bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased rate of pancreatitis in gender diverse and transgender patients on hormone therapy: a case series study
Authors: Podboy Alexander , Casey Catherine , Buerlein Ross C D , Strand Daniel S , Shami Vanessa M , Wang Andrew Y
Published: April 2024

Background

There is limited data on the incidence of gastrointestinal-specific pathology in gender non-conforming (GNC) populations.

Methods

Retrospective analysis of pancreatitis incidence rates in transgender and GNC persons exposed and not exposed to gender-affirming hormone therapy (GAHT).

Results

7 of the 1333 patients on hormone therapy had an incidence of pancreatitis. 0 of the 615 patients with no history of GAHT use developed pancreatitis. Representing a 6.96 (95% CI 2.76 to 848.78) for the development of pancreatitis in patients with exposure to GAHT therapy.

Conclusion

Clinicians working with GNC individuals should be aware of this possible association
Comparison of WHO versus national COVID-19 therapeutic guidelines across the world: not exactly a perfect match
Authors: Cokljat Mia , Cruz Cintia Valeria , Carrara Verena Ilona , Puttaraksa Kanoktip , Capriglioni Camila , Insaurralde Sabrina Marcela , Rousseau-Portalis Maximo , Roldan Agustina , Watson James A , Tarning Joel , White Nicholas J , Guerin Philippe J
Published: April 2024

Background

The COVID-19 pandemic affected all WHO member states. We compared and contrasted the COVID-19 treatment guidelines of each member state with the WHO COVID-19 therapeutic guidelines.

Methods

Ministries of Health or accessed National Infectious Disease websites and other relevant bodies and experts were contacted to obtain national guidelines (NGs) for COVID-19 treatment. NGs were included only if they delineated specific pharmacological treatments for COVID-19, which were stratified by disease severity. We conducted a retrospective review using the adapted Reporting Checklist for Public Versions of Guidelines (RIGHT-PVG) survey checklist and a derived comparative metric based on the WHO guidelines was performed.

Results

COVID-19 therapeutics NGs could be obtained from 109 of the 194 WHO member states. There was considerable variation in guidelines and in disease severity stratifications. Therapeutic recommendations in many NGs differed substantially from the WHO guidelines. Overall in late 2022, 93% of NGs were recommending at least one treatment which had proved to be ineffective in large randomised trials, and was not recommended by WHO. Corticosteroids were not recommended in severe disease in nearly 10% of NGs despite overwhelming evidence of their benefit. NGs from countries with low-resource settings showed the greatest divergence when stratified by gross domestic product per year, Human Development Index and the Global Health Security Index.

Discussion

Our study is limited to NGs that were readily accessible, and it does not reflect the availability of recommended medicines in the field. Three years after the start of the SARS-CoV-2 pandemic, available COVID-19 NGs vary substantially in their therapeutic recommendations, often differ from the WHO guidelines, and commonly recommend ineffective, unaffordable or unavailable medicines.
All Aboard the East Coast Rail
Authors: QARREM Kassim
Published: April 2024

The East Coast Rail Link (ECRL) forms a key component of China’s regional infrastructure plans while promising local development and enhanced economic growth. The project is also Beijing’s answer to its “Malacca Dilemma”. There are, however, immense challenges to the project, such as transparency, economic viability and local stakeholder concerns. This article analyses the geoeconomic regional implications of the ECRL and discusses the project in the context of Malaysia’s internal dynamics.
“Show Them the Playbook That These Companies Are Using”: Youth Voices about Why Computer Science Education Must Center Discussions of Power, Ethics, and Culturally Responsive Computing
Authors: Ryoo Jean J. , Blunt Takeria
Published: April 2024

Culturally responsive computing (CRC), that centers sociopolitical issues and transformational uses of technology, has been described as valuable for increasing engagement with computing, especially for historically underrepresented minoritized students. But what do high school students think? Through a sociocultural lens prioritizing student voices recorded in 56 interviews over a period of 2 years (1–3 years after students’ first experience with computer science (CS) education through Exploring Computer Science or Advanced Placement CS Principles in high school), this study centers the perspectives of 39 primarily low-income, Latine and Black youth from urban California and rural Mississippi public schools to understand what they perceive as the role of technology in our world and what they subsequently desire of their computing education. While none have studied CRC before, the majority responded with CRC ideas about the kind of pedagogy they believe would make for a more meaningful computing learning experience: They see computing as a form of power that impacts both good and bad in the world and want computing educators to prepare them to take on these issues of equity, ethics, social responsibility, and underrepresentation in the field. The students’ perspectives offer important pedagogical insight into how to support deeper engagement with computing in current CS for All initiatives, while also preparing youth for the rapidly evolving and increasingly complex computing landscape that impacts all of our lives.
The Physical Origin of the Stellar Initial Mass Function
Authors: Hennebelle P. , Grudić M.Y.
Published: April 2024

Stars are among the most fundamental structures of our Universe. They comprise most of the baryonic and luminous mass of galaxies; synthesize heavy elements; and inject mass, momentum, and energy into the interstellar medium. They are also home to the planets. Because stellar properties are primarily decided by their mass, the so-called stellar initial mass function (IMF) is critical to the structuring of our Universe. We review the various physical processes and theories that have been put forward as well as the numerical simulations that have been carried out to explain the origin of the stellar IMF. Key messages from this review include the following:
▪Gravity and turbulence most likely determine the power-law, high-mass part of the IMF.▪Depending of the Mach number and the density distribution, several regimes are possible, including ΓIMF ≃ 0, −0.8, −1, or −1.3, where dN/d log M ∝ M
ΓIMF
. These regimes are likely universal; however, the transition between these regimes is not.▪Protostellar jets can play a regulating influence on the IMF by injecting momentum into collapsing clumps and unbinding gas.▪The peak of the IMF may be a consequence of dust opacity and molecular hydrogen physics at the origin of the first hydrostatic core. This depends weakly on large-scale environmental conditions such as radiation, magnetic field, turbulence, or metallicity. This likely constitutes one reason for the relative universality of the IMF.
Quality of Life and Psychiatric Comorbidities among Subjects Practicing Artificial Skin Depigmentation in 2020 in the City of Cotonou (Benin)
Authors: Degboe B. , Baloubi M. M. D , Ntouala Noukayaba N. , Akpadjan F. G. , Adegbidi H. , Atadokpede F.
Published: April 2024

