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The use of sulfonium salts in organic synthesis has experienced a dramatic increase during the last years that can arguably be attributed to three main factors; the development of more direct and efficient synthetic methods that make easily available sulfonium reagents of a wide structural variety, their intrinsic thermal stability, which facilitates their structural modification, handling and purification even on large scale, and the recognition that their reactivity resembles that of hypervalent iodine compounds and therefore, they can be used as replacement of such reagents for most of their uses. This renewed interest has led to the improvement of already existing reactions, as well as to the discovery of unprecedented transformations; in particular, by the implementation of photocatalytic protocols. This review aims to summarize the most recent advancements on the area focusing on the work published during and after 2020. The scope of the methods developed will be highlighted and their limitations critically evaluated., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Aims: Circulating blood volume is functionally divided between the unstressed volume, which fills the vascular space, and stressed blood volume (SBV), which generates vascular wall tension and intravascular pressure. With decreases in venous capacitance, blood functionally shifts to the SBV, increasing central venous pressure and pulmonary venous pressures. Obesity is associated with both elevated venous pressure and heart failure with preserved ejection fraction (HFpEF). To explore the mechanisms underlying this association, we evaluated relationships between blood volume distribution, venous compliance, and body mass in patients with and without HFpEF., Methods and Results: Subjects with HFpEF (n = 62) and non-cardiac dyspnoea (NCD) (n = 79) underwent invasive haemodynamic exercise testing with echocardiography. SBV was estimated (eSBV) from measured haemodynamic variables fit to a comprehensive cardiovascular model. Compared to NCD, patients with HFpEF displayed a leftward-shifted central venous pressure-dimension relationship, indicating reduced venous compliance. eSBV was 81% higher at rest and 69% higher during exercise in HFpEF than NCD (both P < 0.0001), indicating reduced venous capacitance. Despite greater augmented eSBV with exercise, the increase in cardiac output was reduced in HFpEF, suggesting operation on the plateau of the Starling curve. Exercise eSBV was directly correlated with higher body mass index (r = 0.77, P < 0.0001) and inversely correlated with right ventricular-pulmonary arterial coupling (r = -0.57, all P < 0.0001)., Conclusions: Patients with HFpEF display reductions in systemic venous compliance and increased eSBV related to reduced venous capacitance, abnormalities in right ventricular-pulmonary artery interaction, and increased body fat. These data provide new evidence supporting an important role of venous dysfunction in obesity-related HFpEF and suggest that therapies that improve venous function may hold promise to improve clinical status in this cohort., (© 2021 European Society of Cardiology.)

Restrictive ventilatory defects and elevated pulmonary artery pressure (PAP) are common in patients with chronic heart failure (CHF) and those with interstitial lung disease (ILD). However, as oxyhemoglobin desaturation seldom occurs in stable CHF patients at peak exercise, we hypothesized that the pathophysiology may be different between them. This study aimed to investigate: (1) PAP and lung function at rest, (2) pulmonary gas exchange (PGX) and breathing patterns at peak exercise, (3) mechanisms of dyspnea at peak exercise in patients with CHF compared to healthy subjects and ILD patients. We consecutively enrolled 83 participants (27 with CHF, 23 with ILD, and 33 healthy controls). The CHF and ILD groups had similar functional status. Lung function and cardiopulmonary exercise tests with Borg Dyspnea Score were performed. PAP was estimated using echocardiography. Resting lung function, PAP and peak exercise data in the CHF group were compared to the healthy and ILD groups. Correlation analysis was performed to elucidate the mechanisms of dyspnea in the CHF and ILD groups. Compared to the healthy group, the CHF group had normal lung function, PAP at rest, and normal dyspnea score and PGX at peak exercise, whereas the ILD group had abnormal values compared to the CHF group. Dyspnea score was positively correlated with pressure gradient, lung expansion capabilities, and expiratory tidal flow in the CHF group (all p < 0.05), but inversely correlated with inspiratory time-related variables in the ILD group (all p < 0.05). Normal lung function and PAP at rest, and dyspnea scores and PGX at peak exercise indicated that pulmonary hypertension and fibrosis were insignificant in the patients with CHF. The factors affecting dyspnea at peak exercise were different between the CHF and ILD groups. As the sample size in this study was small, large-scale studies are warranted to confirm our findings. Normal lung function and pulmonary arterial pressure at rest, and dyspnea scores and pulmonary gas exchange at peak exercise indicated that pulmonary hypertension and fibrosis in the patients with chronic heart failure were not significant. Dyspnea score was correlated with different physiological variables between the groups with chronic heart failure and interstitial lung disease. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the influence of quantitative reports (QReports) on the radiological assessment of hippocampal sclerosis (HS) from MRI of patients with epilepsy in a setting mimicking clinical reality. Methods: The study included 40 patients with epilepsy, among them 20 with structural abnormalities in the mesial temporal lobe (13 with HS). Six raters blinded to the diagnosis assessed the 3T MRI in two rounds, first using MRI only and later with both MRI and the QReport. Results were evaluated using inter-rater agreement (Fleiss' kappa k ) and comparison with a consensus of two radiological experts derived from clinical and imaging data, including 7T MRI. Results: For the primary outcome, diagnosis of HS, the mean accuracy of the raters improved from 77.5% with MRI only to 86.3% with the additional QReport (effect size d = 1.43 ). Inter-rater agreement increased from k = 0.56 to k = 0.72 . Five of the six raters reached higher accuracies, and all reported higher confidence when using the QReports. Conclusion: In this pre-use clinical evaluation study, we demonstrated clinical feasibility and usefulness as well as the potential impact of a previously suggested imaging biomarker for radiological assessment of HS. [ABSTRACT FROM AUTHOR]

Online retail is currently profoundly restructuring the working conditions in the retail sector. Existing studies generally describe the working conditions in the large warehouses of online retail as 'digital Taylorism'. This article broadens this perspective and draws on the theoretical concept of the local labour control regime. It explores how managements' technological and social labour control strategies vary spatially between online retail warehouses located in inner and outer metropolitan areas of the four largest German cities. The study uses qualitative methods and is mainly based on expert interviews with executives, representatives of trade unions and works councils, representatives of associations, and further experts. This study gains insights on the spatial variety of labour control and thus is relevant for international research on labour control and for practitioners' ability to create decent and humane work. [ABSTRACT FROM AUTHOR]

