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Identification of circRNA-miRNA-mRNA network as biomarkers for interstitial cystitis/bladder pain syndrome

Aging (Albany NY). 2023 Nov 2;15. doi: 10.18632/aging.205170. Online ahead of print.

ABSTRACT

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a long-lasting and incapacitating disease, and the exact factors that affect its onset and advancement are still uncertain. Thus, the main aim was to explore new biomarkers and possible therapeutic targets for IC/BPS. Next-generation high-throughput sequencing experiments were performed on bladder tissues. Based on the interactions between circRNA and miRNA, as well as miRNA and mRNA, candidates were selected to build a network of circRNA-miRNA-mRNA. The STRING database and Cytoscape software were utilized to build a protein-protein interaction (PPI) network to pinpoint the hub genes associated with IC/BPS. The expression levels of circRNA and miRNA in the network were confirmed through quantitative polymerase chain reaction. Western blot was applied to confirm the stability of the lipopolysaccharide-induced IC/BPS model, and the effect of overexpression of circ.5863 by lentivirus on inflammation. Ten circRNA-miRNA interactions involving three circRNAs and six miRNAs were identified, and IFIT3 and RSAD2 were identified as hub genes in the resulting PPI network with 19 nodes. Circ.5863 showed a statistically significant decrease in the constructed model, which is consistent with the sequencing results, and overexpression via lentiviral transfection of circ.5863 was found to alleviate inflammation damage. In this study, a circRNA-miRNA-mRNA network was successfully constructed, and IFIT3 and RSAD2 were identified as hub genes. Our findings suggest that circ.5863 can mitigate inflammation damage in IC/BPS. The identified marker genes may serve as valuable targets for future research aimed at developing diagnostic tools and more effective therapies for IC/BPS.

PMID:37925174 | DOI:10.18632/aging.205170

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Baseline Liver Ultrasound Findings in Preschool Children From the Praziquantel in Preschoolers Trial in Lake Albert, Uganda

Pediatr Infect Dis J. 2023 Oct 30. doi: 10.1097/INF.0000000000004119. Online ahead of print.

ABSTRACT

BACKGROUND: Periportal fibrosis is a late-stage manifestation of chronic infection with Schistosoma mansoni. Praziquantel (PZQ), the only drug available for the treatment of schistosomiasis, has limited effect in treating established morbidity. Preschool-aged children (PSAC) are not considered to be an at-risk population for severe morbidity. However, the prevalence of periportal fibrosis in PSAC in S. mansoni endemic settings is unknown.

METHODS: As part of a phase II clinical trial comparing different dosing regimens of PZQ in children age 12-47 months infected with S. mansoni in Uganda (“praziquantel in preschoolers” trial), we present baseline results assessing liver ultrasound (US) findings as per the WHO Niamey Protocol.

RESULTS: A total of 7/347 (2%) PSAC had Image Pattern C with pipe stems and echogenic rings suggestive of periportal fibrosis, 29/347 (8%) had Image Pattern B and 58 (17%) had evidence of periportal thickening There were higher adjusted odds of periportal thickening with older age [odds ratio (OR): 1.04; 95% confidence interval (CI): 1.00-1.07], primary maternal education (OR: 1.04; 95% CI: 1.00-1.07) and being taken to the lake weekly (OR: 3.02; 95% CI: 1.19-7.63). A further 44/347 children (13%) had a rounded caudal liver edge which was associated with high S. mansoni infection intensity (adjusted OR: 3.31; 95% CI: 1.46-7.51).

CONCLUSIONS: Incipient schistosomiasis-related liver morbidity was detected in young children enrolled in the praziquantel in preschoolers trial. Adequate age-adjusted reference measurements for liver ultrasound findings in very small children are lacking but urgently needed. Schistosomiasis-related fibrosis may be delayed or averted with early and repeated PZQ treatment.

PMID:37922490 | DOI:10.1097/INF.0000000000004119

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Attitudes About the Human Papillomavirus Vaccine Among Patients With and Without Cervical Dysplasia

J Low Genit Tract Dis. 2023 Nov 3. doi: 10.1097/LGT.0000000000000778. Online ahead of print.

ABSTRACT

OBJECTIVES: The aims of the study are to examine the perception of the human papillomavirus (HPV) vaccine among those with and without a history of cervical dysplasia and to examine perceptions of the vaccine for their children.

MATERIALS AND METHODS: Patients were recruited to complete a survey about the HPV vaccine for both themselves and their children. Patients in a colposcopy clinic with a history of abnormal cervical cytology and patients in a benign gynecology clinic without a history of abnormal cervical cytology were recruited. Participants’ medical records were reviewed. Demographics and survey answers were described, and Fisher exact test was used to compare the groups.