Introduction. The purpose of this study was to study the quality of life and psychiatric comorbidities of subjects practicing voluntary skin depigmentation in the city of Cotonou. Methods. A cross-sectional, prospective, and analytical study, based on a three-stage probabilistic sampling method, included from June to October 2020, consenting subjects over 15 years of age, practicing artificial skin depigmentation, and residing for at least one year in Cotonou. The Dermatology Life Quality Index, Rosenberg, and Hospital Anxiety and Depression scales allowed us to evaluate the quality of life and self-esteem, and identify anxiety and depression, respectively. A p value <0.05 indicated a significant result. Results. We included 330 subjects. The mean age was 33.6 ± 11.6 years and the sex ratio was 0.4. Impaired quality of life was observed in 93.7% of subjects. Anxiety was diagnosed in 11.2% and depression in 5.8% of them. Self-esteem was low or very low in 24.2%. The degree of quality of life and the alteration of self-esteem, and the frequency of anxiety and depression were proportional to the number of skin lesions, the lightening products used, and the monthly cost of the products. Conclusion. The use of several lightening products exposes patients to numerous skin lesions, which are a source of impaired quality of life and whose persistence leads to psychiatric comorbidities.
Tissue Regeneration on Rise: Dental Hard Tissue Regeneration and Challenges—A Narrative Review
Authors: Alnasser Muhsen , Alshammari Abdullah Hammad , Siddiqui Amna Yusuf , Alothmani Osama Shujaa , Issrani Rakhi , Iqbal Azhar , Khattak Osama , Prabhu Namdeo
Published: April 2024

Background. As people live longer, there is an increasing need for hard tissue regeneration and whole-tooth regeneration. Despite the advancements in the field of medicine, the field of regenerative dentistry is still challenging due to the complexity of dental hard tissues. Cross-disciplinary collaboration among material scientists, cellular biologists, and odontologists aimed at developing strategies and uncovering solutions related to dental tissue regeneration. Methodology. A search of the literature was done for pertinent research. Consistent with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 Statement, the electronic databases looked at were PubMed, Science Direct, Scopus, and Google Scholar, with the keyword search “hard dental tissue regeneration.” Results. Database analysis yielded a total of 476 articles. 222 duplicate articles have been removed in total. Articles that have no connection to the directed regeneration of hard dental tissue were disregarded. The review concluded with the inclusion of four studies that were relevant to our research objective. Conclusion. Current molecular signaling network investigations and novel viewpoints on cellular heterogeneity have made advancements in understanding of the kinetics of dental hard tissue regeneration possible. Here, we outline the fundamentals of stem hard dental tissue maintenance, regeneration, and repair, as well as recent advancements in the field of hard tissue regeneration. These intriguing findings help establish a framework that will eventually enable basic research findings to be utilized towards oral health-improving medicines.
Mutant RAS-driven Secretome Causes Skeletal Muscle Defects in Breast Cancer
Authors: Wang Ruizhong , Khatpe Aditi S. , Kumar Brijesh , Mang Henry Elmer , Batic Katie , Adebayo Adedeji K. , Nakshatri Harikrishna
Published: April 2024

Cancer-induced skeletal muscle defects differ in severity between individuals with the same cancer type. Cancer subtype-specific genomic aberrations are suggested to mediate these differences, but experimental validation studies are very limited. We utilized three different breast cancer patient-derived xenograft (PDX) models to correlate cancer subtype with skeletal muscle defects. PDXs were derived from brain metastasis of triple-negative breast cancer (TNBC), estrogen receptor–positive/progesterone receptor–positive (ER+/PR+) primary breast cancer from a BRCA2-mutation carrier, and pleural effusion from an ER+/PR− breast cancer. While impaired skeletal muscle function as measured through rotarod performance and reduced levels of circulating and/or skeletal muscle miR-486 were common across all three PDXs, only TNBC-derived PDX activated phospho-p38 in skeletal muscle. To further extend these results, we generated transformed variants of human primary breast epithelial cells from healthy donors using HRASG12V or PIK3CAH1047R mutant oncogenes. Mutations in RAS oncogene or its modulators are found in approximately 37% of metastatic breast cancers, which is often associated with skeletal muscle defects. Although cells transformed with both oncogenes generated adenocarcinomas in NSG mice, only HRASG12V-derived tumors caused skeletal muscle defects affecting rotarod performance, skeletal muscle contraction force, and miR-486, Pax7, pAKT, and p53 levels in skeletal muscle. Circulating levels of the chemokine CXCL1 were elevated only in animals with tumors containing HRASG12V mutation. Because RAS pathway aberrations are found in 19% of cancers, evaluating skeletal muscle defects in the context of genomic aberrations in cancers, particularly RAS pathway mutations, may accelerate development of therapeutic modalities to overcome cancer-induced systemic effects.

