Mediterranean diet for the management of metabolic dysfunction-associated steatotic liver disease in non-Mediterranean, Western countries: What's known and what's needed?

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide, affecting 30% of the population in Western countries. MASLD is considered the hepatic manifestation of the metabolic syndrome, pathophysiologically underpinned by insulin resistance and frequently co-exists with hypertension, central obesity and dyslipidaemia. Currently, safe and effective pharmacotherapies for MASLD are limited, making weight loss with lifestyle changes the mainstay therapy. A Mediterranean diet (MedDiet) has emerged as an effective dietary pattern for preventing and managing MASLD, but most studies have been conducted in Mediterranean countries, necessitating further investigation into its benefits in Western populations. Additionally, the effect of holistic multimodal lifestyle interventions, including physical activity combined with the MedDiet, is not well established. Finally, MASLD's widespread prevalence and rapid growth require improved accessibility to interventions. Digital health delivery platforms, designed for remote access, could be a promising approach to providing timely support to individuals with MASLD. This narrative review summarises the current evidence related to the effects of the MedDiet in Western, multicultural populations with MASLD. This includes a detailed description of the composition, prescription and adherence to dietary interventions in terms of how they have been designed and applied. The evidence related to the role of physical activity or exercise interventions prescribed in combination with the MedDiet for MASLD will also be reviewed. Finally, recommendations for the design and delivery of dietary and physical activity or exercise interventions to inform the design of future randomised controlled trials to facilitate the optimal management of MASLD are outlined.

Preclinical Female Model of Urogenital Dysfunction and Pathophysiological Changes After Pelvic Radiation Therapy.

Introduction Radiation therapy (RT) is the gold standard for many pelvic cancers and improves overall patient survival. However, pelvic RT is associated with increased sexual dysfunction and urinary incontinence. Although the side effects of pelvic RT are well-documented, the pathological mechanisms leading to pelvic organ dysfunction are unknown, and a preclinical model has not been established. This study characterized the impact of pelvic RT at early and late timepoints on female rat bladder, vaginal, and urethral physiology and morphology. Methods Adult female Sprague-Dawley rats were divided into three groups (n = 8/group): (I) Sham, (II) four weeks RT (4wk RT), and (III) nine weeks RT (9wk RT). The RT groups received a single dose of 20 Gy external beam radiation, and experiments were conducted at 4wk and 9wk post-RT. Nerve-mediated vaginal blood flow was measured via laser Doppler. Tissue bath studies assessed vaginal contractility to electric field stimulation (EFS), adrenergic and cholinergic agonists, and relaxation to a nitric oxide donor. Bladder and urethral sphincters were evaluated for cholinergic, caffeine, and EFS-mediated contractility. Quantitative polymerase chain reaction (qPCR) measured gene expression of markers of oxidative stress. Vaginal, bladder, and urethral fibrosis were assessed with Masson's trichrome staining. Results At 4wk post-RT, total vaginal blood flow decreased, and at 9wk post-RT, returned to baseline levels. At 9wk post-RT, vaginal neurogenic and adrenergic-mediated contractile responses increased significantly. Vaginal epithelial thickness decreased post-RT and correlated with an acute rise in vaginal inflammatory gene expression. At 4wk post-RT, bladder neurogenic contractions decreased and remained lowered. Internal urethral contractions increased at 4wk post-RT and returned to Sham levels after 9wk post-RT. Pelvic RT increased external urethral neurogenic contractions, which remained elevated. Conclusion This novel preclinical model provides valuable insights into the temporal pathophysiology of pelvic RT-induced sexual and urinary dysfunction. The establishment of this model is crucial for understanding the underlying mechanisms involved in RT-induced pelvic injury. A reliable, clinically relevant model will allow for the testing of therapeutic strategies to prevent adverse effects with RT in pelvic cancer survivors.

Functional Analysis of the Channelrhodopsin Genes from the Green Algae of the White Sea Basin.

