Simultaneous Positron Emission Tomography and Molecular Magnetic Resonance Imaging of Cardiopulmonary Fibrosis in a Mouse Model of Left Ventricular Dysfunction.

BACKGROUND: Aging-associated left ventricular dysfunction promotes cardiopulmonary fibrogenic remodeling, Group 2 pulmonary hypertension (PH), and right ventricular failure. At the time of diagnosis, cardiac function has declined, and cardiopulmonary fibrosis has often developed. Here, we sought to develop a molecular positron emission tomography (PET)-magnetic resonance imaging (MRI) protocol to detect both cardiopulmonary fibrosis and fibrotic disease activity in a left ventricular dysfunction model. METHODS AND RESULTS: Left ventricular dysfunction was induced by transverse aortic constriction (TAC) in 6-month-old senescence-accelerated prone mice, a subset of mice that received sham surgery. Three weeks after surgery, mice underwent simultaneous PET-MRI at 4.7 T. Collagen-targeted PET and fibrogenesis magnetic resonance (MR) probes were intravenously administered. PET signal was computed as myocardium- or lung-to-muscle ratio. Percent signal intensity increase and Δ lung-to-muscle ratio were computed from the pre-/postinjection magnetic resonance images. Elevated allysine in the heart (P=0.02) and lungs (P=0.17) of TAC mice corresponded to an increase in myocardial magnetic resonance imaging percent signal intensity increase (P<0.0001) and Δlung-to-muscle ratio (P<0.0001). Hydroxyproline in the heart (P<0.0001) and lungs (P<0.01) were elevated in TAC mice, which corresponded to an increase in heart (myocardium-to-muscle ratio, P=0.02) and lung (lung-to-muscle ratio, P<0.001) PET measurements. Pressure-volume loop and echocardiography demonstrated adverse left ventricular remodeling, function, and increased right ventricular systolic pressure in TAC mice. CONCLUSIONS: Administration of collagen-targeted PET and allysine-targeted MR probes led to elevated PET-magnetic resonance imaging signals in the myocardium and lungs of TAC mice. The study demonstrates the potential to detect fibrosis and fibrogenesis in cardiopulmonary disease through a dual molecular PET-magnetic resonance imaging protocol.

Rapid differentiation of cystic fibrosis-related bacteria via reagentless atmospheric pressure photoionisation mass spectrometry.

Breath analysis is an area of significant interest in medical research as it allows for non-invasive sampling with exceptional potential for disease monitoring and diagnosis. Volatile organic compounds (VOCs) found in breath can offer critical insight into a person's lifestyle and/or disease/health state. To this end, the development of a rapid, sensitive, cost-effective and potentially portable method for the detection of key compounds in breath would mark a significant advancement. Herein, we have designed, built and tested a novel reagent-less atmospheric pressure photoionisation (APPI) source, coupled with mass spectrometry (MS), utilising a bespoke bias electrode within a custom 3D printed sampling chamber for direct analysis of VOCs. Optimal APPI-MS conditions were identified, including bias voltage, cone voltage and vaporisation temperature. Calibration curves were produced for ethanol, acetone, 2-butanone, ethyl acetate and eucalyptol, yielding R2 > 0.99 and limits of detection < 10 pg. As a pre-clinical proof of concept, this method was applied to bacterial headspace samples of Escherichia coli (EC), Pseudomonas aeruginosa (PSA) and Staphylococcus aureus (SA) collected in 1 L Tedlar bags. In particular, PSA and SA are commonly associated with lung infection in cystic fibrosis patients. The headspace samples were classified using principal component analysis with 86.9% of the total variance across the first three components and yielding 100% classification in a blind-sample study. All experiments conducted with the novel APPI arrangement were carried out directly in real-time with low-resolution MS, which opens up exciting possibilities in the future for on-site (e.g., in the clinic) analysis with a portable system.

The "Fact of the Matter": A Model for Working with Activated Internal Object Relations in Psychodynamic Couple Therapy.

Extensive clinical scholarship has described the application of object-relational principles, particularly the operation of projective identification, to psychodynamic psychotherapy with couples. The author explores the way in which a more complete depiction of projective processes, one that incorporates each partner's intrapersonal management of multiple internal object relations, interacting interpersonally in the couple therapy process, can explain the escalating cycles of conflict between couples that are elaborated in the family-systems literature, and be helpful in understanding the object-relational substrate of chronic conflict in couples more generally. A description of how to map each partner's internal object world through the identification of these cycles in the early couple therapy process is elaborated in a theoretical model and illustrated with case material.

