Diet influences knee osteoarthritis osteophyte formation via gut microbiota and serum metabolites.

Osteophyte formation, a key indicator of osteoarthritis (OA) severity, remains poorly understood in its relation to gut microbiota and metabolites in knee osteoarthritis (KOA). We conducted 16S rDNA sequencing and untargeted metabolomics on fecal and serum samples from 20 healthy volunteers, 80 KOA patients in Guangdong, and 100 in Inner Mongolia, respectively. Through bioinformatics analysis, we identified 3 genera and 5 serum metabolites associated with KOA osteophyte formation. Blautia abundance negatively correlated with meat, cheese, and bean consumption. The 5 serum metabolites negatively correlated with dairy, beef, cheese, sugar, and salt intake, yet positively with age and oil consumption. Higher Blautia levels in the gut may contribute to KOA osteophyte formation, with serum metabolites LTB4 and PGD2 potentially serving as biomarkers. KOA patients in Inner Mongolia exhibited lower Blautia levels and reduced expression of 5 serum metabolites, possibly due to cheese consumption habits, resulting in less osteophyte formation.

The influence of supervisory support on clinical learning as experienced by Czech Nursing and health professional students in the context of patient safety events: A qualitative study.

AIM: To explore the influence of supervisory and mentoring relationships on the clinical learning experiences of Czech Nursing and health professional students in the context of patient safety events BACKGROUND: Clinical experience is integral to healthcare education, shaping skills, behaviours, values and professional identity. During clinical placements, students may encounter memorable patient safety events and experience varied reactions from mentors/supervisors/others. Some research has highlighted challenges faced by students on clinical placement. Few studies involve multiple professions, most emanating from Western Europe, the UK, the USA and Australia with little relating to central European countries such as the Czech Republic. DESIGN: Two stage interpretivist qualitative study based in social constructionism METHODS: Convenience sample across 13 undergraduate and 18 postgraduate health professions courses. Stage 1 (2022): using SLIPPS Learning Event Recording Tool translated into Czech. 20 students' (Midwifery=11, Nursing=1, Paramedic=1, Occupational therapy =7) submitted 21 patient safety learning event narratives. Stage 2 (2022): Focus group with 2 nursing and nine midwifery students. Phased thematic analysis involving multiple researchers. RESULTS: Three themes illustrate the circumstances and impact of placement mentoring/supervision experiences, conceptualised as: 'Clinical and Emotional Companionship', 'Clinical and Emotional Abandonment' and 'Sense of agency - Professional and personal growth'. 'Companionship' reflected the students' feelings of being welcomed, respected, heard, trusted and supported. Conversely 'abandonment' emerged from feelings of being unheard, vulnerable, humiliated, afraid, leaving students feeling abandoned, lonely and 'useless'. Notwithstanding these conditions, students showed the ability to identify patient safety issues with agency evident in reactions such as stepping-in to try to ameliorate a situation, rather than speaking-up. Professional and personal growth was also apparent in their narratives and a conceptual diagram illustrates the students' learning journeys in a patient safety context. CONCLUSION: The findings and new conceptualisations around abandonment and companionship emerging from this study expand the evidence base regarding the profound impact of clinical experience and mentorship/supervision on learning and students' emotional wellbeing. A sense of companionship appears to play a buffering role even in challenging circumstances of involvement in or witnessing compromised patients' safety. Allowing students a sense of belonging, to vent, grow, feel supported and safe to ask/learn - contributing to 'emotional safety for learning', promotes students' behaviour that may prevent/minimize hazards or ameliorate the aftermath. However, we must not simply blame mentors/supervisors, staff, or the students themselves- they are simply part of a much larger complex environment of professional education encompassing hidden curriculums, power dynamics and professional socialisation.

Developing education in environmental health and medicine focusing on neurology: Initiatives in Sweden (the UPRISE model), France, and Turkey.

