Heart failure with preserved ejection fraction: everything the clinician needs to know.

Heart failure with preserved ejection fraction (HFpEF) is increasingly recognised and diagnosed in clinical practice, a trend driven by an ageing population and a rise in contributing comorbidities, such as obesity and diabetes. Representing at least half of all heart failure cases, HFpEF is recognised as a complex clinical syndrome. Its diagnosis and management are challenging due to its diverse pathophysiology, varied epidemiological patterns, and evolving diagnostic and treatment approaches. This Seminar synthesises the latest insights on HFpEF, integrating findings from recent clinical trials, epidemiological research, and the latest guideline recommendations. We delve into the definition, pathogenesis, epidemiology, diagnostic criteria, and management strategies (non-pharmacological and pharmacological) for HFpEF. We highlight ongoing clinical trials and future developments in the field. Specifically, this Seminar offers practical guidance tailored for primary care practitioners, generalists, and cardiologists who do not specialise in heart failure, simplifying the complexities in the diagnosis and management of HFpEF. We provide practical, evidence-based recommendations, emphasising the importance of addressing comorbidities and integrating the latest pharmacological treatments, such as SGLT2 inhibitors.

Methods for the optimal preservation of blow fly intra-puparial forms for morphological analysis in forensic casework.

Accurate minimum post-mortem interval (minPMI) estimations often rely on a precise age determination of insect developmental stages, which is significantly influenced by environmental temperature. An optimal preservation of the entomological samples collected at crime scenes is pivotal for a reliable aging of immature insect samples. For blow flies (Diptera: Calliphoridae), the most widely used insect indicators in forensic investigations, an appropriate preservation of tissues is particularly important in the case of puparial samples because aging methods for intra-puparial forms usually depend on morphological analyses; however, although informative soft tissues and structures could be discoloured and/or distorted if they are not properly fixed, there is a lack of studies to assess different methods for the optimal preservation of intra-puparial forms collected in forensic investigations. The present study compares three preservation methods for intra-puparial forms of the blow fly Calliphora vicina Robineau-Desvoidy, 1830: (i) direct immersion into 80% ethanol, (ii) puncturing of the puparium and hot water killing (HWK) prior to preservation in 80% ethanol, and (iii) HWK without puncturing before preservation in 80% ethanol. External and internal morphological analyses of intra-puparial forms of different ages were conducted to assess the quality of preservation. The results indicate that direct immersion in ethanol led to poor preservation, affecting both external and internal tissues. Both methods with HWK resulted in a better preservation, but puncturing resulted, in some cases, in physical damage of the specimens. HWK without puncturing emerged as the optimal preservation method, consistently yielding high preservation scores for both external and internal morphological analyses. These findings have practical implications for forensic practitioners and emphasise the need for updating some published guidelines and protocols in forensic entomology.

Preservation of human heart valves for replacement in children with heart valve disease: past, present and future.

Valvular heart disease affects 30% of the new-borns with congenital heart disease. Valve replacement of semilunar valves by mechanical, bioprosthetic or donor allograft valves is the main treatment approach. However, none of the replacements provides a viable valve that can grow and/or adapt with the growth of the child leading to re-operation throughout life. In this study, we review the impact of donor valve preservation on moving towards a more viable valve alternative for valve replacements in children or young adults.

Polyamine Signal through HCC Microenvironment: A Key Regulator of Mitochondrial Preservation and Turnover in TAMs.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and, with increasing research on the tumor immune microenvironment (TIME), the immunosuppressive micro-environment of HCC hampers further application of immunotherapy, even though immunotherapy can provide survival benefits to patients with advanced liver cancer. Current studies suggest that polyamine metabolism is not only a key metabolic pathway for the formation of immunosuppressive phenotypes in tumor-associated macrophages (TAMs), but it is also profoundly involved in mitochondrial quality control signaling and the energy metabolism regulation process, so it is particularly important to further investigate the role of polyamine metabolism in the tumor microenvironment (TME). In this review, by summarizing the current research progress of key enzymes and substrates of the polyamine metabolic pathway in regulating TAMs and T cells, we propose that polyamine biosynthesis can intervene in the process of mitochondrial energy metabolism by affecting mitochondrial autophagy, which, in turn, regulates macrophage polarization and T cell differentiation. Polyamine metabolism may be a key target for the interactive dialog between HCC cells and immune cells such as TAMs, so interfering with polyamine metabolism may become an important entry point to break intercellular communication, providing new research space for developing polyamine metabolism-based therapy for HCC.

