Short-term effects of teriparatide versus placebo on bone biomarkers, structure, and fracture healing in women with lower-extremity stress fractures: A pilot study

Aims In this pilot, placebo-controlled study, we evaluated whether brief administration of teriparatide (TPTD) in premenopausal women with lower-extremity stress fractures would increase markers of bone formation in advance of bone resorption, improve bone structure, and hasten fracture healing according to magnetic resonance imaging (MRI). Methods: Premenopausal women with acute lower-extremity stress fractures were randomized to injection of TPTD 20-µg subcutaneous (s.c.) (n = 6) or placebo s.c. (n = 7) for 8 weeks. Biomarkers for bone formation N-terminal propeptide of type I procollagen (P1NP) and osteocalcin (OC) and resorption collagen type-1 cross-linked C-telopeptide (CTX) and collagen type 1 cross-linked N-telopeptide (NTX) were measured at baseline, 4 and 8 weeks. The area between the percent change of P1NP and CTX over study duration is defined as the anabolic window. To assess structural changes, peripheral quantitative computed topography (pQCT) was measured at baseline, 8 and 12 weeks at the unaffected tibia and distal radius. The MRI of the affected bone assessed stress fracture healing at baseline and 8 weeks. Results: After 8 weeks of treatment, bone biomarkers P1NP and OC increased more in the TPTD- versus placebo-treated group (both p ≤ 0.01), resulting in a marked anabolic window (p ≤ 0.05). Results from pQCT demonstrated that TPTD-treated women showed a larger cortical area and thickness compared to placebo at the weight bearing tibial site, while placebo-treated women had a greater total tibia and cortical density. No changes at the radial sites were observed between groups. According to MRI, 83.3% of the TPTD- and 57.1% of the placebo-treated group had improved or healed stress fractures (p = 0.18). Conclusions: In this randomized, pilot study, brief administration of TPTD showed anabolic effects that TPTD may help hasten fracture healing in premenopausal women with lower-extremity stress fractures. Larger prospective studies are warranted to determine the effects of TPTD treatment on stress fracture healing in premenopausal women

Blood Lead Levels Among Pregnant Women: Historical Versus Contemporaneous Exposures

Blood lead among pregnant women, even at modest levels, may impair offspring cognitive development. We examine whether blood lead levels (BLLs) result from current versus historic exposures, among a cohort of pregnant women. Cumulative logit models were used to characterize the relationship between maternal risk factors and higher BLLs. Maternal blood lead levels more likely result from lead remobilization from historic versus contemporaneous exposures. Even if all lead sources were abated immediately, women and their fetuses would experience lead exposure for decades. This work emphasizes the importance of addressing sources of environmental lead exposure in the United States and internationally

Evaluating stratospheric ozone and water vapour changes in CMIP6 models from 1850 to 2100

Stratospheric ozone and water vapour are key components of the Earth system, and past and future changes to both have important impacts on global and regional climate. Here, we evaluate long-term changes in these species from the pre-industrial period (1850) to the end of the 21st century in Coupled Model Intercomparison Project phase 6 (CMIP6) models under a range of future emissions scenarios. There is good agreement between the CMIP multi-model mean and observations for total column ozone (TCO), although there is substantial variation between the individual CMIP6 models. For the CMIP6 multi-model mean, global mean TCO has increased from ∼300 DU in 1850 to ∼ 305 DU in 1960, before rapidly declining in the 1970s and 1980s following the use and emission of halogenated ozone-depleting substances (ODSs). TCO is projected to return to 1960s values by the middle of the 21st century under the SSP2-4.5, SSP3-7.0, SSP4-3.4, SSP4-6.0, and SSP5-8.5 scenarios, and under the SSP3-7.0 and SSP5-8.5 scenarios TCO values are projected to be ∼ 10 DU higher than the 1960s values by 2100. However, under the SSP1-1.9 and SSP1-1.6 scenarios, TCO is not projected to return to the 1960s values despite reductions in halogenated ODSs due to decreases in tropospheric ozone mixing ratios. This global pattern is similar to regional patterns, except in the tropics where TCO under most scenarios is not projected to return to 1960s values, either through reductions in tropospheric ozone under SSP1-1.9 and SSP1-2.6, or through reductions in lower stratospheric ozone resulting from an acceleration of the Brewer-Dobson circulation under other Shared Socioeconomic Pathways (SSPs). In contrast to TCO, there is poorer agreement between the CMIP6 multi-model mean and observed lower stratospheric water vapour mixing ratios, with the CMIP6 multi-model mean underestimating observed water vapour mixing ratios by ∼ 0.5 ppmv at 70 hPa. CMIP6 multi-model mean stratospheric water vapour mixing ratios in the tropical lower stratosphere have increased by ∼ 0.5 ppmv from the pre-industrial to the present-day period and are projected to increase further by the end of the 21st century. The largest increases (∼ 2 ppmv) are simulated under the future scenarios with the highest assumed forcing pathway (e.g. SSP5-8.5). Tropical lower stratospheric water vapour, and to a lesser extent TCO, shows large variations following explosive volcanic eruptions. © Author(s) 2021

