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Sperm functionality is differentially regulated by porcine oviductal extracellular vesicles from the distinct phases of the estrous cycle

Reprod Fertil Dev. 2024 May;36:RD23239. doi: 10.1071/RD23239.

ABSTRACT

Context Extracellular vesicles (EVs) derived from the oviductal fluid (oEVs) play a critical role in various reproductive processes, including sperm capacitation, fertilisation, and early embryo development. Aims To characterise porcine oEVs (poEVs) from different stages of the estrous cycle (late follicular, LF; early luteal, EL; mid luteal, ML; late luteal, LL) and investigate their impact on sperm functionality. Methods poEVs were isolated, characterised, and labelled to assess their binding to boar spermatozoa. The effects of poEVs on sperm motility, viability, acrosomal status, protein kinase A phosphorylation (pPKAs), tyrosine phosphorylation (Tyr-P), and in in vitro fertility were analysed. Key results poEVs were observed as round or cup-shaped membrane-surrounded vesicles. Statistical analysis showed that poEVs did not significantly differ in size, quantity, or protein concentration among phases of the estrous cycle. However, LF poEVs demonstrated a higher affinity for binding to sperm. Treatment with EL, ML, and LL poEVs resulted in a decrease in sperm progressive motility and total motility. Moreover, pPKA levels were reduced in presence of LF, EL, and ML poEVs, while Tyr-P levels did not differ between groups. LF poEVs also reduced sperm penetration rate and the number of spermatozoa per penetrated oocyte (P Conclusions poEVs from different stages of the estrous cycle play a modulatory role in sperm functionality by interacting with spermatozoa, affecting motility and capacitation, and participating in sperm-oocyte interaction. Implications The differential effects of LF and LL poEVs suggest the potential use of poEVs as additives in IVF systems to regulate sperm-oocyte interaction.

PMID:38713808 | DOI:10.1071/RD23239

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Statistical optimization and sequential scale-up of alpha-galactosidase production by Actinoplanes utahensis B1 from shake flask to pilot scale

Prep Biochem Biotechnol. 2024 May 7:1-10. doi: 10.1080/10826068.2024.2344500. Online ahead of print.

ABSTRACT

α-Galactosidase (α-GAL) is a class of hydrolase that releases galactose from galacto-oligosaccharides and synthetic substrates such as pNPG. In this study, the production of α-GAL by Actinoplanes utahensis B1 in submerged fermentation was enhanced by using statistical methods. The effects of temperature, pH, and inoculum percentage on enzyme secretion were optimized using BBD of RSM. The optimized process was scaled up from the shake flask to the laboratory scale (5 L) and to pilot scale (30 L) using KLa based scale-up strategy. By using BBD, a maximum yield of 62.5 U/mL was obtained at a temperature of 28 °C, a pH of 6.9, and an inoculum of 6.4%. Scale-up was performed successfully and achieved a yield of 74.4 U/mL and 76.8 U/mL in laboratory scale and pilot scale fermenters. The TOST was performed to validate the scale-up strategy and the results showed a confidence level of 95% for both scales indicating the perfect execution of scale-up procedure. Through the implementation of BBD and scale-up strategy, the overall enzyme yield has been significantly increased to 76%. This is the first article to explore the scale-up of α-GAL from the A. utahensis B1 strain and provide valuable insights for industrial applications.

PMID:38713771 | DOI:10.1080/10826068.2024.2344500

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Lumbar Facet Arthroplasty Versus Fusion for Grade-I Degenerative Spondylolisthesis with Stenosis: A Prospective Randomized Controlled Trial

J Bone Joint Surg Am. 2024 May 7. doi: 10.2106/JBJS.23.00719. Online ahead of print.

ABSTRACT

BACKGROUND: The comparative effectiveness of decompression plus lumbar facet arthroplasty versus decompression plus instrumented lumbar spinal fusion in patients with lumbar spinal stenosis and grade-I degenerative spondylolisthesis is unknown.

METHODS: In this randomized, controlled, Food and Drug Administration Investigational Device Exemption trial, we assigned patients who had single-level lumbar spinal stenosis and grade-I degenerative spondylolisthesis to undergo decompression plus lumbar facet arthroplasty (arthroplasty group) or decompression plus fusion (fusion group). The primary outcome was a predetermined composite clinical success score. Secondary outcomes included the Oswestry Disability Index (ODI), visual analog scale (VAS) back and leg pain, Zurich Claudication Questionnaire (ZCQ), Short Form (SF)-12, radiographic parameters, surgical variables, and complications.

