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Background: There is a disparity in health outcomes between indigenous and nonindigenous Australians, with higher chronic disease burden and shorter life expectancy in this minority population. Although rates of breast cancer among indigenous women are lower than nonindigenous women, they face a higher breast cancer-associated mortality, which may not entirely be explained by socio-economic disadvantage., Methods: This retrospective cohort study investigated previously described pathologic prognostic factors in indigenous Australians in the Northern Territory., Results: Data analyzed confirmed that indigenous women were more likely to have poorer prognostic disease features, including ER/PR negative and human epidermal growth factor receptor 2 amplified tumors, larger tumors, and higher stage disease., Conclusion: These pathologic features portend to a poor prognosis, raising the possibility these factors contribute to the disparity in health outcomes between indigenous and nonindigenous women with breast cancer, in addition to known socio-economic factors., (© 2023 John Wiley & Sons Australia, Ltd.)

BACKGROUND This study aimed to evaluate the effect of standing and sitting positions on spinal curvatures evaluated using projection moire and muscle tone and stiffness using the MyotonPRO hand-held device in young women. MATERIAL AND METHODS Thirty-three healthy women, aged 21 to 23 years, volunteered in the study. We used the projection moire method to examine spinal curvatures in both positions and the MyotonPRO device to measure the tone and stiffness of muscles in 3 regions. We evaluated the effects of positions (standing vs sitting), regions (cervical, thoracic, and lumbar), and side factor (right vs left) using multivariate analysis. RESULTS The sitting position significantly decreased the lumbosacral and thoracolumbar angles (P<0.001), but had no effect on the superior thoracic angle. Muscle tension and stiffness were the highest (P<0.001) in the cervical region and did not differ between positions (P>0.05) in this region. We found significantly higher muscle tone and stiffness in the thoracic and lumbar regions during sitting than during standing (P<0.001). There was symmetry in the muscle tone and the stiffness between the right and left sides of the spine. CONCLUSIONS The sitting posture decreased lumbosacral and thoracolumbar angles but increased muscle tension and stiffness in the lumbar and thoracic regions only. The symmetry of muscle tone and transverse stiffness in both positions was the normative value. This study provides insight into the adaptive physiological changes in spinal curvature and muscle mechanical properties in young women and serves as an important reference point for clinical studies of women.

DNA mismatch repair (MMR) deficiency and the associated microsatellite instability (MSI) phenotype has become a subject of enormous interest in recent years due to the demonstrated efficacy of immune checkpoint inhibitors (ICI) in advanced tumours. Assessing MSI in patients with gastrointestinal tract (GI) cancers is useful to exclude Lynch syndrome, but also to predict benefit for ICI. Following review of the relevant literature, this review article aims to outline the clinicopathologic spectrum of MSI and mismatch repair deficiency (dMMR) in the GI tract, hepatobiliary system and pancreas and discuss the therapeutic consideration in this disease., Competing Interests: Declaration of Competing Interest JM, AA, VA: no interested to declare. NS: Honoraria from Eli Lilly, Merck, MSD, Servier, GSK, Amgen; Research funding: AZ, BMS, Pfizer MG receives research funding from Merck KG and BMS, (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

As the management of gastrointestinal malignancy has evolved, tumor response assessment has expanded from size-based assessments to those that include tumor enhancement, in addition to functional data such as those derived from PET and diffusion-weighted imaging. Accurate interpretation of tumor response therefore requires knowledge of imaging modalities used in gastrointestinal malignancy, anticancer therapies, and tumor biology. Targeted therapies such as immunotherapy pose additional considerations due to unique imaging response patterns and drug toxicity; as a consequence, immunotherapy response criteria have been developed. Some gastrointestinal malignancies require assessment with tumor-specific criteria when assessing response, often to guide clinical management (such as watchful waiting in rectal cancer or suitability for surgery in pancreatic cancer). Moreover, anatomic measurements can underestimate therapeutic response when applied to molecular-targeted therapies or locoregional therapies in hypervascular malignancies such as hepatocellular carcinoma. In these cases, responding tumors may exhibit morphologic changes including cystic degeneration, necrosis, and hemorrhage, often without significant reduction in size. Awareness of pitfalls when interpreting gastrointestinal tumor response is required to correctly interpret response assessment imaging and guide appropriate oncologic management. Data-driven image analyses such as radiomics have been investigated in a variety of gastrointestinal tumors, such as identifying those more likely to respond to therapy or recur, with the aim of delivering precision medicine. Multimedia-enhanced radiology reports can facilitate communication of gastrointestinal tumor response by automatically embedding response categories, key data, and representative images. © RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

