Search

Abstract Osteoblastoma is a locally aggressive tumour of bone. Until recently, its underlying genetic features were largely unknown. During the past two years, reports have demonstrated that acquired structural variations affect the transcription factor FOS in a high proportion of cases. These rearrangements modify the terminal exon of the gene and are believed to stabilise both the FOS transcript and the encoded protein, resulting in high expression levels. Here, we applied in‐depth genetic analyses to a series of 29 osteoblastomas, including five classified as epithelioid osteoblastoma. We found recurrent homozygous deletions of the NF2 gene in three of the five epithelioid cases and in one conventional osteoblastoma. These events were mutually exclusive from FOS mutations. Structural variations were determined by deep whole genome sequencing and the number of FOS‐rearranged cases was less than previously reported (10/23, 43%). One conventional osteoblastoma displayed a novel mechanism of FOS upregulation; bringing the entire FOS gene under the control of the WNT5A enhancer that is itself activated by FOS. Taken together, we show that NF2 loss characterises a subgroup of osteoblastomas, distinct from FOS‐rearranged cases. Both NF2 and FOS are involved in regulating bone homeostasis, thereby providing a mechanistic link to the excessive bone growth of osteoblastoma.

Abstract Neurotrophic tyrosine receptor kinase (NTRK) fusions are promising molecular targets that have been described in a broad range of malignant tumours. Fusions commonly lead to the expression of chimeric proteins with constitutive tyrosine kinase activation that drives tumorigenesis. Despite a low prevalence among most solid tumours (

Introduction: People with HIV (PWH) are at an increased risk of developing cardiovascular disease (CVD) compared to HIV-negative individuals. We sought to evaluate the adherence to medications for CVD in PWH and identify factors associated with non-adherence to these medications., Methods: We conducted a cross-sectional study at the University Hospitals of Leicester NHS Trust between 16 April 2019 and 8 November 2022. We recruited consecutive PWH, who were attending a routine follow-up outpatient appointment and were prescribed at least one medication for CVD. In addition, we included urinary adherence results of patients with samples collected as part of routine clinical care. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess if their prescribed medications (antihypertensives, diuretics, beta-blockers, lipid-lowering agents, antiplatelets, anticoagulants, antidiabetic medications) were present in the participant's urine sample. Multivariable models were used to identify demographic or clinical features that were associated with non-adherence., Results: A total of 162 PWH were included in the analysis. Median age was 55 [interquartile range (IQR): 50-61] years, 63% were male, average time living with HIV was 15 years (IQR: 11-19) and the majority (98%) had an undetectable HIV viral load. In approximately one-third of patients (59/162), at least one prescribed medication of interest was not detected in urine. Non-adherence to lipid-lowering agents was common (35/88, 40%). On multivariable logistic regression, the number of prescribed cardiovascular medications, was associated with medication non-adherence [medication non-adherence, per one medication increase: adjusted odds ratio (95% confidence interval) = 1.78 (1.34-2.36); p < 0.001]., Conclusion: We found sub-optimal adherence to medications for CVD in PWH. In order to maximize the clinical benefit of statin therapy in PWH, factors requiring consideration include: improved medication adherence, awareness of polypharmacy, educational interventions and quantitative assessment of sub-optimal adherence through chemical adherence testing., (© 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Purpose: Hypertension (HTN) is one of the most common risk factors for non-communicable chronic diseases. The aim of the current study is to evaluate the prescribing patterns of antihypertensive medications in Kermanshah Province, west of Iran., Methods: The Ravansar Non-Communicable Diseases (RaNCD) cohort study is the first Kurdish community-based study; subjects' age ranged from 35 to 65 years. In order to examine the use of medications to control blood pressure, participants were asked to bring all prescribed medications to the study center. Treatments were compared with 2013 European Society of Hypertension (ESH)/European Society of Cardiology (ESC) Guidelines for the management of arterial HTN., Results: From a total of 10 040 participants in RaNCD cohort, 1575 (15.7%) individuals were hypertensive, of whom, 1271 (80.7%) people were aware of their condition. From 1153 (73.20%) people under treatment, 840 (72.8%) had their HTN properly controlled. The most common medications used to treat HTN were losartan (27.5%), metoprolol (14.3%), and captopril (11.9%). Regardless of type of treatment, 49.3% of all patients have received the medication for l 6 ≥ years. The most commonly used drugs were β-blockers and angiotension receptor blockers as 620 (31.0%) and 612 (30.6%), respectively. Multivariable analysis showed that female gender, those receive ≥3 antihypertensive agents, and using preferred combinations were associated with a better blood pressure control. In addition, the probability of hypertension control was less likely with increasing duration of treatment (i.e >6 years) and in obese patients with ≥35 kg/m 2 ., Conclusions: Even though adherence to the international guidelines was acceptable, improvements can be made for better control of HTN. Therefore, it is imperative to educate healthcare professionals on improving their selection of antihypertensive medications and combination therapy for hypertensive patients., (© 2023 John Wiley & Sons Ltd.)

