The Effects of Three and Six Sessions of Low Energy Extracorporeal Shockwave Therapy on Graft Incorporation and Knee Functions Post Anterior Cruciate Ligament Reconstruction.

Introduction: One session of high energy extracorporeal shockwave therapy (ESWT) was found to improve the healing of anterior cruciate ligament (ACL) after reconstruction in animal and human studies. This study investigated the effects of three and six sessions of low energy ESWT on graft incorporation and knee functions post ACL reconstruction in humans. Materials and methods: Thirty participants with ACL injuries were recruited and assigned equally into three groups with 10 participants per group (n=10). Participants in the control group received physiotherapy alone without low energy ESWT. Participants in the 3ESWT group underwent three sessions of low energy ESWT (one session per week) combined with physiotherapy, and participants in the 6ESWT group received six sessions of low energy ESWT (one session per week) combined with physiotherapy. However, five participants were lost to follow-up. Evaluations of graft incorporation of the tibial tunnel using magnetic resonance (MRI) and Lysholm score were carried out before ACL reconstruction and after six months post ACL reconstruction. Results: The number of grafts with partial incorporation in the tibia tunnel in 6ESWT was significantly higher compared with the number of grafts with non-incorporation at six months post-operatively, X2 (1, N=9) =5.44, p =0.02. However, there was no significant difference between frequencies of graft incorporation in tibia tunnel in the control and 3ESWT groups, X2 (1, N=7) =3.57, p =0.06 and X2 (1, N=9) =2.78, p =0.10, respectively at 6 months postoperatively. Lysholm scores were significantly higher at 6 months post ACL reconstruction compared to the baseline value for each group (p<0.002, respectively). However, there was no significant difference in the Lysholm score between each group (F = 2.798, p = 0.083). Conclusions: Six sessions of low energy ESWT improved graft incorporation in the tibial tunnel. Both three and six sessions of low energy of ESWT does not affect the knee function score at six months post ACL reconstruction.

Synthetic cathinone poisoning from ingestion of drug-laced "instant coffee packets" in Taiwan.

BACKGROUND: Synthetic cathinone abuse is a global health issue. Synthetic cathinones emerged in Taiwan in 2009, and their prevalence rapidly rose. They are usually made into "instant coffee packets," and these so-called "toxic coffee packets" may also contain psychoactive drugs other than synthetic cathinones. Due to the diversity of the ingredients, clinical presentations can be complex. METHODS: Retrospective analysis of emergency department (ED) patients who reported ingesting toxic coffee packets at three Chang-Gung Memorial Hospitals located in northern Taiwan between January, 2015 and December, 2019. RESULTS: Sixty patients were included. Their mean age was 28.85 ± 9.24 years and 47(78.33%) were male. The most common presentations were palpitation, agitation, hallucination, and altered consciousness. Tachycardia and hypertension were common, while hyperthermia was observed in only three patients. Three patients (5%) developed rhabdomyolysis, and one underwent transient hemodialysis. Most patients were discharged from the ED, but 15(25%) were admitted, of whom nine (15%) were admitted to the intensive care unit (ICU), and one eventually died. Confirmation tests (mass-spectrometry-based analysis) were available in 10 patients; all reported positive for at least one type of synthetic cathinone. Polysubstance exposure was common. In multivariate logistic regression analyses, Glasgow coma scale ≤13 and the presence of seizure were associated with ICU admission. CONCLUSION: Patients who report ingesting toxic coffee packets are very likely to have been exposed to synthetic cathinones. Polysubstance exposure is common following ingestion. Cardiovascular and neurological symptoms are the main presentations, and severe complications such as rhabdomyolysis and life-threatening dysrhythmia can occur.

Effect of compression fracture on trabecular bone score at lumbar spine.