Significance:

Mutant RAS- and PIK3CA-driven breast cancers distinctly affect the function of skeletal muscle. Therefore, research and therapeutic targeting of cancer-induced systemic effects need to take aberrant cancer genome into consideration.
Kidney Failure Secondary to Hereditary Xanthinuria due to a Homozygous Deletion of the XDH Gene in the Absence of Overt Kidney Stone Disease
Authors: Gonçalves Pedro Lisboa , Diniz Hugo , Tavares Isabel , Dória Sofia , Dong Juan , Kyriss McKenna , Fairbanks Lynette , Oliveira João Paulo
Published: April 2024

Hereditary xanthinuria (HXAN) is a rare metabolic disorder that results from mutations in either the xanthine dehydrogenase (XDH) or the molybdenum cofactor sulfurase genes (MOCOS), respectively defining HXAN type I and type II. Hypouricemia, hypouricosuria, and abnormally high plasma and urine levels of xanthine, causing susceptibility to xanthine nephrolithiasis and deposition of xanthine crystals in tissues, are the metabolic hallmarks of HXAN. Several pathogenic variants in the XDH gene have so far been identified in patients with HXAN type I, but the clinical phenotype associated with the whole deletion of the human XDH gene is unknown. Herein, we report the case of a woman diagnosed with HXAN, whose molecular genetic testing revealed a homozygous microdeletion involving the XDH gene. Distinctive features of her medical history were the diagnosis of arterial hypertension and microalbuminuria at 22 years of age; a single pregnancy at the age of 25, complicated by proteinuria and transient kidney function deterioration in the third trimester; unexplained severe hypouricemia incidentally discovered during pregnancy; inability to breastfeed her newborn daughter due to primary agalactia; chronic kidney disease (CKD) stage 3 diagnosed at age 35; and progression to end-stage kidney disease over the next 12 years. Protocol noninvasive laboratory and imaging investigation was not informative as to the cause of CKD. This is the first description of the clinical phenotype associated with a natural knockout of the human XDH gene. Despite the lack of kidney histopathology data, the striking similarities with the phenotypes exhibited by comparable murine models validate the latter as useful sources of mechanistic insights for the pathogenesis of the human disease, supporting the hypothesis that the absence of xanthine dehydrogenase activity might represent a susceptibility factor for chronic tubulointerstitial nephritis, even in patients without kidney stones.
Prevalence and Risk Factors of Poststroke Dysphagia: A Meta-Analysis
Authors: Gu Haiyan , Ren Dan
Published: April 2024

Introduction: In patients with stroke, poststroke dysphagia (PSD) is a common complication that plays an important role in morbidity and mortality. The aim of this paper was to assess the prevalence and risk factors of PSD using a systemic review and meta-analysis. Methods: PubMed, Embase, Cochrane Library, and Web of Science databases were systematically searched for potentially eligible studies published until September 2023. Further, the pooled incidence and risk factors for PSD were determined using a random-effects model. Overall, 58 studies involving 37,404 patients with acute stroke were selected for the meta-analysis. Results: The pooled incidence of PSD in patients with acute stroke was 42% (95% confidence interval [CI]: 36–48%), which is the highest in South America (47%) and lowest in Asia (37%). Notably, older age (odds ratio [OR]: 2.13; 95% CI: 1.53–2.97; p < 0.001), hypertension (OR: 1.23; 95% CI: 1.06–1.44; p = 0.007), diabetes mellitus (OR: 1.22; 95% CI: 1.04–1.44; p = 0.014), stroke history (OR: 1.26; 95% CI: 1.04–1.53; p = 0.019), and atrial fibrillation (OR: 1.58; 95% CI: 1.02–2.44; p = 0.039) were found to be associated with an increased risk of PSD. Conversely, sex differences, smoking, alcoholism, obesity, hyperlipidemia, ischemic heart disease, stroke type, and the hemisphere affected were not associated with the risk of PSD. Conclusion: The abstract reports the prevalence of PSD in patients with acute stroke and identified potential risk factors for PSD, including older age, hypertension, diabetes mellitus, stroke history, and atrial fibrillation.
Prenatal Management and Perinatal Outcome in a Large Series of Hydrops Fetalis
Authors: Sebastián de Lucas Lorena María , Ordás Álvarez Polán , de Castro Marzo Laura , Illescas Molina Tamara , Herrero Beatriz , Bartha José Luis , Antolín Eugenia
Published: April 2024

Introduction: Nonimmune hydrops fetalis (NIHF) is the most frequent etiology of hydrops fetalis (HF), accounting for around 95% of cases. It associates high perinatal mortality and morbidity rates. The aim of the study was, first, to investigate etiology, prenatal management, and perinatal outcome in a large single-center series of HF; second, to identify prenatal prognostic factors with impact on perinatal outcome. Materials and Methods: Observational retrospective study of 80 HF diagnosed or referred to a single tertiary center between 2012 and 2021. Clinical characteristics, etiology, prenatal management, and perinatal outcome were recorded. Adverse perinatal outcome was defined as intrauterine fetal death (IUFD), early neonatal death (first 7 days of life) and late neonatal death (between 7 and 28 days). Results: Seventy-six of the 80 cases (95%) were NIHF, main etiology being genetic disorders (28/76; 36.8%). A total of 26 women (32.5%) opted for termination of pregnancy, all of them in the NIHF group. IUFD occurred in 24 of 54 patients (44.4%) who decided to continue the pregnancy. Intrauterine treatment was performed in 29 cases (53.7%). There were 30 newborns (55.6%). Adverse perinatal outcome rate was 53.7% (29/54), significantly higher in those diagnosed <20 weeks of gestation (82.4% < 20 weeks vs. 40.5% ≥ 20 weeks; p = 0.004). Survival rate was higher when fetal therapy was performed compared to the expectantly managed group (58.6% vs. 32%; p = 0.05). Intrauterine blood transfusion and thoraco-amniotic shunt were the procedures that achieved the highest survival rates (88.9% and 100%, respectively, p = 0.003). Conclusion: NIHF represented 95% of HF with genetic disorders as the main etiology. Most of them were diagnosed before 20 weeks of gestation, with worse prognosis than cases detected later in gestation. Rates of TOP, IUFD, and early neonatal death were higher in NIHF. Intrauterine therapy, when indicated, improved the perinatal outcome.
Effect of Liraglutide in Different Abdominal Fat Layers Measured by Ultrasound: The Importance of Perirenal Fat Reduction
Authors: Cuatrecasas Guillem , Calbo Marta , Rossell Olga , Dachs Laia , Aguilar-Soler Gerardo , Coves Maria-José , Patrascioiu Ioana , Benito Camila Eugenia , March Sonia , Balfegó Mariona , Cuatrecasas Gabriel , Di Gregorio Silvana , Marina Inaki , Garcia-Lorda Pilar , Munoz-Marron Elena , De Cabo Francisco
Published: April 2024

