Use of Sensitivity Analyses to Assess Uncontrolled Confounding from Unmeasured Variables in Observational, Active Comparator Pharmacoepidemiologic Studies: A Systematic Review.

Understanding the potential for, direction, and magnitude of uncontrolled confounding is critical for generating informative real-world evidence. Many sensitivity analyses are available to assess robustness of study results to residual confounding, but it is unclear how researchers are using these methods. We conducted a systematic review of published active comparator cohort studies of drugs or biologics to summarize use of sensitivity analyses aimed at assessing uncontrolled confounding from an unmeasured variable. We reviewed articles in five medical and seven epidemiologic journals published between January 1, 2017, and June 30, 2022. We identified 158 active comparator cohort studies, 76 from medical and 82 from epidemiologic journals. Residual, unmeasured, or uncontrolled confounding was noted as a potential concern in 93% of studies, but only 84 (53%) implemented one or more sensitivity analysis to assess uncontrolled confounding from an unmeasured variable. The most common analyses were E-values among medical journal articles (21%) and restriction on measured variables among epidemiologic journal articles (22%). Researchers must rigorously consider the role of residual confounding in their analyses and the best sensitivity analyses for assessing this potential bias.

Seasonal variation and human health risk assessment of potentially toxic elements in pharmaceutical effluents around Ilorin metropolis, Nigeria.

Potentially toxic elements (PTEs) are widely released into the environment as a result of increased urban and industrial development in recent years. The bulk of PTEs are cancer-causing and harm human health by producing free radicals. As a result, it is crucial to monitor, evaluate, and limit the effects of the elements on human health. In this study, levels of PTEs (As, Cr, Cd, Ni, Co, and Pb) in pharmaceutical effluents discharged along the Asa River around the Ilorin metropolis and their seasonal variations were evaluated. Water samples were collected from eight different locations over a two-season period along the river and analyzed for PTEs using atomic absorption spectrophotometry and an inductively coupled plasma optical emission spectrometer. As, Cd, Pb, Cr, Ni, and Co had mean PTE values in the effluents (both seasons) of 0.0258, 0.0233, 0.00193, 0.0176, and 0.0164 mg/L, respectively, with As and Pb surpassing the WHO standard. Maximum temperature and pH were measured for the physicochemical parameters in the wet season, whereas electrical conductivity and total dissolved solids were seen in the dry season. The average values of the metals in the human risk assessment for carcinogenicity were As > Cd > Pb > Cr > Ni > Co, with As above the recommended threshold in several locations. However, all of the metal hazard indices were < 1, indicating that the waters were suitable for domestic purposes. Nonetheless, the relevant authorities should mandate that pharmaceutical effluents be treated before being released into bodies of water.

Electrocardiographic findings in Nigerian athletes with the sickle cell trait.

BACKGROUND: In spite of the high prevalence of the sickle cell trait (SCT) in Nigeria, the electrocardiographic characteristics of SCT athletes remain unknown. OBJECTIVE: To compare the electrocardiographic findings in athletes of the University of Port Harcourt based on hemoglobin genotype. METHODS: 76 athletes (41 males, 35 females) were recruited. All had normal ECGs and echocardiograms. The prevalence of SCT was 31.6%. RESULTS: Mean heart rate was lower among the SCT athletes (57.3 [8.6] vs 64.6 [10.4] beats/min; p = .002; Hedges' g = 0.74). Mean T-wave axis was also higher among SCT athletes (39.1 [12.8] vs 32.3 [12.9] degrees; p = .036 Hedges' g = 0.53). CONCLUSION: SCT is associated with significant electrocardiographic changes in Nigerian athletes. The biological basis and clinical significance of these changes are presently uncertain.

Effect of Low-Dose Nano Titanium Dioxide Intervention on Cd Uptake and Stress Enzymes Activity in Cd-Stressed Cowpea [Vigna unguiculata (L.) Walp] Plants.