Bone mineral density (BMD) may be increased due to vertebral compression fractures (VCF). Our study showed trabecular bone scores (TBS) was less affected than BMD by fractured vertebrae. The TBS of most compression fractures, including old and recent VCF with mild or moderate deformity and old VCF with severe deformity, could still be used in predicting fracture risk. INTRODUCTION: Trabecular bone score (TBS), a noninvasive tool estimating bone microarchitecture, provides complementary information to lumbar spine bone mineral density (BMD). Lumbar spine BMD might be increased due to both degenerative disease and vertebral compression fractures (VCF). Lumbar spine TBS has been confirmed not influenced by osteoarthrosis, but the effects of VCF are still not been well evaluated. This study aimed to investigate whether lumbar spine TBS was affected by fractured vertebrae. METHODS: We studied postmenopausal women and men above 50 years old who underwent DXA between January 1, 2017, and May 31, 2019. By calculating the difference of BMD and TBS between L1 and the mean of L2-3, the study compared the difference of values between the control group and fracture group to determine the effects of fractured vertebrae on BMD and TBS. RESULTS: A total of 377 participants were enrolled with 202 in the control group (157 females; age: 68.06 ± 6.47 years) and 175 in the fracture group (147 females; age: 71.71 ± 9.44 years). The mean BMD of the L1 vertebrae in the fracture group was significantly higher than that in the control group (p < 0.0001). There was no significant difference between the mean differences of TBS between L1 and the means of L2-3 vertebrae in the control group and the most compression fractures, including old and recent VCF with mild or moderate deformity and old VCF with severe deformity. CONCLUSION: Lumbar spine TBS, unlike BMD, is less affected by fractured vertebrae. The TBS of most compression fractures, including old and recent VCF with mild or moderate deformity and old VCF with severe deformity, could still be used in predicting fracture risk.

Psychiatrists' Attitude and Use of Second-generation Antipsychotics for the Treatment of Schizophrenia in Taiwan.

OBJECTIVES: This survey aimed to understand the attitude of psychiatrists and their use of commonly prescribed second-generation antipsychotics (SGAs) for the treatment of schizophrenia in Taiwan. It also attempted to identify the factors that might influence their preference for selecting SGAs. METHODS: Psychiatrists were interviewed face-to-face using a structured questionnaire. The questionnaire addressed various issues involved in the treatment of patients with schizophrenia, including the reasons for selecting SGAs, psychiatrists' level of satisfaction with commonly prescribed SGAs, and their current use of SGAs in clinical practice. RESULTS: Gender and age of the psychiatrists, and practice setting were not related to SGA selection. The selection of a SGA might be influenced by characteristics of the psychiatrist, properties of the drugs, and the healthcare insurance system. Most psychiatrists agreed that the performance of brand-name drugs was superior to that of generic drugs. Better symptom control, improvement in cognition, and higher tolerability were among the major factors considered by psychiatrists in Taiwan when prescribing antipsychotics. CONCLUSION: Selection of a SGA in Taiwan is potentially influenced by the characteristics of the psychiatrist, properties of the drug, and the healthcare insurance system. Efficacy and tolerability were among the major determining factors when prescribing antipsychotics for the treatment of patients with schizophrenia.

Survival without peripheral neuropathy after massive acute arsenic poisoning: Treated by 2,3-dimercaptopropane-1-sulphonate.

WHAT IS KNOWN AND OBJECTIVE: Massive acute arsenic poisoning is rare yet potentially life-threatening. 2,3-dimercaptopropane-1-sulphonate (DMPS) appears to have the appropriate chelating property. However, clinical experience on the use of DMPS in massive arsenic poisoning is limited. CASE DESCRIPTION: A 37-year-old woman attempted suicide by ingesting 37.5 g of arsenic trioxide. DMPS was promptly initiated based on history and clinical symptoms. The patient recovered completely, with no complications or side effects of the therapy. WHAT IS NEW AND CONCLUSION: TDMPS is useful for the treatment of massive acute arsenic poisoning.

Targeting curcumin to specific tumour cell environments: the influence of ancillary ligands.

Tumour-activation of prodrugs has the potential to improve the efficacy of anticancer agents while minimising systemic toxicity. Cobalt complexes are of interest in this respect as chaperones to deliver and release anticancer agents in the low oxygen, reducing environment of solid tumours. In addition to being able to release a cytotoxic ligand under the conditions of the tumour microenvironment, it is fundamental that the chaperone complex must also be able to penetrate through multiple cell layers to deliver the cytotoxin to all regions of the tumour. Herein, we report an investigation of the distribution and metabolism of two chaperone complexes of the anticancer agent curcumin within monolayer tumour cells and multicellular tumour spheroids. Using a combination of X-ray fluorescence microscopy, confocal fluorescence microscopy, and X-ray absorption spectroscopy, we demonstrate how the nature of the chaperone complex can profoundly influence the cellular uptake, distribution, and release mechanism of curcumin, providing key insights into the design of this class of prodrug.

Cytosolic PKM2 stabilizes mutant EGFR protein expression through regulating HSP90-EGFR association.

This corrects the article DOI: 10.1038/onc.2015.397.

Cytosolic PKM2 stabilizes mutant EGFR protein expression through regulating HSP90-EGFR association.