RESULTS: One hundred eighty-three patients participated: 73 in colposcopy clinic and 110 in benign clinic. The majority self-identified as Black (74% colposcopy, 71% benign, p = .588) and reported an income less than $39,000 a year (77% colposcopy, 65% benign, p = .089). Fifty-six percent in benign clinic agreed the HPV vaccine is a good way to protect oneself from disease compared with 48% in colposcopy clinic (p = .022). When examining results based on cytology, fewer patients in the highest-grade cytology group agreed the vaccine was effective (30% high-grade, 48% normal, 57% low-grade, p = .027) or a good way to protect themselves from disease (29% high-grade, 53% normal, 62% low-grade, p = .002). There was otherwise no statistically significant difference between the groups on questions regarding self or child vaccination.

CONCLUSIONS: In a majority Black, low-income population, patients without a history of abnormal cervical cytology have more favorable perceptions of the HPV vaccine’s effectiveness in preventing disease. Those with the highest-grade cytology had more negative perceptions of the vaccine’s effectiveness and protectability.

PMID:37922471 | DOI:10.1097/LGT.0000000000000778

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Earth Mover’s Distance as a Metric to Evaluate the Extent of Charge Transfer in Excitations Using Discretized Real-Space Densities

J Chem Theory Comput. 2023 Nov 3. doi: 10.1021/acs.jctc.3c00894. Online ahead of print.

ABSTRACT

This paper presents a novel theoretical measure, μEMD, based on the earth mover’s distance (EMD), for quantifying the density shift caused by electronic excitations in molecules. As input, the EMD metric uses only the discretized ground- and excited-state electron densities in real space, rendering it compatible with almost all electronic structure methods used to calculate excited states. The EMD metric is compared against other popular theoretical metrics for describing the extent of electron-hole separation in a wide range of excited states (valence, Rydberg, charge transfer, etc.). The results showcase the EMD metric’s effectiveness across all excitation types and suggest that it is useful as an additional tool to characterize electronic excitations. The study also reveals that μEMD can function as a promising diagnostic tool for predicting the failure of pure exchange-correlation functionals. Specifically, we show statistical relationships among the functional-driven errors, the exact exchange content within the functional, and the magnitude of μEMD values.

PMID:37922416 | DOI:10.1021/acs.jctc.3c00894

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Stiffness and Oligomer Content Affect the Initial Adhesion of Staphylococcus aureus to Polydimethylsiloxane Gels

ACS Appl Mater Interfaces. 2023 Nov 3. doi: 10.1021/acsami.3c11349. Online ahead of print.

ABSTRACT

The growing prevalence of methicillin-resistant Staphylococcus aureus (S. aureus) infections necessitates a greater understanding of their initial adhesion to medically relevant surfaces. In this study, the influence of the mechanical properties and oligomer content of polydimethylsiloxane (PDMS) gels on the initial attachment of Gram-positive S. aureus was explored. Small-amplitude oscillatory shear rheological measurements were conducted to verify that by altering the base to curing (B:C) ratio of the commonly used Sylgard 184 silicone elastomer kit (B:C ratios of 60:1, 40:1, 10:1, and 5:1), PDMS gels could be synthesized with Young’s moduli across four distinct regimes: ultrasoft (15 kPa), soft (30 kPa), standard (400 kPa), and stiff (1500 kPa). These as-prepared gels (unextracted) were compared to gels prepared from the same B/C ratios that underwent Soxhlet extraction to remove any unreacted oligomers. While the Young’s moduli of unextracted and extracted PDMS gels prepared from the same B:C ratio were statistically equivalent, the associated adhesion failure energy statistically decreased for the ultrasoft gels after extraction (from 25 to 8 J/mm2). The interactions of these eight well-characterized gels with bacteria were tested by using S. aureus SH1000, a commonly studied laboratory strain, as well as S. aureus ATCC 12600, which was isolated from a human lung infection. Increased S. aureus inactivation occurred only when the bacteria were incubated directly on top of the unextracted gels prepared at high B:C ratios (40:1 and 60:1), whereas none of the extracted gels (no unreacted oligomers) had significant levels of inactivated bacteria. S. aureus adhered the least to the stiffest extracted PDMS gels (no unreacted oligomers) and the most to soft, unextracted PDMS gels (with ∼17% unreacted oligomers). These findings suggest that both unreacted oligomers and Young’s moduli are important material factors to consider when exploring the attachment behavior of Gram-positive S. aureus to hydrophobic elastomer gels.