(1) Background: Lower back pain is often caused by lumbar facet joint syndrome. This study investigated the effectiveness of three different injection methods under ultrasound guidance in treating elderly patients with lumbar facet joint syndrome. The difficulty in performing these injections was also evaluated; (2) Methods: A total of 60 elderly patients with facet joint syndrome as the cause of lower back pain were recruited and divided into 3 groups. Group 1 received medial branch block (MBB). Group 2 received intra-articular facet joint injections. Group 3 received injection into the multifidus muscle portion that covers the facet joint. Five percent dextrose water (D5W) was used as the injectant. The visual analog scale (VAS) was used to measure the degree of lower back pain; (3) Results: Before the injection treatments, the VAS score averaged about 7.5. After three consecutive injection treatments (two weeks interval), the VAS score decreased significantly to an average of about 1 in all 3 groups, representing mild to no pain. Between group analyses also did not reveal significant statistical differences, suggesting that these procedures are equally effective; (4) Conclusions: Ultrasound-guided injection of the multifidus muscle may be a feasible option in treating elderly patients with lower back pain caused by facet joint syndrome as it is easier to perform as compared to MBB and intra-articular facet joint injection. [ABSTRACT FROM AUTHOR]

Preprocessing fMRI data requires striking a fine balance between conserving signals of interest and removing noise. Typical steps of preprocessing include motion correction, slice timing correction, spatial smoothing, and high‐pass filtering. However, these standard steps do not remove many sources of noise. Thus, noise‐reduction techniques, for example, CompCor, FIX, and ICA‐AROMA have been developed to further improve the ability to draw meaningful conclusions from the data. The ability of these techniques to minimize noise while conserving signals of interest has been tested almost exclusively in resting‐state fMRI and, only rarely, in task‐related fMRI. Application of noise‐reduction techniques to task‐related fMRI is particularly important given that such procedures have been shown to reduce false positive rates. Little remains known about the impact of these techniques on the retention of signal in tasks that may be associated with systemic physiological changes. In this paper, we compared two ICA‐based, that is FIX and ICA‐AROMA, two CompCor‐based noise‐reduction techniques, that is aCompCor, and tCompCor, and standard preprocessing using a large (n = 101) fMRI dataset including noxious heat and non‐noxious auditory stimulation. Results show that preprocessing using FIX performs optimally for data obtained using noxious heat, conserving more signals than CompCor‐based techniques and ICA‐AROMA, while removing only slightly less noise. Similarly, for data obtained during non‐noxious auditory stimulation, FIX noise‐reduction technique before analysis with a covariate of interest outperforms the other techniques. These results indicate that FIX might be the most appropriate technique to achieve the balance between conserving signals of interest and removing noise during task‐related fMRI. [ABSTRACT FROM AUTHOR]

Orthopedic patients need to perform limb immobilization for several days to several weeks due to fracture or other special circumstances. When the function of a certain part or the whole body is restricted, the activity of osteoclasts will be enhanced and its life activity will surpass that of osteoblasts, so local or even whole body bone loss will occur. Acute bone loss usually occurs within a few weeks after the immobilization of limbs. At this stage, the patient's bone mass will decrease sharply, and the patient is prone to osteoporotic refracture. After that, the bone mass will gradually recover, but the speed of bone formation and bone absorption is difficult to reach a balanced state, and the bone mass of patients will continue to decline after it has recovered to a certain degree. After acute progressive bone loss, a large number of bones were lost and the strength of bones decreased. It is often difficult to recover to the level before fracture for a long time, which undoubtedly increases the risk of osteoporosis and related refractures. According to this common phenomenon of bone loss, clinical treatment varies greatly. After a series of research and practice, clinicians summed up some rules and put forward some feasible suggestions, thus strengthening clinicians' understanding of the treatment of acute bone loss, effectively improving the treatment effect of acute bone loss, having far-reaching significance for preventing and treating osteoporosis, reducing the risk of fracture, and improving the long-term prognosis of patients. [ABSTRACT FROM AUTHOR]

Purpose of Review: Inflammatory bowel disease (IBD) is associated with bone loss leading to osteoporosis and increased fracture risk. Bone loss is the result of changes in the balanced process of bone remodeling. Immune cells and cytokines play an important role in the process of bone remodeling and it is therefore not surprising that cytokines as observed in IBD are involved in bone pathology. This review discusses the role of cytokines in IBD-associated bone loss, including the consequences for treatment., Recent Findings: Many studies have been conducted that showed the effect of a single cytokine on bone cells in vitro, including interleukin (IL)-1β, IL-6, IL-8, IL-12/IL-23, IL-17, IL-18, IL-32 and interferon-γ. Recently new members of the IL-1 family (IL-1F) have been related to IBD but the consequences for bone health remain uncertain., Summary: Overall, patients have to deal with a cocktail of cytokines, present in their serum. The combination of cytokines can affect bone cells differently compared to the effects of a single cytokine. This implicates that treatment, focused on reducing the inflammation could work best for bone health as well. Vitamin D might also play a role in this., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Electron-withdrawing nitro-substituents were installed onto terpyridine- and phenanthroline-based metallosurfactants with 4d6 ruthenium(II), which were deposited as Langmuir–Blodgett monolayers aiming to study the feasibility of charge transport in Au‖LB‖Au junctions. The nitro groups are intended to modulate the energy of the frontier molecular orbitals to near to, or match that of Fermi levels in the gold electrodes. A series of heteroleptic metallosurfactants [RuII(C18OPh-terpy)(X-terpy)](PF6)2 and [RuII(C18OPh-terpy)(X-phen)Cl]PF6 were synthesized, where C18OPh-terpy is the 4′-[4-(octadecyloxy)phenyl]-2,2′:6′,2′′-terpyridine amphiphile common to all species, X-terpy is a terpyridine with—H (1) or—phenyl-NO2 (2) and X-phen is a phenanthroline with—H (3) or—NO2 (4) groups. These metallosurfactants were characterized by experimental and computational methods, and the presence of nitro groups affect more affordable reductions at less negative potentials, as well as slightly more positive oxidations, these changes are less pronounced in species 2 than in 4. Species 1 and 2 showed limited Pockels-Langmuir and Langmuir–Blodgett film formation with lower collapse pressure of 27 mN m−1. In contrast, metallosurfactants 3 and 4 showed enhanced hydrophilicity indicated by higher collapse pressures of ca. 36 mN m−1. The LB monolayers of 3 and 4 were deposited on gold electrodes to form Au‖LB‖Au junctions and electron transport was measured as I/V curves. The NO2-bearing species 4 showed asymmetric curves associated with directional electron transport with amplitudes up to −2.0 nA and rectification ratios from 5 to 26 between −1 to +1 V and from 3 to 14 between −3 to +3 V. [ABSTRACT FROM AUTHOR]

