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Journal of Clinical Lipidology Apr 2024Elevated lipoprotein(a) (Lp(a)) is an established risk factor for cardiovascular disease (CVD). To date, the only approved treatment to lower Lp(a) is lipoprotein...
BACKGROUND
Elevated lipoprotein(a) (Lp(a)) is an established risk factor for cardiovascular disease (CVD). To date, the only approved treatment to lower Lp(a) is lipoprotein apheresis (LA). Previous studies have demonstrated that LA is effective in reducing cardiovascular (CV) risk in patients with elevated low-density lipoprotein cholesterol (LDL-C) and/or Lp(a). Here we report our long-term experience with LA and its effectiveness in reducing CVD events in patients with elevated Lp(a).
METHODS
This retrospective open-label, single-center study included 25 individuals with Lp(a) elevation >60 mg/dL and LDL-C < 2.59 mmol/L who had indication for LA. The primary endpoint of this study was the incidence of any CV event (determined by medical records) after initiation of LA.
RESULTS
Mean LA treatment duration was 7.1 years (min-max: 1-19 years). Median Lp(a) was reduced from 95.0 to 31.1 mg/dL after LA (-67.3 %, p < 0.0001). Mean LDL-C was reduced from 1.85 to 0.76 mmol/L after LA (-58.9 %, p < 0.0001). Prior LA, 81 CV events occurred in total (0.87 events/patient/year). During LA, 49 CV events occurred in total (0.24 events/patient/year; -0.63, p = 0.001). Yearly major adverse cardiac event (MACE) rate was reduced from 0.34 to 0.006 (-0.33, p = 0.0002). Similar results were obtained when considering only individuals with baseline LDL-C below 1.42 mmol/L.
CONCLUSION
In this observational study of a heterogeneous CV high-risk cohort with elevated Lp(a), LA reduced Lp(a) levels and was paralleled by a decrease in CV events and MACE. We recommend LA for patients with high Lp(a) who still have CV events despite optimal lipid-lowering medication and lifestyle changes.
PubMed: 38908966
DOI: 10.1016/j.jacl.2024.04.134 -
Cells & Development Jun 2024Using a transgenic zebrafish line harboring a heat-inducible dominant-interference pou5f3 gene (en-pou5f3), we reported that this PouV gene is involved in isthmus...
Using a transgenic zebrafish line harboring a heat-inducible dominant-interference pou5f3 gene (en-pou5f3), we reported that this PouV gene is involved in isthmus development at the midbrain-hindbrain boundary (MHB), which patterns the midbrain and cerebellum. Importantly, the functions of pou5f3 reportedly differ before and after the end of gastrulation. In the present study, we examined in detail the effects of en-pou5f3 induction on isthmus development during embryogenesis. When en-pou5f3 was induced around the end of gastrulation (bud stage), the isthmus was abrogated or deformed by the end of somitogenesis (24 hours post-fertilization). At this stage, the expression of MHB markers -- such as pax2a, fgf8a, wnt1, and gbx2 -- was absent in embryos lacking the isthmus structure, whereas it was present, although severely distorted, in embryos with a deformed isthmus. We further found that, after en-pou5f3 induction at late gastrulation, pax2a, fgf8a, and wnt1 were immediately and irreversibly downregulated, whereas the expression of en2a and gbx2 was reduced only weakly and slowly. Induction of en-pou5f3 at early somite stages also immediately downregulated MHB genes, particularly pax2a, but their expression was restored later. Overall, the data suggested that pou5f3 directly upregulates at least pax2a and possibly fgf8a and wnt1, which function in parallel in establishing the MHB, and that the role of pou5f3 dynamically changes around the end of gastrulation. We next examined the transcriptional regulation of pax2a using both in vitro and in vivo reporter analyses; the results showed that two upstream 1.0-kb regions with sequences conserved among vertebrates specifically drove transcription at the MHB. These reporter analyses confirmed that development of the isthmic organizer is regulated by PouV through direct regulation of pax2/pax2a in vertebrate embryos.
PubMed: 38908828
DOI: 10.1016/j.cdev.2024.203933 -
Journal of Dairy Science Jun 2024Poor limb conformation in cattle is believed to be closely associated with claw and limb disorders. Limb conformation is part of genetic evaluation and is assessed...