PMID:37922414 | DOI:10.1021/acsami.3c11349

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Enhancing the effectiveness of CBT for patients with unipolar depression by integrating digital interventions into treatment: A pilot randomized controlled trial

Psychother Res. 2023 Nov 3:1-16. doi: 10.1080/10503307.2023.2277866. Online ahead of print.

ABSTRACT

OBJECTIVE: Blended cognitive behavioral therapy (bCBT) combines face-to-face therapy with digital elements, such as digital health apps. This pilot study aimed to explore the effectiveness and safety of a novel bCBT application for treating unipolar depression in adults combined with cognitive behavioral therapy (CBT) compared to CBT alone in routine care.

METHODS: Patients (N = 82) were randomly assigned to bCBT (n = 42) or CBT (n = 40) over 12 weeks. bCBT consisted of weekly CBT sessions accompanied by the elona therapy depression module (a bCBT application for unipolar depression) for use between sessions. Standard CBT consisted of weekly CBT sessions. Outcomes (6,12 weeks) were analyzed with linear mixed models.

RESULTS: Improvements in depressive symptoms (BDI-II, PHQ-9) were descriptively larger for the bCBT group. Yet, this difference did not reach statistical significance. bCBT was superior to standard CBT in secondary outcome measures of psychological health (d = .50) and generalized anxiety symptoms (d = -.45). In other secondary outcomes (BAI, PSWQ, GSE, WHOQOL-BREF), improvements were descriptively larger for bCBT compared to CBT.

CONCLUSION: This pilot study provided preliminary evidence that bCBT might be advantageous in comparison to CBT alone in the treatment of depression, but larger RCTs of the bCBT application are needed.

PMID:37922395 | DOI:10.1080/10503307.2023.2277866

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Root resorption during maxillary molar intrusion with clear aligners: a randomized controlled trial

Angle Orthod. 2023 Nov 1;93(6):629-637. doi: 10.2319/010723-14.1.

ABSTRACT

OBJECTIVES: To compare changes in maxillary molar root resorption, intrusion amount, dentoskeletal measures, and maximum bite force (MBF) between clear aligners (CA) and fixed appliances with miniscrew (FM) during molar intrusion.

MATERIALS AND METHODS: Forty adults with anterior open bite were randomized into either CA or FM groups. Lateral cephalograms, cone-beam computed tomography (CBCT), and MBF were collected at pretreatment (T0) and 6 months of treatment (T1). Maxillary molar intrusion in FM were intruded by nickel-titanium (NiTi) closed-coil spring delivered force (150 grams/side) while clear aligners combined with squeezing exercise were performed in CA. Parametric tests were used for statistical analysis.

RESULTS: After 6 months of treatment, significant root resorption of 0.21-0.24 mm in CA and 0.38-0.47 mm in FM were found while maxillary molars were intruded 0.68 and 1.49 mm in CA and FM, respectively. CA showed significant less root resorption and intrusion than FM. Overbite, bite closing, and MBF increased significantly. CA showed significantly less overbite and SN-MP changes but more MBF increase than FM. MBF in CA was correlated with the amount of maxillary molar intrusion (r = 0.736, P < .05).

CONCLUSIONS: Maxillary molar intrusion and root resorption in CA were half the amount in FM in 6 months. The amount of maxillary molar root resorption was one-third of the intrusion distance. CA displayed less overbite increase and bite closing but more MBF increase than FM. MBF in CA was positively correlated with the molar intrusion amount.

PMID:37922387 | DOI:10.2319/010723-14.1

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Impact of attenuation correction of radiotherapy hardware for positron emission tomography-magnetic resonance in ano-rectal radiotherapy patients

J Appl Clin Med Phys. 2023 Nov 3:e14193. doi: 10.1002/acm2.14193. Online ahead of print.

ABSTRACT

BACKGROUND: Positron Emission Tomography-Magnetic Resonance (PET-MR) scanners could improve ano-rectal radiotherapy planning through improved Gross Tumour Volume (GTV) delineation and enabling dose painting strategies using metabolic measurements. This requires accurate quantitative PET images acquired in the radiotherapy treatment position.

PURPOSE: This study aimed to evaluate the impact on GTV delineation and metabolic parameter measurement of using novel Attenuation Correction (AC) maps that included the radiotherapy flat couch, coil bridge and anterior coil to see if they were necessary.

METHODS: Seventeen ano-rectal radiotherapy patients received a 18 F-FluoroDeoxyGlucose PET-MR scan in the radiotherapy position. PET images were reconstructed without (CTACstd ) and with (CTACcba ) the radiotherapy hardware included. Both AC maps used the same Computed Tomography image for patient AC. Semi-manual and threshold GTVs were delineated on both PET images, the volumes compared and the Dice coefficient calculated. Metabolic parameters: Standardized Uptake Values SUVmax , SUVmean and Total Lesion Glycolysis (TLG) were compared using paired t-tests with a Bonferroni corrected significance level of p = 0.05 / 8 = 0.006 $p = 0.05/8 = 0.006$ .