Optogenetics, the method of light-controlled regulation of cellular processes is based on the use of the channelrhodopsins that directly generate photoinduced currents. Most of the channelrhodopsin genes have been identified in the green microalgae Chlorophyta, and the demand for increasing the number of functionally characterized channelrhodopsins and the diversity of their photochemical parameters keeps growing. We performed the expression analysis of cation channelrhodopsin (CCR) genes in natural isolates of microalgae of the genera Haematococcus and Bracteacoccus from the unique Arctic Circle region. The identified full-length CCR transcript of H. lacustris is the product of alternative splicing and encodes the Hl98CCR2 protein with no photochemical activity. The 5'-partial fragment of the B. aggregatus CCR transcript encodes the Ba34CCR protein containing a conserved TM1-TM7 membrane domain and a short cytosolic fragment. Upon heterologous expression of the TM1-TM7 fragment in CHO-K1 cell culture, light-dependent current generation was observed with the parameters corresponding to those of the CCR. The first discovered functional channelrhodopsin of Bracteacoccus has no close CCR homologues and may be of interest as a candidate for optogenetics.

Epigenetic Phenomenon of Paramutation in Plants and Animals.

The phenomenon of paramutation describes the interaction between two alleles, in which one allele initiates inherited epigenetic conversion of another allele without affecting the DNA sequence. Epigenetic transformations due to paramutation are accompanied by the change in DNA and/or histone methylation patterns, affecting gene expression. Studies of paramutation in plants and animals have identified small non-coding RNAs as the main effector molecules required for the initiation of epigenetic changes in gene loci. Due to the fact that small non-coding RNAs can be transmitted across generations, the paramutation effect can be inherited and maintained in a population. In this review, we will systematically analyze examples of paramutation in different living systems described so far, highlighting common and different molecular and genetic aspects of paramutation between organisms, and considering the role of this phenomenon in evolution.

Exploring the Feasibility of Digital Voice Assistants for Delivery of a Home-Based Exercise Intervention in Older Adults With Obesity and Type 2 Diabetes Mellitus: Randomized Controlled Trial.

BACKGROUND: Current clinical guidelines for the management of type 2 diabetes mellitus (T2DM) in older adults recommend the use of antihyperglycemic medications, monitoring of blood glucose levels, regular exercise, and a healthy diet to improve glycemic control and reduce associated comorbidities. However, adherence to traditional exercise programs is poor (<35%). Common barriers to adherence include fear of hypoglycemia and the need for blood glucose level monitoring before exercise. Digital health strategies offer great promise for managing T2DM as they facilitate patient-practitioner communication, support self-management, and improve access to health care services for underserved populations. We have developed a novel web-based software program allowing practitioners to create tailored interventions and deliver them to patients via digital voice assistants (DVAs) in their own homes. OBJECTIVE: We aim to evaluate the feasibility of a 12-week, home-based, personalized lifestyle intervention delivered and monitored by DVAs for older adults with obesity and T2DM. METHODS: In total, 50 older adults with obesity aged 50-75 years with oral hypoglycemic agent-treated T2DM were randomized to the intervention (DVA, n=25) or a control group (n=25). Participants allocated to the DVA group were prescribed a home-based muscle strengthening exercise program (~20- to 30-min sessions) and healthy eating intervention, delivered via DVAs (Alexa Echo Show 8; Amazon) using newly developed software ("Buddy Link"; Great Australian Pty Ltd). Control group participants received generalized physical activity information via email. Outcomes were feasibility, DVA usability (System Usability Scale), and objectively assessed physical activity and sedentary time (wrist-worn accelerometers). RESULTS: In total, 45 (90%) out of 50 participants completed this study. Mean adherence to prescribed exercise was 85% (SD 43%) with no intervention-related adverse events. System usability was rated above average (70.4, SD 16.9 out of 100). Compared with controls, the DVA group significantly decreased sedentary time (mean difference -67, SD 23; 95% CI -113 to -21 min/d), which was represented by a medium to large effect size (d=-0.6). CONCLUSIONS: A home-based lifestyle intervention delivered and monitored by health professionals using DVAs was feasible for reducing sedentary behavior and increasing moderate-intensity activity in older adults with obesity and T2DM. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621000307808; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381364&isReview=true.

The loss of hepatitis B virus receptor NTCP/SLC10A1 in human liver cancer cells is due to epigenetic silencing.

