bluuebunny/crossref_metadata_2025 huggingface dataset:
RETRACTED: Influences of evidence‐based nursing intervention on pressure ulcers in intensive care units: A meta‐analysis
Authors: Xu Yan‐Bing , Chen Zhi‐Qiang , Su Xiao‐Hong , Cao Ying
Published: April 2024

A meta‐analysis was conducted comprehensively to investigate the impact of evidence‐based nursing (EBN) interventions on pressure injury (PI) in the intensive care unit (ICU) patients. Computer searches were performed, from databases inception to November 2023, in Wanfang, PubMed, China National Knowledge Infrastructure, Google Scholar, Embase, and Cochrane Library for randomized controlled trials (RCTs) on the application of EBN interventions in ICU patients. Two independent researchers conducted screenings of the literature, extracted data, and carried out quality evaluations. Stata 17.0 software was employed for data analysis. Overall, 25 RCTs, involving 2494 ICU patients, were included. It was found that compared to conventional care methods, the implementation of EBN interventions in ICU patients markedly decreased the occurrence of PI (odds ratio [OR]: 0.22, 95% confidence interval [CI]: 0.17–0.30, p < 0.001), delayed the onset time of pressure ulcers (standardized mean difference [SMD]: −1.61, 95% CI: −2.00 to −1.22, p < 0.001), and also improved nursing satisfaction (OR: 1.18, 95% CI: 1.14–1.23, p < 0.001). Our findings suggest the implementation of EBN interventions in the care of PI in ICU patients is highly valuable, can reduce the occurrence of PI, can delay the time of appearance, and is associated with relatively higher nursing satisfaction, making it worthy of promotion.
RETRACTED: The effect of negative pressure wound therapy on the outcome of diabetic foot ulcers: A meta‐analysis
Authors: Zhang Ning , Liu Yibin , Yan Weiqi , Liu Fei
Published: April 2024

Negative pressure injury is one of the auxiliary methods of treating diabetes foot ulcers. It has been shown to be superior to conventional techniques in randomized controlled trials (RCTs). Nevertheless, the results of observational research are still scarce. A systematic review of RCTs and observations was carried out to evaluate the effectiveness and security of negative pressure wound therapy (NPWT) treatment for diabetes foot ulcers. Three English e‐databases have been found for NPWT research. The meta‐analyses of the comparative studies provided point estimates of results. Intermediate results were given as median and binary values were given in the form of odds ratios (OR). Seventeen trials, 13 RCTs and four randomized, controlled trials were found in the survey. Of these, 831 were treated with NPWT, 834 were treated with standard therapy. A total of 14 studies have been conducted to investigate the influence of NPWT on the healing of diabetic foot ulcers(DFU). In the study, NPWT was shown to speed up the healing of the wound in DFU patients(OR, 2.57; 95% CI, 1.72, 3.85 p < 0.0001). A subgroup analysis showed that NPWT was associated with an acceleration of the wound healing rate in 10 RCT trials (OR, 2.48; 95% CI, 1.58, 3.89 p < 0.001). In the four nRCT trials, NPWT was also shown to speed up the healing of the wound(OR, 2.95; 95% CI, 1.03, 8.42 p = 0.04). In 11 studies, the influence of NPWT on amputations of diabetes mellitus (DM) foot ulcers was investigated. The results showed that NPWT was associated with a reduction in amputations (OR, 0.53; 95% CI, 0.37, 0.74 p = 0.0002).In a subgroup of RCT trials, nine RCT trials showed a reduction in amputations(OR, 0.61; 95% CI, 0.43, 0.87 p = 0.007). In both nRCT trials, NPWT also showed a reduction in amputations (OR, 0.03; 95% CI, 0.00, 0.24 p = 0.001). Generally speaking, NPWT can help to heal the wound and lower the risk of amputations in people with diabetes. The subgroup analysis showed similar results for the RCT and non‐RCT trials. NPWT can be used to treat diabetes foot ulcers caused by diabetes.
Estimated reproductive parameters for a vulnerable Australian humpback dolphin population
Authors: Hawkins Elizabeth R. , Dunleavy Merryn
Published: April 2024

Understanding reproductive output and success is integral to the conservation and management of threatened species and populations. Little is known about the reproductive parameters of Australian humpback dolphins (Sousa sahulensis), a species subject to cumulative pressures from anthropogenic threats due to their coastal distribution and strong site fidelity. This study assesses several reproductive parameters, including crude birth, recruitment, fecundity, and calf survival rates, in addition to interbirth intervals of Australian humpback dolphins inhabiting the near‐urban embayment of Moreton Bay, Queensland. Between 2014 and 2020, 106 adult females were photographically identified during 222 boat surveys. Of these, 75.5% (n = 80) were observed with calves. Birth seasonality was apparent and coincided with austral autumn and winter months. Interbirth intervals ranged between 1 and >6 years, with an average of 3.1 (SD = 1.1) years if offspring survived. Findings indicate declining fecundity rates (p < .05, M = 0.12, SD = 0.02), relatively low recruitment rates (M = 0.04, SD = 0.01) and calf survival rates to 1 year of age (M = 0.63, SD = 0.15). This study provides a useful baseline that can inform viability assessments and conservation measures, for both this population and others throughout the species range.
Small intestinal bacterial overgrowth in diabetic gastroenteropathy
Authors: Varma Revati , Chakraborty Subhankar , Burton Duane D. , Bailey Kent R. , Bharucha Adil E.
Published: April 2024

Background

Although diabetic gastroenteropathy (DGE) is associated with small intestinal bacterial overgrowth (SIBO), most studies have evaluated SIBO with a hydrogen breath test, which may be affected by altered transit in DGE. The risk factors for the consequences of SIBO in DGE are poorly understood. We aimed to evaluate the prevalence of, risk factors for, and gastrointestinal symptoms associated with SIBO in patients with DGE.