Sport concussion affects millions of athletes each year at all levels of sport. Increasing evidence demonstrates clinical and physiological recovery are becoming more divergent definitions, as evidenced by several studies examining blood-based biomarkers of inflammation and imaging studies of the central nervous system (CNS). Recent studies have shown elevated microglial activation in the CNS in active and retired American football players, as well as in active collegiate athletes who were diagnosed with a concussion and returned to sport. These data are supportive of discordance in clinical symptomology and the inflammatory response in the CNS upon symptom resolution. In this review, we will summarize recent advances in the understanding of the inflammatory response associated with sport concussion and broader mild traumatic brain injury, as well as provide an outlook for important research questions to better align clinical and physiological recovery. [ABSTRACT FROM AUTHOR]

The objective of this review is to investigate the commonalities of microvascular (small vessel) disease in heart failure with preserved ejection fraction (HFpEF) and cerebral small vessel disease (CSVD). Furthermore, the review aims to evaluate the current magnetic resonance imaging (MRI) diagnostic techniques for both conditions. By comparing the two conditions, this review seeks to identify potential opportunities to improve the understanding of both HFpEF and CSVD. [ABSTRACT FROM AUTHOR]

Despite the introduction of new anti-seizure medications in recent years, approximately one-third of the epileptic population continues to experience seizures. Recently, the anti-obesity medication fenfluramine (FFA) has been successfully repurposed, and it has received approval from various regulatory agencies for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome. The potential antiseizure effects of FFA were initially observed in patients with photosensitive epilepsy in the 1980s but it was not rigorously explored as a treatment option until 30 years later. This narrative review aims to provide an overview of the historical progression of FFA's use, starting from initial clinical observations to preclinical studies and, ultimately, successful clinical trials in the field of epilepsy. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) now accounts for the majority of new heart failure diagnoses and continues to increase in prevalence in the United States. Importantly, HFpEF is a highly morbid, heterogeneous syndrome lacking effective therapies. Inflammation has emerged as a potential contributor to the pathogenesis of HFpEF. Many of the risk factors for HFpEF are also associated with chronic inflammation, such as obesity, hypertension, aging, and renal dysfunction. A large amount of preclinical evidence suggests that immune cells and their associated cytokines play important roles in mediating fibrosis, oxidative stress, metabolic derangements, and endothelial dysfunction, all potentially important processes in HFpEF. How inflammation contributes to HFpEF pathogenesis, however, remains poorly understood. Recently, a variety of preclinical models have emerged which may yield much needed insights into the causal relationships between risk factors and the development of HFpEF, including the role of specific immune cell subsets or inflammatory pathways. Here, we review evidence in animal models and humans implicating inflammation as a mediator of HFpEF and identify gaps in knowledge requiring further study. As the understanding between inflammation and HFpEF evolves, it is hoped that a better understanding of the mechanisms underlying immune cell activation in HFpEF can open up new therapeutic avenues. [ABSTRACT FROM AUTHOR]

We have devised the unified redox scale EabsH2O, which is valid for all solvents. The necessary single ion Gibbs transfer energy between two different solvents, which only can be determined with extra‐thermodynamic assumptions so far, must clearly satisfy two essential conditions: First, the sum of the independent cation and anion values must give the Gibbs transfer energy of the salt they form. The latter is an observable and measurable without extra‐thermodynamic assumptions. Second, the values must be consistent for different solvent combinations. With this work, potentiometric measurements on silver ions and on chloride ions show that both conditions are fulfilled using a salt bridge filled with the ionic liquid [N2225][NTf2]: if compared to the values resulting from known pKL values, the silver and chloride single ion magnitudes combine within a uncertainty of 1.5 kJ mol−1 to the directly measurable transfer magnitudes of the salt AgCl from water to the solvents acetonitrile, propylene carbonate, dimethylformamide, ethanol, and methanol. The resulting values are used to further develop the consistent unified redox potential scale EabsH2O that now allows to assess and compare redox potentials in and over six different solvents. We elaborate on its implications. [ABSTRACT FROM AUTHOR]

Although the piriform cortex (PC) has been previously implicated as a critical node for seizure generation and propagation, the underlying neural mechanism has remained unclear. Here, we found increased excitability in PC neurons during amygdala kindling acquisition. Optogenetic or chemogenetic activation of PC pyramidal neurons promoted kindling progression, whereas inhibition of these neurons retarded seizure activities induced by electrical kindling in the amygdala. Furthermore, chemogenetic inhibition of PC pyramidal neurons alleviated the severity of kainic acid‐induced acute seizures. These results demonstrate that PC pyramidal neurons bidirectionally modulate seizures in temporal lobe epilepsy, providing evidence for the efficacy of PC pyramidal neurons as a potential therapeutic target for epileptogenesis. Key points: While the piriform cortex (PC) is an important olfactory centre critically involved in olfactory processing and plays a crucial role in epilepsy due to its close connection with the limbic system, how the PC regulates epileptogenesis is largely unknown.In this study, we evaluated the neuronal activity and the role of pyramidal neurons in the PC in the mouse amygdala kindling model of epilepsy.PC pyramidal neurons are hyperexcited during epileptogenesis.Optogenetic and chemogenetic activation of PC pyramidal neurons significantly promoted seizures in the amygdala kindling model, whereas selective inhibition of these neurons produced an anti‐epileptic effect for both electrical kindling and kainic acid‐induced acute seizures.The results of the present study indicate that PC pyramidal neurons bidirectionally modulate seizure activity. [ABSTRACT FROM AUTHOR]