Poor limb conformation in cattle is believed to be closely associated with claw and limb disorders. Limb conformation is part of genetic evaluation and is assessed visually. In this descriptive study, the assessment of conformation in calves was evaluated objectively using joint angle measurements. A total of 100, 30- to 90-d-old, heifer calves of the Brown Swiss (n = 50) and Holstein (n = 50) breeds were photographed from both sides and the front and rear. Carpal, tarsal, autopodium and fetlock joint angles of the fore- or hind limbs were measured on the images using anatomic reference points and the ImageJ/Fiji® program. Each angle was measured 3 times, and the mean was used for analysis. Values from both sides were pooled. Deviations from defined standard angles were classified as slight or moderate. The positions of the front and hind feet were measured and scored. On average, the calves had moderate "knock-kneed" carpal conformation, and the autopodium of the front limb had a slight lateral deviation. In the rear view, the calves had slight, but close to moderate, "cow-hocked" tarsal conformation, and the autopodium of the hind limbs was parallel, but close to slightly deviated. Holstein calves were moderately, and Brown Swiss calves were slightly "cow-hocked". A moderate lateral deviation occurred in the metacarpal-digit angle in the front view and a slight lateral deviation occurred in the metatarsal-digit angle in the rear view. The front feet position score was >17° in 69% of the calves, and the hind feet position score was <17° in 90% of the calves. In the side views, the calves were slightly "over at the carpus" and slightly "straight-hocked" and had average fetlock conformation. In the mean values, most measured joint angles did not correspond to the straight or parallel classifications in our calves; moderate "knock-kneed" and slight "cow-hocked", and "toed-out" classifications were most common. The limb angles measured were based on anatomical features and therefore are unlikely to change substantially with increasing age. These aspects should be considered when assessing linear traits and investigating the relationship between limb conformation and claw diseases.
PubMed: 38908704
DOI: 10.3168/jds.2024-24765 -
International Journal of Biological... Jun 2024Understanding how shear affects whey protein stability is crucial to deal with typical industrial issues occurring at the bulk solution/surface interface, such as...
Understanding how shear affects whey protein stability is crucial to deal with typical industrial issues occurring at the bulk solution/surface interface, such as fouling during heat treatments. However, at the state of the art, this effect remains unclear, contrary to that of temperature. This article presents a novel strategy to study the impact of shear rate and concentration on the accumulation of whey protein surficial deposits. It consists in applying a range of shear rates (0-200 s) at controlled temperature (65 °C) on whey protein solutions (5-10 wt%) by a parallel plate rheometer equipped with a glass disc, thus allowing the off-line characterization of the deposits by microscopy. Our results highlight an unequivocal effect of increasing shear stress. At 5 wt%, it fosters the formation of primary deposits (≈ 10 μm), whereas at 10 wt% it results in the development of complex branched structures (≈ 50 μm) especially for shear rates ranging from 140 s to 200 s. Based on the classification by size of the observed populations, we discuss possible hypotheses for the deposit growth kinetics, involving the interplay of different physico-chemical protein-surface interactions and paving the way to future further investigations.
PubMed: 38908625
DOI: 10.1016/j.ijbiomac.2024.133291 -
The Journal of Nutrition, Health & Aging Jun 2024To assess the impact of medium-term supplementation with dihydrogen and pyrroloquinoline quinone (PQQ) on mitochondrial biomarkers, brain metabolism, and cognition in...
The impact of six-week dihydrogen-pyrroloquinoline quinone supplementation on mitochondrial biomarkers, brain metabolism, and cognition in elderly individuals with mild cognitive impairment: a randomized controlled trial.
OBJECTIVES
To assess the impact of medium-term supplementation with dihydrogen and pyrroloquinoline quinone (PQQ) on mitochondrial biomarkers, brain metabolism, and cognition in elderly individuals diagnosed with mild cognitive impairment.
DESIGN
A parallel-group, randomized, placebo-controlled, double-blind experimental design, maintaining a 1:1 allocation ratio between the experimental group (receiving the dihydrogen-producing minerals and PQQ) and the control group (receiving the placebo) throughout the trial.