In the maize-soybean intercropping system, shade is the major chronic restraint that affects normal growth of soybean. Different spatial patterns of this system affect the microclimate of soybean through shading from maize plants. However, the negative impacts of shading stress can be mitigated by providing optimal ratios of different fertilizers. Therefore, to test this hypothesis, soybean plants were grown under different light conditions (normal light or shade) to evaluate the response to varying NH 4 + /NO 3 - ratios. Seeds of soybean (Glycine max L. cv. Nan-99-6) were grown in nutrient solution with a total concentration of 5 mM N using different NH 4 + /NO 3 - ratios (T 0  = 0:0, T 1  = 0:100, T 2  = 25:75, T 3  = 50:50 and T 4  = 75:25) for 40 days in a greenhouse at PPFD 320.95 μmol m -2  s -1 (low light) or 967.53 μmol m -2  s -1 (normal light). Under low light, growth and photosynthesis of soybean seedlings significantly decreased as compared to normal light conditions. However, the optimal ratios of NH 4 + / NO 3 - improved growth and photosynthesis of soybean seedlings under both light conditions. Our results indicated that soybean seedlings supplied with optimal NH 4 + /NO 3 - ratios (25:75 and 50:50) have maximum biomass yield, chlorophyll pigments, leaf gas exchange, photochemical activity and root growth as compared to low and high NH 4 + /NO 3 - ratios (T 1 and T 4 ). High ratios of NH 4 + /NO 3 - (T 4 ) resulted in reduced plant growth due to nutrient accumulation in plant tissues; therefore, we suggest that optimal ratios of NH 4 + /NO 3 - (T 2 and T 3 ) can enhance the shade tolerance of soybean seedlings., (© 2020 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.)