Heart Failure with Preserved Ejection Fraction: The Pathophysiological Mechanisms behind the Clinical Phenotypes and the Therapeutic Approach.

Heart failure (HF) with preserved ejection fraction (HFpEF) is an increasingly frequent form and is estimated to be the dominant form of HF. On the other hand, HFpEF is a syndrome with systemic involvement, and it is characterized by multiple cardiac and extracardiac pathophysiological alterations. The increasing prevalence is currently reaching epidemic levels, thereby making HFpEF one of the greatest challenges facing cardiovascular medicine today. Compared to HF with reduced ejection fraction (HFrEF), the medical attitude in the case of HFpEF was a relaxed one towards the disease, despite the fact that it is much more complex, with many problems related to the identification of physiopathogenetic mechanisms and optimal methods of treatment. The current medical challenge is to develop effective therapeutic strategies, because patients suffering from HFpEF have symptoms and quality of life comparable to those with reduced ejection fraction, but the specific medication for HFrEF is ineffective in this situation; for this, we must first understand the pathological mechanisms in detail and correlate them with the clinical presentation. Another important aspect of HFpEF is the diversity of patients that can be identified under the umbrella of this syndrome. Thus, before being able to test and develop effective therapies, we must succeed in grouping patients into several categories, called phenotypes, depending on the pathological pathways and clinical features. This narrative review critiques issues related to the definition, etiology, clinical features, and pathophysiology of HFpEF. We tried to describe in as much detail as possible the clinical and biological phenotypes recognized in the literature in order to better understand the current therapeutic approach and the reason for the limited effectiveness. We have also highlighted possible pathological pathways that can be targeted by the latest research in this field.

Preparation and Characterization of Pullulan-Based Packaging Paper for Fruit Preservation.

Improving the shelf lives of fruits is challenging. The biodegradable polysaccharide pullulan exhibits excellent film-forming ability, gas barrier performance, and natural decomposability, making it an optimal material for fruit preservation. To overcome problems of high cost and film porosity of existing packaging technologies, we aimed to develop pullulan-based packaging paper to enhance the shelf lives of fruits. A thin paper coating comprising a mixture of 15 wt.% pullulan solution at various standard viscosities (75.6, 77.8, and 108.5 mPa·s) with tea polyphenols (15:2) and/or vitamin C (150:1) improved the oxygen transmission rate (120-160 cm3 m-2·24 h·0.1 MPa), water vapor transmission rate (<5.44 g·mm-1 m-2·h·kPa), maximum free radical clearance rate (>87%), and antibacterial properties of base packaging paper. Grapes wrapped with these pullulan-based papers exhibited less weight loss (>4.41%) and improved hardness (>16.4%) after 10 days of storage compared to those of control grapes (wrapped in untreated/base paper). Grapes wrapped with pullulan-based paper had >12.6 wt.% total soluble solids, >1.5 mg/g soluble protein, >0.44 wt.% titratable acidity, and ≥4.5 mg 100 g-1 ascorbic acid. Thus, pullulan-based paper may prolong the shelf life of grapes with operational convenience, offering immense value for fruit preservation.

Does flapless immediate implant placement lead to significant preservation of buccal bone compared to flap surgical protocol?