Human Na+-taurocholate cotransporting polypeptide (hNTCP) is predominantly expressed in hepatocytes, maintaining bile salt homeostasis and serving as a receptor for hepatitis B virus (HBV). hNTCP expression is downregulated during hepatocellular carcinoma (HCC) development. In this study, we investigated the molecular mechanisms underlying hNTCP dysregulation using HCC tissues and cell lines, and primary human hepatocytes (PHHs). Firstly, we observed a significant reduction of hNTCP in HCC tumors compared to adjacent and normal tissues. Additionally, hNTCP mRNA levels were markedly lower in HepG2 cells compared to PHHs, which was corroborated at the protein level by immunoblotting. Sanger sequencing confirmed identical sequences for hNTCP promoter, exons, and mRNA coding sequences between PHH and HepG2 cells, indicating no mutations or splicing alterations. We then assessed the epigenetic status of hNTCP. The hNTCP promoter, with low CG content, showed no significant methylation differences between PHH and HepG2 cells. Chromatin immunoprecipitation coupled with qPCR (ChIP-qPCR) revealed a loss of activating histone posttranslational modification (PTM) H3K27ac near the hNTCP transcription start site (TSS) in HepG2 cells. This loss was also confirmed in HCC tumor cells compared to adjacent and background cells. Treating HepG2 cells with histone deacetylase inhibitors enhanced H3K27ac accumulation and glucocorticoid receptor (GR) binding at the hNTCP TSS, significantly increasing hNTCP mRNA and protein levels, and rendering the cells susceptible to HBV infection. In summary, histone PTM-related epigenetic mechanisms play a critical role in hNTCP dysregulation in liver cancer cells, providing insights into hepatocarcinogenesis and its impact on chronic HBV infection. IMPORTANCE: HBV is a hepatotropic virus that infects human hepatocytes expressing the viral receptor hNTCP. Without effective antiviral therapy, chronic HBV infection poses a high risk of liver cancer. However, most liver cancer cell lines, including HepG2 and Huh7, do not support HBV infection due to the absence of hNTCP expression, and the mechanism underlying this defect remains unclear. This study demonstrates a significant reduction of hNTCP in hepatocellular carcinoma samples and HepG2 cells compared to normal liver tissues and primary human hepatocytes. Despite identical hNTCP genetic sequences, epigenetic analyses revealed a loss of the activating histone modification H3K27ac near the hNTCP transcription start site in cancer cells. Treatment with histone deacetylase inhibitors restored H3K27ac levels, reactivated hNTCP expression, and rendered HepG2 cells susceptible to HBV infection. These findings highlight the role of epigenetic modulation in hNTCP dysregulation, offering insights into hepatocarcinogenesis and its implications for chronic HBV infection.

Mediterranean Diet and Ultra-Processed Food Intake in Older Australian Adults-Associations with Frailty and Cardiometabolic Conditions.

Dietary patterns contribute to overall health and diseases of ageing but are understudied in older adults. As such, we first aimed to develop dietary indices to quantify Mediterranean Diet Score (MDS) utilisation and Ultra-processed Food (UPF) intake in a well-characterised cohort of relatively healthy community-dwelling older Australian adults. Second, we aimed to understand the relationship between these scores and the association of these scores with prevalent cardiometabolic disease and frailty. Our major findings are that in this population of older adults, (a) pre-frailty and frailty are associated with reduced MDS and increased UPF intake; (b) adherence to MDS eating patterns does not preclude relatively high intake of UPF (and vice versa); and (c) high utilisation of an MDS eating pattern does not prevent an increased risk of frailty with higher UPF intakes. As such, the Mediterranean Diet pattern should be encouraged in older adults to potentially reduce the risk of frailty, while the impact of UPF intake should be further explored given the convenience these foods provide to a population whose access to unprocessed food may be limited due to socioeconomic, health, and lifestyle factors.

Rational (supra)molecular design and catalytic activity of cage-like Cu4-based phenylsilsesquioxanes.

An extended (i.e., 19 distinct species) family of cage-like Cu4-phenylsilsesquioxanes allowed us to accentuate the general regularities behind their structural organization. Influencing factors, namely the (i) size of external alkali metal ions (from Li to Cs) and (ii) nature of bridging linkers (including the smallest possible ones, like a water molecule) on the self-assembly/supramolecular assembly of such Cu4-building blocks have been thoroughly explored. A Cu4K4-based complex has been evaluated as a precatalyst in the oxidation of alkanes (cyclohexane, n-heptane, methylcyclohexane) and alcohols. The experimental evidence that radical species participate in the oxidation of alkanes is provided.

