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Profiling baseline performance on the Longitudinal Early-Onset Alzheimer’s Disease Study (LEADS) cohort near the midpoint of data collection

Alzheimers Dement. 2023 May 31. doi: 10.1002/alz.13160. Online ahead of print.

ABSTRACT

OBJECTIVE: The Longitudinal Early-Onset Alzheimer’s Disease Study (LEADS) seeks to provide comprehensive understanding of early-onset Alzheimer’s disease (EOAD; onset <65 years), with the current study profiling baseline clinical, cognitive, biomarker, and genetic characteristics of the cohort nearing the data-collection mid-point.

METHODS: Data from 371 LEADS participants were compared based on diagnostic group classification (cognitively normal [n = 89], amyloid-positive EOAD [n = 212], and amyloid-negative early-onset non-Alzheimer’s disease [EOnonAD; n = 70]).

RESULTS: Cognitive performance was worse for EOAD than other groups, and EOAD participants were apolipoprotein E (APOE) ε4 homozygotes at higher rates. An amnestic presentation was common among impaired participants (81%), with several clinical phenotypes present. LEADS participants generally consented at high rates to optional trial procedures.

CONCLUSIONS: We present the most comprehensive baseline characterization of sporadic EOAD in the United States to date. EOAD presents with widespread cognitive impairment within and across clinical phenotypes, with differences in APOE ε4 allele carrier status appearing to be relevant.

HIGHLIGHTS: Findings represent the most comprehensive baseline characterization of sporadic early-onset Alzheimer’s disease (EOAD) to date. Cognitive impairment was widespread for EOAD participants and more severe than other groups. EOAD participants were homozygous apolipoprotein E (APOE) ε4 carriers at higher rates than the EOnonAD group. Amnestic presentation predominated in EOAD and EOnonAD participants, but other clinical phenotypes were present.

PMID:37256497 | DOI:10.1002/alz.13160

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Aronia melanocarpa (Michx.) Elliott 1821 Extract Has Moderate Ameliorative Influence on Biochemical and Hematological Parameters in Gentamicin-Induced Nephropathy in Wistar Rats

Appl Biochem Biotechnol. 2023 May 31. doi: 10.1007/s12010-023-04573-z. Online ahead of print.

ABSTRACT

Gentamicin (GM) is an aminoglycoside antibiotic used to treat bacterial infections. Nephrotoxicity refers to the impairments of the kidneys caused by the use of GM and can result in decreased kidney function and in severe cases, kidney failure. Aronia melanocarpa extract (AME), also known as the black chokeberry, has been used for its protective effects on the kidneys. AME concentration of 3.38 mg/kg (max antioxidant activity in vitro) was used to determine its effectiveness against induced nephropathy during 30 days. GM treatment caused significant hypoalbuminemia and high values of globulins, creatinine, and urea compared to the control group. GM application lead to hemolysis occurrence, echinocytosis, and platelets aggregation. Significantly high values of segmented neutrophils and low values of non-segmented neutrophils were recorded in the blood of rats treated with chokeberry extract (AME). In the pre-treatment (AME + GM), severe hypochromic anemia and a significant improvement in hematological parameters, as well as a reduction of anemia in the post-treatment (GM + AME), were noted. Post-treatment AME also significantly regulates urea and creatinine values. Statistically significantly low hemoglobin values were found in all groups treated with AME. Current study suggests that compounds in the AME have a moderate beneficial effect against renal injury and anti-inflammatory properties that may help protect the kidneys from injury caused by GM.

PMID:37256488 | DOI:10.1007/s12010-023-04573-z

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Denoising approach with deep learning-based reconstruction for neuromelanin-sensitive MRI: image quality and diagnostic performance

Jpn J Radiol. 2023 May 31. doi: 10.1007/s11604-023-01452-9. Online ahead of print.

ABSTRACT

PURPOSE: Neuromelanin-sensitive MRI (NM-MRI) has proven useful for diagnosing Parkinson’s disease (PD) by showing reduced signals in the substantia nigra (SN) and locus coeruleus (LC), but requires a long scan time. The aim of this study was to assess the image quality and diagnostic performance of NM-MRI with a shortened scan time using a denoising approach with deep learning-based reconstruction (dDLR).