Evaluating stratospheric ozone and water vapour changes in CMIP6 models from 1850 to 2100

Stratospheric ozone and water vapour are key components of the Earth system, and past and future changes to both have important impacts on global and regional climate. Here, we evaluate long-term changes in these species from the pre-industrial period (1850) to the end of the 21st century in Coupled Model Intercomparison Project phase 6 (CMIP6) models under a range of future emissions scenarios. There is good agreement between the CMIP multi-model mean and observations for total column ozone (TCO), although there is substantial variation between the individual CMIP6 models. For the CMIP6 multi-model mean, global mean TCO has increased from ∼300 DU in 1850 to ∼ 305 DU in 1960, before rapidly declining in the 1970s and 1980s following the use and emission of halogenated ozone-depleting substances (ODSs). TCO is projected to return to 1960s values by the middle of the 21st century under the SSP2-4.5, SSP3-7.0, SSP4-3.4, SSP4-6.0, and SSP5-8.5 scenarios, and under the SSP3-7.0 and SSP5-8.5 scenarios TCO values are projected to be ∼ 10 DU higher than the 1960s values by 2100. However, under the SSP1-1.9 and SSP1-1.6 scenarios, TCO is not projected to return to the 1960s values despite reductions in halogenated ODSs due to decreases in tropospheric ozone mixing ratios. This global pattern is similar to regional patterns, except in the tropics where TCO under most scenarios is not projected to return to 1960s values, either through reductions in tropospheric ozone under SSP1-1.9 and SSP1-2.6, or through reductions in lower stratospheric ozone resulting from an acceleration of the Brewer-Dobson circulation under other Shared Socioeconomic Pathways (SSPs). In contrast to TCO, there is poorer agreement between the CMIP6 multi-model mean and observed lower stratospheric water vapour mixing ratios, with the CMIP6 multi-model mean underestimating observed water vapour mixing ratios by ∼ 0.5 ppmv at 70 hPa. CMIP6 multi-model mean stratospheric water vapour mixing ratios in the tropical lower stratosphere have increased by ∼ 0.5 ppmv from the pre-industrial to the present-day period and are projected to increase further by the end of the 21st century. The largest increases (∼ 2 ppmv) are simulated under the future scenarios with the highest assumed forcing pathway (e.g. SSP5-8.5). Tropical lower stratospheric water vapour, and to a lesser extent TCO, shows large variations following explosive volcanic eruptions

Design and Synthesis VEGFR-2 Kinase Inhibitors

The goal of this project was to synthesize VEGFR-2 Kinase inhibitors to control cancer metastasis. Twelve different VEGFR inhibitors were synthesized and analyzed with molecular docking. The future steps for this project include biological testing

Chronic Disorders of the Peroneal Tendons: Current Concepts Review of the Literature

Chronic disorders of the peroneal tendons are a common cause of posterolateral ankle pain, including tendinopathy, tendon instability, and chronic tendon tears. They are often preceded by ligamentous instability or predisposing anatomic abnormalities such as a shallow fibular groove or a cavovarus foot deformity. Given the substantial disability associated with chronic peroneal tendon disorders, it is important for orthopaedic surgeons to optimize the diagnostic and treatment strategies of these entities based on contemporary studies. This article reviews both classic and recent scientific evidence regarding the diagnosis and treatment of patients with chronic peroneal tendon disorders

Open Ankle Arthrodesis With a Fibular-Sparing Technique

Background: Many ankle arthrodesis techniques excise the fibula or require a fibular osteotomy. Advantages of fibular preservation include increased surface area for bony union, preservation of the peroneal groove, prevention of valgus drift in cases of delayed union, and facilitation of future ankle arthroplasty. The goal of this study was to evaluate fusion rate and clinical outcomes of a novel open fibular-sparing ankle arthrodesis technique. Methods: A total of 50 consecutive ankle arthrodeses using this technique were included in this study. These consisted of 46 patients with an average age of 52 (range, 30 to 71) years. Outcomes assessed postoperatively included radiographs, complications, patient satisfaction, and functional scoring. Results: At an average of 28 (range, 19 to 56) months postoperatively, 38 patients (42 ankles) were available for review. Of the 42 cases, 39 (93%) achieved union at an average of 12 weeks postoperatively. Of patients, 86% reported being “completely satisfied” with the outcome. Average AOFAS Ankle-Hindfoot Scale was 84 ± 12 and average Foot Function Index pain subscale was 1 ± 0.9. Two ankles (5%) were fused in excessive varus; no patient required revision surgery for malalignment. Conclusion: This method of open ankle arthrodesis preserved the fibula and had a high fusion rate with good patient outcome scores. Level of Evidence: Level IV, retrospective case series. </jats:sec