The incremental risk of fragility fractures in aging men.

INTRODUCTION: While the United States Preventative Services Task Force recommends osteoporosis screening for women 65 years and older, there is no definitive recommendation for routine osteoporosis screening in men. The purpose of this study was to determine the age at which the odds of fragility fractures (FFx) increase in men to help guide future policy discussions evaluating an optimal screening strategy in this population. METHODS: Men older than 49 years were identified in the PearlDiver Patient Records Database. Patients were excluded if they had a prior fragility fracture, if they were at high risk for osteoporosis due to comorbidities, or if they carried a diagnosis of and/or were on treatment for osteoporosis. The prevalence of FFx was trended for each age group. A stratum-specific likelihood ratio (SSLR) analysis was conducted to identify data-driven strata that maximize the incremental FFx risk by age for men. Logistic regression analyses controlling for potential confounders were conducted to test these identified strata. RESULTS: The incidence of FFx started to increase after the age of 64 years for men. Further, the identified data-driven age strata associated with a significant and incremental difference in fragility fractures were the following: 50-64, 65-69, 70-72, 73-75, 76-78, 79-80, and 81+. When compared to the youngest age stratum (50-64 years), multivariable regression showed the risk of fragility fracture incrementally increased starting in those aged 70-72 (RR, 1.31; 95% CI. 1.21-1.46; p < 0.001) with the highest risk in those aged 81+ (RR, 5.35; 95% CI, 5.10-5.62; p < 0.001). CONCLUSION: In men without a pre-existing history of osteoporosis, the risk of fragility fractures starts to increase after the age of 70. Further work building upon these data may help to identify a specific age at which routine bone health screening in males can help to minimize fractures and their associated morbidity and mortality.

[Occupational hazards of crystalline silicon solar cell manufacturing industry].

The wide use of crystalline silicon solar cells in the field of new energy is an important boost for China to achieve the environmental protection goal as soon as possible. However, the production and manufacturing processes of these cells give rise to various occupational hazards at workplace, thus posing health risks to workers. This review provided an overview of production processes of crystalline silicon solar cells, the characteristics of occupational health hazards (productive dust; physical factors, productive toxicant) and proposed occupational protection suggestions.

Comparing nanoparticle polymeric micellar paclitaxel and solvent-based paclitaxel as first-line treatment of advanced non-small-cell lung cancer: an open-label, randomized, multicenter, phase III trial.

BACKGROUND: Polymeric micellar paclitaxel (pm-Pac) is a novel Cremophor EL-free, nanoparticle micellar formulation of paclitaxel. We aimed to compare the efficacy and safety between pm-Pac plus cisplatin and solvent-based paclitaxel (sb-Pac) plus cisplatin in advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 448 stage IIIB to IV NSCLC patients were randomly assigned (2:1) to receive six 3-week cycles of either pm-Pac (230 mg/m2) plus cisplatin (70 mg/m2; n = 300), followed by dose escalation of pm-Pac to 300 mg/m2 from the second 3-week cycle if prespecified toxic effects were not observed after the first cycle, or sb-Pac (175 mg/m2) plus cisplatin (70 mg/m2; n = 148). The primary end point was objective response rate (ORR) assessed by independent review committees (IRCs). The secondary end points included IRC-assessed progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Patients in the pm-Pac-plus-cisplatin group showed significant improvements in IRC-assessed ORR compared with those in the sb-Pac-plus-cisplatin group (50% versus 26%; rate ratio 1.91; P < 0.0001). Additionally, subgroup analysis showed that a higher ORR was consistently observed in both squamous and nonsquamous histological types. IRC-assessed median PFS was significantly higher in the pm-Pac-plus-cisplatin group than in the sb-Pac-plus-cisplatin group (6.4-month versus 5.3-month; hazard ratio 0.63; P = 0.0001). Median OS was not significantly different between the two groups. The incidence of treatment-related serious adverse events (9% versus 18%; P = 0.0090) was significantly lower in the pm-Pac-plus-cisplatin group than in the sb-Pac-plus-cisplatin group. CONCLUSION: Pm-Pac plus cisplatin yielded superior ORR and PFS along with a favorable safety profile and should become an option for patients with advanced NSCLC. CLINICAL TRIAL IDENTIFIER: ClinicalTrials.gov NCT02667743; https://clinicaltrials.gov/ct2/show/NCT02667743.