Introduction: Ultrasonography (US) in patients with obesity allows us to measure different layers of abdominal fat (superficial subcutaneous, deep subcutaneous, preperitoneal, omental, and perirenal), not assessable by DEXA or CT scan. Omental and perirenal fat depots are considered predictors of metabolic complications. Liraglutide is particularly effective in reducing weight in patients with insulin-resistance, but its direct impact on each abdominal fat layer is unknown. Methods: We measured, at the L4 level, all 5 abdominal fat depots in 860 patients with obesity (72.8% women, mean age 56.6 ± 1.5 years, BMI 34.4 ± 4.7 kg/m2, body fat 47 ± 2%, abdominal circumference 105.8 ± 3 cm), before and after 6 months of liraglutide treatment. Laboratory tests for glucose, insulin, and lipid profile were routinely done. T-student was used to compare intraindividual differences. Results: Weight loss was 7.5 ± 2.8 kg (7.96% from baseline), with no differences by sex/age/BMI. Greater loss was observed in patients with higher dosages and NAFLD. All US-measured fat layers showed a significant reduction (p < 0.05) at 6th months. Preperitoneal fat showed a −26 ± 5.5% reduction and 46% of the patients went below metabolic syndrome (MS) risk cut-off values. Omental fat was reduced by −17.8 ± 5% (67% of the patients below MS risk) and perirenal fat by −22.4 ± 4.4% (56% of the patients below MS). Both omental and perirenal fat reduction correlated with total and LDL cholesterol. Higher perirenal fat reduction (−28%) was seen among patients with obesity and hypertension. Perirenal fat also correlated with blood pressure reduction. Conclusion: Liraglutide induces greater fat loss in the layers involved with MS. However, the maximal reduction is seen at perirenal fat, which has been recently related with hypertension and could play an important role in modulating kidney’s expansion and intraglomerular pressure. US is a reproducible clinical tool to assess pathologic fat depots in patients living with obesity.
Larvae of neotropical Coleoptera. V. Carabidae, Morionini
Authors: Jorge-Silva Maria Eulina , Costa Cleide
Published: April 2024

.
Ibidionini (Coleoptera, Cerambycidae). IV Divisão: descrições, sinonímias e chave para espécies do gênero Cycnidolon Thomson, 1864
Authors: Napp Dilma Solange , Martins Ubirajara R.
Published: April 2024

.
Estudo Anatômico sobre Megalobulimus a Uritus (Sowerby. 1838) (Gastropoda, Megalobulimidae)
Authors: Leme J. L. M.
Published: April 2024

.
O Aparelho de Ferrão de Formigas. Parte I. Pseudomyrmex Gracilis (Fabricius) (Pseudomyrmecinae) e Myrmecia Nigriscapa Roger (Myrmeciinae) (Hymenoptera, Formicidae)
Authors: Diniz Jorge L. M.
Published: April 2024

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Variation on ovariole number in meliponinae (Hymenoptera, Apidae) queen's ovaries, with comments on ovary development and caste differentiation
Authors: Cruz-Landim Carminda da , Reginato Rejane Daniele , Imperatriz-Fonseca Vera Lucia
Published: April 2024

The presente paper concerns the variation of the number of ovariole per ovary in the females of some Meliponinae species. In workers, the number of ovarioles was always of 4 per ovary, but in some species the queens had avariable number of ovarioles, from 4 to 15 perovary (asinPlebeiaremota, Nannotrigona testaceicomis, Trigonaspinipes, Schwarziana quadripunctata. The variation of the number of ovarioles was also found in the same species from individual to individual and among the ovaries of a single individual
A New Genus of Troglobitic Carabid Beetle from Brazil (Coleoptera, Carabidae, Zuphiini)
Authors: Gnaspini Pedro , Vanin Sergio A. , Godoy Nilza M.
Published: April 2024

The new Zuphiini genus Coarazuphium gen.n. is described for three troglobitic species of central-eastern Brazil: C. tessai (Godoy&Vanin,1990)comb, n., type species, from "Grutado Padre", Santana, Bahiastate; C. cessaimas p.n., from "Lapado Bode", Itaete, Bahia state; and C. bezerra, sp.n., from "Lapa do Bezerra", São Domingos, Goiás state. All three species have very reduced eyes and pigmentation
Abstract 4163: Higher Dose Exposure of Lovastatin is Not Associated with Adverse Hepatic Outcomes in Patients with Existing Liver Disease
Authors: Avins Andrew L , Manos M Michelle , Ackerson Lynn , Levin TR , Zhao Wei , Murphy Rosemary , Watson Douglas J , Hwang Peggy M , Replogle Amy R , Levine Jeffrey G
Published: April 2024

OBJECTIVE: We have previously shown that the rate of subjects developing adverse liver outcomes was substantially lower during lovastatin-exposed periods compared to non-exposed periods in patients with pre-existing liver disease. The objective of this analysis was to estimate the dose-response relationship between differing levels of lovastatin exposure and adverse hepatic outcomes.