DESIGN: A systematic review and meta-analysis of randomized clinical trials. DATA SOURCES: The electronic search included Pubmed, Web of Science, Embase, and Cochrane databases up to June 2022. Cross-referencing, searching for gray literature at ( www. CLINICALTRIALS: gov ), and hand searching of seven relevant journals were also performed. SELECTION CRITERIA: Inclusion criteria consisted of: randomized clinical trials (RCTs) published in English comparing flapless to flap surgery for IIP using single titanium implants in the esthetic zone of healthy ≥18 years old patients. Prospective and retrospective case series, cross-sectional studies, letters to editors and reviews were excluded. The key study factor was to assess the impact of the surgical approach (flap versus flapless surgery) on buccal hard and soft tissue changes after single immediate implants for the anterior teeth in healthy adult patients. The primary outcome was horizontal buccal bone change (HBBC), measured by CBCT. Secondary outcomes were implant survival, vertical buccal bone change, postoperative pain, and clinical and esthetic parameters. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers conducted both electronic and manual searches for eligible clinical studies. The evaluation was carried out at the title level followed by the abstract level, and the full texts of the qualified articles were then examined. Any disagreements were resolved by discussion with a third reviewer. Quality assessment of the included RCTs was conducted by two additional reviewers who were not part in the search process using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2). A meta-analysis was conducted on outcome variables that were documented in three or more articles. RESULTS: Five RCTs fully met the selection criteria for the final qualitative analysis comprising data of 140 patients who received 140 single immediate implants (flapless: 68; flap:72) with a mean age ranging from 30 to 67 years. Follow-up extended for 6-12 months. Two RCTs showed an overall low risk of bias, whereas the other three RCTs had an overall high risk, basically due to using inappropriate methods of outcome measurements. Meta-analysis included three RCTs and revealed a mean difference of 0.48 mm (95% CI [0.13,0.84], p = 0.007) in HBBC between surgical approaches, favoring flapless surgery. Heterogeneity among the studies was low (I2 = 29%; p = 0.250). For implant survival, however, meta-analysis failed to find a significant difference among the groups (RR 1.00, 95% CI [0.93, 1.07], p = 0.920). Due to limited data, meta-analyses could not be conducted for other secondary outcomes. Available studies consistently showed a favorable effect of flapless surgery in terms of vertical buccal bone change and pain, while only one study assessed the vertical midfacial soft tissue change, and no data were reported on esthetic outcomes. CONCLUSION: According to CBCT data, flapless IIP resulted in greater preservation of buccal bone as compared to flap IIP. However, the clinical significance of this finding remains uncertain since clinical and esthetic outcomes were insufficiently reported.

Comparing preservation substrates under field conditions for efficient DNA recovery in bone.

Often bones are the only biological material left for the identification of human remains. As situations may occur where samples need to be stored for an extended period without access to cooling, appropriate storage of the bone samples is necessary for maintaining the integrity of DNA for profiling. To simulate DNA preservation under field conditions, pig rib bones were used to evaluate the effects of bone cleaning, buffer composition, storage temperature, and time on DNA recovery from bone samples. Bones were stored in three different buffers: TENT, solid sodium chloride, and ethanol-EDTA, at 20 °C and 35 °C for 10, 20, and 30 days. Bones were subsequently dried and ground to powder. DNA was extracted and quantified. Results show that temperature and storage time have no significant influence on DNA yield. DNA recovery from bones stored in solid sodium chloride or ethanol-EDTA was significantly higher compared to bones stored in TENT, and grinding of bones was facilitated by the extent of dehydration in solid sodium chloride and ethanol-EDTA compared to TENT. Overall, solid sodium chloride was found to be superior over ethanol-EDTA; when it comes to transportation, dry material such as salt eliminates the risk of leaking; it is non-toxic and in contrast to ethanol not classified as dangerous goods. Based on this study's results, we recommend NaCl as a storage substrate for forensic samples in cases where no cooling/freezing conditions are available.

Pushing Raman spectroscopy over the edge: purported signatures of organic molecules in fossil animals are instrumental artefacts.

Widespread preservation of fossilized biomolecules in many fossil animals has recently been reported in six studies, based on Raman microspectroscopy. Here, we show that the putative Raman signatures of organic compounds in these fossils are actually instrumental artefacts resulting from intense background luminescence. Raman spectroscopy is based on the detection of photons scattered inelastically by matter upon its interaction with a laser beam. For many natural materials, this interaction also generates a luminescence signal that is often orders of magnitude more intense than the light produced by Raman scattering. Such luminescence, coupled with the transmission properties of the spectrometer, induced quasi-periodic ripples in the measured spectra that have been incorrectly interpreted as Raman signatures of organic molecules. Although several analytical strategies have been developed to overcome this common issue, Raman microspectroscopy as used in the studies questioned here cannot be used to identify fossil biomolecules.