A NEW SIMPLE, PERSONALIZED, AND QUANTITATIVE EMPIRICAL METHOD FOR DETERMINING 131I ACTIVITY IN TREATING GRAVES' DISEASE.

CONTEXT: The 131I activity for treating Graves' disease (GD) is usually determined based on physician's experience. OBJECTIVE: This study aimed to design an empirical method that was not only personalized and quantitative, but also simple, convenient, and easy to grasp. SUBJECTS AND METHODS: The study population comprised patients with GD, selected between May 2013 and May 2016, who received 131I therapy in the Outpatient Department of Shanghai Ninth People's Hospital. The first-visit patients of physician 1 were placed in the traditional group: the activity of 131I (mCi) was calculated using the routine formula: [empirical activity (0.07-0.12 mCi/g) × thyroid mass]/[24-h thyroid 131I uptake]. The first-visit patients of physician 2 were placed in the personalized group. The activity of 131I (mCi) was calculated in two steps. First, the initial activity was calculated: 0.1 mCi/g × thyroid mass (g), and then a personalized and quantitative calibration table of 131I activity was used to obtain a final 131I activity. The cure rate with a single activity of 131I was recorded 1 year later. RESULTS: The traditional and personalized groups included 241 and 282 patients, respectively. Interestingly, the personalized group achieved a higher cure rate [86.5% (244/282) versus 73.4% (177/241), P = 0.000] with a relatively higher 131I activity for the first treatment [8.7 (7, 3.5-30) mCi versus 6.7(6, 2.5-30) mCi, P = 0.000] compared with the traditional group, while the incidence rate of permanent hypothyroidism was not significantly different between the two groups (P = 0.175). CONCLUSION: The empirical method designed in this study was reliable.

Three novel microRNAs based on microRNA signatures for gastric mucosa-associated lymphoid tissue lymphoma.

This study aimed to identify novel microRNAs (miRNAs) that play crucial regulatory roles in the pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphoma by retrieving and analyzing the miRNA expression profile GSE23877. Differentially expressed miRNAs between gastric MALT lymphoma samples and human tonsil tissue samples as well as their target genes were identified. The transcriptional regulatory relationships between miRNAs and target genes were analyzed, and the regulatory network between them was constructed. Target genes annotated as transcription factors (TFs) were screened, and an miRNA-target gene regulatory network was established. Moreover, the expression levels of miRNAs and target genes as well as the correlation between them were verified. In total, 53 upregulated and 25 downregulated miRNAs were obtained, for which 35 and 25 experimentally validated miRNA-target interactions, respectively, were screened. Some miRNAs were significantly enriched in certain pathways; for example, miR-320a was enriched in systemic lupus erythematosus and ribosome, miR-622 in the p53 signaling pathway and chronic myeloid leukemia, and miR-429 in cancer-related pathways. In addition, upregulated miRNAs, including miR-320a, miR-940, and miR-622, and downregulated miRNAs, including miR-331-3p and miR-429, were hub nodes in the miRNA-target gene regulatory network, and the TF MYC was a co-target of miR-320a, miR-622, and miR-429. The expression trends of miR-320a and miR-429 as well as of some of their target genes were consistent with those in the results of microarray analysis. In conclusion, miR-320a, miR-622, and miR-429 are possibly novel miRNAs participating in the pathomechanism of gastric MALT lymphoma.

Alterations to maternal cortical and trabecular bone in multiparous middle-aged mice.