Hyperspectral signals in the soil: Plant-soil hydraulic connection and disequilibrium as mechanisms of drought tolerance and rapid recovery.

Predicting soil water status remotely is appealing due to its low cost and large-scale application. During drought, plants can disconnect from the soil, causing disequilibrium between soil and plant water potentials at pre-dawn. The impact of this disequilibrium on plant drought response and recovery is not well understood, potentially complicating soil water status predictions from plant spectral reflectance. This study aimed to quantify drought-induced disequilibrium, evaluate plant responses and recovery, and determine the potential for predicting soil water status from plant spectral reflectance. Two species were tested: sweet corn (Zea mays), which disconnected from the soil during intense drought, and peanut (Arachis hypogaea), which did not. Sweet corn's hydraulic disconnection led to an extended 'hydrated' phase, but its recovery was slower than peanut's, which remained connected to the soil even at lower water potentials (-5 MPa). Leaf hyperspectral reflectance successfully predicted the soil water status of peanut consistently, but only until disequilibrium occurred in sweet corn. Our results reveal different hydraulic strategies for plants coping with extreme drought and provide the first example of using spectral reflectance to quantify rhizosphere water status, emphasizing the need for species-specific considerations in soil water status predictions from canopy reflectance.

De novo design of proteins housing excitonically coupled chlorophyll special pairs.

Natural photosystems couple light harvesting to charge separation using a 'special pair' of chlorophyll molecules that accepts excitation energy from the antenna and initiates an electron-transfer cascade. To investigate the photophysics of special pairs independently of the complexities of native photosynthetic proteins, and as a first step toward creating synthetic photosystems for new energy conversion technologies, we designed C2-symmetric proteins that hold two chlorophyll molecules in closely juxtaposed arrangements. X-ray crystallography confirmed that one designed protein binds two chlorophylls in the same orientation as native special pairs, whereas a second designed protein positions them in a previously unseen geometry. Spectroscopy revealed that the chlorophylls are excitonically coupled, and fluorescence lifetime imaging demonstrated energy transfer. The cryo-electron microscopy structure of a designed 24-chlorophyll octahedral nanocage with a special pair on each edge closely matched the design model. The results suggest that the de novo design of artificial photosynthetic systems is within reach of current computational methods.

Portable Instrumentation for Ambient Ionization and Miniature Mass Spectrometers.

We critically evaluate the current status of portable mass spectrometry (pMS), particularly where this aligns with ambient ionization. Assessing the field of pMS can be quite subjective, especially in relation to the portable aspects of design, deployment, and operation. In this review, we discuss what it means to be portable and introduce a set of criteria by which pMS and ambient ionization sources can be assessed. Moreover, we consider the recent literature in terms of the most popular and significant advances in portable instrumentation for ambient ionization and miniature mass spectrometers. Finally, emerging trends and exciting future prospects are discussed and some recommendations are offered.

Lung-specific interleukin 6 mediated transglutaminase 2 activation and cardiopulmonary fibrogenesis.

Pulmonary hypertension (PH) pathogenesis is driven by inflammatory and metabolic derangements as well as glycolytic reprogramming. Induction of both interleukin 6 (IL6) and transglutaminase 2 (TG2) expression participates in human and experimental cardiovascular diseases. However, little is known about the role of TG2 in these pathologic processes. The current study aimed to investigate the molecular interactions between TG2 and IL6 in mediation of tissue remodeling in PH. A lung-specific IL6 over-expressing transgenic mouse strain showed elevated right ventricular (RV) systolic pressure as well as increased wet and dry tissue weights and tissue fibrosis in both lungs and RVs compared to age-matched wild-type littermates. In addition, IL6 over-expression induced the glycolytic and fibrogenic markers, hypoxia-inducible factor 1α, pyruvate kinase M2 (PKM2), and TG2. Consistent with these findings, IL6 induced the expression of both glycolytic and pro-fibrogenic markers in cultured lung fibroblasts. IL6 also induced TG2 activation and the accumulation of TG2 in the extracellular matrix. Pharmacologic inhibition of the glycolytic enzyme, PKM2 significantly attenuated IL6-induced TG2 activity and fibrogenesis. Thus, we conclude that IL6-induced TG2 activity and cardiopulmonary remodeling associated with tissue fibrosis are under regulatory control of the glycolytic enzyme, PKM2.