Cadmium contamination of agricultural soils is a serious problem due to its toxic effects on health and yield of crop plants. This study investigates the potential of low-dose nano-TiO2 as soil nanoremediation on Cd toxicity in cowpea plants. To achieve this goal, cowpea seeds were germinated on Cd-spiked soils at 10 mg/kg for 14 days and later augmented with 100 mg nTiO2/kg (nTiO2-50 nm and bTiO2-68 nm, respectively). The results showed that chlorophylls were not altered by nano-TiO2 intervention. Cadmium partitioning in roots and leaves was reduced by the applied nano-TiO2 but significantly higher than control. Ascorbate peroxidase and catalase activities in roots and leaves were promoted by nano-TiO2 intervention compared to control and sole Cd, respectively. However, magnitudes of activity of enzyme activities were higher in nTiO2 compared to bTiO2 treatments. The enhanced enzymes activity led to reduced malonaldehyde content in plant tissues. The study concludes that soil application of nano-TiO2 could be a green alternative to ameliorate soil Cd toxicity in cowpea plants.

Vasodilatory effect of kaempferol-7-O-α-L-rhamnopyranoside via NO-cGMP-PKG signaling.

Hypertension is one of the major causes of mortality. Though a host of drugs are available for the treatment of hypertension, majority have been linked to adverse side effects, necessitating the need for research into natural compounds with fewer side effects. Kaempferol-7-O-α-L-rhamnopyroside (KR) is a glycosylated flavone with neuroprotective and anti-inflammatory effects. However, no available literature exists on its vasodilatory effect. This study examined the pharmacological effect of KR on vasodilation/vasorelaxation and its mechanism of action in endothelial cells and rat thoracic aorta. Treatment of phenylephrine (PE; 2 × 10-6 M)-pre-contracted aortic rings with KR induced endothelium-dependent relaxation, which was suppressed by NG-nitro-l-arginine methyl ester (L-NAME; 10-4 M), (nitric oxide synthase (NOS) inhibitor). Phosphorylation of eNOS in human umbilical vein endothelial cells (HUVECs) was increased after exposure to KR. Pre-treatment of aortic rings with the cyclic GMP (cGMP) inhibitors; methylene blue (MB; 10-5 M) and 1-H-[1,2,4]-oxadiazolole-[4,3-α]-quinoxalin-10-one, (ODQ; 10-6 M) suppressed the KR-induced vasodilation. Furthermore, KR also increased protein kinase G (PKG) levels whereas it suppressed levels of phosphorylated myosin light chain (MLC) and protein kinase C (PKC) in aortic rings. These results suggest that KR induces endothelium-dependent vasorelaxation via the NO-cGMP-PKG pathway.

BEATVIC, a body-oriented resilience therapy using kickboxing exercises for people with a psychotic disorder: a feasibility study.

BACKGROUND: People with a psychotic disorder have an increased risk of becoming the victim of a crime. To prevent victimization a body-oriented resilience therapy using kickboxing exercises was developed. This study aims to explore the feasibility of the therapy, to improve the therapy protocol and to explore suitable outcomes for a RCT. METHODS: Twenty-four adults with a psychotic disorder received 20 weekly group sessions in which potential risk factors for victimization and strategies for dealing with them were addressed. Sessions were evaluated weekly. During pre and post assessment participants completed questionnaires on, among other, victimization, aggression regulation and social functioning. RESULTS: The short recruitment period indicates the interest in such an intervention and the willingness of clients to participate. Mean attendance was 85.3 and 88% of the participants completed fifteen or more sessions. The therapy protocol was assessed as adequate and exercises as relevant with some small improvements to be made. The victimization and aggression regulation questionnaires were found to be suitable outcome measurements for a subsequent RCT. CONCLUSION: The results support the feasibility of the BEATVIC therapy. Participants subjectively evaluated the intervention as helpful in their attempt to gain more self-esteem and assertiveness. With some minor changes in the protocol the effects of BEATVIC can be tested in a RCT. TRIAL REGISTRATION: The trial registration number (TRN) is 35949 (date submitted 09/11/2018). Retrospectively registered.