RESULTS: A total of 321 adult patients were randomized in a 2:1 fashion, with 219 patients assigned to undergo facet arthroplasty and 102 patients assigned to undergo fusion. Of these, 113 patients (51.6%) in the arthroplasty group and 47 (46.1%) in the fusion group who had either reached 24 months of postoperative follow-up or were deemed early clinical failures were included in the primary outcome analysis. The arthroplasty group had a higher proportion of patients who achieved composite clinical success than did the fusion group (73.5% versus 25.5%; p < 0.001), equating to a between-group difference of 47.9% (95% confidence interval, 33.0% to 62.8%). The arthroplasty group outperformed the fusion group in most patient-reported outcome measures (including the ODI, VAS back pain, and all ZCQ component scores) at 24 months postoperatively. There were no significant differences between groups in surgical variables or complications, except that the fusion group had a higher rate of developing symptomatic adjacent segment degeneration.

CONCLUSIONS: Among patients with lumbar spinal stenosis and grade-I degenerative spondylolisthesis, lumbar facet arthroplasty was associated with a higher rate of composite clinical success than fusion was at 24 months postoperatively.

LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

PMID:38713762 | DOI:10.2106/JBJS.23.00719

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Nurses’ knowledge, Practice, and Associated Factors Towards Adult Palliative Care: A Cross-sectional Study

J Hosp Palliat Nurs. 2024 May 6. doi: 10.1097/NJH.0000000000001035. Online ahead of print.

ABSTRACT

The demand for palliative care is increasing rapidly, but inadequate knowledge and practice remain a significant issue. This study aimed to assess nurses’ knowledge, practice, and associated factors toward adult palliative care. A cross-sectional study was conducted including 277 randomly selected nurses from May through September 2021. The data related to knowledge were gathered using the Palliative Care Quiz for Nursing, and an observational checklist to assess the practice was used. EpiData and SPSS software were used for data entry and analysis, respectively. Descriptive statistics and bivariable and multivariable analyses were also applied. Depending on the value of the adjusted odds ratio with a 95% confidence level, statistical significance was declared at a P value of .05. Findings showed that 43.2% and 47% of nurses had good knowledge and practice in palliative care, respectively. The odds of trained nurses having good knowledge were 9.65 times higher than those who did not. There were 2.7 times more odds of practicing palliative care among nurses with good knowledge than those with poor knowledge. Overall, over half of the nurses have poor knowledge and practice in palliative care. To enhance their knowledge and practice, formal palliative care education and training will be beneficial.

PMID:38713759 | DOI:10.1097/NJH.0000000000001035

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Impact of liver fibrosis on COVID-19 in-hospital mortality in Southern Italy

PLoS One. 2024 May 7;19(5):e0296495. doi: 10.1371/journal.pone.0296495. eCollection 2024.

ABSTRACT

BACKGROUND & AIMS: SARS-Cov-2 infection manifests as a wide spectrum of clinical presentation and even now, despite the global spread of the vaccine, contagiousness is still elevated. The aim of the study was the evaluation of the impact of liver fibrosis assessed by FIB-4 and liver impairment, assessed by cytolysis indices, on intrahospital mortality in COVID-19 subjects.

METHODS: This is a retrospective observational cohort study, which involved 23 COVID Hospital Units in Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. According to FIB-4 values, we subdivided the overall population in three groups (FIB-4<1.45; 1.45<FIB-4<3.25; FIB-4>3.25), respectively group 1,2,3.

RESULTS: At the end of the study, 938 individuals had complete discharged/dead data. At admission, 428 patients were in group 1 (45.6%), 387 in group 2 (41.3%) and 123 in group 3 (13.1%). Among them, 758 (81%) subjects were discharged, while the remaining 180 (19%) individuals died. Multivariable Cox’s regression model showed a significant association between mortality risk and severity of FIB-4 stages (group 3 vs group 1, HR 2.12, 95%CI 1.38-3.28, p<0.001). Moreover, Kaplan-Meier analysis described a progressive and statistically significant difference (p<0.001 Log-rank test) in mortality according to FIB-4 groups. Among discharged subjects, 507 showed a FIB-4<1.45 (66.9%, group 1), 182 a value 1.45<FIB-4<3.25 (24.1%, group 2) and 69 a FIB-4>3.25 (9.0%, group 3). Among dead subjects, 42 showed a FIB-4<1.45 (23.3%, group 1), 62 a value 1.45<FIB-4<3.25 (34.4%, group 2) and 76 a FIB-4>3.25 (42.3%, group 3).

CONCLUSIONS: FIB-4 value is significantly associated with intrahospital mortality of COVID-19 patients. During hospitalization, particularly in patients with worse outcomes, COVID-19 seems to increase the risk of acute progression of liver damage.