Interoperable IoMT Approach for Remote Diagnosis with Privacy-Preservation Perspective in Edge Systems.

The emergence of the Internet of Medical Things (IoMT) has brought together developers from the Industrial Internet of Things (IIoT) and healthcare providers to enable remote patient diagnosis and treatment using mobile-device-collected data. However, the utilization of traditional AI systems raises concerns about patient privacy. To address this issue, we present a privacy-enhanced approach for illness diagnosis within the IoMT framework. Our proposed interoperable IoMT implementation focuses on optimizing IoT network performance, including throughput, energy consumption, latency, packet delivery ratio, and network longevity. We achieve these improvements using techniques such as device authentication, energy-efficient clustering, environmental monitoring using Circular-based Hidden Markov Model (C-HMM), data verification using Awad's Entropy-based Ten-Fold Cross Entropy Verification (TCEV), and data confidentiality using Twine-LiteNet-based encryption. We employ the Search and Rescue Optimization algorithm (SRO) for optimal route selection, and the encrypted data are securely stored in a cloud server. With extensive network simulations using ns-3, our approach demonstrates substantial enhancements in the specified performance metrics compared with previous works. Specifically, we observe a 20% increase in throughput, a 15% reduction in packet drop rate (PDR), a 35% improvement in network lifetime, and a 10% decrease in energy consumption and delay. These findings underscore the efficacy of our approach in enhancing IoT network interoperability and protection, fostering improved patient care and diagnostic capabilities.

Clinical outcomes of long-term corneas preserved frozen in Eusol-C used in emergency tectonic grafts.

To report the clinical results on the use of corneas frozen in Eusol-C as tectonic corneal grafts.Retrospective review of medical records of patients who received frozen corneas as emergency tectonic grafts from 2013 to 2020. Corneas had been stored in Eusol-C preservation media at - 78 °C for a mean time of 6.9 months. Diagnosis, transplant characteristics, microbial culture results, anatomic integrity, epithelial healing, neovascularization, transparency, infection and need for additional surgeries were registered. Fifty corneas were used in 40 patients (mean age 60.5 years, 20 males) with a median follow-up of 27.3 months after surgery. Need for tectonic graft was due to: perforation secondary to immune diseases (6, 12%), neurotrophic ulcer (11, 22%), trauma (3, 6%), corneal infection (11, 22%), chronic disorders of the ocular surface (9, 18%) and previous corneal graft failure (10, 22%). Mean size of grafts was 5.6 mm and 36 cases (72%) also received an amniotic membrane graft. Thirty-eight corneas achieved epithelization (76%), 25 (50%) were clear and 19 (38%) developed neovascularization. None of the corneas were rejected. Seventeen corneas (34%) failed: 7 (14%) due to reactivation of baseline disease and 10 (20%) due to primary graft failure. Four corneas (8%) had positive microbial cultures suggestive of contamination and 2 (4%) developed a cornea abscess non-related to a positive microbial culture. Long-term preservation of donor corneas in Eusol-C at - 78 °C is a viable technique to meet the needs of emergency grafts with minimal equipment.

Evaluation of EV Storage Buffer for Efficient Preservation of Engineered Extracellular Vesicles.

Extracellular vesicles (EVs), detectable in all bodily fluids, mediate intercellular communication by transporting molecules between cells. The capacity of EVs to transport molecules between distant organs has drawn interest for clinical applications in diagnostics and therapeutics. Although EVs hold potential for nucleic-acid-based and other molecular therapeutics, the lack of standardized technologies, including isolation, characterization, and storage, leaves many challenges for clinical applications, potentially resulting in misinterpretation of crucial findings. Previously, several groups demonstrated the problems of commonly used storage methods that distort EV integrity. This work aims to evaluate the process to optimize the storage conditions of EVs and then characterize them according to the experimental conditions and the models used previously. Our study reports a highly efficient EV storage condition, focusing on EV capacity to protect their molecular cargo from biological, chemical, and mechanical damage. Compared with commonly used EV storage conditions, our EV storage buffer leads to less size and particle number variation at both 4 °C and -80 °C, enhancing the ability to protect EVs while maintaining targeting functionality.