OBJECTIVES: During the reproductive cycle, altered calcium homeostasis is observed due to variable demand for mineral requirements. This results in increased bone resorption during the time period leading up to parturition and subsequent lactation. During lactation, women will lose 1-3% of bone mineral density per month, which is comparable to the loss experienced on an annual basis post-menopausal. The purpose of this study was to determine the effect of parity on bone formation in middle-aged mice. METHODS: Mice were mated and grouped by number of parity and compared with age matched nulliparous controls. Measurements were taken of femoral trabecular and cortical bone. Calcium, protein and alkaline phosphatase levels were also measured. RESULTS: An increase in trabecular bone mineral density was observed when comparing mice that had undergone parity once to the nulliparous control. An overall decrease in trabecular bone mineral density was observed as parity increased from 1 to 5 pregnancies. No alteration was seen in cortical bone formation. No difference was observed when calcium, protein and alkaline phosphatase levels were assessed. CONCLUSIONS: This study demonstrates that number of parity has an impact on trabecular bone formation in middle-aged mice, with substantial changes in bone density seen among the parous groups.

[Effects of organochloride pesticides on dyslipidemias].

Dyslipidemias is one important risk factor associated with chronic diseases. Persistent organic pollutants are resistant to degradation and can be bio-accumulated and magnified through the food chain. Recently, the relation between dyslipidemias and organochlorine pesticides has attracted more attentions. In this review, we explored the distribution of organochloride pesticides in the environment and human body, as well as the possible underlying mechanisms of the association between dyslipidemias and organochloride pesticides, including accumulation and release of organochloride, simulation of estrogen, impact on PPARs, the metabolic fingerprint, and the inflammatory reaction.

Improving diet recipe and cooking methods attenuates hyperphosphatemia in patients undergoing peritoneal dialysis.

BACKGROUND AND AIMS: Hyperphosphatemia is an independent predictor for cardiovascular and all-cause mortality in patients undergoing peritoneal dialysis (PD). The study aimed to investigate the effect of dietary intervention on reducing serum phosphate concentration in hyperphosphatemic PD patients. METHODS AND RESULTS: In this single-center clinical trial, 97 prevalent PD patients with serum phosphate concentration ≥ 1.6 mmol/l were allocated to the intervention (n = 48) or control (n = 49) group and followed up for 1 year. In addition to phosphate binder (calcium carbonate) therapy, patients in the intervention group were intensively educated to reduce phosphate-rich food intake and improve cooking methods. While stable in the control group (1.97 ± 0.20 to 1.94 ± 0.35 mmol/l, p > 0.05), the serum phosphate concentration decreased significantly in the intervention group (1.98 ± 0.28 to 1.65 ± 0.33 mmol/l, p = 0.015) concurrently with the drop in dietary phosphate intake (13.03 ± 3.39 to 10.82 ± 3.00 mg/kg ideal body weight/day, p = 0.001). Moreover, after 6 months of intervention, fewer patients needed to use calcium carbonate (from 64.6% to 41.5%, p = 0.029) and the medicine dose reduced significantly (from 2.25 (0, 3.94) to 0 (0, 1.50) g/day, p < 0.001). CONCLUSIONS: Our data indicated that intensive dietary intervention of reducing phosphate-rich food intake and improving cooking methods attenuated hyperphosphatemia in PD patients. It suggests that regular assessment of dietary phosphate intake and modification of diet recipe and cooking methods are essential for hyperphosphatemia treatment in PD patients in addition to phosphate binder therapy.

Effects of monobutyl phthalate on steroidogenesis through steroidogenic acute regulatory protein regulated by transcription factors in mouse Leydig tumor cells.

OBJECTIVE: Dibutyl phthalate (DBP) is one of the most widely used phthalate esters, and it is ubiquitous in the environment. DBP and its major metabolite, monobutyl phthalate (MBP), change steroid biosynthesis and impair male reproductive function. However, the regulatory mechanism underlying the steroid biosynthesis disruption by MBP is still unclear. METHODS: We analyzed the progesterone production, steroidogenic acute regulatory protein (StAR) mRNA, protein expression, and DNA-binding affinity of transcription factors (SF-1 and GATA-4). RESULTS: Our results reveal that MBP inhibited progesterone production. At the same time, StAR mRNA and protein were decreased after MBP exposure. Furthermore, electrophoretic mobility shift assay showed that DNA-binding affinity of transcription factors (SF-1 and GATA-4) was decreased in a dose-dependent manner after MBP treatments. Western blot tests next confirmed that protein of SF-1 was decreased, but GATA-4 protein was unchanged. However, phosphorylated GATA-4 protein was decreased with 800 µM of MBP. CONCLUSIONS: This study reveals an important and novel mechanism whereby SF-1 and GATA-4 may regulate StAR during MBP-induced steroidogenesis disruption.