PMID:38713731 | DOI:10.1371/journal.pone.0296495

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Every sip counts: Understanding hydration behaviors and user-acceptability of digital tools to promote adequate intake during early and late pregnancy

PLOS Digit Health. 2024 May 7;3(5):e0000499. doi: 10.1371/journal.pdig.0000499. eCollection 2024 May.

ABSTRACT

Maintaining adequate hydration over the course of pregnancy is critical for maternal and fetal health and reducing risks for adverse pregnancy outcomes (e.g., preeclampsia, low placental and amniotic fluid volume). Recent evidence suggests that women may be at risk for under-hydration in the second and third trimesters when water needs begin to increase. Scant research has examined pregnant women’s knowledge of hydration recommendations, water intake behaviors, and willingness to use digital tools to promote water intake. This study aimed to: 1) describe hydration recommendation knowledge and behaviors by the overall sample and early vs late pregnancy, and 2) identify habits and barriers of using digital tools. Pregnant women (N = 137; M age = 30.9 years; M gestational age = 20.9) completed a one-time, 45-minute online survey. Descriptive statistics quantified women’s knowledge of hydration recommendations, behaviors, and attitudes about utilizing digital tools to promote adequate intake, and Mann-Whitney U and chi-squared tests were used to determine group differences. Most women lacked knowledge of and were not meeting hydration recommendations (63%, 67%, respectively) and were not tracking their fluid consumption (59%). Knowledge of hydration recommendations differed by time of pregnancy, such that women in later pregnancy reported 82 ounces compared to women in early pregnancy (49 ounces). Common barriers included: forgetting to drink (47%), not feeling thirsty (47%), and increased urination (33%). Most were willing to use digital tools (69%) and believed a smart water bottle would help them achieve daily fluid recommendations (67%). These initial findings suggest that pregnant women may benefit from useful strategies to increase knowledge, decrease barriers, and maintain adequate hydration, specifically earlier in pregnancy. These findings will inform the design of a behavioral intervention incorporating smart connected water bottles, wearables for gesture detection, and behavior modification strategies to overcome barriers, promote proper hydration and examine its impact on maternal and infant health outcomes.

PMID:38713720 | DOI:10.1371/journal.pdig.0000499

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Cognitive Behavioral Therapy for Symptom Preoccupation Among Patients With Premature Ventricular Contractions: Nonrandomized Pretest-Posttest Study

JMIR Cardio. 2024 May 7;8:e53815. doi: 10.2196/53815.

ABSTRACT

BACKGROUND: Premature ventricular contractions (PVCs) are a common cardiac condition often associated with disabling symptoms and impaired quality of life (QoL). Current treatment strategies have limited effectiveness in reducing symptoms and restoring QoL for patients with PVCs. Symptom preoccupation, involving cardiac-related fear, hypervigilance, and avoidance behavior, is associated with disability in other cardiac conditions and can be effectively targeted by cognitive behavioral therapy (CBT).

OBJECTIVE: The aim of this study was to evaluate the effect of a PVC-specific CBT protocol targeting symptom preoccupation in patients with symptomatic idiopathic PVCs.

METHODS: Nineteen patients diagnosed with symptomatic idiopathic PVCs and symptom preoccupation underwent PVC-specific CBT over 10 weeks. The treatment was delivered by a licensed psychologist via videoconference in conjunction with online text-based information and homework assignments. The main components of the treatment were exposure to cardiac-related symptoms and reducing cardiac-related avoidance and control behavior. Self-rated measures were collected at baseline, post treatment, and at 3- and 6-month follow-ups. The primary outcome was PVC-specific QoL at posttreatment assessment measured with a PVC-adapted version of the Atrial Fibrillation Effects on Quality of Life questionnaire. Secondary measures included symptom preoccupation measured with the Cardiac Anxiety Questionnaire. PVC burden was evaluated with 5-day continuous electrocardiogram recordings at baseline, post treatment, and 6-month follow-up.

RESULTS: We observed large improvements in PVC-specific QoL (Cohen d=1.62, P<.001) and symptom preoccupation (Cohen d=1.73, P<.001) post treatment. These results were sustained at the 3- and 6-month follow-ups. PVC burden, as measured with 5-day continuous electrocardiogram, remained unchanged throughout follow-up. However, self-reported PVC symptoms were significantly lower at posttreatment assessment and at both the 3- and 6-month follow-ups. Reduction in symptom preoccupation had a statistically significant mediating effect of the intervention on PVC-specific QoL in an explorative mediation analysis.

