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JACC. Advances Oct 2023Little is known regarding the formation of coronary and carotid plaques and their impact on cardiovascular disease in patients with familial hypercholesterolemia (FH).
BACKGROUND
Little is known regarding the formation of coronary and carotid plaques and their impact on cardiovascular disease in patients with familial hypercholesterolemia (FH).
OBJECTIVES
This study aimed to determine: 1) if the development of coronary and carotid plaques is correlated; and 2) if these plaques are associated with major adverse cardiac events (MACEs) defined as cardiovascular-related death, unstable angina, myocardial infarction, or staged revascularization.
METHODS
This was a retrospective review of 622 patients with heterozygous FH (HeFH) at Kanazawa University Hospital, assessed coronary and carotid plaque scores using coronary computed tomography and carotid ultrasound within 1 year. Spearman correlation coefficients were assessed among variables. Risk factors for MACEs were determined using the Cox proportional hazard model.
RESULTS
Coronary and carotid plaque scores were significantly correlated in patients with HeFH in both sexes (Spearman's r = 0.82; < 0.001 in males and Spearman's r = 0.87; < 0.001 in females). We observed 132 MACEs during the median follow-up of 13.2 years. These scores were significantly associated with the occurrence of MACE (HR: 3.33; 95% CI: 1.88-4.78; < 0.001, HR: 2.24; 95% CI: 1.28-3.20; < 0.001, respectively).
CONCLUSIONS
Coronary and carotid plaque scores were significantly correlated, and both were independently associated with MACEs. The assessments for coronary and/or carotid plaque are useful for further risk stratifications in patients with HeFH.
PubMed: 38938338
DOI: 10.1016/j.jacadv.2023.100594 -
Animal Bioscience Jun 2024The objective of this study was to reveal the influence of acute and chronic heat stress (HS) on the abundance and function of rumen microbiome and host metabolism.
OBJECTIVE
The objective of this study was to reveal the influence of acute and chronic heat stress (HS) on the abundance and function of rumen microbiome and host metabolism.
METHODS
The forty mid-lactation goats were randomly divided into two artificial environments a control group and a heat-stressed group. This study was collected from two periods, 1 day and 28 days. The first day was defined as control 1 (CT1) and HS 1 (acute HS), and the last day was defined as CT28 and HS28 (chronic HS). On the first and last day, 6 dairy goats in each group were randomly selected to collect rumen liquid after the morning feeding through oral stomach tubes. The barn temperature and humidity were recorded every day.
RESULTS
Disruption of the rumen microbiome was observed under chronic HS, represented by an increase in the abundance of Prevotella and Bacteroidales (p<0.05), and upregulation of carbohydrate transport and metabolism functions (p<0.05). Additionally, the abundance of Succinimonas and Ruminobacter in chronic HS is lower than in acute HS (p<0.05), and the functions of intracellular trafficking, secretion and vesicular transport, and the cytoskeleton were downregulated (p<0.05).
CONCLUSION
HS affected the interaction between the microbiota and host, thereby regulating milk production in dairy goats. These findings increased understanding of the crosstalk between hosts and microorganisms.
PubMed: 38938027
DOI: 10.5713/ab.24.0120 -
The Journal of Headache and Pain Jun 2024Our recent studies have shown headache disorders to be very common in the central and western sub-Saharan countries of Benin and Cameroon. Here we report headache in...
BACKGROUND
Our recent studies have shown headache disorders to be very common in the central and western sub-Saharan countries of Benin and Cameroon. Here we report headache in nearby Mali, a strife-torn country that differs topographically, culturally, politically and economically. The purposes were to estimate headache-attributed burden and need for headache care.
METHODS
We used cluster-random sampling in seven of Mali's eleven regions to obtain a nationally representative sample. During unannounced household visits by trained interviewers, one randomly selected adult member (18-65 years) from each household was interviewed using the structured HARDSHIP questionnaire, with enquiries into headache in the last year and, additionally, headache yesterday (HY). Headache on ≥ 15 days/month (H15+) was diagnosed as probable medication-overuse headache (pMOH) when associated with acute medication use on ≥ 15 days/month, and as "other H15+" when not. Episodic headache (on < 15 days/month) was recorded as such and not further diagnosed. Burden was assessed as impaired participation (days lost from paid and household work, and from leisure activity). Need for headache care was defined by criteria for expectation of benefit.