Effects of preservation by ethanol on δ13 C and δ15 N of three tissues of the critically endangered European eel Anguilla anguilla.

The temporal effects of ethanol preservation on the δ13 C and δ15 N values of tissues excised from European eel Anguilla anguilla were assessed. Preservation significantly enriched 13 C values of fin and mucus but not dorsal muscle. The 13 C enrichment occurred in the initial 15 days of preservation and was independent of initial eel mass. Tissue preservation effects on δ15 N values were negligible. These tissue-specific isotopic shifts should be considered when ethanol-preserved eel samples are used.

Ginsenoside F1-Mediated Telomere Preservation Delays Cellular Senescence.

Telomeres play pivotal roles in processes closely related to somatic senescence and aging, making them a compelling target for interventions aimed at combating aging and age-related pathologies. Ginsenoside, a natural compound, has emerged as a potential remedy for promoting healthy aging, yet how it protects telomeres remains incompletely understood. Here, we show that treatment of F1 can effectively restore the level of TRF2, thereby preserving telomere integrity. This restoration leads to inhibition of the DNA damage response and improvements in mitochondrial function and, ultimately, delays in cellular senescence. Conversely, depletion of TRF2 causes mitochondrial dysfunction, accompanied by increased oxidative stress, autophagy inhibition, insufficient energy metabolism, and the onset of cellular senescence. These observations underscore the critical role of TRF2 in maintaining telomere integrity and direct association with the initiation of cellular senescence. We conduct a further analysis, suggesting F1 could bind in proximity to the TRF2 heterodimer interface, potentially enhancing dimerization stability. These findings suggest that F1 may be a promising natural remedy for anti-aging, and restoring TRF2 could potentially prevent telomere-dependent diseases commonly associated with the aging process.

Upgrading Treatment and Molecular Diagnosis in Endometrial Cancer-Driving New Tools for Endometrial Preservation?

One emerging problem for onco-gynecologists is the incidence of premenopausal patients under 40 years of age diagnosed with stage I Endometrial Cancer (EC) who want to preserve their fertility. Our review aims to define a primary risk assessment that can help fertility experts and onco-gynecologists tailor personalized treatment and fertility-preserving strategies for fertile patients wishing to have children. We confirm that risk factors such as myometrial invasion and The International Federation of Gynecology and Obstetrics (FIGO) staging should be integrated into the novel molecular classification provided by The Cancer Genome Atlas (TCGA). We also corroborate the influence of classical risk factors such as obesity, Polycystic ovarian syndrome (PCOS), and diabetes mellitus to assess fertility outcomes. The fertility preservation options are inadequately discussed with women with a diagnosis of gynecological cancer. A multidisciplinary team of gynecologists, oncologists, and fertility specialists could increase patient satisfaction and improve fertility outcomes. The incidence and death rates of endometrial cancer are rising globally. International guidelines recommend radical hysterectomy and bilateral salpingo-oophorectomy as the standard of care for this cancer; however, fertility-sparing alternatives should be tailored to motivated women of reproductive age, establishing an appropriate cost-benefit balance between childbearing desire and cancer risk. New molecular classifications such as that of TCGA provide a robust supplementary risk assessment tool that can tailor the treatment options to the patient's needs, curtail over- and under-treatment, and contribute to the spread of fertility-preserving strategies.

Current Insights and Future Directions in the Treatment of Heart Failure with Preserved Ejection Fraction.