The role of dietary modification in the prevention and management of metabolic dysfunction-associated fatty liver disease: An international multidisciplinary expert consensus.

Metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), has become the leading cause of chronic liver disease worldwide. Optimal dietary intervention strategies for MAFLD are not standardized. This study aimed to achieve consensus on prevention of MAFLD through dietary modification. A multidisciplinary panel of 55 international experts, including specialists in hepatology, gastroenterology, dietetics, endocrinology and other medical specialties from six continents collaborated in a Delphi-based consensus development process. The consensus statements covered aspects ranging from epidemiology to mechanisms, management, and dietary recommendations for MAFLD. The recommended dietary strategies emphasize adherence to a balanced diet with controlled energy intake and personalized nutritional interventions, such as calorie restriction, high-protein, or low-carbohydrate diets. Specific dietary advice encouraged increasing the consumption of whole grains, plant-based proteins, fish, seafood, low-fat or fat-free dairy products, liquid plant oils, and deeply colored fruits and vegetables. Concurrently, it advised reducing the intake of red and processed meats, saturated and trans fats, ultra-processed foods, added sugars, and alcohol. Additionally, maintaining the Mediterranean or DASH diet, minimizing sedentary behavior, and engaging in regular physical activity are recommended. These consensus statements lay the foundation for customized dietary guidelines and proposing avenues for further research on nutrition and MAFLD.

Effect of peanut butter supplementation on physical and cognitive functions in community-dwelling older adults: study protocol for a 6-month randomised controlled trial.

INTRODUCTION: Ageing is associated with physical and cognitive declines, which may be further exacerbated by poor nutrition. Nuts are energy and nutrient dense, and their consumption is associated with better physical and cognitive functions in older adults, but data from interventional studies are limited. This 6-month randomised controlled trial is designed to investigate the effects of consuming 43 g/day of peanut butter (equivalent to 1.5 servings of nuts) on physical function, including walking speed (primary outcome), standing and dynamic balance, upper and lower body strength, lower body power and endurance, and associated factors including muscle mass, cognitive function and DNA telomere length in community-dwelling older adults. METHOD AND ANALYSIS: A total of 120 participants aged ≥65 years will be recruited and randomly allocated (1:1 ratio) to either the intervention group (n=60) that will receive individually packaged sealed containers containing 43 g of peanut butter to be consumed once daily for 6 months alongside habitual diet, or the control group (n=60) that will maintain their habitual diet. Primary and secondary outcomes will be assessed at baseline and at 6 months. The primary outcome is walking speed assessed using the 4 m usual gait speed test. Secondary outcomes include other physical function assessments: standing balance, chair stand time, timed-up-and-go test and four-square step test; and hand grip and knee extensor muscle strength; cognitive function assessed using the Montreal Cognitive Assessment and trail making tests; body composition; nutritional status; and DNA telomere length from participants' buccal cell samples. Linear mixed models will be used to compare changes in outcomes between intervention and control groups. ETHICS AND DISSEMINATION: The study protocol is approved by the Deakin University Human Research Ethics Committee. The trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12622001291774. The results will be disseminated through peer-reviewed journals, conference presentations and media. TRIAL REGISTRATION NUMBER: ANZCTR12622001291774.

Strong Activation of ID1, ID2, and ID3 Genes Is Coupled with the Formation of Vasculogenic Mimicry Phenotype in Melanoma Cells.

Gene expression patterns are very sensitive to external influences and are reflected in phenotypic changes. It was previously described that transferring melanoma cells from a plastic surface to Matrigel led to formation of de novo vascular networks-vasculogenic mimicry-that are characteristic to a stemness phenotype in aggressive tumors. Up to now there was no detailed data about the gene signature accompanying this process. Here, we show that this transfer shortly led to extremely strong epigenetic changes in gene expression in the melanoma cells. We observed that on Matrigel numerous genes controlling ribosome biogenesis were upregulated. However, most of the activated genes were inhibitors of the differentiation genes (ID1, ID2, and ID3). At the same time, the genes that control differentiation were downregulated. Both the upregulated and the downregulated genes are simultaneously targeted by different transcription factors shaping sets of co-expressed genes. The specific group of downregulated genes shaping contacts with rDNA genes are also associated with the H3K27me3 mark and with numerous lincRNAs and miRNAs. We conclude that the stemness phenotype of melanoma cells is due to the downregulation of developmental genes and formation of dedifferentiated cells.