RESULTS
Data collection coincided with the SARS-CoV-2 pandemic. The participating proportion was nonetheless extremely high (99.4%). The observed 1-year prevalence of any headache was 90.9%. Age- and gender-adjusted estimates were 86.3% for episodic headache, 1.4% for pMOH and 3.1% for other H15+. HY was reported by 16.8% with a mean duration of 8.7 h. Overall mean headache frequency was 3.5 days/month. Participants with pMOH lost more days from paid (8.8 days/3 months) and household work (10.3 days/3 months) than those with other H15+ (3.1 and 2.8 days/3 months) or episodic headache (1.2 and 0.9 days/3 months). At population level, 3.6-5.8% of all time was spent with headache, which led to a 3.6% decrease in all activity (impaired participation). Almost a quarter (23.4%) of Mali's adult population need headache care.
CONCLUSION
Headache is very common in Mali, as in its near neighbours, Benin and Cameroon, and associated with substantial losses of health and productivity. Need for headache care is high - a challenge for a low-income country - but lost productivity probably translates into lost gross domestic product.
Topics: Humans; Adult; Mali; Male; Female; Middle Aged; Cross-Sectional Studies; Young Adult; Adolescent; Cost of Illness; Headache; Needs Assessment; Aged; Prevalence
PubMed: 38937699
DOI: 10.1186/s10194-024-01811-5 -
Nature Communications Jun 2024Refraction is a basic beam bending effect at two media's interface. While traditional studies focus on stationary boundaries, moving boundaries or potentials could...
Refraction is a basic beam bending effect at two media's interface. While traditional studies focus on stationary boundaries, moving boundaries or potentials could enable new laws of refractions. Meanwhile, media's discretization plays a pivotal role in refraction owing to Galilean invariance breaking principle in discrete-wave mechanics, making refraction highly moving-speed dependent. Here, by harnessing a synthetic temporal lattice in a fiber-loop circuit, we observe discrete time refraction by a moving gauge-potential barrier. We unveil the selection rules for the potential moving speed, which can only take an integer v = 1 or fractional v = 1/q (odd q) value to guarantee a well-defined refraction. We observe reflectionless/reflective refractions for v = 1 and v = 1/3 speeds, transparent potentials with vanishing refraction/reflection, refraction of dynamic moving potential and refraction for relativistic Zitterbewegung effect. Our findings may feature applications in versatile time control and measurement for optical communications and signal processing.
PubMed: 38937459
DOI: 10.1038/s41467-024-49747-3 -
PloS One 2024The Youth Risk Behavior Survey (YRBS) among high school students includes standard questions about sexual identity and sex of sexual contacts, but these questions are...
PURPOSE
The Youth Risk Behavior Survey (YRBS) among high school students includes standard questions about sexual identity and sex of sexual contacts, but these questions are not consistently included in every state that conducts the survey. This study aimed to develop and apply a method to predict state-level proportions of high school students identifying as lesbian, gay, or bisexual (LGB) or reporting any same-sex sexual contacts in those states that did not include these questions in their 2017 YRBS.
METHODS
We used state-level high school YRBS data from 2013, 2015, and 2017. We defined two primary outcomes relating to self-reported LGB identity and reported same-sex sexual contacts. We developed machine learning models to predict the two outcomes based on other YRBS variables, and comparing different modeling approaches. We used a leave-one-out cross-validation approach and report results from best-performing models.
RESULTS
Modern ensemble models outperformed traditional linear models at predicting state-level proportions for the two outcomes, and we identified prediction methods that performed well across different years and prediction tasks. Predicted proportions of respondents reporting LGB identity in states that did not include direct measurement ranged between 9.4% and 12.9%. Predicted proportions of respondents reporting any same-sex contacts, where not directly observed, ranged between 7.0% and 10.4%.
CONCLUSION
Comparable population estimates of sexual minority adolescents can raise awareness among state policy makers and the public about what proportion of youth may be exposed to disparate health risks and outcomes associated with sexual minority status. This information can help decision makers in public health and education agencies design, implement and evaluate community and school interventions to improve the health of LGB youth.