Risk of bladder cancer in renal transplant recipients: a meta-analysis.

BACKGROUND: Renal transplantation has been associated with a significantly increased risk of developing cancers during long-term follow-up, but for bladder cancer, this risk is less clear. We therefore performed a meta-analysis to determine whether bladder cancer risk in renal transplant recipients was increased. METHODS: Eligible studies were identified through searches of PubMed and other public resources. Random-effects meta-analyses were used to pool overall estimates for standardised incidence ratios (SIRs). Heterogeneity test, sensitivity analysis, and assessment of publishing bias were also performed. RESULTS: We identified a 3.18-fold higher SIR (95% confidence intervals (CI): 1.34-7.53, P=0.008) of bladder cancer in patients following renal transplantation compared with the general population, based on data from 79,988 patients with a total follow-up of 308,458 patient-years. When stratified by ethnicity, the SIRs for bladder cancer were 2.00 (95% CI: 1.51-2.65, P=0.001) and 14.74 (95% CI: 3.66-59.35, P<0.001) between European and Asian renal transplant recipients, respectively. CONCLUSIONS: Our study demonstrated that the risk of developing bladder cancer in transplant populations was increased. Such association suggests that physicians should be more vigilant in checking for bladder cancer in transplantation recipient population.

Quantification and genetic diversity of total and microcystin-producing Microcystis during blooming season in Tai and Yang-cheng lakes, China.

AIMS: The aims of present study were to evaluate the abundances, genetic diversity of total and microcystin-producing Microcystis over temporal and spatial scales, and to investigate relationships among Microcystis and water parameters in Tai and Yang-cheng lakes. METHODS AND RESULTS: Abundances of total and microcystin-producing Microcystis varied across sampling periods and locations, which were assessed using qPCR with primers specific to Microcystis 16S rDNA and mcyA genes. The 16S rDNA from two lakes were relatively diverse. However, mcyA genes were rather conservative and were >97% identical to reference sequences. The highly positive correlations between mcyA and microcystin presence (r = 0·671 in Tai; r = 0·799 in Yang-cheng) suggested that mcyA can be used as a good biomarker for microcystin productions. CONCLUSION: The results demonstrated that Microcystis were genetically diverse between these conjunctive lakes; however, mcyA genes were relatively conservative in two lakes. Quantifying mcyA by qPCR was an efficient tool for monitoring toxic Microcystis. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has improved our understanding of observable differences within and between each lake on spatial and temporal scales. And the discovery of new mcyA sequences in natural water enriched the understanding of phylogenetic diversity of Microcystis and toxin-production-related mcy gene.

Transformer-Based Spatio-Temporal Analysis for Classification of Aortic Stenosis Severity From Echocardiography Cine Series.

Aortic stenosis (AS) is characterized by restricted motion and calcification of the aortic valve and is the deadliest valvular cardiac disease. Assessment of AS severity is typically done by expert cardiologists using Doppler measurements of valvular flow from echocardiography. However, this limits the assessment of AS to hospitals staffed with experts to provide comprehensive echocardiography service. As accurate Doppler acquisition requires significant clinical training, in this paper, we present a deep learning framework to determine the feasibility of AS detection and severity classification based only on two-dimensional echocardiographic data. We demonstrate that our proposed spatio-temporal architecture effectively and efficiently combines both anatomical features and motion of the aortic valve for AS severity classification. Our model can process cardiac echo cine series of varying length and can identify, without explicit supervision, the frames that are most informative towards the AS diagnosis. We present an empirical study on how the model learns phases of the heart cycle without any supervision and frame-level annotations. Our architecture outperforms state-of-the-art results on a private and a public dataset, achieving 95.2% and 91.5% in AS detection, and 78.1% and 83.8% in AS severity classification on the private and public datasets, respectively. Notably, due to the lack of a large public video dataset for AS, we made slight adjustments to our architecture for the public dataset. Furthermore, our method addresses common problems in training deep networks with clinical ultrasound data, such as a low signal-to-noise ratio and frequently uninformative frames. Our source code is available at: https://github.com/neda77aa/FTC.git.