Aims: Comorbidities play a significant role towards the pathophysiology of heart failure with preserved ejection fraction (HFpEF), characterized by abnormal macrovascular function and altered ventricular–vascular coupling. However, our understanding of the role of comorbidities and arterial stiffness in HFpEF remains incomplete. We hypothesized that HFpEF is preceded by a cumulative rise in arterial stiffness as cardiovascular comorbidities accumulate, beyond that associated with ageing. Methods and results: Arterial stiffness was assessed using pulse wave velocity (PWV) in five groups: Group A, healthy volunteers (n = 21); Group B, patients with hypertension (n = 21); Group C, hypertension and diabetes mellitus (n = 20); Group D, HFpEF (n = 21); and Group E, HF with reduced ejection fraction (HFrEF) (n = 11). All patients were aged 70 and above. Mean PWV increased from Groups A to D (PWV 10.2, 12.2, 13.0, and 13.7 m/s, respectively) as vascular comorbidities accumulated independent of age, renal function, haemoglobin, obesity (body mass index), smoking status, and hypercholesterolaemia. HFpEF exhibited the highest PWV and HFrEF displayed near‐normal levels (13.7 vs. 10 m/s, P = 0.003). PWV was inversely related to peak oxygen consumption (r = −0.304, P = 0.03) and positively correlated with left ventricular filling pressures (E/e′) on echocardiography (r = −0.307, P = 0.014). Conclusions: This study adds further support to the concept of HFpEF as a disease of the vasculature, underlined by an increasing arterial stiffness that is driven by vascular ageing and accumulating vascular comorbidities, for example, hypertension and diabetes. Reflecting a pulsatile arterial afterload associated with diastolic dysfunction and exercise capacity, PWV may provide a clinically relevant tool to identify at‐risk intermediate phenotypes (e.g. pre‐HFpEF) before overt HFpEF occurs. [ABSTRACT FROM AUTHOR]

While guidelines for management of heart failure with reduced ejection fraction (HFrEF) are consensual and have led to improved survival, treatment options for heart failure with preserved ejection fraction (HFpEF) remain limited and aim primarily for symptom relief and improvement of quality of life. Due to the shortage of therapeutic options, several drugs have been investigated in multiple clinical trials. The majority of these trials have reported disappointing results and have suggested that HFpEF might not be as simply described by ejection fraction as previously though. In fact, HFpEF is a complex clinical syndrome with various comorbidities and overlapping distinct phenotypes that could benefit from personalized therapeutic approaches. This review summarizes the results from the most recent phase III clinical trials for HFpEF and the most promising drugs arising from phase II trials as well as the various challenges that are currently holding back the development of new pharmacotherapeutic options for these patients. [ABSTRACT FROM AUTHOR]

Aims: Diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging in patients presenting with chronic dyspnoea. We sought to determine the diagnostic value of reduced left atrial (LA) compliance during exercise to diagnose HFpEF. Methods and results: Ergometry exercise stress echocardiography was performed in 225 patients with HFpEF and 262 non‐heart failure controls (non‐cardiac dyspnoea [NCD]) in Protocol 1, where the diagnosis of HFpEF was defined by the HFA‐PEFF algorithm. In Protocol 2, the diagnosis of HFpEF was ascertained by exercise right heart catheterization in 67 participants (49 HFpEF and 18 NCD). Speckle‐tracking echocardiography was performed at rest and during exercise to determine LA compliance (ratio of LA reservoir strain to E/e'). As compared with NCD, patients with HFpEF demonstrated decreased LA reservoir strain and compliance at rest, and these differences further increased during exercise in Protocol 1. Exercise LA compliance discriminated HFpEF from NCD (area under the curve 0.87, p < 0.0001), with a superior diagnostic ability to exercise E/e' ratio (DeLong p = 0.005). Exercise LA compliance demonstrated incremental diagnostic value over clinical factors (age, systemic hypertension, and atrial fibrillation) and resting LA compliance (χ2 212.4 vs. 166.2, p < 0.0001). These findings were confirmed in Protocol 2. Conclusion: Left atrial compliance during exercise demonstrated superior diagnostic ability to exercise E/e' ratio, with incremental diagnostic value over the resting LA compliance. Exercise LA compliance may enhance the diagnosis of HFpEF among patients with dyspnoea. [ABSTRACT FROM AUTHOR]

The execution of voluntary movements is primarily governed by the cerebral hemisphere contralateral to the moving limb. Previous research indicates that the ipsilateral motor network, comprising the primary motor cortex (M1), supplementary motor area (SMA), and premotor cortex (PM), plays a crucial role in the planning and execution of limb movements. However, the precise functions of this network and its interplay in different task contexts have yet to be fully understood. Twenty healthy right-handed participants (10 females, mean age 26.1 ± 4.6 years) underwent functional MRI scans while performing biceps brachii representations such as bilateral, unilateral flexion, and bilateral flexion-extension. Ipsilateral motor evoked potentials (iMEPs) were obtained from the identical set of participants in a prior study using transcranial magnetic stimulation (TMS) targeting M1 while employing the same motor tasks. The voxel time series was extracted based on the region of interest (M1, SMA, ventral PM and dorsal PM). Directed functinal connectivity was derived from the extracted time series using timeresolved partial directed coherence. We found increased connectivity from left- PMv to both sides M1, as well as right-PMv to both sides SMA, in unilateral flexion compared to bilateral flexion. Connectivity from left M1 to left-PMv, and left-SMA to right-PMd, also increased in both unilateral flexion and bilateral flexionextension compared to bilateral flexion. However, connectivity between PMv and right-M1 to left-PMd decreased during bilateral flexion-extension compared to unilateral flexion. Additionally, during bilateral flexion-extension, the connectivity from right-M1 to right-SMA had a negative relationship with the area ratio of iMEP in the dominant side. Our results provide corroborating evidence for prior research suggesting that the ipsilateral motor network is implicated in the voluntary movements and underscores its involvement in cognitive processes such as movement planning and coordination. Moreover, ipsilateral connectivity from M1 to SMA on the dominant side can modulate the degree of ipsilateral M1 activation during bilateral antagonistic contraction. [ABSTRACT FROM AUTHOR]