Effects of manufactured nano-copper on copper uptake, bioaccumulation and enzyme activities in cowpea grown on soil substrate.

Increased use of nanoparticles-based products in agriculture portends important implications for agriculture. Therefore, the impact of nano-copper particles (<25 nm and 60-80 nm) on Cu uptake, bioaccumulation (roots, leaves and seeds), activity of ascorbate peroxidase (APX), catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), and lipid peroxidation in leaves and roots of Vigna unguiculata (cowpea) was studied. Plants were exposed to four levels (0, 125, 500 and 1000 mg/kg) of 25 nm or 60-80 nm nano-Cu for 65 days. Results indicated significant (P<.05) uptake of Cu at all nano-Cu levels compared to control, and bioaccumulation increased in seeds by at least 250%. Response of antioxidant enzymes to both nano-Cu types was concentration-dependent. Activity of APX and GR was enhanced in leaves and roots in response to both nano-Cu treatments in similar patterns compared to control. Both nano-Cu increased CAT activity in roots while SOD activity reduced in both leaves and roots. This shows that response of antioxidant enzymes to nano-Cu toxicity was organ-specific in cowpea. Malondialdehyde, a measure of lipid peroxidation, increased at 500 -1000 mg/kg of 25 nm nano-Cu in leaves by average of 8.4%, and 60-80 nm nano-Cu in root by 52.8%, showing particle-size and organ-dependent toxicity of nano-Cu. In conclusion, exposure of cowpea to nano-Cu treatments increased both the uptake and bioaccumulation of Cu, and also promoted the activity of APX and GR in root and leaf tissues of cowpea. Therefore, APX- and GR-activity level could be a useful predictive biomarker of nano-Cu toxicity in cowpea.

Citrus Epicarp-Derived Biochar Reduced Cd Uptake and Ameliorates Oxidative Stress in Young Abelmoschus esculentus (L.) Moench (okra) Under Low Cd Stress.

Due to the important role of biochar (BC) in reducing metal-toxicity in plants, this study was aimed at assessing the potential of citrus epicarp-derived BC in ameliorating Cd toxicity in young Abelmoschus esculentus (okra) under low Cd toxicity. Okra was grown in soil amended with BC at four treatment levels for 49 days as follows: control (A), sole 1.4 mg Cd/kg-spiked soil (B), 1.4 mg Cd/kg-spiked soil + 1% BC (C) and 1.4 mg Cd/kg-spiked soil + 3% BC (D). The results showed a dose-dependent reduction in shoot accumulation of Cd due to the BC application. In addition, compared to control and sole Cd-amended soil, BC treatments (both at 1% and 3% w/w) decreased the oxidative stress, and enhanced activities of enzymatic and non-enzymatic antioxidants in the young okra. Generally, the application of BC to the soil was effective in ameliorating the Cd-induced oxidative stress in okra with limited shoot bioaccumulation of Cd.

Potential of Three Ethnomedicinal Plants as Antisickling Agents.

Sickle cell disease (SCD) is a genetic blood disorder that affects the shape and transportation of red blood cells (RBCs) in blood vessels, leading to various clinical complications. Many drugs that are available for treating the disease are insufficiently effective, toxic, or too expensive. Therefore, there is a pressing need for safe, effective, and inexpensive therapeutic agents from indigenous plants used in ethnomedicines. The potential of aqueous extracts of Cajanus cajan leaf and seed, Zanthoxylum zanthoxyloides leaf, and Carica papaya leaf in sickle cell disease management was investigated in vitro using freshly prepared 2% sodium metabisulfite for sickling induction. The results indicated that the percentage of sickled cells, which was initially 91.6% in the control, was reduced to 29.3%, 41.7%, 32.8%, 38.2%, 47.6%, in the presence of hydroxyurea, C. cajan seed, C. cajan leaf, Z. zanthoxyloides leaf, and C. papaya leaf extracts, respectively, where the rate of polymerization inhibition was 6.5, 5.9, 8.0, 6.6, and 6.0 (×10-2) accordingly. It was also found that the RBC resistance to hemolysis was increased in the presence of the tested agents as indicated by the reduction of the percentage of hemolyzed cells from 100% to 0%. The phytochemical screening results indicated the presence of important phytochemicals including tannins, saponins, alkaloids, flavonoids, and glycosides in all the plant extracts. Finally, gas chromatography-mass spectrometry analysis showed the presence of important secondary metabolites in the plants. These results suggest that the plant extracts have some potential to be used as alternative antisickling therapy to hydroxyurea in SCD management.