[11C]-methionine positron emission tomography in the evaluation of pediatric low-grade gliomas.

Background: [11C]-Methionine positron emission tomography (PET; [11C]-MET-PET) is principally used for the evaluation of brain tumors in adults. Although amino acid PET tracers are more commonly used in the evaluation of pediatric brain tumors, data on [11C]-MET-PET imaging of pediatric low-grade gliomas (pLGG) is scarce. This study aimed to investigate the roles of [11C]-MET-PET in the evaluation of pLGGs. Methods: Eighteen patients with newly diagnosed pLGG and 26 previously treated pLGG patients underwent [11C]-MET-PET met the inclusion and exclusion criteria. Tumor-to-brain uptake ratio (TBR) and metabolic tumor volumes were assessed for diagnostic performances (newly diagnosed, 15; previously treated 26), change with therapy (newly diagnosed, 9; previously treated 7), and variability among different histology (n = 12) and molecular markers (n = 7) of pLGGs. Results: The sensitivity of [11C]-MET-PET for diagnosing pLGG, newly diagnosed, and previously treated combined was 93% for both TBRmax and TBRpeak, 76% for TBRmean, and 95% for qualitative evaluation. TBRmax showed a statistically significant reduction after treatment, while other PET parameters showed a tendency to decrease. Median TBRmax, TBRpeak, and TBRmean values were slightly higher in the BRAFV600E mutated tumors compared to the BRAF fused tumors. Median TBRmax, and TBRpeak in diffuse astrocytomas were higher compared to pilocytic astrocytomas, but median TBRmean, was slightly higher in pilocytic astrocytomas. However, formal statistical analysis was not done due to the small sample size. Conclusions: Our study shows that [11C]-MET-PET reliably characterizes new and previously treated pLGGs. Our study also shows that quantitative parameters tend to decrease with treatment, and differences may exist between various pLGG types.

The evolution of feedback: Toward a multicultural orientation.

There have been great strides in psychology regarding diversity, equity, inclusion, and multicultural competence, but a need remains to translate these values into actionable practices in psychotherapy. While the case has been made that measurement-based care is an evidence-based intervention that improves outcomes and reduces dropouts (de Jong et al., 2021) and recently that it provides a transparent collaborative process to engage clients in treatment (Boswell et al., 2023), it has not been widely considered as a methodology for multicultural competence. We trace the evolution of what was once called "patient-focused research" (Lambert, 2001) and identify a significant change in recent writings to include important clinical and collaborative processes, a transition from a strictly normative or nomothetic understanding of the value of feedback to an appreciation of its communicative or idiographic processes. We propose that systematic client feedback promotes a "multicultural orientation" (Owen, 2013) at the individual therapist-client level and that client responses to outcome and process measures can foster cultural humility and create cultural opportunities (Hook et al., 2017) to address marginalization and other sociocultural factors relevant to treatment. Using one system to illustrate what is possible for all feedback approaches, we present client examples that demonstrate an integration of a multicultural orientation. We suggest that systematic client feedback can provide a structure to address diversity, marginalization, and privilege in psychotherapy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The dangers of having only one pandemic exit strategy.

BACKGROUND: When it comes to pandemic response, preparation can be the key. Between 2020 and 2024, the fast-paced development of COVID-19-often compounded by pubic policies' failures to reflect the latest reality and the public's divergent reactions to the pandemic and the policies-means that society should prepare for exit strategies that can reflect the reality of the pandemic and the interests of the people. Yet oftentimes societies only have one exit strategy with limited scope. This paper investigates the dangers of having only one pandemic exit strategy for pandemics like COVID-19. METHODS: Analyses were based on a review of the literature on COVID-19 exit strategies and our own research. The PubMed literature search focused on two concepts-"COVID-19″ and "exit strategy"-and was limited to peer-reviewed papers published between 2020 and 2024 in English. RESULTS: A total of 31 articles were included in the final review. Analyses showed that existing studies on COVID-19 exit strategies often focused on using the modelling method to gauge one exit strategy. Exit strategies were often discussed in the context of implementing, easing, or lifting specific pharmaceutical or non-pharmaceutical interventions. Staged and country-wide coordinated exit strategies were also discussed in the literature, both of which were often deemed as comparatively rigorous options compared to single or stand-alone exit strategies. Drawing on the overall development of COVID-19 and our own research, we presented and discussed the importance of having multiple exit strategies that are considerate of all possible pandemic trajectories, diverse interests of the public, and the communication challenges officials might face in introducing or implementing pandemic policies. CONCLUSION: This paper underscored the importance of having multiple exit strategies for societies to prepare for pandemics. The insights of this study can help inform health policies so that they can more comprehensively and compassionately protect the needs and wants of the "public" in public health, particularly in grave times like COVID-19.