Cementless versus cemented unicompartmental knee arthroplasty: a systematic review of comparative studies.

There are still some controversies regarding the clinical use of cementless UKAs. The aim of this systematic review was to determine whether cementless medial UKA leads to similar outcomes compared to cemented medial UKA. This search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews guidelines (PRISMA). The random effects model with 95% confidence interval (CI) was applied to the analysis. The I2 statistic was used to assess study heterogeneity. Six studies were eligible for inclusion (4784 UKAs, 4776 patients): 2947 cemented UKAs (61.6%) and 1837 cementless UKAs (38.4%). The overall mean follow-up was 4.9 years. The all-cause reoperation rate was 11.3% (80 of 706) at mean 5.7-year follow-up for cemented UKA and 6.9% (57 of 824) at mean 4.1-year follow-up for the cementless. The overall revision rate was 10.2% (303 of 2947) for the cemented and 5.8% (108 of 1837) for the cementless. Aseptic loosening was the most frequent reason of revision (2.3% cemented vs 0.5% cementless). The overall rate of radiolucent lines (RLL) was 28.3% (63 of 223) in the cemented cohort and 11.1% in the cementless (26 of 234). All the studies reported improved functional outcomes. Cementless UKA provides at least equivalent if not better results compared to cemented UKA. Despite the use of cemented UKA outnumber cementless fixation, available data shows that cementless UKA had a reduced midterm revision rate, while providing similar functional outcomes.

The effect of guideline-consistent antiemetic therapy on chemotherapy-induced nausea and vomiting (CINV): the Pan European Emesis Registry (PEER).

BACKGROUND: While guidelines for preventing chemotherapy-induced nausea and vomiting (CINV) are widely available, clinical uptake of guidelines remains low. Our objective was to evaluate the effect of guideline-consistent CINV prophylaxis (GCCP) on patient outcomes. PATIENTS AND METHODS: This prospective, observational multicenter study enrolled chemotherapy-naive adults initiating single-day highly or moderately emetogenic chemotherapy (HEC or MEC) for cancer. Patients completed 6-day daily diaries beginning with cycle 1 for up to three chemotherapy cycles. The primary study end point, complete response (no emesis and no use of rescue therapy) during 120 h after cycle 1 chemotherapy, was compared between GCCP and guideline-inconsistent CINV prophylaxis (GICP) cohorts using multivariate logistic regression, adjusting for potential confounding factors. RESULTS: In cycle 1 (N=991), use of GCCP was 55% and 46% during acute and delayed phases, respectively, and 29 % for the overall study period (acute plus delayed phases). Complete response was recorded by 172/287 (59.9%) and 357/704 (50.7%) patients in GCCP and GICP cohorts, respectively (P=0.008). The adjusted odds ratio for complete response was 1.43 (95% confidence interval 1.04-1.97; P=0.027) for patients receiving GCCP versus GICP. CONCLUSION: GCCP reduces the incidence of CINV after single-day HEC and MEC.

Staggered bilateral total knee arthroplasty during a single hospitalization: is it still an option? a systematic review.

BACKGROUND: Bilateral knee osteoarthritis requiring total knee arthroplasty (TKA) can be addressed simultaneously in one surgical setting, staggered a few days apart during a single hospitalization, or staged several weeks to months apart. Several studies have reported on the complications and clinical outcomes of staggered bilateral TKA (BTKA) in a single hospitalization. However, there is no consensus regarding the safety and efficacy of this practice. MATERIALS AND METHODS: We performed a systematic review of the literature, utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and identifying articles that reported the clinical outcomes and postoperative complications following staggered BTKA. RESULTS: Overall, six articles were included for analysis, including 43,892 patients in total. Females (n = 25,931; 59% of all patients) outnumbered males (n = 17,961; 40.1% of all patients), and most patients were middle-aged or elderly (mean age: 68.0 years). The majority of studies (83%) used a 1-week interval as the maximum time for single-hospitalization staggered BTKA. Five studies (83%) reported no difference in mortality rates between staggered, simultaneous, or staged BTKA. Compared to staged BTKA, staggered BTKA conferred an increased rate of blood transfusions. There was no consensus that staggered BTKA led to reduced complications rates, compared to simultaneous or staged BTKA. CONCLUSIONS: Single-hospitalization staggered BTKA does not appear to be safer than the well-established simultaneous or staged procedures. Overall, the data suggest that staggered BTKA will continue to decline in utilization, as staggered BTKA does not appear to yield clinical advantage over simultaneous BTKA in a medically appropriate patient. LEVEL OF EVIDENCE III: systematic review (lowest level of studies included).