Background: Patients with anaphylaxis are at risk for ST-segment elevation myocardial infarction (STEMI). However, the pathological links between anaphylaxis and STEMI remain unclear. Here, we aimed to explore shared biological processes, immune effector cells, and hub genes of anaphylaxis and STEMI. Methods: Gene expression data for anaphylactic (GSE69063) and STEMI (GSE60993) patients with corresponding healthy controls were pooled from the Gene Expression Omnibus database. Differential expression analysis, enrichment analysis, and CIBERSORT were used to reveal transcriptomic signatures and immune infiltration profiles of anaphylaxis and STEMI, respectively. Based on common differentially expressed genes (DEGs), Gene Ontology analysis, cytoHubba algorithms, and correlation analyses were performed to identify biological processes, hub genes, and hub gene-related immune cells shared by anaphylaxis and STEMI. The robustness of hub genes was assessed in external anaphylactic (GSE47655) and STEMI (GSE61144) datasets. Furthermore, a murine model of anaphylaxis complicated STEMI was established to verify hub gene expressions. The logistic regression analysis was used to evaluate the diagnostic efficiency of hub genes. Results: 265 anaphylaxis-related DEGs were identified, which were associated with immune-inflammatory responses. 237 STEMI-related DEGs were screened, which were involved in innate immune response and myeloid leukocyte activation. M0 macrophages and dendritic cells were markedly higher in both anaphylactic and STEMI samples compared with healthy controls, while CD4+ naïve T cells and CD8+ T cells were significantly lower. Enrichment analysis of 33 common DEGs illustrated shared biological processes of anaphylaxis and STEMI, including cytokine-mediated signaling pathway, response to reactive oxygen species, and positive regulation of defense response. Six hub genes were identified, and their expression levels were positively correlated with M0 macrophage abundance and negatively correlated with CD4+ naïve T cell abundance. In external anaphylactic and STEMI samples, five hub genes (IL1R2, FOS, MMP9, DUSP1, CLEC4D) were confirmed to be markedly upregulated. Moreover, experimentally induced anaphylactic mice developed impaired heart function featuring STEMI and significantly increased expression of the five hub genes. DUSP1 and CLEC4D were screened as blood diagnostic biomarkers of anaphylaxis and STEMI based on the logistic regression analysis. Conclusion: Anaphylaxis and STEMI share the biological processes of inflammation and defense responses. Macrophages, dendritic cells, CD8+ T cells, and CD4+ naïve T cells constitute an immune cell population that acts in both anaphylaxis and STEMI. Hub genes (DUSP1 and CLEC4D) identified here provide candidate genes for diagnosis, prognosis, and therapeutic targeting of STEMI in anaphylactic patients. [ABSTRACT FROM AUTHOR]

Aims: Cardiac and extracardiac abnormalities play important roles in heart failure with preserved ejection fraction (HFpEF). Biventricular cardiac power output (BCPO) quantifies the total rate of hydraulic work performed by both ventricles, suggesting that it may help to identify patients with HFpEF and more severe cardiac impairments to better individualize treatment. Methods and results: Patients with HFpEF (n = 398) underwent comprehensive echocardiography and invasive cardiopulmonary exercise testing. Patients were categorized as low BCPO reserve (n = 199, < median of 1.57 W) or preserved BCPO reserve (n = 199). As compared to those with preserved BCPO reserve, those with low reserve were older and leaner, with more atrial fibrillation, higher N‐terminal pro‐B‐type natriuretic peptide levels, worse renal function, more impaired left ventricular (LV) global longitudinal strain, worse LV diastolic function and right ventricular longitudinal function. Cardiac filling pressures and pulmonary artery pressures at rest were higher in low BCPO reserve, but central pressures were similar during exercise to those with preserved BCPO reserve. Exertional systemic and pulmonary vascular resistances were higher and exercise capacity was more impaired in those with low BCPO reserve. Reduced BCPO reserve was associated with increased risk for the composite endpoint of heart failure hospitalization or death over 2.9 (interquartile range 0.9–4.5) years of follow‐up (hazard ratio 2.77, 95% confidence interval 1.73–4.42, p < 0.0001). Conclusions: Inability to enhance BCPO during exercise is associated with more advanced HFpEF, increased systemic and pulmonary vascular resistance, reduced exercise capacity and increased adverse events in patients with HFpEF. Novel therapies that enhance biventricular reserve merit further investigation for patients with this phenotype. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) represents a highly heterogeneous clinical syndrome affected in its development and progression by many comorbidities. The left ventricular diastolic dysfunction may be a manifestation of various combinations of cardiovascular, metabolic, pulmonary, renal, and geriatric conditions. Thus, in addition to treatment with sodium–glucose cotransporter 2 inhibitors in all patients, the most effective method of improving clinical outcomes may be therapy tailored to each patient's clinical profile. To better outline a phenotype‐based approach for the treatment of HFpEF, in this joint position paper, the Heart Failure Association of the European Society of Cardiology, the European Heart Rhythm Association and the European Hypertension Society, have developed an algorithm to identify the most common HFpEF phenotypes and identify the evidence‐based treatment strategy for each, while taking into account the complexities of multiple comorbidities and polypharmacy. [ABSTRACT FROM AUTHOR]

Purpose of Review: People with HIV have an elevated risk of developing heart failure even with optimally controlled disease. In this review, we outline the various mechanisms through which HIV infection may directly and indirectly contribute to heart failure pathology and highlight the emerging relationship between HIV, chronic inflammation, and cardiometabolic disease., Recent Findings: HIV infection leads to chronic inflammation, immune dysregulation, and metabolic imbalances even in those with well controlled disease. These dysregulations occur through several diverse mechanisms which may lead to manifestations of different phenotypes of heart failure in people with HIV. While it has long been known that people with HIV are at risk of developing heart failure, recent studies have suggested numerous complex mechanisms involving chronic inflammation, immune dysregulation, and metabolic derangement through which this may be mediated. Further comprehensive studies are needed to elucidate the precise relationship between these mechanisms and the development of different subtypes of heart failure in people with HIV., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In oncologic patients, optimal postoperative wound healing is crucial for the maintenance of systemic therapies and improved survival. Although several risk factors for postoperative wound complications have been identified, the clinical effect of new antineoplastic agents on wound healing remains uncertain. The available literature on the effect of antineoplastic agents in wound healing is complex to analyze because of other confounding risk factors such as radiation therapy and certain patient-specific variables. Available perioperative drug recommendations are based on database opinion and case reports from adverse event alerts. This review highlights the characteristics of old and new antineoplastic agents commonly used in the treatment of sarcoma, carcinoma, and other cancers and their potential effects on the wound-healing process. It also aims to provide perioperative treatment cessation recommendations to guide orthopaedic surgeons and prevent drug-related wound complications to the fullest extent possible., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