As the use of liquid biopsies are increasing across multiple indications in cancer medicine, the detection of incidental findings on circulating tumour DNA is of increasing importance. We report the finding of leukaemia detected in a patient who underwent plasma-based circulating tumour DNA next generation screening as part of a screening liquid biopsy study. A BRAF V600E mutation detected was deemed pathogenic following discussion at a molecular tumour board, and recommendation of further investigations led to the diagnosis of an occult haematological malignancy. We report the importance of molecular tumour board discussion and recommendations in the identification of incidental, pathogenic findings on circulating tumour DNA., (© 2024. The Author(s).)

The pollution of soil by trace elements is a global problem. Conventional methods of soil remediation are often inapplicable, so it is necessary to search intensively for innovative and environment-friendly techniques for cleaning up ecosystems, such as phytoremediation. Basic research methods, their strengths and weaknesses, and the effects of microorganisms on metallophytes and plant endophytes resistant to trace elements (TEs) were summarised and described in this manuscript. Prospectively, bio-combined phytoremediation with microorganisms appears to be an ideal, economically viable and environmentally sound solution. The novelty of the work is the description of the potential of "green roofs" to contribute to the capture and accumulation of many metal-bearing and suspended dust and other toxic compounds resulting from anthropopressure. Attention was drawn to the great potential of using phytoremediation on less contaminated soils located along traffic routes and urban parks and green spaces. It also focused on the supportive treatments for phytoremediation using genetic engineering, sorbents, phytohormones, microbiota, microalgae or nanoparticles and highlighted the important role of energy crops in phytoremediation. Perceptions of phytoremediation on different continents are also presented, and new international perspectives are presented. Further development of phytoremediation requires much more funding and increased interdisciplinary research in this direction.

The study aimed to determine whether four weeks of motor imagery training (MIT) of goal-directed reaching (reaching to grasp task) would affect the cortical activity during motor imagery of reaching (MIR) and grasping (MIG) in the same way. We examined cortical activity regarding event-related potentials (ERPs) in healthy young participants. Our study also evaluated the subjective vividness of the imagery. Furthermore, we aimed to determine the relationship between the subjective assessment of motor imagery (MI) ability to reach and grasp and the cortical activity during those tasks before and after training to understand the underlying neuroplasticity mechanisms. Twenty-seven volunteers participated in MIT of goal-directed reaching and two measurement sessions before and after MIT. During the sessions 128-channel electroencephalography (EEG) was recorded during MIR and MIG. Also, participants assessed the vividness of the MI tasks using a visual analog scale (VAS). The vividness of imagination improved significantly (P < .05) after MIT. A repeated measures ANOVA showed that the task (MIR/MIG) and the location of electrodes had a significant effect on the ERP's amplitude (P < .05). The interaction between the task, location, and session (before/after MIT) also had a significant effect on the ERP's amplitude (P < .05). Finally, the location of electrodes and the interaction between location and session had a significant effect on the ERP's latency (P < .05). We found that MIT influenced the EEG signal associated with reaching differently than grasping. The effect was more pronounced for MIR than for MIG. Correlation analysis showed that changes in the assessed parameters due to MIT reduced the relationship between the subjective evaluation of imagining and the EEG signal. This finding means that the subjective evaluation of imagining cannot be a simple, functional insight into the bioelectrical activity of the cerebral cortex expressed by the ERPs in mental training. The changes we noted in ERPs after MIT may benefit the use of non-invasive EEG in the brain-computer interface (BCI) context.Trial registration: NCT04048083., (© 2022. The Author(s).)

Circulating tumour DNA (ctDNA) has potential applications in gastric cancer (GC) with respect to screening, the detection of minimal residual disease (MRD) following curative surgery, and in the advanced disease setting for treatment decision making and therapeutic monitoring. It can provide a less invasive and convenient method to capture the tumoural genomic landscape compared to tissue-based next-generation DNA sequencing (NGS). In addition, ctDNA can potentially overcome the challenges of tumour heterogeneity seen with tissue-based NGS. Although the evidence for ctDNA in GC is evolving, its potential utility is far reaching and may shape the management of this disease in the future. This article will review the current and future applications of ctDNA in GC.