SETTING AND PARTICIPANTS
Thirty-four elderly individuals with mild cognitive impairment (mean age 71.9 ± 3.8 years; 28 females) voluntarily provided written consent to participate in this trial. Participants were assigned in a double-blind parallel-group design to receive either a dihydrogen-PQQ mixture (Alpha Hope®, CalerieLife, Irvine, CA) or placebo twice daily for a 6-week intervention period.
METHODS
The primary endpoint was the change in serum brain-derived neurotrophic factor (BDNF) from baseline to the 6-week follow-up; secondary outcomes included cognitive function indices, specific metabolites in brain tissue, brain oxygenation, and the prevalence and severity of side effects. Interaction effects (time vs. intervention) were evaluated using two-way ANOVA with repeated measures and Friedman's 2-way ANOVA by ranks, for normally distributed data with homogeneous variances and non-homogeneous variances, respectively.
RESULTS
Dihydrogen-PQQ resulted in a significant elevation in serum BDNF levels at the six-week follow-up (P = 0.01); conversely, no changes in BDNF levels were observed in the placebo group throughout the study duration (P = 0.27). A non-significant trend in the impact of interventions on BDNF levels was observed (treatment vs. time interaction, P = 0.14), suggesting a tendency for dihydrogen-PQQ to upregulate BDNF levels compared to the placebo. A significant interaction effect was observed for the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores in the orientation domain (P = 0.03), indicating the superiority of dihydrogen-PQQ over placebo in enhancing this cognitive aspect. Cerebral oxygenation saturation exhibited a significant increase following the administration of the dihydrogen-PQQ mixture, from 48.4 ± 7.2% at baseline to 52.8 ± 6.6% at 6-week post-administration (P = 0.005). In addition, brain N-acetyl aspartate levels significantly increased at seven out of thirteen locations post-intervention in participants receiving the mixture (P ≤ 0.05).
CONCLUSIONS
Despite the limited number of participants included in the study for interpreting clinical parameters, the dihydrogen-PQQ mixture blend shows promise as a potential dietary intervention for enhancing mental orientation and brain metabolism in individuals with age-related mild cognitive decline.
PubMed: 38908296
DOI: 10.1016/j.jnha.2024.100287 -
Medicina Oral, Patologia Oral Y Cirugia... Jun 2024Achieving the best outcomes in surgical procedures requires optimizing all patient-related psychological and physiological factors. This study was carried out to...
BACKGROUND
Achieving the best outcomes in surgical procedures requires optimizing all patient-related psychological and physiological factors. This study was carried out to evaluate the preoperative anxiety and fear levels, and postoperative symptoms in patients undergoing impacted third molar surgery, and to compare the relevant psychological and physical findings between genders and between women in different menstrual cycle phases.
MATERIAL AND METHODS
The population of this prospective and clinical study consisted of patients who applied to faculty of dentistry for the extraction of impacted third molars. The menstrual cycles of the female patients included in the study ranged from 26 to 32 days. The female patients included in the study were divided into three groups according to the first day of the menstrual cycle and bleeding status. All patients were administered Spielberger State-Trait Anxiety Inventory Short Version (STAI-S), Dental Fear Survey (DFS), Modified Dental Anxiety Scale (MDAS) preoperatively, and postoperative satisfaction and complication questionnaires.
RESULTS
The mean age of the 128 patients included in the study was 27.04±4.62 years. Of these patients, 79 (61.7%) were female and 49 (38.3%) were male. Female patients had significantly higher STAI-S, MDAS and DFS scores than male patients (94 vs. 53; 16 vs. 9; 58 vs. 27; p<0.001, respectively). In parallel, female patients had significantly higher complication rates, thus significantly lower satisfaction levels than male patients (116 vs. 51; 40 vs. 13; p<0.001, respectively). STAI-S, MDAS and DFS scores were high in women during the secretory phase (p<0.001). In the secretory phase, complications were high and satisfaction was low (p<0.001).
CONCLUSIONS
The findings of the study reveal that women have a harder time getting through the operation process and that timing is important in reducing preoperative anxiety and fear levels and increasing postoperative satisfaction levels and complication rates.