METHODS: This was a retrospective cohort study. Eligible subjects were adult members of Northern California Kaiser Permanente with at least 2-fold ALT or AST elevations 6–18 months apart, evidence of chronic hepatitis B or C infection, or a diagnosis of a chronic liver disease. Outcomes included the composite of events as well as individual components:

liver injury, defined as moderate (3X ULN<ALT<10X ULN) or severe (ALT<10X ULN);

development of clinical cirrhosis;

liver failure.

The dose-response relationships were analyzed by estimating the risk of each outcome in subgroups defined by quartiles of total cumulative lovastatin exposure. Each of these risks was compared to that in the lovastatin-unexposed reference group and a test for trend applied, using orthogonal polynomial contrasts on the coefficients of categorical levels of the exposure variable.

RESULTS: 93,106 eligible patients were identified, of whom 15% had been exposed to lovastatin. A strong and monotonic dose-response relationship was found for the composite outcome and moderate liver-injury endpoints. For the composite endpoint, hazard ratios declined from 0.81 in the quartile with least lovastatin exposure to 0.44 in the highest exposed group (
p<
.00001). Similarly, for the moderate liver-injury endpoint, hazard ratios declined from 0.97 to 0.27 with increasing lovastatin exposure (
p<
.00001).

CONCLUSIONS: Among patients with liver disease, lovastatin exposure was associated with a dose-dependent reduction in the risk of several liver-disease outcomes. These results do not support labeling recommendations for avoiding the use of lovastatin at higher doses in patients with liver disease nor the need to closely monitor LFTs during lovastatin treatment.
Abstract 4168: Two Independent Apolipoprotein A5 Haplotypes Modulate Postprandial Lipoprotein Metabolism in a Caucasian Healthy Population.
Authors: Perez-Martinez Pablo , Lopez-Miranda Jose , Moreno Rafael , Jimenez-Gomez Yolanda , Marin Carmen , Gomez Maria J , Garcia-Salas Mercedes , Gomez Purificacion , Galan Enrique , Lozano Aquiles , Perez-Jimenez Francisco
Published: April 2024

Background:
APOA5 plays an important role in plasma plasma triglyceride (TG) homeostasis. Five polymorphisms (1131T>C, c.-3A>G, c.56C>G, IVS3+476G>A, c.1259T>C) in the
APOA5
gene were found to define three common haplotypes (denoted
APOA5
*1,
APOA5
*2 and
APOA5*
3) in Caucasian individuals.

Our
aim
was to determine whether these haplotypes could modulate the postprandial response in young healthy males, in order to explain the higher risk of coronary artery disease (CHD) associated with less common alleles

Design and methods:
84 apo E3E3 volunteers [63 with (-1131T and 56C) haplotype 1, 12 with (-1131C and 56C) haplotype 2 and 9 with (-1131T and 56G) haplotype 3] underwent a fat-load test consisting of 1 g of fat/kg body weight and 60,000 IU of vitamin A. Blood samples were taken at time 0 and every hour until the 6
th
and every 2.5 hr until the 11
th
. Cholesterol (Chol) and TG were determined in plasma and Chol, TG, Apo B-100, Apo B-48, and retinyl palmitate (RP) were determined in lipoprotein fractions.

Results:
Data of postprandial lipemia revealed that subjects with the haplotypes 2 and 3 had a higher area under the curve than subjects with the haplotype 1 of total plasma TG (0.28±0.1 and 0.31±0.1 vs 0.21±0.1 mmol/L s, p0.04), large triacylglycerol-rich lipoproteins (TRL)-TG (0.19±0.07 and 0.22±0.09 vs 0.10±0.04 mmol/L s, p=0.01), small TRL-TG (0.15±0.06 and 0.14±0.07 vs 0.9±0.05 mmol/L s, p=0.03), large TRL-Cho (0.05±0.01 and 0.06±0.01 vs 0.03±0.061 mmol/L s, p=0.04), and small apoB100 (639±315 and 219±158 vs 140±86, p=0.03).

Conclusions
: Our findings show that the presence of the haplotype 2 and 3 in the
APO5
gene are associated with a higher postprandial response and could be involved in a higher risk of CHD.
Abstract 193: Role of Sarcoplasmic Reticulum Calcium Cycling in Arrhythmias in a 2-D Experimental Model of Calcium Overload
Authors: Chang Marvin G , Chang Connie Y , Xu Linmiao , Sekar Rajesh B , Cysyk Josh , Marbán Eduardo , Tung Leslie , Abraham M. Roselle
Published: April 2024

Ca
2+
overload and/or altered sarcoplasmic reticulum (SR) Ca cycling has been argued to underlie ventricular tachyarrhythmias seen in patients with mutations of RyR2 and calsequestrin2 as well as heart failure.

Aim
: We investigated the role of SR Ca cycling on triggered activity and spiral wave dynamics in a 2-D model of Ca overload.

Methods:
We studied control neonatal rat ventricular myocytes (NRVM-only) monolayers and co-cultures of skeletal myoblasts and NRVMs. Initially, Ca overload was induced by superfusion with BAYK8644 (BayK, 2.5μM) and Isoproterenol (ISO, 1μM) for 5 mins. Subsequently, SR Ca cycling was modulated by 10mM caffeine for 5 min followed by Caffeine + 1μM thapsigargin (CAF/THAP) for 5 mins. Triggered activity and reentry were induced by rapid pacing. Optical mapping (voltage or Ca imaging) was performed. Degree of meandering was assessed using mutual information analysis of tip trajectories.