[The Place of Groin, Colson and McGregor Flaps in the Acute Care of Deep Burns to the Hand Dorsum : A Series of 6 Cases In Lille's Burn Centre]. / Place Des Lambeaux Inguinaux Et Des Empochements Dans La Prise En Charge Aiguë Des Brûlures Profondes Du Dorsum De Main: Série De 6 Cas Au Centre De Traitement Des Brûlés De Lille.

The acute management of deep burns to the dorsum of the hand and fingers represents a challenge for the reconstructive surgeon. The exposure of osteo-tendinous structures often requires flap coverage, in a context where loco-regional or free flaps are not always feasible. The aims of reconstruction are to preserve a maximum of digital length, provide supple tissue, obtain protective sensitivity, and achieve a functional hand at 1 year. We report here on a series of 8 deep burns to the dorsum of the hand. Six hands were covered by Colson abdominal flap-graft and two by pedicled inguinal flap. Four out of 6 patients were reviewed in consultation, 1 patient was lost to follow-up, and 1 patient died. Clinical evaluation was performed by a surgeon other than the operator. Functional results are highly variable. Coverage time varies according to lesion depth and patient severity. Flap weaning took place at an average of 30 days. DASH scores ranged from 17.5 to 93/100, with average to poor total active motion (TAM) scores. The aesthetic result was satisfactory, with a Vancouver score of 4.5/13 on average, and an overall patient opinion of 3.75/10 on the POSAS scale. For deep burns to the dorsum of the hand and fingers, local flaps are rarely possible, and loco-regional flaps are not feasible in cases of associated upper limb damage. For medium to large surface areas, pedicled inguinal flaps and pocketing are two reliable techniques. Nevertheless, they require relative immobilization of the upper limb, which leads to stiffness. The question of digital pinning in the intrinsic or straight position remains unresolved, and does not appear to prevent secondary deformities. There is also a learning curve for these two flaps, even though they are reputed to be easy to lift. McGregor's flap or pocketing can be weighed against free flaps. However, the operating time is long, the surgical technique is complex, and vascular damage is common in the burn patient population. Although there have been enormous technical advances since their descriptions, the pedicled inguinal flap and pocketing remain alternatives to be considered in the acute management of deep burns to the dorsum of the hand. In this presentation, we propose a surgical management algorithm to situate these two techniques in the plastic surgeon's therapeutic armament.

Regional lymph node evaluation in pediatric conventional melanoma subtype: a single-center 10-year review.

PURPOSE: To assess the prognostic and therapeutic significance of sentinel lymph node biopsy (SLNB) and completion lymph node dissection (CLND) in pediatric conventional melanoma (CM), while evaluating potential predictive factors for outcomes. METHODS: We conducted a retrospective analysis of medical records spanning 2009-2020, focusing on patients aged 18 or younger with localized cutaneous conventional melanoma. RESULTS: Among the 33 patients, SLNB detected metastasis in 57.6% of cases, with 52.6% undergoing CLND. Positive SLN patients had higher relapse risk (HR 5.92; 95% CI 1.27-27.7; P = 0.024) but similar overall survival (HR 3.19; 95% CI 0.31-33.1, P = 0.33). No significant differences in disease-free survival (DFS) and OS were found between patients who underwent CLND and those who did not (HR 1.91; 95% CI 0.49-7.43, P = 0.35, and HR 0.52; 95% CI 0.03-8.32, P = 0.64, respectively). Univariate analysis showed age at diagnosis (P = 0.02) correlated with higher recurrence risk, with a 21% hazard increase per additional year of age. CONCLUSIONS: Positive SLN status and age at diagnosis were associated with worse DFS in CM patients. Our study did not find any prognostic or therapeutic value in CLND for pediatric melanoma. Further multicenter trials are needed to confirm our single-institution experience. LEVEL OF EVIDENCE: Level IV.