Topics: Humans; Adolescent; Sexual and Gender Minorities; Male; Female; United States; Sexual Behavior; Surveys and Questionnaires; Machine Learning; Risk-Taking; Students
PubMed: 38935807
DOI: 10.1371/journal.pone.0304175 -
Archivio Italiano Di Urologia,... Jun 2024To present state of the art on the management of urinary stones from a panel of globally recognized urolithiasis experts who met during the Experts in Stone Disease... (Review)
Review
AIM
To present state of the art on the management of urinary stones from a panel of globally recognized urolithiasis experts who met during the Experts in Stone Disease Congress in Valencia in January 2024. Options of treatment: The surgical treatment modalities of renal and ureteral stones are well defined by the guidelines of international societies, although for some index cases more alternative options are possible. For 1.5 cm renal stones, both m-PCNL and RIRS have proven to be valid treatment alternatives with comparable stone-free rates. The m-PCNL has proven to be more cost effective and requires a shorter operative time, while the RIRS has demonstrated lower morbidity in terms of blood loss and shorter recovery times. SWL has proven to be less effective at least for lower calyceal stones but has the highest safety profile. For a 6mm obstructing stone of the pelviureteric junction (PUJ) stone, SWL should be the first choice for a stone less than 1 cm, due to less invasiveness and lower risk of complications although it has a lower stone free-rate. RIRS has advantages in certain conditions such as anticoagulant treatment, obesity, or body deformity. Technical issues of the surgical procedures for stone removal: In patients receiving antithrombotic therapy, SWL, PCN and open surgery are at elevated risk of hemorrhage or perinephric hematoma. URS, is associated with less morbidity in these cases. An individualized combined evaluation of risks of bleeding and thromboembolism should determine the perioperative thromboprophylactic strategy. Pre-interventional urine culture and antibiotic therapy are mandatory although UTI treatment is becoming more challenging due to increasing resistance to routinely applied antibiotics. The use of an intrarenal urine culture and stone culture is recommended to adapt antibiotic therapy in case of postoperative infectious complications. Measurements of temperature and pressure during RIRS are vital for ensuring patient safety and optimizing surgical outcomes although techniques of measurements and methods for data analysis are still to be refined. Ureteral stents were improved by the development of new biomaterials, new coatings, and new stent designs. Topics of current research are the development of drug eluting and bioresorbable stents. Complications of endoscopic treatment: PCNL is considered the most invasive surgical option. Fever and sepsis were observed in 11 and 0.5% and need for transfusion and embolization for bleeding in 7 and 0.4%. Major complications, as colonic, splenic, liver, gall bladder and bowel injuries are quite rare but are associated with significant morbidity. Ureteroscopy causes less complications, although some of them can be severe. They depend on high pressure in the urinary tract (sepsis or renal bleeding) or application of excessive force to the urinary tract (ureteral avulsion or stricture). Diagnostic work up: Genetic testing consents the diagnosis of monogenetic conditions causing stones. It should be carried out in children and in selected adults. In adults, monogenetic diseases can be diagnosed by systematic genetic testing in no more than 4%, when cystinuria, APRT deficiency, and xanthinuria are excluded. A reliable stone analysis by infrared spectroscopy or X-ray diffraction is mandatory and should be associated to examination of the stone under a stereomicroscope. The analysis of digital images of stones by deep convolutional neural networks in dry laboratory or during endoscopic examination could allow the classification of stones based on their color and texture. Scanning electron microscopy (SEM) in association with energy dispersive spectrometry (EDS) is another fundamental research tool for the study of kidney stones. The combination of metagenomic analysis using Next Generation Sequencing (NGS) techniques and the enhanced quantitative urine culture (EQUC) protocol can be used to evaluate the urobiome of renal stone formers. Twenty-four hour urine analysis has a place during patient evaluation together with repeated measurements of urinary pH with a digital pH meter. Urinary supersaturation is the most comprehensive physicochemical risk factor employed in urolithiasis research. Urinary macromolecules can act as both promoters or inhibitors of stone formation depending on the chemical composition of urine in which they are operating. At the moment, there are no clinical applications of macromolecules in stone management or prophylaxis. Patients should be evaluated for the association with systemic pathologies.
PROPHYLAXIS
Personalized medicine and public health interventions are complementary to prevent stone recurrence. Personalized medicine addresses a small part of stone patients with a high risk of recurrence and systemic complications requiring specific dietary and pharmacological treatment to prevent stone recurrence and complications of associated systemic diseases. The more numerous subjects who form one or a few stones during their entire lifespan should be treated by modifications of diet and lifestyle. Primary prevention by public health interventions is advisable to reduce prevalence of stones in the general population. Renal stone formers at "high-risk" for recurrence need early diagnosis to start specific treatment. Stone analysis allows the identification of most "high-risk" patients forming non-calcium stones: infection stones (struvite), uric acid and urates, cystine and other rare stones (dihydroxyadenine, xanthine). Patients at "high-risk" forming calcium stones require a more difficult diagnosis by clinical and laboratory evaluation. Particularly, patients with cystinuria and primary hyperoxaluria should be actively searched.