Results
: Ca imaging during 2Hz pacing revealed that caffeine produced a sharp rise in Ca transients followed by a return to steady state pre-caffeine levels; addition of CAF/THAPS produced a sharp and permanent decrease in Ca transients. Triggered activity (DADs) was observed in co-cultures (n=10) and controls (n=10) with 3–5 Hz pacing in the presence of BAYK/ISO. In co-cultures, DADs occurred from 2 or more sites and tended to drift; pseudo EKGs resembled polymorphic VT, while in controls it was stationary and pseudo EKGs resembled monomorphic VT. Surprisingly, DADs continued to occur even after abolition of SR Ca cycling by CAF/THAPS. Caffeine (n=4) significantly increased reentry pathlength (PL) by 59% but did not significantly change reentry cycle length (CL), conduction velocity (CV), wavelength (WL), or wavefront curvature. Addition of CAF/THAP (n=3) increased reentry WL by 17%, PL by 73%; decreased reentry CV by 28% and increased tip meandering without affecting reentry CL. Additional rotors and wavebreaks were observed during perfusion of BayK/ISO as well as after addition of CAF/THAP; power spectrum showed a single dominant frequency.

Conclusion
: DADs can occur from cytoplasmic Ca overload even in the absence of SR Ca cycling. Abolition of SR Calcium cycling in the presence of BayK/ISO produced wavebreak but did not induce spiral wave breakup.
Abstract 4171: Olive Oil Phenolic Antioxidants Reduce Metalloproteinase (MMP)-9 Expression and Release in Human Monocytoid Cells: Possible Contribution to Plaque Stability
Authors: Carluccio Maria Annunziata , Massaro Marika , Scoditti Egeria , Storelli Carlo , Distante Alessandro , Visioli Francesco , De Caterina Raffaele
Published: April 2024

Background: Mediterranean diets, of which olive oil is an important component, are associated with low prevalence of cardiovascular diseases, but active dietary components and their mechanisms of action are incompletely understood. The local production of active matrix metalloproteinases (MMPs) by macrophages likely contributes to plaque matrix degradation and plaque instability leading to acute coronary events.

Aim: To examine the effect of the olive oil phenolic antioxidants, hydroxytyrosol (HT)and oleuropein (OE), on MMP-9 expression and activity in monocytoid cells and to explore mechanisms of action.

Methods: U937 human monocytoid cells were pre-treated with HT or OE (0–100 μmol/L) for 30 min before stimulation with 50 nmol/L phorbol myristate acetate (PMA) in a serum-free medium for 24 h. Cell supernatants were then tested for the release of MMP-9 and tissue inhibitor of metallopro-teinases (TIMP)-1 antigens (ELISA) and for gelatinase activity by zymography. MMP-9 mRNA expression was investigated by RT-PCR and the activation of transcription factors Nuclear Factor(NF)-κB and Activator Protein(AP)-1 by EMSA.

Results: MMP-9 antigen and activity in U937 cells increased by about 50 fold after stimulation with PMA for 24 h (from 0.5 ± 0.3 to 24 ± 1.5, p<0.01). HT and OE (1–100 μmol/L) reduced PMA-induced MMP-9 activity, at zymography analysis, in a concentration dependent manner with inhibitory concentration producing 50% of the effect (IC50) at 10 μmol/L (p<0.01) and 25 μmol/L (p<0.01) respectively. In addition HT and OE reduced MMP-9 protein release and MMP-9 mRNA levels by about 65% and 45% respectively at 25 mmol/L (p<0.01), without significantly TIMP-1 release. HT and OE at micromolar concentrations also significantly (p<0.05) inhibited PMA-induced activation of NF-κB and AP-1, suggesting a plausible mechanism for the downregulation of MMP-9 expression.

Conclusions: The olive oil phenolic antioxidants inhibit MMP-9 expression and release in monocytoid cells, associated with reduced activation of NF-κB and AP-1. This may contribute to plaque stabilization explaining at least in part the cardiovascular protection by specific components of Mediterranean diets.
Abstract 4175: Isoflavone Does not Acutely Alter Endothelial Function in Patients with Cardiovascular Diseases
Authors: Chan Yap-Hang , Lau Kui-Kai , Yiu Kai-Hang , Li Sheung-Wai , Shu Xiao-Ou , Tse Hung-Fat , Lau Chu-Pak
Published: April 2024

Introduction:
Prior in-vitro studies demonstrated a stimulatory effect of isoflavone on the endothelial nitric-oxide synthase system within a period of 48–96 hours, and may lead to an improvement in vascular endothelial function. However, the acute effect of high dose intake of isoflavone on endothelial function in patients (pts) with cardiovascular disease remains unclear.

Methods:
We studied the effect of high dose intake of isoflavone on vascular endothelial function in pts with cardiovascular diseases. 32 pts with ischemic stroke were randomized to receive either 80mg/day isoflavone (n=15) or placebo (n=17) for 3 days. Brachial endothelial function was assessed to determine flow-mediated dilation (FMD) and nitroglycerin-mediate dilation (NMD) at baseline and after treatment using high resolution ultrasound.

Results:
As shown in Table

, there were no significant differences in the mean changes in heart rate, systolic (SBP) and diastolic blood pressure (DBP) in both groups. Furthermore, there were no significant changes in FMD and NMD after 3 days treatment of isoflavone

Conclusion:
High dose intake of isoflavone (80mg/day) does not acutely alter vascular function in patients with ischemic stroke.

Table:

Mean Change in Parameters After Isoflavone Treatment
Abstract 4177: High Serum Dehydroepiandrosterone Sulfate Levels are Strikingly Associated with Less Mortality in Men: 27-Year Follow-Up Study
Authors: Enomoto Mika , Adachi Hisashi , Shigetoh Yoshiyuki , Otsuka Maki , Kumagai Shun-ichi , Furuki Kumiko , Satoh Akira , Imaizumi Tsutomu
Published: April 2024

Background:
Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are secreted adrenal steroids. DHEAS concentrations decline with aging. Supplementary use of DHEAS is common nowadays with a hope of longevity. But, there has been no data available. We investigated whether DHEAS levels could predict survival in humans.

