patients were divided into the following 4 groups: lordosis with CSM (LC), kyphosis with CSM (KC), lordosis with OPLL (LO), and kyphosis with OPLL (KO). The clinical outcome measures included the visual analogue scale (VAS) and modified Japanese Orthopedic Association (mJOA) scores, the range of motion (ROM), and the cervical global angle (CGA). RESULTS The mean VAS and mJOA scores improved significantly in all groups after surgery. The changes in VAS and mJOA scores were significantly smaller, and the JOA recovery rate was significantly lower, in the KC group than in the LC and KO groups. The mean change in the CGA was greatest in the KC group (>8° towards kyphosis). The preoperative ROM was negatively correlated with the change in CGA and the JOA recovery rate in the KO and KC groups. CONCLUSIONS We found that laminoplasty is suitable for patients with cervical lordosis and those with mild cervical kyphosis and OPLL, but is not recommended for patients with kyphosis and CSM, particularly those with a large ROM preoperatively.