CONCLUSIONS: This uncontrolled pilot study shows preliminary promising results for PVC-specific CBT as a potentially effective treatment approach for patients with symptomatic idiopathic PVCs and symptom preoccupation. The substantial improvements in PVC-specific QoL and symptom preoccupation, along with the decreased self-reported PVC-related symptoms warrant further investigation in a larger randomized controlled trial.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05087238; https://clinicaltrials.gov/study/NCT05087238.

PMID:38713500 | DOI:10.2196/53815

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Health Literacy and Health Care System Confidence as Determinants of Attitudes to Vaccines in France: Representative Cross-Sectional Study

JMIR Public Health Surveill. 2024 May 7;10:e45837. doi: 10.2196/45837.

ABSTRACT

BACKGROUND: Health literacy involves individuals’ knowledge, personal skills, and confidence to take action to evaluate and appraise health-related information and improve their health or that of their community.

OBJECTIVE: This study aimed to analyze the association between health literacy and attitude toward vaccines, adjusted with other factors.

METHODS: We used the SLAVACO Wave 3, a survey conducted in December 2021 among a sample of 2022 individuals, representative of the French adult population. We investigated factors associated with the attitude toward vaccines using respondents’ different sociodemographic data, health literacy levels, and the health care system confidence levels using a multinomial logistic regression analysis.

RESULTS: Among the participants, 440.4 (21.8%) were classified as “distrustful of vaccines in general,” 729.2 (36.1%) were “selectively hesitant,” and 852.4 (42.2%) were “nonhesitant.” In our model, the level of health literacy was not statistically different between the “distrustful of vaccines in general” and the “selectively hesitant” (P=.48), but it was associated with being a “nonhesitant” (adjusted odds ratio [aOR] 1.86, 95% CI 1.25-2.76). The confidence in the health care system was a strong predictor for a “nonhesitant” attitude toward vaccines (aOR 12.4, 95% CI 7.97-19.2). We found a positive correlation of 0.34 (P<.001) between health literacy and confidence in the health care system, but the interaction term between health literacy and health care system confidence was not significant in our model.

CONCLUSIONS: Health literacy was associated with a “nonhesitant” attitude toward vaccines. The findings demonstrated that health literacy and confidence in the health care system are modestly correlated. Therefore, to tackle the subject of vaccine hesitancy, the main focus should be on increasing the population’s confidence and on increasing their health literacy levels or providing vaccine information addressing the needs of less literate citizens.

PMID:38713494 | DOI:10.2196/45837

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Focused Ultrasound as a Novel Non-Invasive Method for the Delivery of Gold Nanoparticles to Retinal Ganglion Cells

Transl Vis Sci Technol. 2024 May 1;13(5):5. doi: 10.1167/tvst.13.5.5.

ABSTRACT

PURPOSE: The blood-retinal barrier (BRB) restricts the delivery of intravenous therapeutics to the retina, necessitating innovative approaches for treating retinal disorders. This study sought to explore the potential of focused ultrasound (FUS) to non-invasively deliver intravenously administered gold nanoparticles (AuNPs) across the BRB. FUS-BRB modulation can offer a novel method for targeted retinal therapy.

METHODS: AuNPs of different sizes and shapes were characterized, and FUS parameters were optimized to permeate the BRB without causing retinal damage in a rodent model. The delivery of 70-kDa dextran and AuNPs to the retinal ganglion cell (RGC) layer was visualized using confocal and two-photon microscopy, respectively. Histological and statistical analyses were conducted to assess the effectiveness and safety of the procedure.

RESULTS: FUS-BRB modulation resulted in the delivery of dextran and AuNPs to the RGC and inner nuclear layer. Smaller AuNPs reached the retinal layers to a greater extent than larger ones. The delivery of dextran and AuNPs across the BRB with FUS was achieved without significant retinal damage.

CONCLUSIONS: This investigation provides the first evidence, to our knowledge, of FUS-mediated AuNP delivery across the BRB, establishing a foundation for a targeted and non-invasive approach to retinal treatment. The results contribute to developing promising non-invasive therapeutic strategies in ophthalmology to treat retinal diseases.

TRANSLATIONAL RELEVANCE: Modifying the BRB with ultrasound offers a targeted and non-invasive delivery strategy of intravenous therapeutics to the retina.

PMID:38713474 | DOI:10.1167/tvst.13.5.5

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Social Determinants of Health and the Availability of Cancer Clinical Trials in the United States

JAMA Netw Open. 2024 May 1;7(5):e2410162. doi: 10.1001/jamanetworkopen.2024.10162.

NO ABSTRACT

PMID:38713468 | DOI:10.1001/jamanetworkopen.2024.10162