Heart failure is a clinical syndrome associated with poor quality of life, substantial healthcare resource utilization, and premature mortality, in large part related to high rates of hospitalizations. The clinical manifestations of heart failure are similar regardless of the ejection fraction. Unlike heart failure with reduced ejection fraction, there are few therapeutic options for treating heart failure with preserved ejection fraction. Molecular therapies that have shown reduced mortality and morbidity in heart failure with reduced ejection have not been proven to be effective for patients with heart failure and preserved ejection fraction. The study of pathophysiological processes involved in the production of heart failure with preserved ejection fraction is the basis for identifying new therapeutic means. In this narrative review, we intend to synthesize the existing therapeutic means, but also those under research (metabolic and microRNA therapy) for the treatment of heart failure with preserved ejection fraction.

[Research status of insect infestation of Chinese medicinal materials during storage].

During the storage process, Chinese medicinal materials are susceptible to insect infestation due to their own nature and external storage factors. Infestation by insects can have varying impacts on the materials. In mild cases, it affects the appearance and reduces consumer purchasing power, while in severe cases, it affects the quality, reduces medicinal value, and introduces impurities such as insect bodies, excrement, and secretions, resulting in significant contamination of the medicinal materials. This study reviewed the rele-vant factors influencing insect infestation in Chinese medicinal materials and the compositional changes that occur after infestation and summarized maintenance measures for preventing insect infestation. Additionally, it provided an overview of detection techniques applicable to identifying insect infestation during the storage of Chinese medicinal materials. During the storage process, insect infestation is the result of the combined effects of biological factors(source, species, and population density of insects), intrinsic factors(moisture, chemical composition, and metabolism), and environmental factors(temperature, relative humidity, and oxygen content). After infestation, there are significant changes in the content of constituents in the medicinal materials. By implementing strict pre-storage inspections, regular maintenance after storage, and appropriate storage and maintenance methods, the occurrence of insect infestation can be reduced, and the preservation rate of Chinese medicinal materials can be improved. The storage and maintenance of Chinese medicinal materials are critical for ensuring their quality. Through scientifically standardized storage and strict adherence to operational management standards, the risk of insect infestation can be minimized, thus guaranteeing the quality of Chinese medicinal materials.

Biogenic Iron Preserves Structures during Fossilization: A Hypothesis: Iron from Decaying Tissues May Stabilize Their Morphology in the Fossil Record.

It is hypothesized that iron from biological tissues, liberated during decay, may have played a role in inhibiting loss of anatomical information during fossilization of extinct organisms. Most tissues in the animal kingdom contain iron in different forms. A widely distributed iron-bearing molecule is ferritin, a globular protein that contains iron crystallites in the form of ferrihydrite minerals. Iron concentrations in ferritin are high and ferrihydrites are extremely reactive. When ancient animals are decaying on the sea floor under anoxic environmental conditions, ferrihydrites may initialize the selective replication of some tissues in pyrite FeS2 . This model explains why some labile tissues are preserved, while other more resistant structures decay and are absent in many fossils. A major implication of this hypothesis is that structures described as brains in Cambrian arthropods are not fossilization artifacts, but are instead a source of information on anatomical evolution at the dawn of complex animal life.

Collagen matrices are preserved following decellularization of a bovine bone scaffold.

The decellularization of bovine bone has emerged as a strategy for the repair, replacement, and regeneration of bone defects. To evaluate the effects of a new protocol of bone decellularization and its impact on the structure and collagen scaffold. Cancellous bone from bovine femur was dissected in fragments and decellularized based on protocol of multiple steps. The residual protein levels, histological, morphometric, and scanning electronic microscopy analyses were carried out to evaluate the effects of decellularization and the impact on the structure and collagen scaffold. A cytotoxicity assay was performed. Residual protein analysis showed an important removal of bone marrow components and cell debris from the bone. Sections revealed that collagen fibers presented integrity and absence of cells in the decellularized bone. Sirius Red-stained sections of collagen fiber collagen matrix were maintained after decellularization. Scanning electron microscopy revealed that the main bone structure, despite being irregular, was maintained in both groups, with no significant visual differences between the surface characteristics according to the groups. Decellularized bovine bone demonstrated a degree of toxicity of 3, indicating moderate reactivity. The present data demonstrate that the main bone structure was maintained. Additionally, the chemical and physical treatments were able to remove cellular debris, and extracellular matrix architecture and collagen were preserved. However, the tissue showed moderate toxicity.