Methods

In 75 patients with DGE and dyspepsia, we tested for SIBO (≥105 colony forming units /mL of aerobic and/or anaerobic bacteria in a duodenal aspirate) and assessed gastric emptying (GE) of solids, symptoms during a GE study and during an enteral lipid challenge (300 kcal/2 h), and daily symptoms with a Gastroparesis Cardinal Symptom Index diary for 2 weeks. Symptoms and GE were compared in patients with versus without SIBO.

Key Results

Of 75 patients, 34 (45%) had SIBO, which was not associated with the use of proton pump inhibitors, daily symptoms, GE, or symptoms during a GE study. During enteral lipid challenge, severe nausea (p = 0.006), fullness (p = 0.02) and bloating (p = 0.009) were each associated with SIBO. Twenty patients (59%) with versus 13 (32%) without SIBO had at least one severe symptom during the lipid challenge (p = 0.006).

Conclusions & Inferences

Among patients with DGE 45% had SIBO, which was associated with symptoms during enteral lipid challenge but not with delayed GE, symptoms during a GE study, or daily symptoms. Perhaps bacterial products and even fatty acids are recognized by and activate mast cells that drive the increased lipid sensitivity in SIBO.
The efficiency of public expenditures on basic services: The case of South African municipalities
Authors: Adedeji Amusa Hammed , Fadiran David
Published: April 2024

This paper examines the efficiency of service delivery across 213 local and metropolitan municipalities in South Africa, focusing on four critical areas: electricity, water, sewerage and waste removal. Utilising a order‐
partial frontier efficiency analysis (PFEA), the study calculates output‐oriented efficiency scores for each municipality, incorporating adjustments for service quality based on an ‘infrastructure quality‐index’. Our empirical findings indicate marked variations in efficiency, with electricity services exhibiting the highest efficiency rate at 35%, while waste removal lags behind at 22%. Additionally, municipalities centred around small urban towns are found to be more efficient, challenging the widely held view that larger municipalities are better equipped for efficient service delivery. The analysis offers empirical insights into local government performance in South Africa, underscoring the need for targeted policy interventions to address efficiency gaps. These results not only inform fiscal and administrative decentralisation strategies but also set the groundwork for future research exploring the underlying factors affecting municipal efficiency.
Synthesizing the Global English‐Language Abortion Narrative: A Comparative Analysis of Media Discourse*
Authors: Adamczyk Amy , Lerner Lindsay J.
Published: April 2024

Abortion is one of the most politically divisive topics currently being discussed in the media. No study has yet attempted to make cross‐national comparisons assessing the nuances associated with various views on abortion in the English public press. Using an original hand‐coded sample of over 800 English‐language newspaper articles from 41 countries that mentioned abortion, we examine how country‐level influences and newspaper characteristics shape newspaper portrayals of abortion. Our three‐level hierarchical models find that democracy and the freedom it engenders increase the likelihood that newspapers discuss laws, policies, and government claimsmakers when abortion is mentioned. When abortion is legal, newspapers are less likely to mention social movements and protest activities, possibly because the issue may be more settled. We also provide previously untapped insight into the role that a country's religious culture and level of economic development play. Surprisingly, religion and economics have relatively little influence in shaping abortion discussions.
Blockchain Database for Improved Recording of Property Deeds
Authors: Zeid Abe , Cohen Dylan , Justice Eva , Mendoza Sofia , Schlagman Eliana , Simon Sarah
Published: April 2024

The current manual process for property deed recording lacks automation, efficiency, and transparency. Real estate transactions require disjointed efforts from multiple parties, and they only become legally binding once they are recorded in a public, physical repository: the Registry of Deeds. Sensitive information is centralized, leaving it vulnerable to misuse, fraudulent activity, and destruction. A blockchain database offers real-time traceability for transactions and a peer-to-peer network to connect the tasks of attorneys, title agents, notaries, grantors, and grantees into a seamless process. Records in a blockchain database are immutable and protected from misuse. Replacing the manual recording process with an automated blockchain eliminates waste in time, money, and third-party efforts, providing grantors and grantees with added protection in the legitimacy of their transactions. This paper aims to provide a proof-of-concept prototype to replace the current paper-based traditional process with an electronic-based blockchain process. A full replacement of the existing relational database will improve throughput, error rates, and cycle times in the recording process. The solution comprises an immutable, decentralized blockchain database of property deeds with an interactive website to add and query records.
Exploring the Influence of Requirement Representation on Idea Generation
Authors: Patel Akash , Summers Joshua D. , Morkos Beshoy , Karmakar Sourabh
Published: April 2024

The objective of this research is to understand how different representations of requirements influence idea generation in terms of quantity, addressment, novelty, and variety of conceptual sketches. Requirements are testable statements of need, desires, and wishes of the stakeholders that are used by engineers to frame the problem. Project success is highly dependent on well-defined requirements documents. An experimental study was conducted with 52 fourth-year mechanical engineering undergraduate students. Two design problems are used with three different representations: a problem statement with embedded requirements, a problem statement and a traditional requirement list, and a problem statement with contextualized scrum stories. Each student addressed both design problems with two different representations of requirements. It was found that the use of contextualized scrum story representations significantly affected the novelty of solution fragments and addressment of requirements, while no significant change in variety and quantity was seen. Finally, it was found that quantity is not directly related to the number of requirements addressed in the sketches.
Optimal Positioning of Small Wind Turbines Into a Building Using On-Site Measurements and Computational Fluid Dynamic Simulation
Authors: Vallejo Díaz Alexander , Herrera Moya Idalberto , Castellanos Juan E. , Garabitos Lara Edwin
Published: April 2024