Background: The relationship between metatarsal length and various forefoot pathologies is a topic of contention in Orthopaedics. The results of such investigations have been shown to depend on the method of metatarsal length measurement used. The aim of this study was to assess the inter- and intra-rater reliability of the Maestro and Barroco metatarsal length measurement techniques., Methods: A retrospective and quantitative study was performed on 15 randomly selected radiographs to determine the reliability of the two measurement techniques across all five metatarsals (M1 to M5). This was done at one week apart for three weeks by three raters. The intraclass correlation coefficient (ICC), and the 95% lower confidence limit (95% LCL) were calculated., Results: The Maestro and Barroco techniques produced high to very high ICC vlaues for length measurements across all metatarsals. The 95% lower confidence limit for inter-rater measurements ranged between 0.92-0.98 for Maestro's and 0.86-0.99 for Barroco's technique. For intra-rater measurements the 95% LCL ranged between 0.83-0.99 for Maestro's and 0.75-0.99 for Barroco's technique., Conclusions: Our study found that both the Maestro and Barroco methods of measurements produced high to very high inter- and intra-rater reliability. Both methods may be suitable for the use of peri-operative planning and clinical research relating metatarsal length and forefoot pathology. Besides having a more simplistic method of application, the novel Barroco technique is comparable to the more established Maestro method in both repeatability and reproducibility., Competing Interests: The University of Western Australia’s human ethics board approved this study (no. RA/4/1/8153). All participants had signed an informed consent form allowing their podiatric radiographs to be used for future research by the University of Western Australia (UWA) podiatry clinic.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objective: To compare the effectiveness and safety of carbetocin, misoprostol, and oxytocin for the prevention of postpartum hemorrhage following cesarean deliveries., Methods: A double-blind randomized controlled trial enrolled patients with a singleton pregnancy scheduled for an elective cesarean delivery at a maternity hospital in Cairo, Egypt, between October 1, 2012 and June 30, 2013. Participants were randomized using a computer-generated sequence to receive treatment with carbetocin, misoprostol, or oxytocin. The primary outcome was the occurrence of uterine atony necessitating additional uterotonics. Per-protocol analyses were performed. Patients, investigators, and data analysts were masked to treatment assignments., Results: The present study enrolled 263 patients; data were analyzed from 88 patients treated with carbetocin, 89 treated with misoprostol, and 86 women treated with oxytocin. Further uterotonics were needed for the treatment of 5 (6%) patients who were treated with carbetocin, 20 (22%) patients treated with misoprostol, and 11 (13%) patients treated with oxytocin. In the prevention of uterine atony, carbetocin was comparable with oxytocin (RR 0.41, 95%CI 0.14-1.25) and superior to misoprostol (RR 0.21, 95%CI 0.07-0.58)., Conclusion: Additional uterotonics were needed less frequently by patients treated with carbetocin. Carbetocin was comparable to oxytocin and superior to misoprostol in the prevention of uterine atony following an elective cesarean delivery. ClinicalTrials.gov: NCT02053922., (Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Slower psychomotor speed is very common in patients with type 1 diabetes mellitus (T1D), but the underlying mechanisms are not clear. We propose that hyperglycemia is associated with slower psychomotor speed via disruption of brain activation. Eighty-five adults (48% women, mean age: 49.0 years, mean duration: 40.8) with childhood onset T1D were recruited for this cross-sectional study. Median response time in seconds (longer = worse performance) and brain activation were measured while performing a psychomotor speed task. Exposure to hyperglycemia, measured as glycosylated hemoglobin A1c, was associated with longer response time and with higher activation in the inferior frontal gyrus and primary sensorimotor and dorsal cingulate cortex. Higher activation in inferior frontal gyrus, primary sensorimotor cortex, thalamus, and cuneus was related to longer response times; in contrast, higher activation in the superior parietal lobe was associated with shorter response times. Associations were independent of small vessel disease in the brain or other organs. In this group of middle-aged adults with T1D, the pathway linking chronic hyperglycemia with slower processing speed appears to include increased brain activation, but not small vessel disease. Activation in the superior parietal lobe may compensate for dysregulation in brain activation in the presence of hyperglycemia.

Bilateral symmetrical basal ganglia lesions may be caused by hypoxic/ischemic injury. However, similar lesions have not been described in the cerebellar cortex. To report a case of bilateral basal ganglia and cerebellar lesions in an alcoholic patient with hyperglycemia and hypotension. A 47-year-old alcoholic man with hypotension of unknown duration and hyperosmolarity had mild weakness of the left upper extremity. Neuroimaging revealed abnormality of bilateral symmetric globus pallidus and inferior cerebellum. Prolonged hypotension with hyperosmolarity may give rise to bilateral basal ganglia and cerebellar lesions.

In a prospective randomized trial, anterior lesser curve seromytomy with posterior truncal vagotomy (ASPTV, n = 50) was compared with proximal gastric vagotomy (PGV, n = 50). Most of our patients were young men with ASA grade I risk, and 80% were expatriates. They were followed up for 3 to 8 years after surgery. The mean reductions of basal acid output (BAO) and insulin-stimulated peak acid output (IPAO) were 85% and 88%, respectively, soon after surgery for both ASPTV and PGV groups. These values remained at 70% and 60% of their preoperative level for 1 year. Good to excellent results (Visick I and II) were recorded in 76% of cases in both groups. The recurrent ulcer rate was 14% for PGV and 12% for ASPTV. This trial suggests that for the treatment of duodenal ulcer ASPTV is as good an operation as PGV.