Where should "Humans" be in "One Health"? Lessons from COVID-19 for One Health.

The culling of animals that are infected, or suspected to be infected, with COVID-19 has fuelled outcry. What might have contributed to the ongoing debates and discussions about animal rights protection amid global health crises is the lack of a unified understanding and internationally agreed-upon definition of "One Health". The term One Health is often utilised to describe the imperative to protect the health of humans, animals, and plants, along with the overarching ecosystem in an increasingly connected and globalized world. However, to date, there is a dearth of research on how to balance public health decisions that could impact all key stakeholders under the umbrella of One Health, particularly in contexts where human suffering has been immense. To shed light on the issue, this paper discusses whether One Health means "human-centred connected health" in a largely human-dominated planet, particularly amid crises like COVID-19. The insights of this study could help policymakers make more informed decisions that could effectively and efficiently protect human health while balancing the health and well-being of the rest of the inhabitants of our shared planet Earth.

Nuclear Medicine Imaging Tools in Fever of Unknown Origin: Time for a Revisit and Appropriate Use Criteria.

Fever of unknown origin (FUO) is a clinical conundrum for patients and clinicians alike, and imaging studies are often performed as part of the diagnostic workup of these patients. Recently, the Society of Nuclear Medicine and Molecular Imaging convened and approved a guideline on the use of nuclear medicine tools for FUO. The guidelines support the use of 2-18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in adults and children with FUO. 18F-FDG PET/CT allows detection and localization of foci of hypermetabolic lesions with high sensitivity because of the 18F-FDG uptake in glycolytically active cells that may represent inflammation, infection, or neoplasia. Clinicians should consider and insurers should cover 18F-FDG PET/CT when evaluating patients with FUO, particularly when other clinical clues and preliminary studies are unrevealing.

Competing itinerant and local spin interactions in kagome metal FeGe.

The combination of a geometrically frustrated lattice, and similar energy scales between degrees of freedom endows two-dimensional Kagome metals with a rich array of quantum phases and renders them ideal for studying strong electron correlations and band topology. The Kagome metal, FeGe is a noted example of this, exhibiting A-type collinear antiferromagnetic (AFM) order at TN ≈ 400 K, then establishes a charge density wave (CDW) phase coupled with AFM ordered moment below TCDW ≈ 110 K, and finally forms a c-axis double cone AFM structure around TCanting ≈ 60 K. Here we use neutron scattering to demonstrate the presence of gapless incommensurate spin excitations associated with the double cone AFM structure of FeGe at temperatures well above TCanting and TCDW that merge into gapped commensurate spin waves from the A-type AFM order. Commensurate spin waves follow the Bose factor and fit the Heisenberg Hamiltonian, while the incommensurate spin excitations, emerging below TN where AFM order is commensurate, start to deviate from the Bose factor around TCDW, and peaks at TCanting. This is consistent with a critical scattering of a second order magnetic phase transition with decreasing temperature. By comparing these results with density functional theory calculations, we conclude that the incommensurate magnetic structure arises from the nested Fermi surfaces of itinerant electrons and the formation of a spin density wave order.

Bis[µ-bis-(pyridin-2-yl)methanone oxime-κ3N:,N',N'']bis-[di-acetato-κ2O,O';κO-zinc(II)].

The structure of the title complex, [Zn2(C2H3O2)4(C11H9N3O)2], is triclinic containing half of the mol-ecule in the asymmetric unit. Each zinc atom is coordinated to a pyridyl and oxime nitro-gen from one di-2-pyridyl ketone oxime (dpko) ligand and a third nitro-gen from the other dpko pyridyl ring. Additionally, each zinc is coordinated to two acetato anions, one of which is bidentate and the other monodentate. The uncoordinated oxygen of the monodentate acetato group is involved in a hydrogen bond with the oxime hydrogen. The packing in the crystal is assisted by weak C-H⋯O inter-actions between acetato groups and neighboring pyridyl rings.