Secondary mutation of epidermal growth factor receptor (EGFR) resulting in drug resistance is one of the most critical issues in lung cancer therapy. Several drugs are being developed to overcome EGFR tyrosine kinase inhibitor (TKI) resistance. Here, we report that pyruvate kinase M2 (PKM2) stabilized mutant EGFR protein by direct interaction and sustained cell survival signaling in lung cancer cells. PKM2 silencing resulted in markedly reduced mutant EGFR expression in TKI-sensitive or -resistant human lung cancer cells, and in inhibition of tumor growth in their xenografts, concomitant with downregulation of EGFR-related signaling. Mechanistically, PKM2 directly interacted with mutant EGFR and heat-shock protein 90 (HSP90), and thus stabilized EGFR by maintaining its binding with HSP90 and co-chaperones. Stabilization of EGFR relied on dimeric PKM2, and the protein half-life of mutant EGFR decreased when PKM2 was forced into its tetramer form. Clinical levels of PKM2 positively correlated with mutant EGFR expression and with patient outcome. These results reveal a previously undescribed non-glycolysis function of PKM2 in the cytoplasm, which contribute to EGFR-dependent tumorigenesis and provide a novel strategy to overcome drug resistance to EGFR TKIs.

A genome-wide association study of growth trait-related single nucleotide polymorphisms in Chinese Yancheng chickens.

Chicken (Gallus gallus) growth traits are important economic traits, and many studies have been conducted on genetic selection for body weight. However, most of these studies have detected functional chromosome mutations or regions by conventional molecular markers or gene chips. In this study, we performed a new genome-wide association study using specific-locus amplified fragment sequencing (SLAF-seq) technology in purebred Yancheng chickens. Single nucleotide polymorphisms (SNPs) that were significantly associated with phenotypic traits were identified by GAPIT-compressed mixed linear models. Eighteen SNP markers reached 5% Bonferroni genome-wide significance. A region spanning 72.3 to 82.1 Mb on GGA4 had a strong influence on growth traits. Four genes (FAM184B, KCNIP4, MIR15A, and GLI3) were closely associated with body weight. Some SNPs were coincident with previously reported quantitative trait locus regions. Our results would promote the researches of Chinese chickens and accelerate the utilization of Chinese chicken, specially Yancheng chicken.

Preparation and identification of an antiserum against recombinant UL31 protein of pseudorabies virus.

Pseudorabies virus (PRV) early protein UL31 is a homologue of herpes simplex virus 1 (HSV-1) UL31, which is a multifunctional protein important for HSV-1 infection. However, the precise roles of PRV UL31 in virus life cycle are still poorly understood. A relatively crucial tool for uncovering the function of UL31 is an antiserum that specifically detects UL31 in the PRV-infected cells. For this purpose, a recombinant UL31 protein consisting of N-terminal 27 aa of UL31 fused to EYFP and His-tag was expressed, purified and used for the preparation of antiserum in BALB/c mice. Our results show that Western blot analysis and immunofluorescence assay showed that this antiserum could specifically detect the purified recombinant UL31 as well as full-length UL31 in the PRV infected cells. These results demonstrate that the prepared antiserum could serve as a valuable tool for further studies of UL31 functions in PRV infection.

Development and Impact of De Novo Anti-HLA Antibodies in Pediatric Heart Transplant Recipients.

There is increasing evidence that de novo anti-HLA antibodies, more specifically de novo donor-specific antibodies (DSA) following solid organ transplantation may be associated with negative outcomes including rejection in the first year and graft loss. Limited data are available in pediatric heart transplant recipients. We sought to prospectively determine the incidence, class and early impact of de novo anti-HLA antibodies in a cohort of pediatric heart transplant recipients. Serial panel reactive antibody testing posttransplant was performed in 25 patients (14 males) transplanted between January 2008 and June 2010. Five patients were sensitized pretransplant; all patients had negative direct crossmatch. Seventy-two percent developed de novo anti-HLA antibodies at a median of 2.6 weeks (IQR 1.2 weeks to 6.2 months) posttransplant; 67% of these were DSA. The majority of recipients in our cohort developed de novo anti-HLA antibodies within the first year posttransplant, with two-thirds being donor-specific. Acute cellular rejection, though frequent, was not different in patients with antibody development regardless of class or specificity, and there was no antibody-mediated rejection, graft loss or early cardiac allograft vasculopathy.

Alendronate and risk of lower limb ischemic vascular events: a population-based cohort study.