α-Klotho is associated with cardiovascular and all-cause mortality in patients with stage 3b and 4 chronic kidney disease (CKD): a long-term prospective cohort study.

BACKGROUND: α-Klotho deficiency may increase cardiovascular risks and worsen survival. We evaluated the association of α-Klotho with cardiovascular and all-cause mortality in pre-dialysis chronic kidney disease (CKD) patients. METHODS: In this prospective study, 75 non-diabetic CKD stage 3b-4 patients were followed-up for a median of 8 years. Primary and secondary outcomes were all-cause and cardiovascular mortality, respectively. Human soluble α-Klotho ELISA Assay (IBL-Takara 27,998-96Well), Human Fibroblast Growth Factor-23 ELISA Assay (intact FGF23, Merck Millipore MILLENZ FGF23-32 K), and Human Sclerostin ELISA kits (Biomedica, Vienna, BI-20492) were used to measure serum α-Klotho, FGF23 and sclerostin levels in the certified laboratory at the Sechenov University according to the manufacturers' protocols. All patients underwent echocardiography to evaluate left ventricular mass index (LVMI), left ventricular ejection fraction by Simpson method, and cardiac (valve) calcification score by a semi-quantitative point scale. Lateral abdominal radiography by Kauppila method was used to estimate calcification of the abdominal aorta. Cox multivariate regression and receiver-operating characteristic curve (ROC)-analysis were used to evaluate risk factors for death and their cut-off values. RESULTS: Primary and secondary endpoints were reached in 15 (20%) and 9 (12%) patients, respectively. Median α-Klotho levels in deceased and surviving patients were 344 and 484 pg/ml, respectively (p = 0.002). In a multivariate Cox regression model, baseline α-Klotho levels (HR 0.99, 95% CI 0.98-1.00, p = 0.023), aortic calcification (HR 1.18, 95% CI 1.02-1.36, p = 0.029) and left ventricular mass index (LVMI) (HR 1.04, 95% CI 1.00-1.08, p = 0.033) were associated with the primary endpoint, whereas α-Klotho (HR 0.99, 95% CI 0.98-1.00, p = 0.029), aortic calcification (HR 1.23, 95% CI 1.07-1.42, p = 0.003) and LVMI (HR 1.04, 95% CI 1.00-1.08, p = 0.021) were associated with the secondary endpoint. α-Klotho levels had the highest area under the curve (AUC) by ROC analysis, that is, 0.766 (95% CI 0.70-0.82) for the primary endpoint and 0.842 (95% CI 0.79-0.90) for the secondary endpoint with cut-off values of 412 pg/ml (HR 3.06, 95% CI 1.36-6.89, p = 0.007) and 368 pg/ml (HR 4.84, 95% CI 1.59-14.73, p = 0.005), respectively. CONCLUSION: In pre-dialysis CKD patients, α-Klotho levels are associated with all-cause and cardiovascular mortality and may be considered an early prognostic marker.

Regulatory Pathways for Qualification and Acceptance of Digital Health Technology-Derived Clinical Trial Endpoints: Considerations for Sponsors.

Despite widespread interest and substantial investment in the adoption of sensor-based digital health technologies (sDHTs) for remote data capture in drug development trials, no drug has been approved based on an sDHT-derived primary endpoint in the United States (US). One reason for this lack of advancement is the complexity of obtaining regulatory endorsement for those endpoints within current US regulatory pathways. The goal of our review is to describe the two choices currently available to pharmaceutical study Sponsors: (i) they may navigate the traditional route of compiling the evidence to support the sDHT-derived endpoint in their investigational new drug (IND) application, requiring specific expertise and substantial resources; or (ii) they may navigate the drug development tool (DDT) pathway with the goal of qualifying their sDHT-derived endpoint as a biomarker or clinical outcome assessment applicable to a broader context of use (COU), either alone or as part of a partnership or consortium. We describe the nuances of each pathway; the evidentiary requirements for supporting an sDHT-derived endpoint and the technology used to capture it; and the impact that an sDHT's regulatory status may have on a Sponsor's decision to use it for data capture. By systematically comparing the IND and DDT pathways, our over-arching goals are to support the increasing deployment of sDHTs within the clinical research setting and help advance regulatory science in the field of digital medicine.