MATERIALS AND METHODS: We enrolled 22 healthy volunteers, 22 non-PD patients and 22 patients with PD who underwent NM-MRI, and performed manual ROI-based analysis. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in ten healthy volunteers were compared among images with a number of excitations (NEX) of 1 (NEX1), NEX1 images with dDLR (NEX1 + dDLR) and 5-NEX images (NEX5). Acquisition times for NEX1 and NEX5 were 3 min 12 s and 15 min 58 s, respectively. Diagnostic performances using the contrast ratio (CR) of the SN (CR_SN) and LC (CR_LC) and those by visual assessment for differentiating PD from non-PD were also compared between NEX1 and NEX1 + dDLR.

RESULTS: Image quality analyses revealed that SNRs and CNRs of the SN and LC in NEX1 + dDLR were significantly higher than in NEX1, and comparable to those in NEX5. In diagnostic performance analysis, areas under the receiver operating characteristic curve (AUC) using CR_SN and CR_LC of NEX1 + dDLR were 0.87 and 0.75, respectively, which had no significant difference with those of NEX1. Visual assessment showed improvement of diagnostic performance by applying dDLR.

CONCLUSION: Image quality for NEX1 + dDLR was comparable to that of NEX5. dDLR has the potential to reduce scan time of NM-MRI without degrading image quality. Both 1-NEX NM-MRI with and without dDLR showed high AUCs for diagnosing PD by CR. The results of visual assessment suggest advantages of dDLR. Further tuning of dDLR would be expected to provide clinical merits in diagnosing PD.

PMID:37256470 | DOI:10.1007/s11604-023-01452-9

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Effect of sires’ expected progeny difference for scrotal circumference and juvenile ADG on the puberty of crossbred beef heifers

Trop Anim Health Prod. 2023 May 31;55(3):230. doi: 10.1007/s11250-023-03600-9.

ABSTRACT

The early attainment of puberty in heifers is essential for the profitability of the cow-calf farm. This study aimed to evaluate the impact of juvenile average daily gain (ADG) and sire’s expected progeny difference (EPD) on puberty of crossbred beef heifers. Sixty Angus × Nellore heifers early weaned (age = 102 ± 4.3 d; initial BW = 103 ± 4.7 kg) were used in a 2 × 2 factorial arrangement. The factor 1 was the sire’s EPD for scrotal circumference, in which heifers born from sires with positive EPD were considered precocious (P), and heifers born from sires with negative EPD were considered non-precocious (NP). The factor 2 was the high (HG; ADG = 0.9 kg; ad libitum) and medium ADG (MG; ADG = 0.7 kg) from 3rd to 7th month of age (1st phase). After 1st phase until puberty, all heifers were fed ad libitum (2nd phase). Statistical analysis was performed by SAS. There was an interaction between factors for DMI in the 1st phase (P = 0.02), which PHG heifers had higher DMI than NPHG. There was no effect on puberty rate, BW, age and BCS at puberty comparing HG vs. MG. However, favorable sires’ EPD for scrotal circumference induced a higher proportion of puberty (P 87% vs. NP 59%) at 15 months of age. Thus, the ADG in juvenile age did not affect puberty rate, but sires with positive EPD increased puberty rate of Angus × Nellore heifers in heifers fed a high gain diet.

PMID:37256457 | DOI:10.1007/s11250-023-03600-9

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Synthesised thymoquinone-oxime induces cytotoxicity, genotoxicity and apoptosis in hepatocellular cancer cells: in vitro study

Nat Prod Res. 2023 May 31:1-9. doi: 10.1080/14786419.2023.2217705. Online ahead of print.