BACKGROUND: The role of environmental factors in neurological disorders constitutes a topic of increasing importance. Teaching in European universities should expand and update this field gaining future health professionals including adjacent disciplines. AIM: To describe recent efforts to create courses that cover crucial interdisciplinary content that we believe should be included in modern education, and to adapt modern pedagogic strategies. METHODS: In collaboration with RISE (Rencontres Internationales Santé Environnement), elective courses focused on Environmental Health and Medicine (EHM) were developed, in France, Sweden, and Turkey. The courses combined classic teaching methods and new pedagogic and digital solutions to create environment-related health awareness and facilitate future interprofessional collaboration in this field. RESULTS: UPRISE is an innovative elective course introduced in 2020 in Sweden's Uppsala University with the participation of lecturers from several countries and aim to recruit students from different universities. A total of 45, mainly female students (68%), participated in the course. In Strasbourg, France, a novel course on environmental medicine was held in 2019-2023 and examined 90 students, of which more than half were female. Nine graduate nurse students in Turkey attended ten seminar series focused on EHM. Overall, students expressed satisfaction with the courses. CONCLUSIONS: This European project for courses in higher education arising from RISE was met with appreciation and challenges from academic institutions. However, due to considerable efforts to introduce the EHM concept, a unique compulsory course for all medical students in the second year of training started in 2023 in all French medical faculties. In 2023, UPRISE was integrated into ENLIGHT, the European University Network to promote equitable quality of Life, sustainability, and Global engagement through Higher education Transformation.

Protocol for three-dimensional whole-mount imaging of the vascular network in the intestinal muscle.

Three-dimensional (3D) imaging of vascular networks is essential for the investigation of vascular patterning and organization. Here, we present a step-by-step protocol for the 3D visualization of the vasculature within whole-mount preparations of the mouse intestinal muscularis propria layer. We then detail the quantitative analysis of the resulting images for parameters such as vessel density, vessel diameter, the number of endothelial cells, and proliferation. The protocol can be easily extended to study cell-cell interactions such as neuro-vascular or immune-vascular interactions. For complete details on the use and execution of this protocol, please refer to Schrenk et al.1.

Sleep, physical activity, and sedentary behaviors in relation to overall cancer and site-specific cancer risk: A prospective cohort study.

Large prospective studies are required to better elucidate the associations of physical activity, sedentary behaviors (SBs), and sleep with overall cancer and site-specific cancer risk, accounting for the interactions with genetic predisposition. The study included 360,271 individuals in UK Biobank. After a median follow-up of 12.52 years, we found higher total physical activity (TPA) level and higher sleep scores were related to reduced risk of cancer while higher SB level showed a positive association with cancer. Compared with high TPA-healthy sleep group and low SB-healthy sleep group, low TPA-poor sleep group and high SB-poor sleep group had the highest risk for overall cancer, breast cancer, and lung cancer. Adherence to a more active exercise pattern was associated with a lower risk of cancer irrespective of genetic risk. Our study suggests that improving the quality of sleep and developing physical activity habits might yield benefits in mitigating the cancer risk.

Monoclonal antibody biosimilars for cancer treatment.

Monoclonal antibodies are important cancer medicines. The European Medicines Agency (EMA) approved 48 and the Food and Drug Administration (FDA) 56 anticancer monoclonal antibody-based therapies. Their high prices burden healthcare systems and hamper global drug access. Biosimilars could retain costs and expand the availability of monoclonal antibodies. In Europe, five rituximab biosimilars, six trastuzumab biosimilars, and eight bevacizumab biosimilars are available as anti-cancer drugs. To gain insight into the biosimilar landscape for cancer treatment, we performed a literature search and analysis. In this review, we summarize cancer monoclonal antibodies' properties crucial for the desired pharmacology and point out sources of variability. The analytical assessment of all EMA-approved bevacizumab biosimilars is highlighted to illustrate this variability. The global landscape of investigational and approved biosimilars is mapped, and the challenges for access to cancer biosimilars are identified.

Clinical features and multiomics profiles indicate coagulation and platelet dysfunction in COVID-19 viral sepsis.