Renewable energy solutions are essential for addressing several pressing issues, including climate change, the fossil fuels supply chain fragility and fuel price fluctuations. One promising technological solution is rooftop-mounted turbines into buildings. This study presents an evaluation of the potential for wind energy utilization on the rooftop of a 29 m tall building. The primary objective of this research is to develop a methodology that can effectively investigate the integration of small wind turbines (SWTs) into urban buildings, intending to promote energy sufficiency in urban areas. A robust framework has been developed that consists of seven steps. These steps include site selection, evaluating urban wind energy with computational fluid dynamics (CFD) simulation and on-site measurements, selecting an appropriate SWT, estimating the annual energy production (AEP), conducting an evaluation of the environmental impact, resilience, and economic analysis, and finally, installing the system. This straightforward yet reliable framework provides a comprehensive approach to assessing the viability of wind energy utilization in urban areas. The findings revealed that the most suitable location for installation had an estimated AEP of around 1030 kWh, leading to a reduction in emissions of 0.64 tCO2/y. Additionally, it was observed that the building's geometry and orientation significantly affected the wind flow, causing a substantial decrease in wind speed downstream. Selecting optimal sites and considering wind patterns are essential for maximizing energy generation in wind energy projects.
Bacterial genome sequences of uncharacterized
Chitinophaga
species isolated from the International Space Station
Authors: Castro Christian L. , Schwengers Oliver , Stahl-Rommel Sarah , Nguyen Hang N. , Dunbar Brandon , Wallace William T. , Castro-Wallace Sarah L.
Published: April 2024

We report four
Chitinophaga
sp. strains isolated from wastewater collected onboard the International Space Station. Here, we present three finished and one draft genome. Taxonomic ranks established by genome-based analysis indicate that these
Chitinophaga
sp. strains represent candidates for a new species.
Intake of compound probiotics accelerates the construction of immune function and gut microbiome in Holstein calves
Authors: Cai Xinghua , Yi Ping , Chen Xuewen , Wu Junhua , Lan Ganqiu , Li Shijian , Luo Shasha , Huang Fengdie , Huang Jinrong , Shen Peihong
Published: April 2024

Acquired immunity is an important way to construct the intestinal immune barrier in mammals, which is almost dependent on suckling. To develop a new strategy for accelerating the construction of gut microbiome, newborn Holstein calves were continuously fed with 40 mL of compound probiotics (containing
Lactobacillus plantarum
T-14,
Enterococcus faecium
T-11,
Saccharomyces cerevisiae
T-209, and
Bacillus licheniformis
T-231) per day for 60 days. Through diarrhea rate monitoring, immune index testing, antioxidant capacity detection, and metagenome sequencing, the changes in diarrhea incidence, average daily gain, immune index, and gut microbiome of newborn calves within 60 days were investigated. Results indicated that feeding the compound probiotics reduced the average diarrhea rate of calves by 42.90%, increased the average daily gain by 43.40%, raised the antioxidant indexes of catalase, superoxide dismutase, total antioxidant capacity, and Glutathione peroxidase by 22.81%, 6.49%, 8.33%, and 13.67%, respectively, and increased the immune indexes of IgA, IgG, and IgM by 10.44%, 4.85%, and 6.12%, respectively. Moreover, metagenome sequencing data showed that feeding the compound probiotics increased the abundance of beneficial strains (e.g.,
Lactococcus lactis
and
Bacillus massionigeriensis
) and decreased the abundance of some harmful strains (e.g.,
Escherichia sp. MOD1-EC5189
and
Mycobacterium brisbane
) in the gut microbiome of calves, thus contributing to accelerating the construction of healthy gut microbiome in newborn Holstein calves.

IMPORTANCE

The unstable gut microbiome and incomplete intestinal function of newborn calves are important factors for the high incidence of early diarrhea. This study presents an effective strategy to improve the overall immunity and gut microbiome in calves and provides new insights into the application of compound probiotics in mammals.
Explaining QPOs data for black holes in the Starobinsky–Bel–Robinson gravity
Authors: Abdulkhamidov Farukh , Narzilloev Bakhtiyor , Hussain Ibrar , Abdujabbarov Ahmadjon , Ahmedov Bobomurat
Published: April 2024

In this work we explore the properties of the spacetime around the Schwarzschild-like black hole in the Starobinsky–Bel–Robinson gravity through a test particle motion and its quasi periodic oscillations (QPOs) in the circular orbits in the close vicinity of the black hole horizon. We show how the extra spacetime parameter $$\beta $$
β
affects the effective potential, energy, angular momentum, inner most circular orbit (ISCO) radius, and trajectory of a test particle. Next, we focus on the QPOs of particles and explore it in the relativistic precision model. Finally, we apply our analysis to explain the observational data obtained for several black hole candidates including GRO J1655-40, GRS 1915+105, XTE J1859+226, and XTE J1550-564 and get constraints on their spacetime parameters by employing the Markov Chain Monte Carlo analysis methodology.
Are We Overusing Coagulation Studies in the Emergency Department?
Authors: Alyahya Bader , Alalshaikh Abdulaziz , Alkhulaif Ali , Al-Salamah Tareq , Aldawood Badr , Alsubaie Alwaleed , Alohali Meshal , Alshenaifi Saud , Alohali Abdulaziz , Alzin Majed B. , Almana Abdullah , Habib Mohammed , Hasanato Rana
Published: April 2024