Substituents' Effect on the Photophysics of Trinuclear Copper(I) and Silver(I) Pyrazolate-Phosphine Cages.

A series of structurally similar trinuclear macrocyclic copper(I) and silver(I) pyrazolate complexes bearing various short-bite diphosphine R2PCH(R')PR2 ligands are reported. Upon diphosphine coordination, the planar geometry of the initial complexes undergoes bending along the line between two metal atoms coordinated to the phosphorus moieties. The complexes based on dcpm ligands (R = cyclohexyl, R' = H, Ph) do not exhibit dynamic behavior in solution at room temperature on the 31P NMR time scale as it was previously observed for similar trinuclear copper complexes bearing the dppm (R = Ph, R' = H) scaffold. All copper(I) complexes exhibit thermally activated delayed fluorescence (TADF) behavior in the solid state. Importantly, the use of aliphatic substituents on the phosphorus atoms instead of aromatic ones leads to an almost double increase in the quantum efficiency (ΦPL) of photoluminescence by eliminating nonradiative decay from the 3LCPh states of the dppm aromatic rings. The higher donating ability of the substituents in the pyrazolate ligand (CF3 vs CH3) lowers the energy of the metal-centered excited state, allowing for a significant metal impact on the T1 state. Finally, the Ag(I) complex displays an emission efficiency of approximately 14%, being the highest among known trinuclear silver(I) pyrazolate homometallic derivatives.

The Ames room and the misunderstood versions and depictions.

The Ames room illusion is one of the best-known geometrical illusions but its geometrical properties are often misunderstood. This study discusses the differences in the geometrical properties between the original Ames room and what have been often referred to as "Ames rooms" in recent studies.

Improving quality control procedures for the measurement of total daily energy expenditure using the two-point doubly labeled water method.

RATIONALE: The precision of the doubly labeled water (DLW) method is determined by the precision and accuracy of the isotopic measurements. Quality control (QC) procedures to mitigate sample variability require additional measurements if sample duplicates differ more than a factor of instrument precision. We explored the effect of widening QC ranges on total daily energy expenditure (TDEE) determined using the two-point sampling method. METHODS: We screened DLW data from 121 individuals for instances where samples were analyzed more than twice using our existing QC criteria (±2.0 per mil [δ] for 2H and ±0.5 δ for 18O). We then applied wider QC ranges for accepting duplicate measures and recalculated TDEE. RESULTS: Widening the 2H QC range to ±10.0 δ in samples collected on the first day (most enriched) and to ±5.0 δ in samples collected on the final day (less enriched) produced almost identical mean TDEE compared to the originally calculated TDEE (2684 ± 508 vs. 2687 ± 512 kcal/day, p = 0.40). There was a strong correlation with the originally calculated TDEE (r2 = 0.97, p < 0.001). CONCLUSIONS: Expanding the 2H QC range to ±10.0 δ for samples collected on the first day and ±5.0 δ for samples collected on the final day provides similar mean TDEE results. These findings may help DLW labs optimize QC criteria and reduce analytical costs.

Microfluidic Detection of SPIONs and Co-Ferrite Ferrofluid Using Amorphous Wire Magneto-Impedance Sensor.

The detection of magnetic nanoparticles in a liquid medium and the quantification of their concentration have the potential to improve the efficiency of several relevant applications in different fields, including medicine, environmental remediation, and mechanical engineering. To this end, sensors based on the magneto-impedance effect have attracted much attention due to their high sensitivity to the stray magnetic field generated by magnetic nanoparticles, their simple fabrication process, and their relatively low cost. To improve the sensitivity of these sensors, a multidisciplinary approach is required to study a wide range of soft magnetic materials as sensing elements and to customize the magnetic properties of nanoparticles. The combination of magneto-impedance sensors with ad hoc microfluidic systems favors the design of integrated portable devices with high specificity towards magnetic ferrofluids, allowing the use of very small sample volumes and making measurements faster and more reliable. In this work, a magneto-impedance sensor based on an amorphous Fe73.5Nb3Cu1Si13.5B9 wire as the sensing element is integrated into a customized millifluidic chip. The sensor detects the presence of magnetic nanoparticles in the ferrofluid and distinguishes the different stray fields generated by single-domain superparamagnetic iron oxide nanoparticles or magnetically blocked Co-ferrite nanoparticles.