Identification of Sesbania sesban (L.) Merr. as an Efficient and Well Adapted Phytoremediation Tool for Cd Polluted Soils.

A pot experiment was carried out to assess Cd uptake and accumulation efficiency of Sesbania sesban. Plants were grown in soil spiked with 25, 50, 100, 150, 200, 250, and 300 mg/kg Cd. After 120 days, plants were harvested and analyzed for Cd content. A steady increase in Cd accumulation with increasing metal concentration in soil was observed for all treatments. Accumulation of Cd was greatest in roots (86.7 ± 6.3 mg/kg), followed by stem (18.59 ± 1.9 mg/kg), and leaf (3.16 ± 1.1 mg/kg). Chlorophyll content declined with increasing Cd concentration, while proline and protein content increased as compared to control. At higher Cd levels, root, shoot length, and biomass were all significantly reduced (p ≤ 0.001). An increase in total protein along with greater A250/A280 value suggested an increase in metal-protein complexes. Considering the rapid growth, high biomass, accumulation efficiency, and adaptive properties, this plant could be used as a valuable tool for the phytoremediation of Cd contaminated soils.

Recent Advances in the Pharmacological Management of Atrial Fibrillation.

Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia that leads to hospitalizations for complications and adverse events each year. Despite significant improvement in our therapeutic approaches in the past decade, management of AF remains a difficult task. Novel therapies have failed to terminate AF and prevent its recurrence, and patients with AF continue to have thromboembolic complications. With the increasingly aging population and associated conditions, the prevalence of AF is expected to progressively increase, becoming a public health problem. Most patients with AF have multiple comorbidities and are of advanced age, making long-term anticoagulation challenging. This article provides an overview of the current pharmacological therapies for the management of AF, with particular emphasis on the emerging agents.

Placental elastography in a murine intrauterine growth restriction model.

OBJECTIVE: To compare placental elasticity in normal versus intrauterine growth restriction (IUGR) murine pregnancies using shear wave elastography (SWE). METHODS: Intrauterine growth restriction was created by ligation of the left uterine artery of Sprague-Dawley rats on E17. Ultrasonography (US) and elastography were performed 2 days later on exteriorized horns after laparotomy. Biparietal diameter (BPD) and abdominal diameter (AD) were measured and compared in each horn. Placental elasticity of each placenta was compared in the right and left horns, respectively, using the Young's modulus, which increases with increasing stiffness of the tissue. RESULTS: Two hundred seventeen feto-placental units from 18 rats were included. Fetuses in the left ligated horn had smaller biometric measurements than those in the right horn (6.7 vs 7.2 mm, p < 0.001, and 9.2 vs 11.2 mm, p < 0.001 for BPD and AD, respectively). Mean fetal weight was lower in the pups from the left than the right horn (1.65 vs 2.11 g; p < 0.001). Mean (SD) Young's modulus was higher for placentas from the left than the right horn (11.7 ± 1.5 kPa vs 8.01 ± 3.8 kPa, respectively; p < 0.001), indicating increased stiffness in placentas from the left than the right horn. There was an inverse relationship between fetal weight and placental elasticity (r = 0.42; p < 0.001). CONCLUSION: Shear wave elastography may be used to provide quantitative elasticity measurements of the placenta. In our model, placentas from IUGR fetuses demonstrated greater stiffness, which correlated with the degree of fetal growth restriction.