Introduction: Anti-angiogenic drugs are an efficacious class of therapy in the treatment of patients with metastatic colorectal cancer (mCRC). Aflibercept, a vascular endothelial growth factor (VEGF) trap which binds the angiogenic factors VEGF-A, VEGF-B, and placental growth factor (PIGF) is approved in combination with FOLFIRI chemotherapy following progression after an oxaliplatin-containing regimen., Areas Covered: This report provides a review of the practice-changing clinical studies which have established the use of anti-angiogenic therapy as second-line therapy in mCRC including aflibercept with FOLFIRI (5FU, leucovorin, irinotecan). This review also evaluates aflibercept with other chemotherapy regimens as well as efficacy and safety data from real-world studies., Expert Opinion: Aflibercept in combination with FOLFIRI chemotherapy is an established safe and efficacious regimen for the treatment of mCRC as second-line chemotherapy. Although several toxicities have been described, the majority are either low grade or manageable by drug cessation and supportive therapies. For optimal outcomes, patient selection and close observation of toxicities is essential.

Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) ( NCT03226886 ) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic., (© 2021. The Author(s).)

Background: The aim of the study was to compare the mechanical properties of three human skeletal muscles: biceps brachii (BB), rectus femoris (RF), and tibialis anterior (TA) at rest measured by myoton device in males ( n  = 16, mean age 21.2 ± 0.6 years) and females ( n  = 16; 21.2 ± 0.9 years) and to investigate the influence of skin and subcutaneous tissue thickness (skinfold thickness, SFT) and gender on myometric parameters of the three skeletal muscles., Methods: We measured the following mechanical and viscoelastic muscle properties using MyotonPRO ® : frequency (F [Hz]), decrement (D [log]), stiffness (S [N/m]), relaxation time (R [ms]) and creepability (C [De]). The values of SFT for all selected muscles were assessed by caliper. A mixed-design analysis of variance with gender as between subject comparison was used for assessing the differences between gender and muscles in SFT and each of the myometric parameters separately (F, D, S, R and C). Pearson correlation coefficient or Spearman's rank correlation coefficient between SFT and myometric parameters was conducted for males, females and males and females together. The level of statistical significance was set at α ≤ 0.05 with Bonferroni correction for multiple comparisons., Results: The SFT over the RF, TA, and BB muscles in women was statistically significantly larger compared with that of males. In females and males, the SFT over the RF was larger than over the TA and BB, and the SFT over the TA was larger compared with over the BB. The values of F and S recorded for the TA muscle were the highest among the three muscles, while D, C, and R were lowest in TA but highest in the RF muscle in men and women. The values of F and S were smaller in females than in males. Gender comparison of D, C, and R values showed that only D for the RF was significantly lower in females than in males, and C for the RF and TA was significantly larger in females than in males. Some correlation between SFT and myometric parameters were different between males and females. For example, there was a significant, negative correlation between SFT and F for all muscles in females, and a significant, positive correlation between these parameters for BB and TA (not for RF) in males. For pooled data (males and females together), a negative significant correlation between SFT and F was observed for RF and TA (not significant for BB muscle)., Discussion: It is concluded that the TA compared with the BB and RF has significantly greater F and S but the smallest D and C and the shortest R. Gender and muscle differences in the SFT may affect the measurements of muscle properties using MyotonPRO ® . The relationship between SFT and myometric parameters is different in males and females in the RF, TA, and BB muscles. Therefore, the myometric data should be analyzed in males and females separately., Competing Interests: The authors declare there are no competing interests., (©2021 Mencel et al.)