Methods:
A total of 940 subjects (396 men, 544 women), aged 21 to 88, underwent a health examination in a community-based cohort in 1978–1979. In all subjects, baseline DHEAS measured by radioimmunoassay, and they were followed until 2005.

Results:
DHEAS levels were higher in men than in women and decreased with aging in both sexes. In a Cox proportional hazards model, age, DHEAS (inversely), systolic and diastolic blood pressure, and fasting plasma glucose were significantly associated with mortality in men. Of these variables, elevated DHEAS levels were the strongest predictor of survival after adjustments for age, systolic blood pressure, and fasting plasma glucose. Although elevated DHEAS levels were significantly related to survival in women, the significance disappeared after adjustment for age. DHEAS levels in men were classified into tertiles: group1 <130, group2 130≤-<200, group3 ≥200 ng/ml. Only 74.4% of subjects in the lowest DHEAS tertiles survived compared with more than 93.4% in the highest DHEAS tertiles, after adjustments for age and possible confounding factors (Hazard ratio:0.206; 95%C.I. 0.067– 0.630, p<0.01).

Conclusions:
This study is the first demonstration of the favorable effect survival on a DHEAS in men in a 27-year prospective study.
Abstract 4180: Role of Gender, Age and MI Type on In Hospital Mortality Following Acute Myocardial Infarction: Results from 361,429 patients in NRMI 3–5
Authors: Champney Kimberly P , Frederick Paul D , Bueno Héctor , Mallik Susmita , Foody JoAnne , Bairey-Merz Noel , Canto John G , Vaccarino Viola
Published: April 2024

Background:
Previous reports have shown that younger women, but not older women, have higher mortality after MI compared to men, but studies have included mostly NSTEMI patients. We sought to determine gender differences in hospital mortality for both younger and older women according to MI type, e.g. STEMI and NSTEMI.

Methods:
We studied 126,172 STEMI and 235,257 NSTEMI patients enrolled in the NRMI registry between July 2000 and February 2006. Patients with preexisting LBBB and missing or normal troponin were excluded. Unadjusted and adjusted female to male relative risks (RR) for hospital death were calculated for 10-year age groups. Log-binomial models adjusted for demographic and clinical factors.

Results
: In both STEMI and NSTEMI, younger women, but not older women, had a higher unadjusted RR for hospital mortality than men. The RR decreased with increasing age (p<.01 for the age-gender interaction). Among NSTEMI, after adjusting for race, medical history, primary payor, and presentation characteristics there was no longer a significant gender difference in mortality in younger women, while older women (70+) had better survival compared to men (Figure

). Among STEMI, younger women continued to have a higher, albeit attenuated, risk for in-hospital mortality up to age 70, while there was no mortality difference between older men and women.

Conclusions:
Only younger women with STEMI, but not NSTEMI, have higher adjusted mortality compared with men. Older women with STEMI and NSTEMI have improved outcomes compared with men. Possible sex differences in pathophys-iology of younger women with STEMI and gender differences in treatment of this patient population should be explored.
Abstract 4186: The Association of Central Obesity With Sex Hormones Differs Between Men and Women in the MultiEthnic Study of Atherosclerosis (MESA)
Authors: Vaidya Dhananjay , Ouyang Pamela , Dobs Adrian S , Golden Sherita H , Szklo Moyses , Liu Kiang , Gapstur Susan M
Published: April 2024

Sex hormones affect adipose tissue metabolism and adipose tissue also metabolizes sex hormones for local effects. Central obesity is associated with a pro-atherogenic metabolic state. We analyzed cross sectional associations of endogenous sex hormones (SH: bioavailable Testosterone, BioT; estradiol, E2; dehydroepiandrostenedione, DHEA; SH binding globulin, SHBG) with waist circumference (WC) or waist to hip ratio (WHR) in men and women.

Methods: Analysis included 3163 men and 2051 postmenopausal women who were not on hormone therapy, (45– 84 years, 36% white, 13% Chinese, 28% African-American, 23% Hispanic) at MESA baseline examination. Analyses of interaction by sex were performed on the whole as well as race-stratified dataset. Estimations of association measures were done on sex-stratified race-pooled models. Unadjusted associations were assessed by Spearman rank correlations. WC (or WHR) was regressed on log-transformed SH adjusted for age, race, systolic BP, smoking and fasting glucose.

Results: The WC was 99.2±12.2cm in men and 98.6±15.6cm in women (p= 0.100). WHR was higher in men (96±7%) than women (92±8%, p<0.001). We found an unadjusted negative association of WC with BioT in men, but in women the association was positive (Table

, Spearman rho). DHEA was negatively associated with WC in men. In both men and women, E2 was positively associated and SHBG was negatively associated with WC. In adjusted models (Table

, coefficients), the findings for BioT, E2 and SHBG remained, while DHEA was associated with lower WC in both men and women. Sex differences were similar in race-stratified models. The interactions by sex were qualitatively similar for WHR in pooled and race stratified models.

Conclusions: In men and women, E2 is associated with greater central obesity, while DHEA and SHBG are associated with lower central obesity. This suggests that the hypoandrogenic state may be metabolically favorable in women, but unfavorable in men.

Waist Circumference and Sex Hormones in MESA
Abstract 4198: Short-term Clinical Consequences of Nonadherence in Patients with Hypertension and Multiple Risk Factors
Authors: Cherry Spencer B , Hussein Mohammed A , Nichol Michael B , Tang Simon S , Benner Joshua S
Published: April 2024

Objective:
To quantify the short-term clinical consequences of nonadherence to concomitant antihypertensive (AH) and lipid-lowering (LL) therapy among primary prevention patients with hypertension and multiple risk factors.

