Notes

Suggesting medical weed.
We read with interest the article by Matza et al on ustekinumab in giant cell arteritis (GCA) recently published in Arthritis Care and Research (1). The rationale for using ustekinumab in GCA is that it targets the Th1 and Th17 pathways felt to be centrally involved in GCA pathogenesis, potentially impacting at a more proximal stage than other agents such as tocilizumab (4). It is encouraging to see efforts to explore alternative treatment options for GCA, however we believe a number of aspects of this study require further consideration in order to inform the potential role of ustekinumab in GCA.
Hematopoietic stem cell transplantation (HSCT) and cyclophosphamide (CYC) are treatment options for progressive interstitial lung disease associated with systemic sclerosis (SSc-ILD). The aims of our retrospective observational study were to evaluate 1) the evolution of SSc-ILD assessed by high-resolution computed tomography (HRCT) in SSc patients treated with HSCT. A group of patients treated with CYC was included as frame of reference; 2) how pulmonary function tests (PFTs) associate with HRCT findings; 3) which factors predict ILD reduction.

We semi-quantitatively scored total ILD extent, reticulations and ground glass opacities (GGO) on baseline and 1-year HRCTs of SSc patients treated with HSCT or CYC. Linear association between HRCT and PFT changes, and predictors of ILD improvement, were studied.

We included 51 patients (HSCT n=20; CYC n=31). Mean change in total ILD score was -5.1% (95%CI -10.2 to 0.0) in HSCT (p=0.050), and -1.0% (95%CI -4.3 to 2.3) in CYC group (p=0.535). For all patients, evolution of HRCT scores was weakly associated with relative changes in PFTs. In univariate logistic regression, higher GGO and total ILD scores, and lower diffusing capacity of the lungs for carbon monoxide at baseline (DLCO), predicted improvement of ILD extent after treatment, but a multivariable model could not be built to assess independency of predictors.

One year after treatment with HSCT, a non-significant, but clear, reduction of SSc-ILD extent was observed. Changes in PFTs were associated with changes in HRCT scores but the correlation was weak and cannot be considered conclusive.
One year after treatment with HSCT, a non-significant, but clear, reduction of SSc-ILD extent was observed. Changes in PFTs were associated with changes in HRCT scores but the correlation was weak and cannot be considered conclusive.
The prognosis of postoperative recurrence in patients with non-small cell lung cancer (NSCLC) is poor. However, depending on the recurrence patterns and treatment options, some patients can achieve long-term survival following recurrence. In this study, we investigated the clinicopathological characteristics of NSCLC patients with curable disease who developed postoperative recurrence.

This retrospective study enrolled 535 patients who had developed recurrence from among 1760 consecutive patients with NSCLC who underwent curative resection from 1990 to 2008. Post-recurrence cure was defined as being cancer-free for at least five years after treatment for recurrence in patients who had undergone radical local treatment or chemotherapy. The clinicopathological characteristics associated with post-recurrence cure were analyzed.

Among 535 patients who developed recurrence, 24 (4.5%) achieved post-recurrence cure. The median post-recurrence follow-up duration was 151 (85-275) months for those who achieved po a second recurrence. All patients with post-recurrence cure received only radical local treatment for recurrence and had significantly higher number of solitary recurrent lesions. What this study adds Some patients with solitary recurrent NSCLC lesions after resection can be cured with only radical local treatment.We appreciate the opportunity to respond to the letter by Conway and Molloy regarding our recent manuscript entitled "Ustekinumab for the treatment of giant cell arteritis" [1]. Our results demonstrated that ustekinumab (UST) administered every 8 weeks was well tolerated but did not prevent disease relapse in a significant proportion of giant cell arteritis (GCA) patients when used in combination with 6 months of prednisone. We acknowledge that a small sample size and the lack of a control group are important limitations of our study and agree with Conway and Molloy that further research is needed to assess the utility of UST more definitively in GCA.Macimorelin is an orally active growth hormone secretagogue indicated for the diagnosis of adult growth hormone deficiency. The primary objective of this study was to evaluate the effect of macimorelin on the baseline and placebo-corrected mean QT interval using Fridericia's formula (ΔΔQTcF). Secondary objectives were to determine QTcF for moxifloxacin; evaluate the effects of macimorelin on other cardiac intervals (PR, QRS, RR), heart rate, and electrocardiogram morphology parameters; characterize pharmacokinetics; and assess safety of macimorelin. The phase 1 thorough QT/QTc study, designed according to the International Council for Harmonisation E14 guideline, was a randomized, placebo-controlled, double-blind, 3-way complete crossover study comparing the effect of macimorelin 2.0 mg/kg with placebo and moxifloxacin 400 mg (positive control). Data were collected over a 3-month span from male (n=36) and female participants (n=24) aged 18 to 55 years with body mass index between 18.5 and 30.0 kg/m2 . Fifty-six participants received all 3 treatments. The ΔΔQTcF for macimorelin showed a prolongation with a maximum mean value of 9.61 milliseconds (2-sided 90% confidence interval, 7.81 milliseconds and 11.41 milliseconds) at 4 hours after dosing. The 2-sided 90% confidence interval of this value also exceeded the 10 millisecond threshold at 3 hours after dosing. Assay sensitivity was confirmed with moxifloxacin. Other electrocardiogram parameters evaluated were not influenced by macimorelin. Macimorelin did not raise other safety concerns and was well tolerated. In summary, a single supratherapeutic dose of macimorelin prolonged cardiac repolarization according to the regulatory guideline.Both natural conditions and anthropogenic factors affect the survivability, distribution, and population density of wildlife. To understand the extent and how these factors drive species distributions, a detailed description of animal movement patterns in natural habitats is needed. In this study, we used satellite telemetry to monitor elevational ranges favored by endangered golden snub-nosed monkeys (Rhinopithecus roxellana), in the Qinling Mountains, central China. We investigated the abundance and distribution of food resources through sampling vegetation quadrats at different elevations and sampled anthropogenic activities using field surveys. Our results indicated that although there was no significant variation in food resources between low- ( less then 1500 m) and middle-elevations (1500-2200 m), monkeys were found most often in areas above 1500 m, where there was less anthropogenic development (e.g. houses and roads); however, monkeys rarely ranged above 2200 m and had limited food availability at this altitude. There was limited human disturbance at this elevation. We suggest that both human activity and ecological constraints (i.e. food resources) have considerable effects on elevational use of R. roxellana in the Qinling Mountains. This study highlights the critical roles these factors can play in shaping the vertical distribution of high-altitude primates. This research provides useful insights for habitat-based conservation plans in which human disturbance management and habitat restoration should be prioritized.
microRNAs (miRNAs) have been verified as molecular targets for regulating tumor proliferation, invasion, and metastasis in tumor progression. However, the relationship between miRNAs and cellular energy metabolism in breast cancer still needs to be clarified. This study aimed to investigate the role of miR-429 in breast cancer progression.