Increased cases of sepsis during COVID-19 in the absence of known bacterial pathogens highlighted role of viruses as causative agents of sepsis. In this study, we investigated clinical, laboratory, proteomic, and metabolomic characteristics of viral sepsis patients (n = 45) and compared them to non-sepsis patients with COVID-19 (n = 186) to identify molecular mechanisms underlying the pathology of viral sepsis in COVID-19. We identified unique metabolomic and proteomic signatures that suggest a substantial perturbation in the coagulation, complement, and platelet activation pathways in viral sepsis. Our proteomic data indicated elevated coagulation pathway protein (fibrinogen), whereas a decrease in many of the complement proteins was observed. These alterations were associated with the functional consequences such as susceptibility to secondary bacterial infections and potentially contributing to both local and systemic disease phenotypes. Our data provide novel aspect of COVID-19 pathology that is centered around presence of sepsis phenotype in COVID-19.

DUSP6 deletion protects mice and reduces disease severity in autoimmune arthritis.

Receptor tyrosine kinases (RTKs) have an important role in arthritis severity and in models of rheumatoid arthritis (RA), but their regulation is not fully understood. The dual specificity phosphatase 6 (DUSP6) has been implicated in the regulation of RTK signaling, but never in the context of arthritis and autoimmunity. We used the KRN serum-induced arthritis (KSIA) model of RA and showed that DUSP6-/- mice were protected and had a 50% lower maximum arthritis score (p = 0.006) and reduced joint damage than C57BL/6 DUSP6+/+ controls. Serum levels of interleukin (IL) 10 were significantly increased (>2-fold), and IL6 decreased in DUSP6-/- mice. DUSP6-/- mice had increased numbers of IL10+ cells including Tr1 regulatory cells (p < 0.01). Introduction of the IL10-/- into DUSP6-/- (double knockout [KO]) reversed the DUSP6-/- protection. In conclusion, this study reports a pro-arthritic role for DUSP6. This discovery has the potential to generate a previously unknown target for therapies for RA and inflammatory diseases.

The virtual multiple sclerosis patient.

Multiple sclerosis (MS) diagnosis typically involves assessing clinical symptoms, MRI findings, and ruling out alternative explanations. While myelin damage broadly affects conduction speeds, traditional tests focus on specific white-matter tracts, which may not reflect overall impairment accurately. In this study, we integrate diffusion tensor immaging (DTI) and magnetoencephalography (MEG) data into individualized virtual brain models to estimate conduction velocities for MS patients and controls. Using Bayesian inference, we demonstrated a causal link between empirical spectral changes and inferred slower conduction velocities in patients. Remarkably, these velocities proved superior predictors of clinical disability compared to structural damage. Our findings underscore a nuanced relationship between conduction delays and large-scale brain dynamics, suggesting that individualized velocity alterations at the whole-brain level contribute causatively to clinical outcomes in MS.

Different trends of gastric cancer in China, Japan, Republic of Korea and United States of America.

Gastric cancer exerts a significant healthcare burden worldwide and is highly geographically heterogeneous. This study investigates the burden of gastric cancer in China from 1990 to 2019 and compares it with Japan, South Korea, and the United States. The results indicated a declining trend in ASIR and ASDR in four countries. However, the incidence and death rates in China remain disproportionately high. Significant gender disparities exist in the incidence and death rates, with males experiencing significantly higher rates than females. Incidence and death rates were found to increase with age in all studied countries. In China, a transient upward trend was observed in the period effect, whereas the cohort effect has been declining. In contrast, the remaining countries showed decreasing patterns in both period and cohort effects. The burden of disease remains high in China, therefore, broaden the scope of gastroscopy screening and concentrate on high-risk groups is vital.

Protocol for producing hyperpolarized 13C-bicarbonate for clinical MRI of extracellular pH in aggressive tumors.

Tumor acidosis is one of the hallmarks indicating the initiation and progression of various cancers. Here, we present a protocol for preparing a hyperpolarized (HP) 13C-bicarbonate tissue pH MRI imaging contrast agent to detect aggressive tumors. We describe the steps for the formulation and polarization of a precursor molecule 13C-glycerol carbonate (13C-GLC), the post-dissolution reaction, and converting HP 13C-GLC to an injectable HP 13C-bicarbonate solution. We then detail procedures for MRI data acquisition to generate tumor pH maps for assessing tumor aggressiveness. For complete details on the use and execution of this protocol, please refer to Mu et al.1.