ABSTRACT

Hepatocellular carcinoma is the most common primary malignant tumor of the liver, and its incidence is increasing worldwide. There is a need to develop new therapeutic strategies to treat the disease. In this study, we synthesised the oxime derivative of thymoquinone and investigated cytotoxicity, genotoxicity, and apoptosis in hepatocellular cancer cells. The synthesised thymoquinone-oxime structure was confirmed by NMR. After incubating the hepatocellular cancer cell line for 24 h, the cytotoxicity ATP by luminometric, intracellular reactive oxygen species, and intracellular calcium by fluorometric. The mitochondrial membrane potential was determined by flow cytometry. DNA damage by alkaline single-cell gel electrophoresis, and apoptosis damage by acridine orange/ethidium bromide double dye method. Concentrations of thymoquinone-oxime statistically increased cytotoxicity, intracellular reactive oxygen species, intracellular calcium, apoptosis, and DNA damage in a concentration-dependent manner. Mitochondrial membrane potential and glutathione levels are also decreased. These findings show that thymoquinone-oxime has an anti-tumor effect on hepatocellular carcinoma cells.

PMID:37254835 | DOI:10.1080/14786419.2023.2217705

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Statins in hospitalized COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials

J Med Virol. 2023 Jun;95(6):e28823. doi: 10.1002/jmv.28823.

ABSTRACT

This systematic review and meta-analysis aimed to determine the efficacy of statins in hospitalized patients with coronavirus disease-2019 (COVID-19). A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of COVID-19 with statins, compared with placebo or standard of care, were reviewed. Seven RCTs (enrolling 1830 participants) met the inclusion criteria. There was no statistically significant difference in all-cause mortality (risk ratio [RR]: 0.92, 95% confidence interval [CI]: 0.75-1.13), length of hospital stay (weighted mean difference: -0.21 days, 95% CI: -1.01 to 0.59 days), intensive care unit (ICU) admission (RR: 1.84, 95% CI: 0.45-7.55), and mechanical ventilation (RR: 1.09, 95% CI: 0.70-1.70) between the two groups. Statins failed to reduce mortality, ICU admission, mechanical ventilation, and length of stay in hospitalized patients with COVID-19. Statins probably should not be used routinely in COVID-19 patients.

PMID:37254831 | DOI:10.1002/jmv.28823

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Capsular Contracture Rate in Augmentation Mammoplasty with Motiva Breast Implant Insertion: A Single-Center Experience in Korea

Aesthet Surg J. 2023 May 31:sjad166. doi: 10.1093/asj/sjad166. Online ahead of print.

ABSTRACT

BACKGROUND: Capsular contracture is the most common complication following breast implant surgery, and the implant shell characteristics are important to prevent this complication.

OBJECTIVES: This study aims to evaluate the capsular contracture rate for SmoothSilk Motiva implants (Establishment Labs Holdings Inc., New York, NY) in females who underwent primary and revision breast augmentation over a 3-year period.

METHODS: From 2017 to 2020, a total of 1324 cases were retrospectively analyzed, with 1027 being primary surgeries and 297 being revision surgeries.

RESULTS: In the 1324 cases of augmentation mammoplasty using SmoothSilk Motiva implants, the overall capsular contracture rate was 1.8% (n = 24). The capsular contracture rate in the 1027 primary surgery cases was 1.07% (n = 11), and the capsular contracture rate in the 297 revision surgery cases was significantly different at 4.39% (n = 13, p = 0.0001). More specifically, the capsular contracture rate in 182 revision surgery cases without capsular contracture was 1.12% (n = 2), and it showed no statistically significant difference from the rate in primary surgery cases (p = 0.965). However, the rate in 115 revision surgery cases with capsular contracture was 9.57% (n = 11), and it showed a statistically significant difference from the rate in primary surgery cases (p = 0.000) and the rate in revision surgery cases without capsular contracture (p = 0.001).

CONCLUSIONS: Augmentation mammoplasty using SmoothSilk Motiva implants demonstrated a lower rate of capsular contracture than the traditional smooth or textured implants. Revision surgery cases without capsular contracture showed a similar rate of capsular contracture as primary surgery cases, but the rates were higher in revision surgery cases with capsular contracture.

PMID:37254824 | DOI:10.1093/asj/sjad166

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Interprofessional Simulation as an Educational Tool to Assess Cultural Competence Among Health Professions Students

Simul Healthc. 2023 Jun 1;18(3):163-171. doi: 10.1097/SIH.0000000000000655. Epub 2022 Mar 28.