Antisickling and toxicological evaluation of the leaves of Scoparia dulcis Linn (Scrophulariaceae).

BACKGROUND: Scoparia dulcis Linn (Scrophulariaceae) together with other medicinal plants serve as antisickling remedies in Africa. This study was aimed at investigating the antisickling activity of the leaves of the plant as well as establishing the toxicological profile. METHOD: Chemical tests were employed in phytochemical investigations. Evaluation of the antisickling activity involved the inhibition of sodium metabisulphite-induced sickling of the HbSS red blood cells obtained from confirmed sickle cell patients who were not in crises. Concentrations of the crude extract and its fractions were tested with normal saline and p-hydroxybenzoic acid serving as controls. Acute toxicological evaluation was carried out in mice while 30-day assessment was done in rats. RESULTS: Phytochemical screening revealed the presence of alkaloids, tannins, flavonoids and saponins. Percentage sickling inhibitions of the aqueous methanol extracts of S. dulcis were significant all through the period of assay p < 0. 05 compared to normal saline, but not significant with PHBA. The fractions had less activity compared to the crude extracts. The LD 50 of the extract in mice was above 8000 mg/kg body weight when administered orally. Toxicological evaluations at 250 and 500 mg/kg showed mild congestion in virtually all the target organs. CONCLUSION: The antisickling results confirmed traditional usage of Scoparia dulcis in the management of Sickle cell disorders and a candidate for further investigations.

Real time shear waves elastography monitoring of thermal ablation: in vivo evaluation in pig livers.

BACKGROUND: Thermal ablation is a widely used minimally invasive treatment modality for different cancers. However, lack of a real-time imaging system for accurate evaluation of the procedure is one of the reasons of local recurrences. Shear waves elastography (SWE) is a new ultrasound (US) imaging modality to quantify tissue stiffness. The aim of the study was to assess the feasibility and accuracy of US elastography for quantitative monitoring of thermal ablation and to determine the elasticity threshold predictive of coagulation necrosis. METHODS: A total of 29 in vivo thermal lesions were performed in pig livers with radiofrequency system. SWE and B-mode images were acquired simultaneously. Liver elasticity was quantified by using SWE data and expressed in kilopascal. After the procedure, pathologic analysis of treated tissues was compared with US images. The sensitivity and positive predictive value of the SWE maps of tissue elasticity were calculated and compared with the boundaries of the pale coagulation necrosis areas found at pathology. RESULTS: The liver mean elasticity values before and after thermal therapy were 6.4 ± 0.3 and 38.1 ± 2.5 kPa, respectively (P < 0.0001). For a threshold of 20 kPa, sensitivity (i.e., the rate of pixels correctly detected as necrosed tissue) was 0.8, and the positive predictive value (i.e., the rate of pixels in the elastographic map >20 kPa that actually developed coagulation necrosis) was 0.83. CONCLUSIONS: Tissue areas with coagulation necrosis are significantly stiffer than the surrounding tissue. SWE permits the real-time detection of coagulation necrosis produced by radiofrequency and could potentially be used to monitor US-guided thermal ablation.

Characterization, antibacterial, antioxidant, and cytotoxic activities of ZnO nanoparticles using Coptidis Rhizoma.

Here, we report a simple, eco-friendly and inexpensive approach for the synthesis of zinc oxide nanoparticles (ZnO NPs) using Coptidis Rhizoma. The ZnO NPs were characterized by UV-visible absorption spectroscopy, FTIR, SEM-EDX, TGA, TEM, SAED and XRD. TEM images confirmed the presence of spherical and rod shaped ZnO NPs in the range of 2.90-25.20 nm. Green synthesized ZnO NPS exhibited moderate antibacterial activity against Gram-positive and Gram-negative bacteria and excellent DPPH free radical scavenging activity. Synthesized ZnO NPs had no toxic effects on the RAW 264.7 cell line.

Animal models of REM dysfunctions: what they tell us about the cause of narcolepsy and RBD?