Protocol for detecting micro(nano)plastics released from intravenous infusion products.

Approaches for detecting micro(nano)plastics (MNPs) released from intravenous infusion products (IVIPs) are vital for evaluating the safety of both IVIPs and their derived MNPs on human health, yet current understanding is limited. Here, we present a protocol for detecting polyvinyl chloride (PVC) MNPs by combining Raman spectroscopy, scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy (SEM-EDS), and pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS). We describe steps for collecting, pretreating, and measuring PVC MNPs released from IVIPs. For complete details on the use and execution of this protocol, please refer to Li et al.1.

Effects of Transition from Remote to In-Person Learning in University Students: A Longitudinal Study.

Previous studies have shown that the transition from the University environment to remote learning impacted student mental health. Our study aimed to investigate the effects of university environment on anxiety and depressive symptoms in health sciences students. Students at the Technical University of Manabí, Ecuador, with 6-10 in-person semesters, who shifted to remote learning and then returned to face-to-face learning were selected. Students responded to the General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). In addition, questions regarding social interaction, physical exercise, mood and sleep habits were also asked. This longitudinal study tracked 323 students during the return to in-person classes and term end. The results showed similar rates of anxiety (GAD-7, p = 0.011-p = 0.002) and depression (PHQ-9 p = 0.001-p = 0.032) among students at week 1 and week 15. Previous diagnosis of depression (OR, 0.171; CI 0.050-0.579, p < 0.005) was shown to correlate with depression levels in week 1, with no changes seen at follow-up. Anxiety levels were shown to be associated with a previous diagnosis of the disorder at week 1, but not at follow-up (OR 0.233; CI 0.085-0.643, p < 0.005). The return to in-person learning among university students maintained levels of anxiety and depressive symptoms, underscoring ongoing vulnerabilities to mental health disorders in this group.

Developing and conducting a language inclusivity assessment on a health science library's website, LibGuides, and signage.

Background: A Diversity, Equity, and Inclusion (DEI) Team at a university health science library created a checklist for inclusive language and conducted an assessment of their library's website, LibGuides, and physical and digital signage. Inclusive language was defined as "language that is free from words, phrases or tones that reflect prejudiced, stereotyped or discriminatory views of particular people or groups". Case Presentation: The 32-item checklist facilitated the identification of gendered language, stereotypes, ableist language, racist language, stigmatizing language, slang, acronyms, and out-of-date terminology regarding physical and mental health conditions. From the library's website, 20 instances were noted for which improvements were necessary. Out of the 130 LibGuides reviewed, 23 LibGuides had no changes needed and 107 had changes identified relating to language inclusivity (14 strongly recommended changes and 116 suggested changes). Regarding the signage, one flyer was removed for reprinting. Conclusion: The checklist enabled the team to implement a number of improvements to the library's website and LibGuides. The checklist has been shared with Library Technology Services and the wider campus libraries' Usability Committee for future use, and has also been added to the DEI Team's LibGuide for use by others outside of the university.

Protocol for Seahorse analysis of ex vivo mouse brown and white adipose tissues.

The mitochondrial stress test is a gold-standard approach for assessing adipose tissue physiological functions and pathological changes. Here, we present a protocol for conducting Seahorse assays using ex vivo mouse brown and white adipose depots. We describe steps for rehydrating the cartridge, preparing freshly harvested fat depots, placing them onto an islet capture plate, and incubating them in a non-CO2 incubator. We then detail procedures for adding mitochondrial stressor solutions and conducting the mitochondrial stress test using the Seahorse XFe24 Analyzer. For complete details on the use and execution of this protocol, please refer to An et al.1.

Protocol to optimize the Rice-Vannucci rat pup model of perinatal asphyxia to ensure predictable hypoxic-ischemic cerebral lesions.

The Rice-Vannucci model in rodent pups is subject to substantial loss of animals, result inconsistency, and high lab-to-lab variability in extent and composition of induced injury. This protocol allows for highly predictable and reproducible hypoxic-ischemic cerebral injury lesions in post-natal day 10 Wistar rat pups with no mortality. We describe steps for common carotid artery ligation, brief post-operative normothermia, exposure to hypoxia, and post-hypoxic normothermia. Precise timing and temperature control in each step are crucial for a successful procedure. For complete details on the use and execution of this protocol, please refer to Hartman et al.1.