Over the last two decades, the changing paradigm of heart failure with preserved ejection fraction (HFpEF) has transformed our understanding not only of the pathophysiology of this clinical entity but also the diagnostic and therapeutic approaches aimed at treating this complex patient population. No longer HFpEF should be seen as simply left ventricular diastolic dysfunction but as a group of that in addition of having small and thick left ventricles with abnormal diastolic filling patterns as their main pathophysiologic abnormality; they also have whole host of different abnormalities. In fact, this heterogeneous clinical entity embodies numerous mechanisms and is linked to multiorgan dysfunction, with hypertension and obesity playing a major role. Although we have gained an enormous amount of understanding not only on the causes but also the downstream effects of HFpEF, there is still much to be learned before we can fully comprehend this complex clinical entity. It is the main intention of this review to synthesize the most recent attributes, mechanism, diagnostic tools, and most useful therapeutic alternatives to be considered when evaluating patients either complaining of dyspnea on exertion as well as exercise intolerance or those recently admitted with HF symptoms but with normal LVEF in the absence of any other valvular abnormalities [ABSTRACT FROM AUTHOR]

The central aortic pressure waveform, while simple in form, is complex in its physiological interpretation. Although general agreement has been reached on the contour and mechanisms responsible for pressure waveforms in the ascending aorta of healthy humans, in recent years there has been increasing interest in the contour of the pressure wave in elderly patients with aortic valve stenosis (AS). As aortic valve leaflets succumb to fibrosis and calcification, they increase opposition to forward flow. This results in a protracted pressure rise and manifests as the classical finding of pulsus parvus et tardus. Equally, changes to arterial properties (including elasticity and geometry) and pulse wave velocity (PWV) with age, heart failure, or hypertension can cause profound changes to the contour. Increased accessibility of methods to measure the central aortic pressure waveform, as well as the rapid uptake of transcatheter aortic valve implantation technologies, has created a renewed focus on better understanding of characteristic perturbations to the waveform in elderly patients with AS. In this review, we investigate the evolution of our understanding of the central aortic pressure waveform in varying AS disease states to highlight the importance of the physiological and biological basis for alterations in this waveform. [ABSTRACT FROM AUTHOR]

Aims: Pulmonary hypertension (PH) and pulmonary vascular remodelling are common in patients with heart failure with preserved ejection fraction (HFpEF). Many patients with HFpEF demonstrate an abnormal pulmonary haemodynamic response to exercise that is not identifiable at rest. This can be estimated non‐invasively by the mean pulmonary artery pressure–cardiac output relationship (mPAP/CO slope). We sought to characterize the pathophysiology of disproportionate exercise‐induced PH in relation to CO (DEi‐PH) and its prognostic impact in patients with HFpEF. Methods and results: A total of 345 patients (166 HFpEF and 179 controls) underwent ergometry exercise stress echocardiography with simultaneous expired gas analysis. DEi‐PH was defined as the mPAP/CO slope >5.2 mmHg/L/min (median value). At rest, there were no differences in right ventricular (RV) function and severity of PH between HFpEF patients with and without DEi‐PH. Compared with controls (n = 179) and HFpEF without DEi‐PH (n = 83), HFpEF with DEi‐PH (n = 83) demonstrated worse exercise capacity (lower peak oxygen consumption), depressed RV systolic function, impaired RV–pulmonary artery coupling, limitation in CO augmentation, more right‐sided congestion, and worse ventilatory efficiency (higher minute ventilation vs. carbon dioxide volume) during peak exercise. Kaplan–Meier analyses showed that HFpEF patients with DEi‐PH had higher rates of composite outcomes of all‐cause mortality or heart failure events than those without (log‐rank p = 0.0002). Conclusion: Patients with HFpEF and DEi‐PH demonstrated distinct pathophysiologic features that become apparent only during exercise. These data suggest that DEi‐PH is a pathophysiologic phenotype of HFpEF and reinforce the importance of exercise stress echocardiography for detailed characterization of HFpEF. [ABSTRACT FROM AUTHOR]

The piriform cortex (PC) is located at the junction of the temporal and frontal lobes. It is involved physiologically in olfaction as well as memory and plays an important role in epilepsy. Its study at scale is held back by the absence of automatic segmentation methods on MRI. We devised a manual segmentation protocol for PC volumes, integrated those manually derived images into the Hammers Atlas Database (n = 30) and used an extensively validated method (multi‐atlas propagation with enhanced registration, MAPER) for automatic PC segmentation. We applied automated PC volumetry to patients with unilateral temporal lobe epilepsy with hippocampal sclerosis (TLE; n = 174 including n = 58 controls) and to the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n = 151, of whom with mild cognitive impairment (MCI), n = 71; Alzheimer's disease (AD), n = 33; controls, n = 47). In controls, mean PC volume was 485 mm3 on the right and 461 mm3 on the left. Automatic and manual segmentations overlapped with a Jaccard coefficient (intersection/union) of ~0.5 and a mean absolute volume difference of ~22 mm3 in healthy controls, ~0.40/ ~28 mm3 in patients with TLE, and ~ 0.34/~29 mm3 in patients with AD. In patients with TLE, PC atrophy lateralised to the side of hippocampal sclerosis (p <.001). In patients with MCI and AD, PC volumes were lower than those of controls bilaterally (p <.001). Overall, we have validated automatic PC volumetry in healthy controls and two types of pathology. The novel finding of early atrophy of PC at the stage of MCI possibly adds a novel biomarker. PC volumetry can now be applied at scale. [ABSTRACT FROM AUTHOR]