Background and Objectives. Blood tests are often indiscriminately requested in the Emergency department (ED) and many EDs have preset orders that are usually performed at triage before clinical assessment to improve the flow of patients through the department. We conducted this study to evaluate the frequency of requests for coagulation profile, the incidence of abnormal coagulation profiles and the unnecessary use of coagulation profile testing in our institution. Methods. This retrospective observational study, conducted in the ED of King Saud University Medical City (KSUMC) in Riyadh, Saudi Arabia, during July and August of 2021(2 months) examined coagulation profile requests. Patients’ demographic data (age and gender), medical and clinical history (presenting complaint, comorbidities, and diagnosis), the use of antiplatelets or anticoagulant agents and laboratory values for PT, APTT, and INR were collected. We calculated the total cost of unnecessary coagulation profile testing based on the independent assessment of two ED consultants. Results. Of 1,754 patients included in the study, 811 (46.2%) were males and 943 (53.8%) were females, with a mean age of 42.1 ± 18.5 years. There were 29 (1.7%) patients with liver disease and 21 (1.2%) patients had thromboembolic disease. The majority of the patients’ results were within normal levels of PT (n = 1,409, 80.3%), APTT (n = 1,262, 71.9%), and INR (n = 1,711, 97.4%). Evidence of active bleeding was detected in 29 patients (1.7%). Among patients with bleeding only one had an abnormal INR (3.01) and was on warfarin. Forty-six (2.6%) patients had elevated INR level. Cohen’s kappa between the two consultants was recorded at 0.681 (substantial agreement) in their assessment of the appropriateness of coagulation tests requests and both consultants believed that 1,051 tests (59.9%) were not indicated and were unnecessary. The expected annual cost saving if the unnecessary tests were removed would be around SAR 1,897,200 (approximately US$ 503,232) which is about SAR 180000 (US$ 48000)/1000 patients. Conclusion. This study showed that coagulation tests are overused in the ED. More than half of coagulation profile tests in our study population were deemed unnecessary and associated with significant cost. Targeted testing based on specific patient presentation and medical history can guide physicians in wisely choosing who needs coagulation studies.
A Case of Rosai-Dorfman Disease Successfully Treated by Corticotherapy
Authors: Diallo Alioune Badara , Ndiaye Moustapha , Seck Moussa , Keita Mohamed , Bousso Elimane Seydi , Touré Sokhna Aissatou , Faye Blaise Félix , Diop Saliou
Published: April 2024

Rosai-Dorfman disease (RDD) is a benign histiocytic proliferation that results in nodal and extranodal involvements. It is a rare disease, with fewer than 1,000 cases reported in the literature, which explains its lack of knowledge by physicians and the lack of codified therapeutic strategies. We report the case of an 8-year-old girl who presented a rapidly progressive cervical lymph node mass; the diagnosis of RDD was made based on histology and immunohistochemistry. The patient was treated with oral corticosteroids at a dose of 1 mg/kg/d with a favorable outcome and no recurrence after one year of follow-up. This observation illustrates the clinical presentation and diagnosis of this rare clinicopathological entity. The prognosis and treatment options are also discussed.
Long-Term Efficacy and Safety of Damoctocog Alfa Pegol Prophylaxis in Patients with Haemophilia A Aged 12–<18 Years at Enrolment into PROTECT VIII
Authors: Reding Mark T. , Simpson Mindy , Ducore Jonathan , Holme Pål Andrè , Maas Enriquez Monika , Mancuso Maria Elisa
Published: April 2024

Introduction: The phase 2/3 PROTECT VIII study demonstrated long-term efficacy and safety of damoctocog alfa pegol (BAY 94-9027; Jivi®), a B-domain-deleted recombinant factor VIII (FVIII), site-specifically PEGylated to improve its pharmacokinetic profile. We report a post hoc assessment of bleeding and safety outcomes in the subgroup of patients, aged 12–<18 years at enrolment. Method: PROTECT VIII was a multicentre, open-label study of previously treated males aged 12–65 years with severe haemophilia A (FVIII <1%). Twelve patients were included in this analysis. All received damoctocog alfa pegol prophylaxis for the total time in study (median [range] time in study 4.0 [1.3–6.2] years). Results: Overall median (Q1; Q3) total and joint annualised bleeding rates were 1.8 (0.4; 5.1) and 0.7 (0.2; 1.8), respectively, for the entire study. During the last 6 months of treatment, eight (66.7%) and ten (83.3%) out of 12 patients experienced zero total and joint bleeds, respectively. No patient developed FVIII inhibitors. No deaths or thrombotic events were reported. Conclusion: Efficacy and safety of damoctocog alfa pegol were confirmed in adolescent patients with haemophilia A, with data for up to 6 years supporting its use as a long-term treatment option in this group as they transition into adulthood.
Revisão do Gênero Stereomerus Melzer, 1934 (Coleoptera, Cerambycidae, Lamiinae, Desmiphorini)
Authors: Martins Ubirajara R. , Galileo Maria Helena M.
Published: April 2024

.
Abstract 189: Simultaneous Imaging of the Single-Myocyte Optical Action Potentials and Intracellular Ca
2+
Dynamics in Langendorff-Perfused Rat Heart by a Novel Dual-Imaging Confocal Microscopy
Authors: Fujiwara Katsuji , Tanaka Hideo , Nakagami Takuo , Mani Hiroki , Tanabe Takuji , Oyamada Masahito , Takamatsu Tetsuro
Published: April 2024