This study explored the effect of kinesthetic motor imagery training on reaching-to-grasp movement supplemented by a virtual environment in a patient with congenital bilateral transverse upper-limb deficiency. Based on a theoretical assumption, it is possible to conduct such training in this patient. The aim of this study was to evaluate whether cortical activity related to motor imagery of reaching and motor imagery of grasping of the right upper limb was changed by computer-aided imagery training (CAIT) in a patient who was born without upper limbs compared to a healthy control subject, as characterized by multi-channel electroencephalography (EEG) signals recorded before and 4, 8, and 12 weeks after CAIT. The main task during CAIT was to kinesthetically imagine the execution of reaching-to-grasp movements without any muscle activation, supplemented by computer visualization of movements provided by a special headset. Our experiment showed that CAIT can be conducted in the patient with higher vividness of imagery for reaching than grasping tasks. Our results confirm that CAIT can change brain activation patterns in areas related to motor planning and the execution of reaching and grasping movements, and that the effect was more pronounced in the patient than in the healthy control subject. The results show that CAIT has a different effect on the cortical activity related to the motor imagery of a reaching task than on the cortical activity related to the motor imagery of a grasping task. The change observed in the activation patterns could indicate CAIT-induced neuroplasticity, which could potentially be useful in rehabilitation or brain-computer interface purposes for such patients, especially before and after transplantation. This study was part of a registered experiment (ID: NCT04048083)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mencel, Jaskólska, Marusiak, Kamiński, Kurzyński, Wołczowski, Jaskólski and Kisiel-Sajewicz.)

Gastrointestinal (GI) cancers are among the most common and lethal solid tumors worldwide. Unlike in malignancies such as lung, renal and skin cancers, the activity of immunotherapeutic agents in GI cancers has, on the whole, been much less remarkable and do not apply to the majority. Furthermore, while incremental progress has been made and approvals for use of immune checkpoint inhibitors (ICIs) in specific subsets of patients with GI cancers are coming through, in a population of 'all-comers', it is frequently unclear as to who may benefit most due to the relative lack of reliable predictive biomarkers. For most patients with newly diagnosed advanced or metastatic GI cancer, the mainstay of treatment still involves chemotherapy and/or a targeted agent however, beyond the second-line this paradigm confers minimal patient benefit. Thus, current research efforts are concentrating on broadening the applicability of ICIs in GI cancers by combining them with agents designed to beneficially remodel the tumor microenvironment (TME) for more effective anti-cancer immunity with intention of improving patient outcomes. This review will discuss the currently approved ICIs available for the treatment of GI cancers, the strategies underway focusing on combining ICIs with agents that target the TME and touch on recent progress toward identification of predictors of sensitivity to immune checkpoint blockade in GI cancers.

It has been demonstrated that physical training increases serum brain-derived neurotrophic factor (BDNF) in healthy people. The aim of this study was to establish the effect of physical training on the basal serum level of the BDNF in the Parkinson's disease patients (PD patients) in relation to their health status. Twelve PD patients (mean ± S.E.M: age 70 ± 3 years; body mass 70 ± 2 kg; height 163 ± 3 cm) performed a moderate-intensity interval training (three 1-hour training sessions weekly), lasting 8 weeks. Basal serum BDNF in the PD patients before training amounted to 10,977 ± 756 pg x mL(-1) and after 8 weeks of training it has increased to 14,206 ± 1256 pg x mL(-1) (i.e. by 34%, P=0.03). This was accompanied by an attenuation of total Unified Parkinson's Disease Rating Scale (UPDRS) (P=0.01). The training resulted also in a decrease of basal serum soluble vascular cell adhesion molecule 1 (sVCAM-1) (P=0.001) and serum tumor necrosis factor-α (TNF-α) (P=0.03) levels. We have concluded that the improvement of health status of the Parkinson's disease patients after training could be related to the increase of serum BDNF level caused by the attenuated inflammation in those patients.