Simple Summary: Soft tissue and bone sarcomas are a diverse group of aggressive tumors. Lately, the shift in their management, with an emphasis on limb salvage, has deemed the involvement of reconstructive surgeons an integral part of their multidisciplinary treatment. We present our experience with 90 free and pedicled free tissue transfers in the reconstruction of sarcomas at a major sarcoma center over a 5-year period: diabetes, alcohol consumption and male gender were associated with increased wound healing problems, preoperative chemotherapy significantly increased the occurrence of early infection, while preoperative radiotherapy was associated with a higher incidence of lymphedema. Reconstructive surgery with either pedicled or free tissue transfer after sarcoma resection is reliable, but a higher complication rate is to be expected with neoadjuvant therapy and with certain comorbidities. Background: Soft tissue and bone sarcomas are heterogeneous groups of malignant tumors. The shift in their management, with an emphasis on limb salvage, has deemed the involvement of reconstructive surgeons an integral part of their multidisciplinary treatment. We present our experience with free and pedicled flaps in the reconstruction of sarcomas at a tertiary referral university hospital and major sarcoma center. Materials and Methods: All patients undergoing flap reconstruction after sarcoma resection over a 5-year period have been included in the study. Patient-related data and postoperative complications were collected retrospectively, ensuring a minimum follow-up of 3 years. Results: A total of 90 patients underwent treatment with 26 free flaps and 64 pedicled flaps. Postoperative complications occurred in 37.7% of patients, and the flap failure rate was 4.4%. Diabetes, alcohol consumption and male gender were associated with increased early necrosis of the flap. Preoperative chemotherapy significantly increased the occurrence of early infection and late dehiscence, while preoperative radiotherapy was associated with a higher incidence of lymphedema. Intraoperative radiotherapy was associated with late seromas and lymphedema. Conclusions: Reconstructive surgery with either pedicled or free flaps is reliable, but it can be demanding in the setting of sarcoma surgery. A higher complication rate is to be expected with neoadjuvant therapy and with certain comorbidities. [ABSTRACT FROM AUTHOR]

Owing to the overwhelming obesity epidemic, preserved ejection fraction heart failure commonly ensues in patients with severe obesity and the obese phenotype of preserved ejection fraction heart failure is now commonplace in clinical practice. Severe obesity and preserved ejection fraction heart failure share congruent cardiovascular, immune, and renal derangements that make it difficult to ascertain whether the obese phenotype of preserved ejection fraction heart failure is the convergence of two highly prevalent conditions or severe obesity enables the development and progression of the syndrome of preserved ejection fraction heart failure. Nevertheless, the obese phenotype of preserved ejection fraction heart failure provides a unique opportunity to assess whether sustained and sizeable loss of excess body weight via metabolic bariatric surgery reverses the concentric left ventricular remodeling that patients with preserved ejection fraction heart failure commonly display. [ABSTRACT FROM AUTHOR]

Aims: Ancillary analyses from clinical trials have suggested reduced efficacy for neurohormonal antagonists among patients with heart failure and preserved ejection fraction (HFpEF) and higher ranges of ejection fraction (EF). Methods and results: A total of 621 patients with HFpEF were grouped into those with low‐normal left ventricular EF (LVEF) (HFpEF<65%, n = 319, 50% ≤ LVEF <65%) or HFpEF≥65% (n = 302, LVEF ≥65%), and compared with 149 age‐matched controls undergoing comprehensive echocardiography and invasive cardiopulmonary exercise testing. A sensitivity analysis was performed in a second non‐invasive community‐based cohort of patients with HFpEF (n = 244) and healthy controls without cardiovascular disease (n = 617). Patients with HFpEF≥65% had smaller left ventricular (LV) end‐diastolic volume than HFpEF<65%, but LV systolic function assessed by preload recruitable stroke work and stroke work/end‐diastolic volume was similarly impaired. Patients with HFpEF≥65% displayed an end‐diastolic pressure–volume relationship (EDPVR) that was shifted leftward, with increased LV diastolic stiffness constant β, in both invasive and community‐based cohorts. Cardiac filling pressures and pulmonary artery pressures at rest and during exercise were similarly abnormal in all EF subgroups. While patients HFpEF≥57% displayed leftward shifted EDPVR, those with HFpEF<57% had a rightward shifted EDPVR more typical of heart failure with reduced EF. Conclusion: Most pathophysiologic differences in patients with HFpEF and higher EF are related to smaller heart size, increased LV diastolic stiffness, and leftward shift in the EDPVR. These findings may help to explain the absence of efficacy for neurohormonal antagonists in this group and raise a new hypothesis, that interventions to stimulate eccentric LV remodelling and enhance diastolic capacitance may be beneficial for patients with HFpEF and EF in the higher range. [ABSTRACT FROM AUTHOR]

Background: Effects of antihyperglycemic therapies on cardiovascular and heart failure (HF) risks have varied widely across cardiovascular outcome trials (CVOTs), and underlying factors remain incompletely understood. We aimed to determine the relationships of glycated hemoglobin (HbA1c) or bodyweight changes with these outcomes in all CVOTs of antihyperglycemic therapies. Methods: We searched PubMed and EMBASE up to 25 January 2023 for all randomized controlled CVOTs of antihyperglycemic therapies reporting both major adverse cardiovascular events (MACE) and HF outcomes in patients with type 2 diabetes or prediabetes. We performed meta-regression analyses following random-effects meta-analyses to evaluate the effects of HbA1c or bodyweight reductions on each outcome. Results: Thirty-five trials comprising 256,524 patients were included. Overall, antihyperglycemic therapies reduced MACE by 9% [risk ratio (RR): 0.91; 95% confidence interval (CI) 0.88–0.94; P < 0.001; I2 = 36.5%]. In meta-regression, every 1% greater reduction in HbA1c was associated with a 14% reduction in the RR of MACE (95% CI 4–24; P = 0.010), whereas bodyweight change was not associated with the RR of MACE. The magnitude of the reduction in MACE risk associated with HbA1c reduction was greater in trials with a higher baseline prevalence of atherosclerotic cardiovascular disease. On the other hand, antihyperglycemic therapies showed no overall significant effect on HF (RR: 0.95; 95% CI 0.87–1.04; P = 0.28; I2 = 75.9%). In a subgroup analysis based on intervention type, sodium-glucose cotransporter-2 inhibitors (SGLT2i) conferred the greatest HF risk reduction (RR: 0.68; 95% CI 0.62–0.75; P < 0.001; I2 = 0.0%). In meta-regression, every 1 kg bodyweight reduction, but not HbA1c reduction, was found to reduce the RR of HF by 7% (95% CI 4–10; P < 0.001); however, significant residual heterogeneity (P < 0.001) was observed, and SGLT2i reduced HF more than could be explained by HbA1c or bodyweight reductions. Conclusions: Antihyperglycemic therapies reduce MACE in an HbA1c-dependent manner. These findings indicate that HbA1c can be a useful marker of MACE risk reduction across a wide range of antihyperglycemic therapies, including drugs with pleiotropic effects. In contrast, HF is reduced not in an HbA1c-dependent but in a bodyweight-dependent manner. Notably, SGLT2i have shown class-specific benefits for HF beyond HbA1c or bodyweight reductions. [ABSTRACT FROM AUTHOR]