Rapid-scanning confocal imaging of intracellular Ca
2+
([Ca
2+
]
i
) dynamics in the heart has revealed various abnormal [Ca
2+
]
i
dynamics that indicate arrhythmogenic potential. For example, Ca
2+
waves under [Ca
2+
]
i
overload and beat-to-beat alteration of Ca
2
+
transients may lead to triggered arrhythmia and inhomogeneous excitation and conduction, respectively. However, it is unknown whether such abnormal [Ca
2+
]
i
dynamics accompany altered electrical activities in the individual myocytes. To elucidate the link between [Ca
2+
]
i
dynamics and the membrane potentials (V
m
) of the myocytes in the heart we developed a novel dual-imaging system for both the [Ca
2+
]
i
dynamics and optical V
m
at cellular levels. Optical signals for [Ca
2+
]
i
and V
m
were obtained using
in situ
confocal microscopy (x40 objective lens, 2.2 ms/frame, 96x64 pixels) after loading the rat heart with fluo3/AM and RH237, respectively. The subepicardial myocardium of the heart was excited by Argon/Krypton (488/568nm) laser. The dual, non-overlapping signals for fluo3 and RH237, obtained by splitting the emitted light with a dichroic filter (565nm) and the respective emission filters of 535/40 nm and 774/50nm, were detected by a high-speed CCD camera (14 bits). Following results were obtained from 17 hearts.

During sinus rhythm the myocytes exhibited spatially uniform Ca
2+
transients with simultaneous action potentials.

Under perfusion with Ca
2+
-free solution Ca
2+
transients were diminished while the action potentials remained.

The durations of these two parameters were stimulation-frequency dependent: the higher the frequency (up to 5Hz), the shorter the durations.

At a stimulation frequency of 4Hz or higher Ca
2+
transients often showed beat-to-beat alternans while no discernible alternans was obtained in action potentials.

Under [Ca
2+
]
i
overload, cessation of high-frequency pacing at 5 Hz resulted in synchronous emergence of Ca
2+
waves among individual cells which accompanied fluctuations of the optical V
m
.

In summary, we succeed in acquiring [Ca
2+
]
i
dynamics V
m
and optical of individual myocytes simultaneously in the whole heart. This novel approach would provide important information to understand the mechanism of Ca
2+
-mediated arrhythmias.
Abstract 561: A Cathepsin D-Cleaved 16kDa Form of Prolactin Mediates Postpartum Cardiomyopathy: Inhibition of Prolactin as a Novel Therapy Option
Authors: Hilfiker-Kleiner Denise , Struman Ingrid , Luchtefeld Maren , Forster Olaf , Sliwa Karen , Drexler Helmut
Published: April 2024

Background: Postpartum cardiomyopathy (PPCM) is a disease of unknown etiology and exposes women to high risk of mortality after delivery despite optimal medical therapy. Mice with a cardiac specific knockout for STAT3 (KO: ∈±-MHC-Cretg/+; stat3flox/flox) develop PPCM. We used KO mice to investigate potential mechanisms behind PPCM and compared our findings to patients with acute PPCM.

Methods: Cathepsin D (CD) expression was determined by Western blot and immunohistochemistry in left ventricles (LV) of wildtype (WT: stat3flox/flox) and KO mice after two subsequent pregnancies. In mouse LV supernatant CD activity was analyzed by ELISA and cleavage of recombinant prolactin (Prl) was determined by Western blot. Adenoviruses expressing either the16kDa Prl or as control the LacZ protein were injected into LVs of virgin WT mice. Prl secretion was inhibited by oral administration of bromocriptine in mice (BR, 4mg/kg/day 5 days before till 3 weeks postpartum). In serum samples collected from patients with acute PPCM (n=6) and from healthy nursing women (n=5) Prl isoform expression was analyzed by Western blot and CD activity was measured by ELISA.

Results: In LVs from postpartum KO mice CD expression (3x, P<0.05) and activity (4x, P<0.05) was significantly enhanced and was associated with marked generation of the cleaved anti-angiogenic and pro-apoptotic 16kDa form of Prl compared with LVs from postpartum WT mice. Inhibition of Prl secretion by BR prevented the development of PPCM in KO mice completely. In contrast, the forced myocardial generation of 16kDa Prl by adenoviral transfection impaired the cardiac capillary network (−31Â±12%, P<0.05) and the cardiac function (LacZ: 43Â±2% vs 16kDa : 33Â±7%, P<0.05) while no such effect was observed in mice transfected with LacZ expressing adenovirus. In serum probes of patients (n=4) with acute PPCM enhanced CD activity (4x, P<0.05) and elevated levels of 16kDa Prl (2 to 5 times; P<0.05) were observed compared with serum probes of healthy nursing women (n=5).

Conclusions: We propose that a biologically active, derivative of the pregnancy hormone, prolactin, mediates PPCM implying that inhibition of Prl release may represent a novel therapeutic strategy for PPCM.
Abstract 4165: Impact of the National Cholesterol Education Program Third Adult Treatment Panel Lipid-Lowering Recommendations on the Management of Patients With Non-ST-Segment Elevation Acute Coronary Syndromes
Authors: Petersen John L , Roe Matthew T , Mulgund Jyotsna , Blazing Michael A , Foody JoAnne M , Smith Sidney C , Califf Robert M , Pollack Charles V , Harrington Robert A , Ohman E M , Gibler W B , Brindis Ralph G , Peterson Eric D
Published: April 2024

Background
: The National Cholesterol Education Program Third Adult Treatment Panel (NCEP ATP III) recently added an optional secondary prevention low-density lipoprotein (LDL) cholesterol goal (<70 mg/dL) for high-risk patients, such as those with acute coronary syndromes (ACS). The effect of the optional goal on the need for treatment in patients (pts) presenting with non-ST-segment elevation (NSTE) ACS is unclear.