Diabetes causes changes in the myocardium, which are often called diabetic cardiomyopathy. This condition has been extensively investigated in animal models with high glucose levels. Nevertheless, it has not been investigated whether moderate hyperglycemia, in the absence of other features of metabolic syndrome, may also cause similar changes in the heart. The aim of the study was to assess changes in the myocardium in an animal model of mild type 1 diabetes. Moderate hyperglycemia was induced in 8- to 10-week-old male C57BL6J mice by 5 intraperitoneal injections of streptozotocin (40 mg/kg). After 16 weeks, they were sacrificed, and left ventricle (LV) dimensions and extent of cardiac fibrosis were assessed by morphometry. The abundance of CCN proteins in LVsamples was assessed using western blotting, while activity of metalloproteinase 2 was established in zymography. Real time PCR was used to investigate the expression of transforming growth factor beta1 (TGFbeta1) and atrial natriuretic peptide. Mice with moderate hyperglycemia presented comparable cardiac dimensions with fibrosis and hypertrophy parameters as the non-diabetic controls. However, the abundance of profibrotic CCN2 protein was significantly increased in hyperglycemic animals (1.67 +/- 0.28 vs. 1 +/- 0.47, p < 0.05). Interestingly, this change was independent from the TGFbeta1 expression, as its RNA abundance was similar in both groups. Moderate hyperglycemia also caused an increase in the activity of the metalloproteinase 2 (1.21 +/- 0.17 vs. 1 +/- 0.07, p < 0.05). Despite diabetes, no profound changes in cardiac morphology were found. In our animal model, moderate hyperglycemia caused activation of a profibrotic gene expression program, which was counterbalanced by the increase of metalloproteinase activity.

Salmon calcitonin (sCT), a 32-amino-acid peptide, is the active component in many pharmaceuticals used for the management of bone diseases. The degradation pathways of sCT were determined, and the structures of the major degradation products were identified. Aqueous solutions of sCT at pH values of 3, 4, 5, and 6 were degraded, and the major degradation products were detected using reversed phase and size-exclusion high-performance liquid chromatography (HPLC). The degradation rate and pathways of sCT are strongly dependent on pH in the pH range between 3 and 6. The major degradation products were isolated by semipreparative HPLC and identified using a variety of spectroscopic and bioanalytical techniques. The results show that sCT can undergo hydrolyses resulting in cleavage of the 1-2 amide bond and deamidation of the Gln14 and Gln20 residues, sulfide exchange that leads to an unusual trisulfide derivative, and dimerization to reducible and nonreducible dimers. The mechanisms for the pathways can be rationalized from known degradation pathways of peptide and proteins.

Compounds 1a-g consisting of enalaprilat covalently bonded to aryl sulfonamides, including several known thiazide diuretics, were synthesized and tested for ACE inhibitory and diuretic and overall antihypertensive effects. All compounds were potent ACE inhibitors in vitro, with IC50 = 6.5-85 nM. At 10 mg/kg iv or ip in the rat, 1a-g inhibited the AI pressor response by 76-100%; inhibition declined significantly upon oral dosing. Compounds 1a and 1f at 100 mg/kg ip in the sodium-depleted, spontaneously hypertensive rats reduced blood pressure 28-35% and 41-42%, respectively. Compounds 1a and 1f elicited natriuresis and kaliuresis without accompanying volume increases in the rat; 1c at 25 mg/kg iv induced delayed diuresis. Compound 1f has been chosen for further development.

A new analog of salmon calcitonin (N alpha-propionyl Di-Ala1,7,des-Leu19 sCT; RG-12851; here termed CTR), which lacks the ring structure of native calcitonin, was tested for biological activity in several in vitro and in vivo assay systems. The analog (CTR) and salmon calcitonin (sCT) stimulated kidney cell adenylate cyclase activity and inhibited bone resorption in organ cultures of fetal rat long bones with similar potencies and efficacies. Furthermore, CTR and sCT, at similar doses, induced comparable hypocalcemic responses in mice following sc injection or infusions. However, unlike sCT, CTR did not induce anorexia and weight loss in rats following sc injection. These data suggest that the ring structure of sCT may be important for the anorexigenic effect but is not required for effect on bone resorption or calcium homeostasis. Clinical studies appear warranted as, potentially, CTR might induce fewer side effects than does sCT.

This series of reports describe the development of orally active, highly potent, specific antagonists of the peptidoleukotrienes containing a (2-quinolinylmethoxy)phenyl moiety. The compounds reported in this paper contain an additional phenyl ring, which has significantly improved the receptor affinity. The effect of changes in the linkage between the two phenyl rings as well as the orientation of the acidic functional group on biological activity are discussed. Many of these compounds have high affinity to the sulfidopeptide leukotriene D4 receptors with Ki values ranging between 2 and 20 nM and are orally active. Compound 27 [RG 12525, 5-[[2-[[4-(2-quinolinylmethoxy)phenoxy]- methyl]phenyl]methyl]-1H-tetrazole] represents the best combination of in vitro and in vivo biological activity in this series and has been selected for further evaluation in clinical studies of asthma.