Protocol for fiber photometry recording from deep brain regions in head-fixed mice.

To exclude the influence of motion on in vivo calcium imaging, animals usually need to be fixed. However, the whole-body restraint can cause stress in animals, affecting experimental results. In addition, some brain regions are prone to bleeding during surgery, which lowers the success rate of calcium imaging. Here, we present a protocol for calcium imaging using heparin-treated fiber in head-fixed mice. We describe steps for stereotaxic surgery, including virus injection and optic fiber implantation, fiber photometry, and data analysis. For complete details on the use and execution of this protocol, please refer to Du et al.1.

High-throughput screening identifies broad-spectrum Coronavirus entry inhibitors.

The COVID-19 pandemic highlighted the need for antivirals against emerging coronaviruses (CoV). Inhibiting spike (S) glycoprotein-mediated viral entry is a promising strategy. To identify small molecule inhibitors that block entry downstream of receptor binding, we established a high-throughput screening (HTS) platform based on pseudoviruses. We employed a three-step process to screen nearly 200,000 small molecules. First, we identified hits that inhibit pseudoviruses bearing the SARS-CoV-2 S glycoprotein. Counter-screening against pseudoviruses with the vesicular stomatitis virus glycoprotein (VSV-G), yielded sixty-five SARS-CoV-2 S-specific inhibitors. These were further tested against pseudoviruses bearing the MERS-CoV S glycoprotein, which uses a different receptor. Out of these, five compounds, which included the known broad-spectrum inhibitor Nafamostat, were subjected to further validation and tested against pseudoviruses bearing the S glycoprotein of the Alpha, Delta, and Omicron variants as well as bona fide SARS-CoV-2. This rigorous approach revealed an unreported inhibitor and its derivative as potential broad-spectrum antivirals.

Integrative neurovascular coupling and neurotransmitter analyses in anisometropic and visual deprivation amblyopia children.

The association between visual abnormalities and impairments in cerebral blood flow and brain region potentially results in neural dysfunction of amblyopia. Nevertheless, the differences in the complex mechanisms of brain neural network coupling and its relationship with neurotransmitters remain unclear. Here, the neurovascular coupling mechanism and neurotransmitter activity in children with anisometropic amblyopia (AA) and visual deprivation amblyopia (VDA) was explored. The neurovascular coupling of 17 brain regions in amblyopia children was significantly abnormal than in normal controls. The classification abilities of coupling units in brain regions differed between two types of amblyopia. Correlations between different coupling effects and neurotransmitters were different. The findings of this study demonstrate a correlation between the neurovascular coupling and neurotransmitter in children with AA and VDA, implying their impaired neurovascular coupling function and potential molecular underpinnings. The neuroimaging evidence revealed herein offers potential for the development of neural therapies for amblyopia.

Cerebrospinal fluid and plasma concentrations of the inflammatory marker soluble CD27 in a large surgical population.

Soluble CD27 (sCD27) is a potential biomarker for diseases involving immune dysfunction. As there is currently little data on cerebrospinal fluid (CSF) sCD27 concentrations in the general population we measured CSF and plasma concentrations in 486 patients (age range 18-92 years, 57% male) undergoing spinal anesthesia for elective surgery. Across the complete cohort the median [range] sCD27 concentrations were 163 [<50 to 7474] pg/mL in CSF and 4624 [1830 to >400,000] pg/mL in plasma. Plasma sCD27, age and Qalb were the factors most strongly associated with CSF sCD27 levels. Reference sCD27 concentration intervals (central 95% of values) in a sub-group without the indication of neuropsychiatric, inflammatory or systemic disease (158 patients) were <50 pg/mL - 419 pg/mL for CSF and 2344-36422 pg/mL for plasma. These data provide preliminary reference ranges that could inform future studies of the validity of sCD27 as a biomarker for neuro- and systemic inflammatory disorders.