Rapid eye movement sleep behavior disorder (RBD) is a parasomnia characterized by the loss of muscle atonia during paradoxical (REM) sleep (PS). Conversely, cataplexy, one of the key symptoms of narcolepsy, is a striking sudden episode of muscle weakness triggered by emotions during wakefulness, and comparable to REM sleep atonia. The neuronal dysfunctions responsible for RBD and cataplexy are not known. In the present review, we present the most recent results on the neuronal network responsible for PS. Based on these results, we propose an updated integrated model of the mechanisms responsible for PS and explore different hypotheses explaining RBD and cataplexy. We propose that RBD is due to a specific degeneration of a subpopulation of PS-on glutamatergic neurons specifically responsible of muscle atonia, localized in the caudal pontine sublaterodorsal tegmental nucleus (SLD). Another possibility is the occurrence in RBD patients of a specific lesion of the glycinergic/GABAergic premotor-neurons localized in the medullary ventral gigantocellular reticular nucleus. Conversely, cataplexy in narcoleptics would be due to the activation during waking of the caudal PS-on SLD neurons responsible for muscle atonia. A direct or indirect pathway activated during positive emotion from the central amygdala to the SLD PS-on neurons would induce such activation. In normal conditions, the activation of SLD neurons would be blocked by the simultaneous excitation by the hypocretins of the PS-off GABAergic neurons localized in the ventrolateral periaqueductal gray and the adjacent deep mesencephalic reticular nucleus gating the activation of the PS-on SLD neurons.

Human and ecological risk assessments of potentially toxic elements in sediments around a pharmaceutical industry.

Potentially toxic elements (PTEs) in sediment can be highly hazardous to the environment and public health. This study aimed to assess the human and ecological risks of PTEs in sediments around a pharmaceutical industry in Ilorin, Nigeria. Physicochemical parameters and the concentrations of lead (Pb), chromium (Cr), cadmium (Cd), cobalt (Co), arsenic (As), and nickel (Ni) were analyzed in sediment samples collected from seven locations in the wet and dry seasons. Standard two-dimensional principal component analysis (PCA) and risk assessments were also conducted. The concentrations of Pb, Co, Ni, Cr, Cd, and As in the sediments ranged from 0.001 to 0.031 mg/kg, 0-0.005 mg/kg, 0.005-0.012 mg/kg, 0.001-0.014 mg/kg, 0.005-0.024 mg/kg, and 0.001-0.012 mg/kg, respectively. The mean concentrations of the total PTEs content were found in decreasing order of concentration: Pb > Cd > Ni > Cr > As > Co. PCA showed that some of the PTEs were highly concentrated in samples obtained at other locations as well as at the discharge point. The Hazard Index was mostly <1 across locations, indicating little to no probable non-cancerous effect. However, the incremental lifetime cancer risk for arsenic and nickel was high and required attention. The ecological risk assessment showed that lead and arsenic were the major PTEs pollutants in all locations. The study identifies PTEs profiles in sediments and emphasises the necessity of continual monitoring and action to stop long-term negative impacts on the local environment and public health.

Aqueous phase adsorption of phenothiazine derivative onto zinc oxide doped activated carbon.

Plant-mediated synthesis of nanoparticles is a sustainable approach that has gained widespread scientific acceptance due to its numerous benefits and applications. In this study, a zinc oxide-doped activated carbon (ZAC) derived from palm kernel shells (PKS) was synthesized via a bioreduction route using a water-based extract of Nymphaea lotus leaves as a reducing agent. The synthesized ZAC nanocomposites were characterized using microscopic (TEM, SEM) and spectroscopic (FTIR, EDS, XRD, and UV-Vis) analyses. The adsorptive properties of ZAC and efficiency in scavenging a phenothiazine derivative (methylene blue) from an aqueous solution were investigated. Results reveal that nano-scale ZAC particles were crystalline, exhibited irregular shapes, with an average size of 45 nm, and were highly dispersed. The optimum quantity adsorbed was 248 mg/g at a methylene blue concentration of 140 mg/L for 60 min using 0.02 g/100 mL of ZAC. Adsorption and kinetics data closely aligned with the Freundlich isotherm and the pseudo-second-order model, respectively indicating heterogeneous surface adsorption and chemisorption as the dominant mechanisms. The regeneration study of ZAC shows that over five cycles, thermal regeneration maintained high adsorption capacity with minimal decline and chemical regeneration significantly led to reduction in the adsorption capacity but solvent washing offered a balance between efficacy and structural preservation.