FUTURE RESEARCH
Application of Artificial Intelligence are promising for automated identification of ureteral stones on CT imaging, prediction of stone composition and 24-hour urinary risk factors by demographics and clinical parameters, assessment of stone composition by evaluation of endoscopic images and prediction of outcomes of stone treatments. The synergy between urologists, nephrologists, and scientists in basic kidney stone research will enhance the depth and breadth of investigations, leading to a more comprehensive understanding of kidney stone formation.
Topics: Humans; Urinary Calculi; Forecasting
PubMed: 38934520
DOI: 10.4081/aiua.2024.12703 -
Haematologica Jun 2024Chromosomal translocations in non-Hodgkin lymphoma (NHL) result in activation of oncogenes by placing them under the regulation of immunoglobulin heavy chain (IGH)...
Chromosomal translocations in non-Hodgkin lymphoma (NHL) result in activation of oncogenes by placing them under the regulation of immunoglobulin heavy chain (IGH) super-enhancers. Aberrant expression of translocated oncogenes induced by enhancer activity can contribute to lymphomagenesis. The role of the IGH enhancers in normal B-cell development is well established, but knowledge regarding the precise mechanisms of their involvement in control of the translocated oncogenes is limited. The goal of this project was to define the critical regions in the IGH regulatory elements and identify enhancer RNAs (eRNA). We designed a sgRNA library densely covering the IGH enhancers and performed tiling CRISPR interference screens in three NHL cell lines. This revealed three regions crucial for NHL cell growth. With chromatin-enriched RNA-Seq we showed transcription from the core enhancer regions and subsequently validated expression of the eRNAs in a panel of NHL cell lines and tissue samples. Inhibition of the essential IGH enhancer regions decreased expression of eRNAs and translocated oncogenes in several NHL cell lines. The observed expression and growth patterns were consistent with the breakpoints in the IGH locus. Moreover, targeting the Eμ enhancer resulted in loss of B-cell receptor expression. In a Burkitt lymphoma cell line, MYC overexpression partially rescued the phenotype induced by IGH enhancer inhibition. Our results indicated the most critical regions in the IGH enhancers and provided new insights into the current understanding of the role of IGH enhancers in B-cell NHL. As such, this study forms a basis for development of potential therapeutic approaches.
PubMed: 38934080
DOI: 10.3324/haematol.2023.284672 -
Kidney Research and Clinical Practice Jun 2024Cardiorenal syndrome (CRS) type 1 defined as acute kidney injury (AKI) in acute decompensated heart failure (ADHF), is complicated due to diverse definitions. Recently,...
BACKGROUND
Cardiorenal syndrome (CRS) type 1 defined as acute kidney injury (AKI) in acute decompensated heart failure (ADHF), is complicated due to diverse definitions. Recently, a more precise CRS type 1 definition was proposed, mandating concurrent AKI and signs of unimproved heart failure (HF). Our study explores the incidence, predictors, and long-term outcomes of AKI in ADHF under this new definition.
METHODS
A prospective observation study of ADHF patients categorized into the CRS type 1, pseudo-CRS, and non-AKI groups, followed for 12 months. CRS type 1 involved AKI with clinical congestion, while pseudo-CRS included AKI with clinical decongestion (clinical congestion score <2). The primary outcome was a 1-year composite of mortality or HF rehospitalization.
RESULTS
Among 250 consecutive ADHF patients, 46.0% developed CRS type 1; chronic kidney disease (CKD) and blood urea nitrogen were significant risk factors (odds ratios, 1.37; p = 0.002 and OR, 1.05; p < 0.001, respectively). The CRS type 1 group exhibited shorter times to AKI development and peak serum creatinine than the pseudo-CRS group (1 day vs. 4 days and 2 days vs. 4 days, respectively). At 12 months, composite outcomes of mortality or HF rehospitalization and CKD progression were significantly higher in the CRS type 1 group than in the pseudo-CRS and non-AKI groups (63.5% vs. 31.7% vs. 36.1%, p < 0.001; 28.1% vs. 16.2% vs. 11.4%, p = 0.024, respectively).
CONCLUSION
Distinguishing between CRS type 1 and pseudo-CRS is vital, highlighting significant disparities in short-term and long-term outcomes. Notably, pseudo-CRS exhibits comparable long-term cardiovascular and renal outcomes to those without AKI.
PubMed: 38934031
DOI: 10.23876/j.krcp.23.323 -
Frontiers in Endocrinology 2024Despite the fact that China amounts to one-fifth of the world's population, has a higher proportion of the elderly, and has a higher prevalence of osteoporosis and...