Design and Methods:
A microsimulation model was developed to compare cardiovascular event rates over 3 years under 3 treatment scenarios: no treatment, typical adherence, and ideal adherence. Population characteristics were modeled on the ASCOT-LLA study. The “no treatment” scenario represented a natural-history model, with CHD (non-fatal MI, angina pectoris, or CHD death) and stroke probabilities determined by Framingham Heart Study risk equations. “Ideal adherence” incorporated adherence levels and risk reduction from ASCOT-LLA. “Typical adherence” reflected time-dependent annual transitions among three adherence categories based on data from a U.S. Medicaid population: non-adherent (≤ 20% days covered), partially adherent (20 − 80%), or fully adherent (≥ 80%). This scenario assumed a linear association between adherence and risk reduction.

Results:
In the “no treatment” scenario, event rates per 1,000 patient-years were 15.1 and 8.1 for CHD and stroke, respectively. The typical adherence scenario yielded fewer CHD events (relative risk 0.68 [95% CI 0.63– 0.72]) and stroke events (0.68 [0.62– 0.74]). Full adherence to both treatments would yield greater reductions in CHD (0.40 [0.37– 0.43]) and stroke (0.51 [0.47– 0.57]). Increasing adherence from typical to ideal levels would prevent an incremental 1200 CHD events and 400 stroke events per 100,000 treated patients over a 3-year period.

Conclusions:
With typical AH and LL adherence, hypertensive primary prevention patients with multiple risk factors can be expected to receive approximately 57% of the potential protection from CHD and stroke events associated with full adherence.
Abstract 4201: Ankle Brachial Index Improves Prediction of Mortality Determined by Framingham Risk Score in 48,115 Healthy Subjects in Sixteen Studies Worldwide.
Authors: Fowkes Francis G , Criqui Michael , Murray Gordon D
Published: April 2024

Both low ankle brachial index (ABI) and high Framingham Risk Score (FRS) are each associated with an increased risk of death. The aims of our study were

to determine for the first time how the ABI might improve prediction determined by the FRS and

definitively ascertain the normal and at risk levels of the ABI to be used in clinical practice. The study was an individual patient meta-analysis of data from 16 major population cohort studies based in the USA, Europe and Australia and participating in the ABI Collaboration. 24885 men and 23230 women, who had no history of cardiovascular disease and who had an ABI measured at baseline, were included. From a low (≤ 0.6) to a high (>1.4) ABI the risk of death followed a reversed J shaped (ski jump) curve which indicated that the ABI might be categorised usefully in both men and women as ≤ 0.9 (low abnormal), 0.91–1.1 (slightly abnormal), 1.11–1.4 (normal) and > 1.4 (high abnormal). The pooled relative hazard for death for those with a low abnormal compared to normal ABI was 3.23 (95% CI 2.99 to 3.48) for men and 2.79 (95% CI 2.55 to 3.03) for women. For those in the bottom quintile of FRS the 10 year all cause mortality was 8% for men and 9% for women rising to 35% for men and 18% for women in the top quintile. Inclusion of the ABI resulted in those with an ABI of ≤ 0.9 doubling their absolute mortality risk at every FRS level. In those with an ABI > 1.4 a slight increase in mortality was found. Use of the ABI would result in almost 10% of the population having a reclassification of their mortality risk. Similar results were found for cardiovascular mortality. These findings indicate that the ABI has potential to be included as a screening tool for cardiovascular and all cause mortality in the healthy population but further work is required to determine if there are specific groups, for example the elderly, in which use of the ABI is most beneficial.
Abstract 4206: Invasive Treatments for Obese Patients with CAD: An Explanation for the “Obesity Paradox”? Analysis of 130,139 Hospitalizations in Get With The Guidelines
Authors: Steinberg Benjamin A , Fonarow Gregg C , Hernandez Adrian F , Pan Wenqin , Peterson Eric D , Cannon Christopher P
Published: April 2024

BACKGROUND
: Obesity is a well documented risk factor for cardiovascular disease and long-term mortality, yet a previous analysis of the Get With The Guidelines (GWTG) database revealed a paradoxically
lower
short-term mortality rates in patients with coronary artery disease (CAD). We hypothesized that this surprising trend may be the result of more aggressive management of such patients.

METHODS
: The GWTG database was analyzed for CAD hospitalizations from 1/00 to 12/05 with documented height and weight. Patients were divided into BMI (kg/m
2
) categories: underweight (< 18.5), healthy weight (18.5 − 24.9) overweight (25.0 − 29.9), and obese (≥ 30). Reperfusion therapies, as well as baseline characteristics, medications, and in-hospital mortality by BMI category were assessed.

RESULTS
: There were 130,139 hospitalizations from 409 US hospitals analyzed. Patients in the overweight or obese BMI categories were younger, with more obesity-related risk factors for cardiovascular disease. In-hospital mortality was 5.4% in normal weight patients and 3.1% and 2.4% in the overweight and obese categories, respectively. In unadjusted analyses, a higher percentage of obese and overweight patients received indicated, guideline-recommended therapies (see Table

). After adjusting for common confounders, overweight and obese patients were more likely to undergo cardiac catheterization (p<0.01 for both, compared to normal) and PCI (p<0.0001 for overweight and obese vs. normal), as well as CABG surgery (p<0.0001 for both). They also had a significantly shorter length of hospitalization in the multivariate model (p<0.0001).

CONCLUSIONS
: While obesity remains a significant risk factor for the development of CAD, increased body mass does not in of itself represent a barrier to the use of invasive therapies for CAD. It may positively influence clinicians’ use of proven and intensive treatment strategies, contributing to better short-come outcomes in these patients.