PubMed: 38907643
DOI: 10.4317/medoral.26443 -
Trials Jun 2024Due to the burden of musculoskeletal diseases in the elderly and the multifactorial nature of such conditions, controlling the pain caused by these disorders requires...
The effectiveness of multidisciplinary interventions based on health belief model on musculoskeletal pain in the elderly living in nursing homes: a study protocol for a randomized controlled trial.
BACKGROUND
Due to the burden of musculoskeletal diseases in the elderly and the multifactorial nature of such conditions, controlling the pain caused by these disorders requires multidisciplinary approach. This approach requires the participation of the elderly in applying effective prevention measures. This study aims to design a multidisciplinary educational intervention based on health belief model (HBM) for elderly residents of nursing homes.
METHODS
This is a parallel randomized clinical trial among elderly people aged 60 years and over living in a nursing home who suffer from musculoskeletal pain. Eligible participants will be divided into two groups including the intervention group who will receive a multidisciplinary intervention (vitamin D consumption, psycho-social stress management, and physiotherapy) and the control group who will receive usual care. Data collection instruments will include demographic data, the Depression, Anxiety, and Stress Scale (DASS), the visual analogue scale (VAS), and a self-designed questionnaire containing the HBM constructs. The interventions will be carried out by the educational team (general practitioner, psychologist, physiotherapist, and health education specialist). Interventions include changing the wrong beliefs of the elderly, taking 800 units of vitamin D daily, daily walking exercise by the elderly for at least 30 min and maintaining proper body posture during daily activities, muscle relaxation, relaxation techniques, regular exercise, examining their diet and eliminating stimulants (such as smoking and coffee), regular visits with friends and family, and deep breathing techniques. All questionnaires will be completed by the elderly before, after, 3, and 6 months after the intervention.
DISCUSSION
The present study will evaluate the effect of an educational intervention based on a multifaceted pain control approach for elderly people who reside in nursing homes in order to reduce musculoskeletal pain in the elderly living in nursing homes. One of the features of this study is its focus on improving the health of elderly residents in nursing homes. Given the increase in the elderly population worldwide, the findings from the current trial might benefit elderly populations.
TRIAL REGISTRATION
IRCT20220904055881N1 . Registered on 11 February 2023.
Topics: Humans; Nursing Homes; Musculoskeletal Pain; Aged; Homes for the Aged; Randomized Controlled Trials as Topic; Vitamin D; Female; Male; Health Knowledge, Attitudes, Practice; Middle Aged; Physical Therapy Modalities; Treatment Outcome; Stress, Psychological; Aged, 80 and over; Patient Education as Topic
PubMed: 38907349
DOI: 10.1186/s13063-024-08243-1 -
Trials Jun 2024There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic...
BACKGROUND
There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing methamphetamine use. The proposed Tina Trial is the first phase 3 placebo-controlled randomised trial to examine the effectiveness and safety of mirtazapine as an outpatient pharmacotherapy for methamphetamine use disorder.
METHODS
This is a multi-site phase 3 randomised, double-blind, placebo-controlled parallel trial. Participants are randomly allocated (1:1) to receive either mirtazapine (30 mg/day for 12 weeks) or matched placebo, delivered as a take-home medication. The target population is 340 people aged 18-65 years who have moderate to severe methamphetamine use disorder. The trial is being conducted through outpatient alcohol and other drug treatment clinics in Australia. The primary outcome is measured as self-reported days of methamphetamine use in the past 4 weeks at week 12. Secondary outcomes are methamphetamine-negative oral fluid samples, depressive symptoms, sleep quality, HIV risk behaviour and quality of life. Other outcomes include safety (adverse events), tolerability, and health service use. Medication adherence is being monitored using MEMS® Smart Caps fitted to medication bottles.
DISCUSSION
This trial will provide information on the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder when delivered as an outpatient medication in routine clinical practice. If found to be safe and effective, this trial will support an application for methamphetamine use disorder to be included as a therapeutic indication for the prescription of mirtazapine.
TRIAL REGISTRATION
Australian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022.