OBJECTIVE
Despite the fact that China amounts to one-fifth of the world's population, has a higher proportion of the elderly, and has a higher prevalence of osteoporosis and fracture, limited studies have investigated the association between dietary patterns and bone mineral density (BMD) as well as fracture risk among the elderly Chinese population. We aimed to investigate the association between different dietary patterns and BMD as well as the risk of fractures, and this association may vary between elderly women and men.
METHODS
Building upon the China Osteoporosis Prevalence Study, we included 17,489 subjects aged ≥40 years old randomly sampled across 44 counties/districts of 11 provinces or municipalities in China who completed a food frequency questionnaire. BMD was measured by dual x-ray absorptiometry. Vertebral fracture was defined based on lateral spine radiographs using the semi-quantitative technique of Genant.
RESULTS
A diet rich in "carnivorous", "vegetarian", "dairy, fruit, and egg" was significantly associated with higher BMD at total hip (TH), femoral neck (FN), and lumbar spine 1-4 (L1-4). Yet, a diet rich in "beverage and fried food" was associated with a lower BMD at the FN and L1-4. High quartiles of the carnivorous diet were associated with 34%-39% reduced risk of clinical fracture in the past 5 years and vertebral fracture. Stronger associations were observed among women. Sensitivity analysis among postmenopausal women presented even stronger positive associations between carnivorous and vegetarian diets and high BMD, as well as between carnivorous diet and reduced risk of fractures.
CONCLUSIONS
Our study suggested that a diet rich in meat, vegetables, and dairy, fruit, and eggs might be associated with greater BMD and a lower fracture risk, while beverage and fried foods may be associated with a lower BMD at L1-4, especially among elderly women. These findings are relevant to provide recommendations on dietary nutrition regarding the elderly population at high risk of osteoporosis and fractures, especially postmenopausal women.
Topics: Humans; Bone Density; Female; China; Aged; Middle Aged; Prevalence; Osteoporosis; Diet; Male; Risk Factors; Osteoporotic Fractures; Absorptiometry, Photon; Fractures, Bone; Feeding Behavior; Cross-Sectional Studies; Dietary Patterns
PubMed: 38933818
DOI: 10.3389/fendo.2024.1378158 -
Frontiers in Immunology 2024Poisoning by widow-spider (genus ) bites occurs worldwide. The illness, termed latrodectism, can cause severe and persistent pain and can lead to muscle rigidity,...
Poisoning by widow-spider (genus ) bites occurs worldwide. The illness, termed latrodectism, can cause severe and persistent pain and can lead to muscle rigidity, respiratory complications, and cardiac problems. It is a global health challenge especially in developing countries. Equine serum-derived polyclonal anti-sera are commercially available as a medication for patients with latrodectism, but the use of sera imposes potential inherent risks related to its animal origin. The treatment may cause allergic reactions in humans (serum sickness), including anaphylactic shock. Furthermore, equine-derived antivenom is observed to have batch-to-batch variability and poor specificity, as it is always an undefined mix of antibodies. Because latrodectism can be extremely painful but is rarely fatal, the use of antivenom is controversial and only a small fraction of patients is treated. In this work, recombinant human antibodies were selected against alpha-latrotoxin of the European black widow () by phage display from a naïve antibody gene library. Alpha-Latrotoxin (α-LTX) binding scFv were recloned and produced as fully human IgG. A novel alamarBlue assay for venom neutralization was developed and used to select neutralizing IgGs. The human antibodies showed neutralization efficacy both as single antibodies and antibody combinations. This was also confirmed by electrophysiological measurements of neuronal activity in cell culture. The best neutralizing antibodies showed nanomolar affinities. Antibody MRU44-4-A1 showed outstanding neutralization efficacy and affinity to α-LTX. Interestingly, only two of the neutralizing antibodies showed cross-neutralization of the venom of the Southern black widow (). This was unexpected, because in the current literature the alpha-latrotoxins are described as highly conserved. The here-engineered antibodies are candidates for future development as potential therapeutics and diagnostic tools, as they for the first time would provide unlimited supply of a chemically completely defined drug of constant quality and efficacy, which is also made without the use of animals.
Topics: Humans; Animals; Black Widow Spider; Antibodies, Neutralizing; Spider Venoms; Antivenins; Single-Chain Antibodies; Spider Bites; Immunoglobulin G
PubMed: 38933276
DOI: 10.3389/fimmu.2024.1407398