ABSTRACT

BACKGROUND: The concept of collaborative practice within health professions is viewed as “best practice.” Poor collaboration can adversely affect patient safety. Interprofessional (IP) teamwork skills can be developed and nurtured through the health professionals’ education; however, many barriers exist, which deter this from occurring. A lack of cultural diversity exposure within the healthcare setting can result in treatment disparities and place the patient at risk. One healthcare area that has gained considerable interest is the practitioners’ understanding of multiculturalism and how cultural competence subsequently influences health disparities.

OBJECTIVES: This study examined the application of culturally complex clinical simulation scenarios that intentionally integrated IP teamwork and hypothesized that participants’ understanding of cultural competence would improve.

METHODS: Participants were junior-level nursing, bachelor-level social work, graduate-level occupational therapy, and PharmD students (N = 180) who participated in an IP simulation exercise composed of culturally complex clinical scenarios performed by trained standardized patients designed to demonstrate underrepresented populations with diverse religious/spiritual, sexual orientation, racial/ethnic, socioeconomic, psychosocial, and geographic characteristics. Survey tools included an adapted Multicultural Awareness, Knowledge, and Skills Survey (MAKSS) and the Cultural Awareness Assessment Tool (CAAT). Descriptive statistical analyses were conducted to describe the sample population with the use of inferential statistics to analyze the MAKSS and CAAT scores using a statistical significance level of 0.05. Data were analyzed using SPSS v25 using paired t tests to compare pretest-posttest results.

RESULTS: Results showed that there was a statistically significant increase in MAKSS and CAAT scores from presimulation to postsimulation. The findings also suggest that participation in this type of exercise may have increased self-assessment of cultural awareness and multicultural awareness, knowledge, and skills among health professions students.

CONCLUSIONS: This study described the planning and execution of a large multiple scenario simulation event that involved 180 students spanning 5 healthcare disciplines. Findings demonstrated that the IP simulation event improved the students’ self-assessment of multicultural awareness, knowledge, and skills as well as their own cultural awareness. The exploration of cultural competence and humility should be a priority for simulation-based learning.

PMID:37254786 | DOI:10.1097/SIH.0000000000000655

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AGE ASSESSMENT OF THE DYNAMICS OF MORPHOLOGICAL REARRANGEMENT OF BONE TISSUE OF THE ARTICULAR PROCESSES OF THE HUMAN LOWER JAW DEPENDING ON THE LOSS OF THE MASTICATORY TEETH

Pol Merkur Lekarski. 2023;51(2):120-127. doi: 10.36740/Merkur202302103.

ABSTRACT

OBJECTIVE: Aim: To analyze morphometric changes in the structure of bone tissue of the mandibular articular processes and establish their densitometric dependence on the masticatory teeth loss in people of I-II periods of adulthood.

PATIENTS AND METHODS: Materials and methods: We analyzed 136 digital CT recordings of human temporomandibular joints. The research subjects were divided into three groups based on the degree of dentition defect acquisition: the first – a limited defect, the second – a final defect, and the third – a preserved dentition (control); by age into two periods of adulthood of postnatal human ontogenesis. Digital statistical analysis of the bone density is presented as M±σ (mean and standard deviation). We compared the experimental groups with the control group using nonparametric statistical analysis.

RESULTS: Results: Changes in the vertical dimension of occlusion due to limited masticatory teeth loss acquire variable morphometric features, causing an interrelated process of bone atrophy of the cellular part and the trabecular layer of the mandibular processes. The density of bone tissue of the cortical layer of the articular-fossa quadrant (A-Fh/q) of the articular head of the mandibular process increases on the right with limited defects and decreases with final defects. Indicators of bone densitometry of A-Fh/q on the left is characterized by a decrease with limited defects for individuals of the I-st period of adulthood and an increase in the final defects in the II-nd on the left and right.

CONCLUSION: Conclusions: Multifactorial pathomorphological compensatory processes ensure bone density, but with a change in values on the right and a decrease on the left. Morphometric values of trabecular layers, the most vulnerable areas of the neck and base of the mandibular articular processes, indicate the reconstruc¬tion of their bone tissue with limited defects; in the first period of the adulthood, they decrease with a significant predominance on the left.

PMID:37254758 | DOI:10.36740/Merkur202302103

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Impact of a social prescribing intervention in North East England on adults with type 2 diabetes: the SPRING_NE multimethod study

Public Health Res (Southampt). 2023 Mar;11(2):1-185. doi: 10.3310/AQXC8219.