UNLABELLED: While alendronate inhibits atherosclerosis experimentally, its effect on lower limb ischemia risk is unknown. Our results suggest that alendronate reduces the risk of lower limb ischemic vascular events requiring surgical interventions, including amputation. Our results are relevant for patients at risk of lower limb ischemia undergoing fragility fracture treatment. INTRODUCTION: This study aimed to determine the association between alendronate therapy and the risk of lower limb ischemic vascular events (i.e., bypass surgery, endovascular stenting, and major lower limb amputation for lower limb ischemia). METHODS: We used a nationwide population-based cohort of patients aged over 50 years diagnosed with a vertebral or hip fracture between January 1999 and June 2010. We compared the risk of lower limb ischemic vascular events between patients undergoing treatment with alendronate (n = 3,731) and an age- and sex-matched comparison group (n = 7,462) over 5 years of follow-up. Hazard ratios (HR) were estimated using Cox proportional regression analysis with adjustment for treatment status, comorbidities, and other variables. RESULTS: Ten patients (0.3 %) in the alendronate treatment group had a lower limb ischemic vascular event compared with 51 patients (0.7 %) in the comparison group. The incidence of lower limb ischemic vascular events was 8.4 (95 % CI, 4.0-15.5) per 10,000 person-years in the alendronate group and 21.8 (95 % CI, 16.2-28.7) per 10,000 person-years in the comparison group. The risk of a lower limb ischemic vascular event in the alendronate treatment group was lower (adjusted HR, 0.41; 95 % CI, 0.21-0.82). CONCLUSION: Alendronate treatment was associated with a reduced risk of lower limb ischemic vascular events among hip or vertebral fragility fracture patients.

Epigenetic silencing of PTPRR activates MAPK signaling, promotes metastasis and serves as a biomarker of invasive cervical cancer.

Epigenetic modifications are a driving force in carcinogenesis. However, their role in cancer metastasis remains poorly understood. The present study investigated the role of DNA methylation in the cervical cancer metastasis. Here, we report evidence of the overexpression of DNA methyltransferases 3B (DNMT3B) in invasive cervical cancer and of the inhibition of metastasis by DNMT3B interference. Using methyl-DNA immunoprecipitation coupled with microarray analysis, we found that the protein tyrosine phosphatase receptor type R (PTPRR) was silenced through DNMT3B-mediated methylation in the cervical cancer. PTPRR inhibited p44/42 MAPK signaling, the expression of the transcription factor AP1, human papillomavirus (HPV) oncogenes E6/E7 and DNMTs. The methylation status of PTPRR increased in cervical scrapings (n=358) in accordance with disease severity, especially in invasive cancer. Methylation of the PTPRR promoter has an important role in the metastasis and may be a biomarker of invasive cervical cancer.

Effects of spiked metals on the MSW anaerobic digestion.

This study aimed to investigate the effects of eight metals on the anaerobic digestion of the organic fraction of municipal solid waste (OFMSW) in bioreactors. Anaerobic bioreactors containing 200 mL MSW mixed completely with 200 m L sludge seeding. Ca and K (0, 1000, 2000 and 6,000 mg L(-1)) and Cr, Ni, Zn, Co, Mo and W (0, 5, 50 and 100 mg L(-1)) of various dose were added to anaerobic bioreactors to examine their anaerobic digestion performance. Results showed that except K and Zn, Ca (~728 to ~1,461 mg L(-1)), Cr (~0.0022 to ~0.0212 mg L(-1)), Ni (~0.801 to ~5.362 mg L(-1)), Co (~0.148 to ~0.580 mg L(-1)), Mo (~0.044 to ~52.94 mg L(-1)) and W (~0.658 to ~40.39 mg L(-1)) had the potential to enhance the biogas production. On the other hand, except Mo and W, inhibitory concentrations IC(50) of Ca, K, Cr, Ni, Zn and Co were found to be ~3252, ~2097, ~0.124, ~7.239, ~0.482, ~8.625 mg L(-1), respectively. Eight spiked metals showed that they were adsorbed by MSW to a different extent resulting in different liquid metals levels and potential stimulation and inhibition on MSW anaerobic digestion. These results were discussed and compared to results from literature.

Genome-wide association study of bipolar I disorder in the Han Chinese population.

We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 α-N-acetyl- neuraminide α-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with P-values of 4.87 × 10(-7) (rs2709736) and 6.05 × 10(-6) (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P=9.74 × 10(-6)) and in CACNB2 (Calcium channel, voltage-dependent, ß-2 subunit) gene (rs11013860, P=5.15 × 10(-5)), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P=6.55 × 10(-5) and P=1.48 × 10(-5), respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.

Model-based segmentation of flexor tendons from magnetic resonance images of finger joints.