Quality control (QC) for functional connectivity magnetic resonance imaging (FC-MRI) is critical to ensure the validity of neuroimaging studies. Noise confounds are common in MRI data and, if not accounted for, may introduce biases in functional measures affecting the validity, replicability, and interpretation of FC-MRI study results. Although FC-MRI analysis rests on the assumption of adequate data processing, QC is underutilized and not systematically reported. Here, we describe a quality control pipeline for the visual and automated evaluation of MRI data implemented as part of the CONN toolbox. We analyzed publicly available resting state MRI data (N = 139 from 7 MRI sites) from the FMRI Open QC Project. Preprocessing steps included realignment, unwarp, normalization, segmentation, outlier identification, and smoothing. Data denoising was performed based on the combination of scrubbing, motion regression, and aCompCor – a principal component characterization of noise from minimally eroded masks of white matter and of cerebrospinal fluid tissues. Participant-level QC procedures included visual inspection of raw-level data and of representative images after each preprocessing step for each run, as well as the computation of automated descriptive QC measures such as average framewise displacement, average global signal change, prevalence of outlier scans, MNI to anatomical and functional overlap, anatomical to functional overlap, residual BOLD timeseries variability, effective degrees of freedom, and global correlation strength. Dataset-level QC procedures included the evaluation of inter-subject variability in the distributions of edge connectivity in a 1,000-node graph (FC distribution displays), and the estimation of residual associations across participants between functional connectivity strength and potential noise indicators such as participant’s head motion and prevalence of outlier scans (QC-FC analyses). QC procedures are demonstrated on the reference dataset with an emphasis on visualization, and general recommendations for best practices are discussed in the context of functional connectivity and other fMRI analysis. We hope this work contributes toward the dissemination and standardization of QC testing performance reporting among peers and in scientific journals. [ABSTRACT FROM AUTHOR]

One of medicinal chemistry's top priorities is the discovery of new molecules with anticancer potential. Compounds that interact with DNA are an intriguing family of chemotherapeutic medications used to treat cancer. Studies in this area have uncovered a plethora of potential anticancer medicines, such as groove binding, alkylating, and intercalator compounds. The anticancer activity of DNA intercalators (molecules that intercalate between DNA base pairs) has drawn special interest. The current study investigated the promising anticancer drug 1,3,5-Tris(4-carboxyphenyl)benzene (H3BTB) against breast and cervical cancer cell lines. In addition, 1,3,5-Tris(4-carboxyphenyl)benzene binds to DNA by groove binding. The binding of H3BTB to DNA was found to be significant which unwinds the DNA helix. Considerable electrostatic and non-electrostatic contributions were present in the binding's free energy. The cytotoxic potential of H3BTB is effectively demonstrated by the computational study outcomes, which include molecular docking and molecular dynamics (MD) simulations. The minor groove binding for the H3BTB–DNA complex is supported by molecular docking research. This study will promote empirical investigation into the synthesis of metallic and non-metallic H3BTB derivatives and their potential use as bioactive molecules for the treatment of cancer. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate changes in systemic and local immune factors, namely, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, in patients with and without osteoporotic fractures and to explore the effects of active vitamin D3 treatment on immune function and fracture prognosis in patients with osteoporotic fractures. Method: The mRNA expression levels of IL-1β, IL-6 and TNF-α were measured before the operation. After the operation, the patients in the control group were treated with conventional fracture treatment and calcium supplementation, and the patients in the treatment group were treated with calcium plus active vitamin D3 in addition to conventional fracture treatment. The serum of each patient was collected on the seventh day after the operation. Results: The expression levels of the three immune factors (IL-1β, IL-6 and TNF-α) in the fracture end hematoma samples were significantly positively correlated with those in the serum samples (P < 0.05). The mean values of the serums of IL-1β, IL-6 and TNF-α in the osteoporosis group were significantly higher than those in the non-osteoporosis group (P < 0.05). The average number of hematomas in the osteoporosis group was significantly higher than that in the non-osteoporosis group (P < 0.05). The results for the active vitamin D3 treatment group were significantly lower than those for the control group (P < 0.05). The mean wrist function score of the active vitamin D3 treatment group was significantly better than that of the control group (P < 0.05). The average fracture healing time of the treatment group was significantly shorter than that of the control group (P < 0.05). Conclusion: The relative expression of IL-1β, IL-6, and TNF-α in the fracture end hematoma samples was positively correlated with the corresponding levels of these immune factors in the serum samples. The levels of IL-1β, IL-6 and TNF-α in the serum and fracture end hematoma samples of the osteoporotic fracture patients were higher than those of the non-osteoporotic fracture patients. Active vitamin D3 treatment promoted fracture healing by affecting the levels of these immune factors. [ABSTRACT FROM AUTHOR]

Right ventricular–pulmonary artery coupling (RV-PA coupling) refers to the relationship between RV contractility and RV afterload. Normal RV-PA coupling is maintained only when RV function and pulmonary vascular resistance are appropriately matched. RV-PA uncoupling occurs when RV contractility cannot increase to match RV afterload, resulting in RV dysfunction and right heart failure. RV-PA coupling plays an important role in the pathophysiology and progression of cardiovascular diseases. Therefore, early and accurate evaluation of RV-PA coupling is of great significance for a patient's condition assessment, clinical decision making, risk stratification, and prognosis judgment. RV-PA coupling can be assessed by using invasive or noninvasive approaches. The aim of this review was to summarize the pathological mechanism and evaluation methods of RV-PA coupling, the advantages and disadvantages of each method, and the application value of RV-PA coupling in various cardiovascular diseases. [ABSTRACT FROM AUTHOR]