Topics: Humans; Mirtazapine; Double-Blind Method; Amphetamine-Related Disorders; Methamphetamine; Adult; Middle Aged; Adolescent; Clinical Trials, Phase III as Topic; Male; Young Adult; Randomized Controlled Trials as Topic; Aged; Female; Treatment Outcome; Multicenter Studies as Topic; Australia; Time Factors; Medication Adherence; Antidepressive Agents, Tricyclic
PubMed: 38907288
DOI: 10.1186/s13063-024-08238-y -
BMC Health Services Research Jun 2024Interprofessional collaborative care such as a split-shared care model involving family physicians and community pharmacists can reduce the economic burden of diabetes... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Interprofessional collaborative care such as a split-shared care model involving family physicians and community pharmacists can reduce the economic burden of diabetes management. This study aimed to evaluate the economic outcome of a split-shared care model between family physicians and community pharmacists within a pharmacy chain in managing people with uncontrolled type 2 diabetes and polypharmacy.
METHOD
This was a multi-center, parallel arm, open label, randomized controlled trial comparing the direct and indirect economic outcomes of people who received collaborative care involving community pharmacists (intervention) versus those who received usual care without community pharmacist involvement (control). People with uncontrolled type 2 diabetes, defined as HbA1c > 7.0% and taking ≥ 5 chronic medications were included while people with missing baseline economic data (such as consultation costs, medication costs) were excluded. Direct medical costs were extracted from the institution's financial database while indirect costs were calculated from self-reported gross income and productivity loss, using Work Productivity Activity Impairment Global Health questionnaire. Separate generalized linear models with log link function and gamma distribution were used to analyze changes in direct and indirect medical costs.
RESULTS
A total of 175 patients (intervention = 70, control = 105) completed the trial and were included for analysis. The mean age of the participants was 66.9 (9.2) years, with majority being male and Chinese. The direct medical costs were significantly lower in the intervention than the control group over 6 months (intervention: -US$70.51, control: -US$47.66, p < 0.001). Medication cost was the main driver in both groups. There were no significant changes in productivity loss and indirect costs in both groups.
CONCLUSION
Implementation of split-shared visits with frontline community partners may reduce economic burden for patient with uncontrolled type 2 diabetes and polypharmacy.
TRIAL REGISTRATION
Clinicaltrials.gov Reference Number: NCT03531944 (Date of registration: June 6, 2018).
Topics: Humans; Diabetes Mellitus, Type 2; Male; Female; Polypharmacy; Middle Aged; Cost of Illness; Aged; Pharmacists; Physicians, Family; Patient Care Team; Community Pharmacy Services
PubMed: 38907254
DOI: 10.1186/s12913-024-11199-2 -
Scientific Reports Jun 2024As the most abundant animal in the soil, nematodes are directly or indirectly involved in almost all soil ecological processes. Studying soil nematode population...
As the most abundant animal in the soil, nematodes are directly or indirectly involved in almost all soil ecological processes. Studying soil nematode population regulation is essential to understanding soil ecological processes. This study found urea combines nematode-trapping fungi to regulate the population of soil nematodes. In soil, compared with no urea, adding 0.2 mg/mL urea after applying Arthrobotrys oligospora and Dactylellina ellipsospora reduced the number of nematodes by 34.7% and 31.7%. Further, the mechanism of urea couple nematode-trapping fungi to regulate the nematode population was explored in the medium environment. The results showed that the addition of 0.2 mg/ml urea accelerated the trap formation of A. oligospora and D. ellipsosporas by 50% and 46.5%, and increased the yield of traps of A. oligospora and D. ellipsosporas by 39.5% and 40.6%, thus, the predatory efficiency of A. oligospora and D. ellipsospora on nematodes was increased by 34.2% and 32.7%. In conclusion, urea regulates the predation ability of A. oligospora and D. ellipsosporas to regulate the soil nematode population. This study deepens the understanding of the regulatory pathways of the soil nematodes but also provides a potential new strategy for harmful nematode bio-control.
Topics: Animals; Urea; Nematoda; Soil; Soil Microbiology; Ascomycota; Pest Control, Biological
PubMed: 38906980
DOI: 10.1038/s41598-024-65167-1