Trigger finger is a common hand disease, causing swelling, painful popping and clicking in moving the affected finger joint. To better evaluate patients with trigger finger, segmentation of flexor tendons from magnetic resonance (MR) images of finger joints, which can offer detailed structural information of tendons to clinicians, is essential. This paper presents a novel model-based method with three stages for automatically segmenting the flexor tendons. In the first stage, a set of tendon contour models (TCMs) is initialized from the most proximal cross-sectional image via two-step ellipse estimation. Each of the TCMs is then propagated to its distally adjacent image by affine registration. The propagation is sequentially performed along the proximal-distal direction until the most distal image is reached, as the second stage of segmentation. The TCMs on each cross-sectional image are refined in the last stage with the snake deformation. MR volumes of three subjects were used to validate the segmentation accuracy. Compared with the manual results, our method showed good accuracy with small average margins of errors (within 0.5 mm) and large overlapping ratio (dice similarity coefficient above 0.8). Overall, the proposed method has great potential for morphological change assessment of flexor tendons and pulley-tendon system modeling for image guided surgery.

Effects of swimming on eye hand coordination and balance in the elderly.

OBJECTIVE: To evaluate the effects of swimming on upper extremity motor control, and balance in elderly population. DESIGN: Cross-sectional study. SETTING: The biomechanical laboratory in a tertiary hospital. PARTICIPANTS: The swimming group consisted of 20 swimmers (n_20, 65.4 ± 5.5 years) who received regular swimming exercise for more than 2 years. The control group consisted of 34 healthy active subjects (n_34, 67.4 ± 5.7 years) who have regular exercises other than swimming. MEASUREMENTS: The eye hand coordination was evaluated by calculating the mean reaction time required in accurately pointing onto the center of the target sensors that come in three different sizes (1 cm, 1.5 cm, and 2 cm in diameter). The SMART Balance Master device was used to measure posture balance. The maximal stability, center of pressure (COP) velocity, and percentage ankle strategy were obtained under six different balance conditions. RESULTS: In the testing of upper extremity motor control, the swimming group had significant shorter mean reaction time as compared with the control group in all three target sensor sizes (p < 0.05). In balance testing, the swimming group had significant greater percentage of ankle strategy during eyes closed and fixed support (EC), and sway-referenced vision and support (SVSS) conditions as compared with the control group (p < 0.05). CONCLUSION: Regular swimming exercise may result in improved eye hand coordination as faster and more accurate repetitive movements. Swimming may also result in improved balance function under few complicated balance conditions.

Replacing the rod with the cone transducin subunit decreases sensitivity and accelerates response decay.

Cone vision is less sensitive than rod vision. Much of this difference can be attributed to the photoreceptors themselves, but the reason why the cones are less sensitive is still unknown. Recent recordings indicate that one important factor may be a difference in the rate of activation of cone transduction; that is, the rising phase of the cone response per bleached rhodopsin molecule (Rh*) has a smaller slope than the rising phase of the rod response per Rh*, perhaps because some step between Rh* and activation of the phosphodiesterase 6 (PDE6) effector molecule occurs with less gain. Since rods and cones have different G-protein alpha subunits, and since this subunit (Talpha) plays a key role both in the interaction of G-protein with Rh* and the activation of PDE6, we investigated the mechanism of the amplification difference by expressing cone Talpha in rod Talpha-knockout rods to produce so-called GNAT2C mice. We show that rods in GNAT2C mice have decreased sensitivity and a rate of activation half that of wild-type (WT) mouse rods. Furthermore, GNAT2C responses recover more rapidly than WT responses with kinetic parameters resembling those of native mouse cones. Our results show for the first time that part of the difference in sensitivity and response kinetics between rods and cones may be the result of a difference in the G-protein alpha subunit. They also indicate more generally that the molecular nature of G-protein alpha may play an important role in the kinetics of G-protein cascades for metabotropic receptors throughout the body.

Modeling biogas production from organic fraction of MSW co-digested with MSWI ashes in anaerobic bioreactors.

This study aims at investigating the effects of MSW incinerator fly ash (FA) and bottom ash (BA) on the anaerobic co-digestion of OFMSW with FA or BA. It also simulates the biogas production from various dosed and control bioreactors. Results showed that suitable ashes addition (FA/MSW 10 and 20 g L(-1) and BA/MSW 100 g L(-1)) could improve the MSW anaerobic digestion and enhance the biogas production rates. FA/MSW 20 g L(-1) bioreactor had the higher biogas production and rate implying the potential option for MSW anaerobic co-digestion. Modeling studies showed that exponential plot simulated better for FA/MSW 10 g L(-1) and control bioreactors while Gaussian plot was applicable for FA/MSW 20 g L(-1) one. Linear and exponential plot of descending limb both simulated better for BA/MSW 100 g L(-1) bioreactor. Modified Gompertz plot showed higher correlation of biogas accumulation than exponential rise to maximum plot for all bioreactors.