ABSTRACT

BACKGROUND: Link worker social prescribing enables health-care professionals to address patients’ non-medical needs by linking patients into various services. Evidence for its effectiveness and how it is experienced by link workers and clients is lacking.

OBJECTIVES: To evaluate the impact and costs of a link worker social prescribing intervention on health and health-care costs and utilisation and to observe link worker delivery and patient engagement.

DATA SOURCES: Quality Outcomes Framework and Secondary Services Use data.

DESIGN: Multimethods comprising (1) quasi-experimental evaluation of effects of social prescribing on health and health-care use, (2) cost-effectiveness analysis, (3) ethnographic methods to explore intervention delivery and receipt, and (4) a supplementary interview study examining intervention impact during the first UK COVID-19 lockdown (April-July 2020).

STUDY POPULATION AND SETTING: Community-dwelling adults aged 40-74 years with type 2 diabetes and link workers in a socioeconomically deprived locality of North East England, UK.

INTERVENTION: Link worker social prescribing to improve health and well-being-related outcomes among people with long-term conditions.

PARTICIPANTS: (1) Health outcomes study, approximately n = 8400 patients; EuroQol-5 Dimensions, five-level version (EQ-5D-5L), study, n = 694 (baseline) and n = 474 (follow-up); (2) ethnography, n = 20 link workers and n = 19 clients; and COVID-19 interviews, n = 14 staff and n = 44 clients.

MAIN OUTCOME MEASURES: The main outcome measures were glycated haemoglobin level (HbA1c; primary outcome), body mass index, blood pressure, cholesterol level, smoking status, health-care costs and utilisation, and EQ-5D-5L score.

RESULTS: Intention-to-treat analysis of approximately 8400 patients in 13 intervention and 11 control general practices demonstrated a statistically significant, although not clinically significant, difference in HbA1c level (-1.11 mmol/mol) and a non-statistically significant 1.5-percentage-point reduction in the probability of having high blood pressure, but no statistically significant effects on other outcomes. Health-care cost estimates ranged from £18.22 (individuals with one extra comorbidity) to -£50.35 (individuals with no extra comorbidity). A statistically non-significant shift from unplanned (non-elective and accident and emergency admissions) to planned care (elective and outpatient care) was observed. Subgroup analysis showed more benefit for individuals living in more deprived areas, for the ethnically white and those with fewer comorbidities. The mean cost of the intervention itself was £1345 per participant; the incremental mean health gain was 0.004 quality-adjusted life-years (95% confidence interval -0.022 to 0.029 quality-adjusted life-years); and the incremental cost-effectiveness ratio was £327,250 per quality-adjusted life-year gained. Ethnographic data showed that successfully embedded, holistic social prescribing providing supported linking to navigate social determinants of health was challenging to deliver, but could offer opportunities for improving health and well-being. However, the intervention was heterogeneous and was shaped in unanticipated ways by the delivery context. Pressures to generate referrals and meet targets detracted from face-to-face contact and capacity to address setbacks among those with complex health and social problems.

LIMITATIONS: The limitations of the study include (1) a reduced sample size because of non-participation of seven general practices; (2) incompleteness and unreliability of some of the Quality and Outcomes Framework data; (3) unavailability of accurate data on intervention intensity and patient comorbidity; (4) reliance on an exploratory analysis with significant sensitivity analysis; and (5) limited perspectives from voluntary, community and social enterprise.

CONCLUSIONS: This social prescribing model resulted in a small improvement in glycaemic control. Outcome effects varied across different groups and the experience of social prescribing differed depending on client circumstances.

FUTURE WORK: To examine how the NHS Primary Care Network social prescribing is being operationalised; its impact on health outcomes, service use and costs; and its tailoring to different contexts.

TRIAL REGISTRATION: This trial is registered as ISRCTN13880272.

FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme, Community Groups and Health Promotion (grant no. 16/122/33) and will be published in full in Public Health Research; Vol. 11, No. 2. See the NIHR Journals Library website for further project information.

PMID:37254700 | DOI:10.3310/AQXC8219