Bioinformatic analyses were employed to detect the relationship between miR-429 and cancer-related signaling pathways. We used a Kaplan-Meier curve to analyze survival rate in patients with high or low expression of miR-429. We used real-time quantitative PCR (RT-qPCR) to detect the expression of miR-429 in different cell lines. Sh-con, over-miR-429, miR-429 inhibitor, and sh-inhibitor control were transfected. Colony formation and EDU assay were used to detect the proliferation of transfected cells. Wound healing and transwell assays were performed to detect the mobility and invasion ability of transfected cells. Western blot assay was used to detect relative protein expression in transfected cells and different tissues. Bioinformatic analyses were conducted to detect the target proteins expression in different breast cancer databases. Dual luciferase reporter assay was used to confirm the binding site between miR-429 and fibronectin 1 (FN1).

The results of our study indicate that MiR-429 and its target genes are associated with cancer-related signaling pathways and that higher miR-429 expression corresponds with a better prognosis. When miR-429 was overexpressed, the proliferation, invasion of MDA-MB-231 were inhibited. MiR-429 was able to suppress the Wnt/β-catenin signaling pathway, and FN1 overexpression could rescue the influence of over-miR-429.

The results of our study suggest that miR-429 suppresses the proliferation and invasion of breast cancer via inhibiting the Wnt/β-catenin signaling pathway.
The results of our study suggest that miR-429 suppresses the proliferation and invasion of breast cancer via inhibiting the Wnt/β-catenin signaling pathway.
To compare the superficial punctate fluorescein staining in dogs with and without aqueous tear deficiency.

An eye from each client-owned dogs presented to Triangle Animal Eye Clinic between January and December 2018 underwent tear and ocular surface tests, which included the Schirmer tear test (STT), phenol red thread test (PRT), and strip meniscometry tube tear test (SMT). Punctate fluorescein staining of the cornea (PFS-C) and the upper palpebral conjunctiva (PFS-UPC) were also performed. Fifty-seven dogs with STT results of <15mm/min had aqueous tear deficiency (AD); 31 dogs had <10mm/min and 26 dogs had ≥10mm/min. The 162 dogs with STT results of ≥15mm/min did not have AD. The test results of the groups were compared using Kruskal-Wallis and Steel-Dwass multiple comparison tests.

Two hundred and nineteen eyes from 219 dogs were enrolled in this study. The PRT and SMT results, presented as mean±SD, were significantly lower in the AD group than in the non-AD group (PRT 29.5±8.1 vs 36.9±5.6mm/15s; SMT 6.2±3.8 vs 10.8±2.8mm/5s). The PFS scores were significantly higher in the AD group than in the non-AD group (PFS-C 4.4±0.7 and 3.7±0.8; PFS-UPC 2.3±0.5 and 1.7±0.5).

These results suggest that aqueous tear deficiency is not only reflected by PRT and SMT but also PFS-C and PFS-UPC.
These results suggest that aqueous tear deficiency is not only reflected by PRT and SMT but also PFS-C and PFS-UPC.
Studies suggest an association between elevated total serum cholesterol (TC), particularly low-density lipoprotein (LDL), and osteoarthritis (OA). We evaluated the association between total cholesterol, LDL, and high-density lipoprotein (HDL) and risk of knee OA.

We studied participants from the Multicenter Osteoarthritis study (MOST) cohort at risk of developing knee OA. From baseline through 7 years, repeated knee x-rays and MRIs were obtained and knee symptoms were queried. From baseline fasting blood samples, lipids and lipoproteins were analyzed using standard assays. After excluding participants with baseline OA, we defined two sets of cases those developing radiographic OA and those developing symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of cartilage loss and synovitis on MRI and of knee pain using the WOMAC scale. We carried out logistic regression adjusting for age, sex, BMI, education, baseline pain, and depressive symptoms, testing total cholesterol and lipoproteins as continuous measures and did sensitivity analyses examining whether commonly used thresholds for high cholesterol, LDL or low HDL increased risk.
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