Exploring Experiences of People With Knee Osteoarthritis Who Received a Physiotherapist-Delivered Dietary Weight Loss and Exercise Intervention: A Mixed Methods Study.

OBJECTIVE: Explore the experiences of people with knee osteoarthritis (OA) who received a very low energy diet (VLED) and exercise program from a physiotherapist. METHODS: Mixed methods study involving questionnaires (n = 42) and semistructured interviews (n = 22) with randomized control trial participants with knee OA who had received a 6-month physiotherapist-delivered VLED weight loss and exercise intervention. Questionnaires measured participant satisfaction and perceptions about physiotherapist's skills/knowledge in delivery of the dietary intervention (measured on 5-7 point Likert scales). Interviews explored participant's experiences and were analyzed based on the principles of reflexive thematic analysis. RESULTS: Questionnaire response: 90%. Participants were satisfied with the program (95%), confident their physiotherapist had the required skills (84%) and knowledge (79%) to deliver the dietary intervention, felt comfortable talking to the physiotherapist about weight (74%), and would recommend others see a physiotherapist for the intervention they undertook (71%). The following four themes were developed from the interviews: (1) one-stop-shop of exercise and diet; (2) physiotherapist-delivered weight loss works (unsure initially; successfully lost weight); (3) physiotherapists knowledge and skills (exercise is forte; most thought physiotherapists had the necessary weight loss skills/knowledge, but some disagreed); and (4) physiotherapists have a role in weight loss (physiotherapists are intelligent, credible, and trustworthy; specific training in weight loss necessary). CONCLUSION: This study provides, to our knowledge, the first documented perspectives from people with OA who have received a physiotherapist-delivered weight loss intervention. Findings suggest physiotherapists may have a role in delivering a protocolized dietary intervention for some people with knee OA with overweight and obesity.

Spatial Landscape of Malignant Pleural and Peritoneal Mesothelioma Tumor Immune Microenvironments.

Immunotherapies have demonstrated limited clinical efficacy in malignant mesothelioma treatment. We conducted multiplex immunofluorescence analyses on tissue microarrays (n = 3) from patients with malignant pleural mesothelioma (MPM, n = 88) and malignant peritoneal mesothelioma (MPeM, n = 25). Our study aimed to elucidate spatial distributions of key immune cell populations and their association with lymphocyte activation gene 3 (LAG3), BRCA1-associated protein 1 (BAP1), neurofibromatosis type 2 (NF2), and methylthioadenosine phosphorylase (MTAP), with MTAP serving as a cyclin-dependent kinase inhibitor 2A/2B (CDKN2A/B) surrogate marker. Additionally, we examined the relationship between the spatial distribution of major immune cell types and prognosis and clinical characteristics of patients with malignant mesothelioma. We observed a higher degree of interaction between immune cells and tumor cells in MPM compared with MPeM. Notably, within MPM tumors, we detected a significantly increased interaction between tumor cells and CD8+ T cells in tumors with low BAP1 expression compared with those with high BAP1 expression. To support the broader research community, we have developed The Human Spatial Atlas of Malignant Mesothelioma, containing hematoxylin and eosin and multiplex immunofluorescence images with corresponding metadata. SIGNIFICANCE: Considering the limited therapeutic options available to patients with malignant mesothelioma, there is substantial translational potential in understanding the correlation between the spatial architecture of the malignant mesothelioma tumor immune microenvironment and tumor biology. Our investigation reveals critical cell-cell interactions that may influence the immune response against malignant mesothelioma tumors, potentially contributing to the differential behaviors observed in MPM and MPeM. These findings represent a valuable resource for the malignant mesothelioma cancer research community.

The burden of non-alcoholic fatty liver disease in Australia: an analysis of Global Burden of Disease study from 1990 to 2019.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease. Global Burden of Disease (GBD) data from 1990 to 2019 reported a rise in prevalence (9-13%) in Australia, which also ranked third highest for NAFLD prevalence compared to 14 similar countries. As a result of underdiagnosis, NAFLD burden is underestimated by GBD.