Methods
: We evaluated pts with NSTE ACS (positive cardiac markers and/or ischemic ECG changes) included in the CRUSADE initiative between January 2001 and July 2004 with a LDL cholesterol drawn before or during hospitalization. This population was stratified by prehospitalization use of lipid-lowering therapy and divided into LDL cholesterol categories of <70, ≥70 to <100, ≥100 to 130, and ≥130 mg/dL.

Results
: Of 129,054 total pts in CRUSADE, 71,814 (55.7%) had a LDL cholesterol available (Figure

). Of those with an LDL cholesterol, 23,728 (33.0%) received lipid-lowering therapy prior to hospitalization, including 22,046 (30.7%) on statin therapy. Of the 71,814 pts, 34,258 (47.8%) were at the NCEP-ATP III recommended treatment goal of <100 mg/dL, and 12,463 (17.4%) were at the optional aggressive treatment goal of <70 mg/dL on presentation with NSTE ACS.

Conclusions
: The majority of pts presenting with NSTE ACS are not on lipid-lowering therapy prior to admission, most are not at the NCEP ATP III recommended LDL goal, and a minority are at the optional LDL goal for high-risk patients.
Abstract 4166: Clinical Significance of HDL-c Levels among Patients with LDL-c less than 60 mg/dl
Authors: deGoma Emil M , Leeper Nicholas J , Heidenreich Paul A
Published: April 2024

Background: Although studies support an inverse correlation between HDL-cholesterol levels and cardiovascular risk, the clinical relevance of HDL in the context of low LDL levels remains uncertain.

Methods: We identified 6,357 consecutive patients seen at the Palo Alto VA Medical Center or one of 7 community clinics with LDL levels less than 60 mg/dl. The cohort was divided into quartiles based on HDL. The combined primary outcome was myocardial infarction (defined as a Tn I > 0.1 ng/ml) or hospitalization for ischemic heart disease (IHD) at one year. Odds ratios were adjusted for demographics, medical history, laboratory values (hemoglobin, creatinine, HbA1C, liver function tests, LDL, triglycerides), and statin use.

Results: The cohort had a mean age of 65 years, a prior diagnosis of IHD in 42%, diabetes in 46%, hypertension in 73%, and heart failure in 15%. Mean HDL levels (mg/dl) by quartile were: Q1 - 28, Q2 - 36, Q3 - 43, Q4 - 64. The incidence of the combined endpoint of MI or IHD hospitalization at one year was higher in the low HDL quartiles (Q1 - 8.5%, Q2 - 5.8%, Q3 - 5.1%, Q4 - 3.9%, p < 0.0001). The association of HDL with IHD admission and MI persisted following multivariate adjustment (Figure

).

Conclusions: Low HDL-cholesterol levels are a marker for excess coronary risk among patients with an LDL less than 60 mg/dl. HDL-directed therapies may play an important role in the prevention of IHD events across all levels of LDL.
Abstract 566: Altered Expression of Connexin43 Contributes to the Arrhythmogenic Substrate in Early Stage Heart Failure of Cardiomyopathic Hamster
Authors: Sato Takashi , Ohkusa Tomoko , Honjo Haruo , Suzuki Shinsuke , Ishiguro Yuko S , Nakagawa Harumichi , Yamazaki Masatoshi , Yano Masafumi , Kodama Itsuo , Matsuzaki Masunori
Published: April 2024

Background:
Heart failure is known to predispose life-threatening ventricular tachyarrhythmias even before compromising the systemic circulation, but the underlying mechanism is not well understood.

Methods and Results
: We investigated stage-dependent changes in connexin43 (Cx43) expression and consequent electrophysiological properties in UM-X7.1 cardiomyopathic hamster hearts. UM-X7.1 hamsters develop left ventricular (LV) hypertrophy by age 6~10w, and show more pronounced LV hypertrophy and a moderate reduction in LV contractility at age 20w. Appreciable interstitial fibrosis is recognized at these stages. LV mRNA and protein levels of Cx43 in UM-X7.1 were unaffected at 10w, but significantly reduced at 20w (by 33% and 55%, respectively from controls). The relative expression level of serin255-phosphorylated Cx43 was markedly increased in UM-X7.1 at age 20w (by 175%). Electrophysiological properties were examined by optical mapping. In UM-X7.1 at 10w, almost normal LV conduction was preserved, whereas the dispersion of action potential duration (APD) was significantly increased. UM-X7.1 at 20w showed significant reduction of conduction velocity (by 35~40%), significant prolongation of APD (by 68%), marked distortion of activation fronts and a pronounced increase in APD dispersion. Programmed stimulation resulted in no arrhythmias in controls, but sustained ventricular tachycardia or fibrillation (VT/VF >5s) in UM-X7.1 (1/11 at 10w and 5/6 at 20w). LV activation during polymorphic VT was characterized by multiple phase singularities or wavebreaks.

Conclusions
: In the early stage heart failure of cardiomyopathy, down-regulation and serine255-phosphorylation of Cx43 in addition to the interstitial fibrosis may contribute to the arrhythmogenic substrate through the inhibition of cell-to-cell communication.
Abstract 567: Aldosterone Modulates Gap Junction Remodeling in Cultured Rat Ventricular Myocytes
Authors: Suzuki Shinsuke , Ohkusa Tomoko , Sato Takashi , Lee Jong-Kook , Yasui Kenji , Kodama Itsuo , Matsuzaki Masunori
Published: April 2024

Background and Objectives
: A variety of stresses impact the heart and the renin-angiotensin-aldosterone system (RAAS) affects cellular structure and electrophysiology. Modulation of intercellular coupling through gap junction could lead to an alteration in conduction velocity and conduction block. The aim of this study was to investigate the effects of aldosterone (Ald) on the expression of connexin (Cx)43 gap junction in neonatal rat cultured ventricular myocytes and the consequence changes of conduction properties.