In vivo MRI assessment of placental and foetal oxygenation changes in a rat model of growth restriction using blood oxygen level-dependent (BOLD) magnetic resonance imaging.

OBJECTIVES: To evaluate whether changes in BOLD signal intensities following hyperoxygenation are related to intrauterine growth restriction (IUGR) in a rat model. METHODS: IUGR was induced in pregnant rats by ligating the left vascular uterine pedicle at day 16 of gestation. BOLD MR imaging using a balanced steady-state free-precession (balanced-SSFP) sequence on a 1.5-T system was performed on day 19. Signal intensities (SI) before and after maternal hyperoxygenation were compared in the maternal liver and in control and growth-restricted foetoplacental units (FPUs). RESULTS: Maternal hyperoxygenation resulted in a significant increase in SI in all regions of interest (P < 0.05) in the 18 rats. In the control group, the SI (mean ± SD) increased by 21 % ± 15 in placentas (n = 74) and 13 % ± 8.5 in foetuses (n = 53). In the IUGR group, the increase was significantly lower: 6.5 % ± 4 in placentas (n = 36) and 7 %± 5.5 in foetuses (n = 34) (P < 0.05). CONCLUSION: BOLD MRI allows non-invasive assessment of the foetoplacental response to maternal hyperoxygenation in the rat and demonstrates its alteration in an IUGR model. This imaging method may provide a useful adjunct for the early diagnosis, evaluation, and management of human IUGR. KEY POINTS: • Intra-uterine growth restriction is an important cause of perinatal morbidity and mortality. • Blood oxygen level-dependent MRI non-invasively assesses foetoplacental response to maternal hyperoxygenation. • In the rat, foetoplacental response to maternal hyperoxygenation is altered in IUGR. • Functional MRI may help to assess human IUGR.

Shear wave elastography of tumour growth in a human breast cancer model with pathological correlation.

OBJECTIVE: To assess stiffness in a human breast cancer implanted in mice using shear wave elastography (SWE) during tumour growth and to correlate the results with pathology. METHODS: Local ethics committee for animal research approval was obtained. A human invasive ductal carcinoma was implanted subcutaneously in 24 athymic nude female mice. Ultrasound was longitudinally performed in 22 tumours, every 1-2 weeks. Maximum diameter and mean stiffness were collected. Seven tumours were measured both in vivo and ex vivo. Tumours of different sizes were removed for pathological analysis on which the percentages of viable cellular tissue, fibrosis and necrosis were measured. RESULTS: A total of 63 SWE measurements were performed. Stiffness increased during tumour growth with an excellent correlation with size (r = 0.94, P < 0.0001). No differences were found between the values of stiffness in vivo and ex vivo (P = 0.81). There was a significant correlation between elasticity and fibrosis (r = 0.83, P < 0.0001), a negative correlation with necrosis (r = -0.76, p = 0.0004) but no significant correlation with cellular tissue (r = 0.40, p = 0.1). CONCLUSION: Fibrosis plays an important role in stiffness as measured by SWE, whereas necrosis is correlated with softness. KEY POINTS: • In a breast cancer model, ultrasound tumour stiffness is correlated with size. • Stiffness changes with tumour growth are correlated with pathological changes. • Stiffness is very well correlated with proportion of tumour fibrosis. • Stiffness is inversely correlated with proportion of tumour necrosis. • Tumour stiffness measurements are similar in vivo and ex vivo.