Monitoring and evaluation of infectious rotaviruses in various wastewater effluents and receiving waters revealed correlation and seasonal pattern of occurrences.

AIMS: Sewage systems are important nodes to monitor enteric pathogens transmitted via water. The aim of this study was to assess the presence of rotaviruses in effluents from wastewater treatment plants (WWTPs) and receiving streams in Beijing, China, to evaluate the reductions of rotaviruses in WWTPs and to provide viral fate and transport data for further epidemiological studies. METHODS AND RESULTS: Two PCR-based methods, including an RT-qPCR and another quantitative RT-PCR (ICC-RT-qPCR), which was integrated with cell culturing, were applied to conduct a 1-year monitoring of infectious rotaviruses and viral genes in effluents from three WWTPs and the receiving waters in Beijing, China. The ICC-RT-qPCR was able to detect more positive samples than RT-qPCR, showing positive results for 67% of primary effluents, 47% of secondary effluents and 14% of tertiary effluents, in comparison with 44, 22 and 6% by RT-qPCR, respectively. Seasonal variations of rotaviruses were observed in all effluents with higher occurrences in winter than in summer, which correlated well with the seasonal pattern of rotaviruses in the river receiving wastewater effluents. The reduction efficiencies by different treatment processes were assessed. Secondary treatments can remove most of infectious rotaviruses in primary sewage, with annual average reduction values of 2·08 ± 0·63, 2·83 ± 0·49 and 2·00 ± 1·10 log(10) for the three WWTPs, respectively. Tertiary treatments were able to further remove infectious rotaviruses. CONCLUSIONS: The results showed a year-round distribution of rotaviruses in three WWTPs in Beijing and provided important information regarding the transport and susceptibility of rotaviruses to different levels of wastewater treatment processes. SIGNIFICANCE AND IMPACT OF THE STUDY: This study, for the first time, revealed the whole year prevalence and reductions of rotaviruses in WWTPs and the corresponding receiving waters in China, and demonstrated the impact of wastewater discharge on the potential spreading of infectious rotaviruses and public health.

Effect of bacterial growth stage on resistance to chlorine disinfection.

The mechanisms and factors that affect microbial resistance to chlorine disinfection have not been fully elucidated. In this study, we investigated the impact of the cell growth stage on chlorine disinfection efficiency. Specifically, we evaluated the impact of the growth stage on chlorination resistance by comparing the inactivation efficiencies of two indicator bacterial strains (Escherichia coli K12 and Escherichia coli O157:H7) obtained from various growth phases, using Chick-Watson kinetic parameters. For both E. coli strains (K12 and O157:H7), the inactivation rate constants are the lowest at stationary phase (0.19 and 0.32) compared to those at initial lag (0.54 and 0.76) and exponential growth phase (0.63 and 0.69), respectively. These results suggested that the abundance of resistant subpopulations increases at stressed stationary conditions and E. coli cells obtained from the stationary growth phase exhibited more resistance and lower inactivation efficiency compared to those from the lag and exponential phases. This implies that microbes in wastewater treatment process with varying solids retention times (SRTs, which indicate growth rates) may show different extents of chlorine resistance. Comparison of the coefficient of dilution (n) values in both E. coli strains for the various growth phases suggest that cells seem to be more sensitive to disinfectant concentration at the stationary-lag phase than that at the exponential stage. Comparing the two E. coli strains, higher inactivation rates were observed for the pathogenic O157:H7 than for K12 at different stages of growth. The strain-to-strain variability in survivability to chlorine exposure has to be considered when selecting indicator microorganisms for water quality monitoring.