Methods:
Culture was exposed to Ald for 24h. The expression of Cx43 was characterized by western blotting and real-time RT-PCR. Propagation of excitation was visualized by extracellular potential mapping by using a multiple electrode array system.

Results:
Exposure to 10
-4
M Ald resulted in a significant downregulation of Cx43 (by ~0.4-fold in protein). Treatment with 10
-8
M Ald induced a significant increase of Cx43 (by ~1.4-fold in protein and by ~1.3-fold in mRNA). Conduction velocity was increased significantly by the treatment of 10
-8
M Ald (~20% increase) with a random propagation of contraction. Ald is known to bind to two types of binding sites: mineralocorticoid receptors (MR) and glucocorticoid receptors (GR). To clarify the effects of dose dependency of Ald on Cx43 expression, Ald was applied to cardiomyocytes pretreated with GR antagonist (mifepristone) or MR antagonist (eplerenone). Mifepristone inhibited the decrease of Cx43 of cardiomyocytes exposed to 10
-4
M Ald. The increase of Cx43 of cardiomyocytes exposed to 10
-8
M Ald was prevented by eplerenone. On the other hand, losartan did not affect the alterations in Cx43 expression caused by 10
-4
and 10
-8
Ald exposure.

Conclusions:
These results suggest that Ald affects gap junction remodeling in a dose dependent manner by modulating Cx43 synthesis through a different receptor and causes a concomitant change of conduction velocity. An effective prevention of RAAS activation during development of gap junction remodeling might be a new therapeutic strategy for the treatment of arrhythmias.
Abstract 568: Formation of Cardiac Fibers in Matrigel Matrix
Authors: Bakunts Karina , Karabekian Zaruhi , Sarvazyan Narine
Published: April 2024

INTRODUCTION. BD Matrigel Matrix is a basement membrane preparation extracted from the Engelbreth-Holm-Swarm mouse sarcoma, a tumor rich in extracellular matrix proteins. At room temperature, the matrigel polymerizes to produce a biologically active matrix material resembling the mammalian cellular basement membrane. Matrigel is widely used for cellular attachment, cell invasion assays and as a component of cell differentiation media. Here we report a new means for its use.

METHODS. Matrigel is employed to create in vitro cardiac fibers from rat neonatal cardiomyocytes. A semi-solid “pillow” from concentrated matrigel is overlaid with a cardiomyocyte suspension in a diluted matrigel solution. Myocytes submerged in the top matrigel layer form multicellular structures of different sizes. The underling semi-solid matrigel creates an elastic environment which serves as a mechanical load against which myocytes contract.

RESULTS. This new technique creates a net of actively contracting multicellular fibers which can be maintained in vitro for up to six weeks. Presented data illustrate the appearance and development of these fibers. Dependence of the fiber size on myocyte amount and matrigel concentration is also described.

CONCLUSIONS. This new semi-3D model of cardiac muscle offers the ease of both structural and functional monitoring since fiber thickness of 50 –300 micron makes these structures suitable for live confocal microscopy (calcium and potentiometric indicators) and gives easy assess to the epitopes for immunostaining purposes.
Abstract 569: Selective Elimination of I
Ks
and I
Kr
in Transgenic Rabbit Models of LQT1 and LQT2
Authors: Liu Gong Xin , Rana Naveed , Hajjiri Mohammad , Brunner Michael , Folco Eduardo , Pringa Ekaterina , Centracchio Jason , Kirk Malcolm , Zehender Manfred , Peng Xuwen , Koren Gideon
Published: April 2024

LQT1 and LQT2, the two most common inherited long QT syndromes are associated with sudden cardiac death due to due torsades the pointes (TdP). We have created two lines of transgenic rabbits overexpressing pore mutants of the human KvLQT1 (KCNQ1) and HERG (KCNH2) in the heart. Both animal models have prolonged QT interval, however, only LQT2 rabbits suffer from TdP and sudden cardiac death. To investigate the differences in the cellular phenotypes we investigated the whole cell current of acute isolated apical ventricular myocytes from LQT1 and LQT2 rabbit models using patch-clamp techniques by depolarizing to potentials between −30 to +30 mV from a holding potential of −40 mV (room temperature). I
Kr
and I
Ks
were defined as currents sensitive to E-4031 (5 μM) and chromanol 293B (30μM) respectively. Our preliminary data revealed that I
Ks
was selectively abolished in 8 out of 8 LQT1 cardiomyocytes, while I
Kr
was spared (Figure 1

). By contrast, I
Kr
was selectively abolished in 13 out of 14 LQT2 cardiomyocytes while I
Ks
was spared. The selective elimination of I
Kr
resulted in a significant increase in the duration of action potential (APD
90
) from 357±48.68ms (n=13) in control to 533.14±54.22ms (n=14) in LQT2 cardiomyoctes (P<0.05), while the elimination of I
ks
slightly prolonged the APD
90
to 423.37± 52.31 (n=8) (P=NS). In conclusion, expression of the pore mutants resulted in specific inhibition of I
Ks
in LQT1 and I
Kr
in LQT2 rabbits, and established these models as unique genetic counterparts of the human LQT1 and LQT2 syndrome. These models will enable detailed analyses of the electrical remodeling in LQTS.
Abstract 4169: Decreased Serum Ghrelin Level in Patients with Acute Myocardial Infarction: Its Association with the Infarct Size and Left Ventricular Dysfunction
Authors: Yasuda Satoshi , Miyazaki Shunichi , Hosoda Hiroshi , Nagaya Noritoshi , Kataoka Yu , Morii Isao , Kawamura Atsushi , Nonogi Hiroshi , Kangawa Kenji
Published: April 2024

Background
: Ghrelin, a circulating brain-gut peptide, has been identified as potent ligand for the growth-hormone secretagogues receptor, distributed in cardiovascular system. Experimental studies demonstrated that ghrelin has protective effects against ischemia-reperfusion injury and apoptosis. Therefore, the present study was designed to investigate the role of ghrelin in patients with acute myocardial infarction (AMI).

Methods
: Forty-six patients were studied and divided into the following four groups; 16 patients with AMI (M/F=15/1, 67±10[mean±SD]years, body mass index (BMI, kg/m
2
; 23±2), 12 patients with unstable angina pectoris (uAP: M/F=9/3, 64±5years, BMI;23±2), 13 patients with stable AP (sAP: M/F=12/1, 66±6years, BMI;22±2) and 5 control patients with chest pain without any coronary artery disease (M/F=4/1, 66±5years, BMI; 23±2). Serum ghrelin level was measured by newly developed enzyme immunoassay system (MM-402, Mitsubishi Kagaku Medical Inc.). The sensitivity of this system is 2.5fmol/mL.

Results
: In comparison with control, sAP and uAP patients, serum ghrelin levels were significantly decreased on day 0 (on admission) in AMI patients. In next two weeks, ghrelin levels recovered with a time-dependent trend (P<0.01). In patients with AMI, serum level on day 14 divided by that on day 0, an index of MI-related acute change in ghrelin, correlated positively with peak creatinine phosphokinase level (R=0.74, P<0.01) and negatively with left ventricular ejection fraction (R=-0.53, P<0.05).

Conclusions
: In patients with AMI, secretion of ghrelin is suppressed in association with a large infarct size and left ventricular dysfunction. Considering cardioprotective effect of ghrelin, its exogenous administration will provide new perspective for AMI treatment.

Serum ghrelin levels (*P<0.05 vs AMI day 0)
Abstract 4179: The Association of Sex Hormones with Arterial Compliance Differs Between Men and Women in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Vaidya Dhananjay , Golden Sherita H , Heckbert Susan R , Liu Kiang , Gapstur Susan M , Ouyang Pamela
Published: April 2024

Studies show differences in vascular stiffness between older men and women. However, the relationship between sex hormones (SH) and vascular stiffness has not been studied. We examined the cross sectional association between endogenous SH (bioavailable testosterone, BioT; estradiol, E2; dehydroepiandrostenedione, DHEA; and sex-hormone binding globulin, SHBG) and carotid vascular compliance in men and women in MESA.

Methods: We included 2966 men and 1886 postmenopausal women who were not on hormone therapy (45– 84 years, 35% white, 13% Chinese, 27% African-American, 24% Hispanic ethnicity). Baseline systolic and diastolic blood pressure (BP) were measured during carotid ultrasound examination. Carotid strain, a measure of distensibility (fractional change in carotid diameter) was measured from B-mode images. Because men and women differed in the relationship between strain and BP, analyses were performed separately by sex. Log-transformed carotid strain was regressed on log-transformed SH adjusting for log-transformed BP, age, race, glucose, smoking, and BMI. All SH were included in the same model. Differences of coefficients between men and women were evaluated by examining their standard errors.

Results: Carotid strain was 6.8±2.7% in men and 7.0±3.2% in women (p=0.027). In regression analysis (Table

), in men, E2 was significantly associated with lesser carotid strain (increased stiffness) while the BioT was associated with borderline significance to higher strain. In women, there was no association between either E2 or T and carotid strain. DHEA and SHBG were not associated with compliance. No race interaction was found with these associations.

Conclusion: E2 is associated with greater arterial stiffness in men, while BioT is weakly associated with lesser stiffness. Sex hormones are not associated with arterial stiffness in women. The hyperestro-genic hypoandrogenic state may impair vascular health in older men.

Carotid Strain and Sex Hormones
Abstract 4181: The Age and Gender Related Patterns of Insulin Resistance in UK Indian Asians and Northern Europeans: the London Life Sciences Population (LOLIPOP) Study
Authors: Chambers John C , Lim Eric , Elliott Paul , Scott James , Kooner Jaspal S
Published: April 2024

Background

Insulin resistance is a risk factor for cardiovascular disease (CVD). Previous studies have demonstrated that insulin resistance is more common in Indian Asians (IA) compared to Northern Europeans (NE). We report the age and gender related prevalence of insulin resistance, and related metabolic disturbances among IA and NE in the London Life Sciences Population (LOLIPOP) Study.

Methods

The LOLIPOP study is a population based study of IA and NE men and women aged 35–75 years, identified from the lists of 58 primary care physicians in West London. To date 19,272 participants (IA: 8791 male, 4013 Female; NE: 4346 male, 2122 female) have been recruited, with a response rate of 61%. Clinical and anthropometric data and measurements of fasting insulin, glucose, triglycerides and HDL cholesterol were recorded for each subject. Metabolic Syndrome (MS) was defined using Adult Treatment Panel III criteria.

Results

Waist-hip ratio, fasting insulin, glucose and triglycerides were higher, and HDL cholesterol lower, amongst IA compared to NE (all P<0.001). Blood pressure was similar in IA and NE. The prevalence of MS was higher in IA than NE at each age studied (Figure

). Compared to NE, the age-adjusted prevalence of metabolic syndrome was 41% greater in IA men and 140% greater in IA women.

Conclusions

Our results show striking differences in age and gender related disturbances of insulin action in IA compared with NE. MS appears to develop almost 10 years earlier amongst IA men, and 20 years earlier amongst IA women, compared to NE men and women respectively. Follow-up of this cohort will help to determine the extent to which these differences contribute to higher cardiovascular events in IA.