RESULTS: Differences in semi-manual GTV volumes between CTACcba and CTACstd were approaching statistical significance (difference 15.9 % ± 1.6 % $-15.9%pm 1.6%$ , p = 0.007 $p = 0.007$ ), with larger differences in low FDG-avid tumours ( SUV mean < 8.5 g mL 1 $mathrm{SUV_{mean}} &lt; 8.5;mathrm{g: mL^{-1}}$ ). The CTACcba and CTACstd GTVs were concordant with Dice coefficients 0.89 ± 0.01 (manual) and 0.98 ± 0.00 (threshold). Metabolic parameters were significantly different, with SUVmax , SUVmean and TLG differences of 11.5 % ± 0.3 % $-11.5% pm 0.3%$ ( p < 0.001 $p &lt; 0.001$ ), 11.6 % ± 0.3 % $-11.6% pm 0.3%$ ( p < 0.001 $p &lt; 0.001$ ) and 13.7 % ± 0.6 % $-13.7% pm 0.6%$ ( p = 0.003 $p = 0.003$ ) respectively. The TLG difference resulted in 1/8 rectal cancer patients changing prognosis group, based on literature TLG cut-offs, when using CTACcba rather than CTACstd .

CONCLUSIONS: This study suggests that using AC maps with the radiotherapy hardware included is feasible for patient imaging. The impact on tumour delineation was mixed and needs to be evaluated in larger cohorts. However using AC of the radiotherapy hardware is important for situations where accurate metabolic measurements are required, such as dose painting and treatment prognostication.

PMID:37922377 | DOI:10.1002/acm2.14193

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Effect of a community-based primary healthcare programme on adverse pregnancy outcomes in Northern Ghana

Int J Health Plann Manage. 2023 Nov 3. doi: 10.1002/hpm.3730. Online ahead of print.

ABSTRACT

BACKGROUND: Pregnancy complications and adverse birth outcomes are among the major contributors to poor maternal and child health. Mothers in remote communities are at higher risk of adverse birth outcomes due to constraints in access to healthcare services. In Ghana, a community-based primary healthcare programme called the Ghana Essential Health Interventions Programme (GEHIP) was implemented in a rural region to help strengthen primary healthcare delivery and improve maternal and child healthcare services delivery. This study assessed the effect of this programme on adverse pregnancy outcomes.

METHODS: Baseline and end-line survey data from reproductive-aged women from the GEHIP project were used in this analysis. Difference-in-differences and logistic regressions were used to examine the impact and equity effect of GEHIP on adverse pregnancy outcomes using household wealth index and maternal educational attainment as equity measures. The analysis involves the comparison of project baseline and end-line outcomes in intervention and non-intervention districts.

RESULTS: The intervention had a significant effect in the reduction of adverse pregnancy outcomes (OR = 0.96, 95% CI:0.93-0.99). Although disadvantaged groups experience larger reductions in adverse pregnancy outcomes, controlling for covariates, there was no statistically significant equity effect of GEHIP on adverse pregnancy outcomes using either the household wealth index (OR = 0.99, 95% CI:0.85-1.16) or maternal educational attainment (OR = 0.68, 95% CI: 0.44-1.07) as equity measures.

CONCLUSION: GEHIP’s community-based healthcare programme reduced adverse pregnancy outcomes but no effect on relative equity was established. Factoring in approaches for targeting disadvantaged populations in the implementation of community-based health programs is crucial to ensuring equity in health outcomes.

PMID:37922332 | DOI:10.1002/hpm.3730

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Effect of Prolong-life-with-nine-turn-method (Yan Nian Jiu Zhuan) Qigong on fatigue and gastrointestinal function in patients with chronic fatigue syndrome: Study protocol for a randomized controlled trial

PLoS One. 2023 Nov 3;18(11):e0287287. doi: 10.1371/journal.pone.0287287. eCollection 2023.

ABSTRACT

INTRODUCTION: Chronic fatigue syndrome (CFS) is a physical and mental disorder in which long-term fatigue is the main symptom. CFS patients are often accompanied by functional gastrointestinal diseases (FGIDs), which lead to decreased quality of life and increased fatigue. Prolong-life-with-nine-turn-method (PLWNT) is a kind of physical and mental exercise. Its operation includes adjusting the mind, breathing and cooperating with eight self-rubbing methods and one upper body rocking method. PLWNT was used to improve the digestive function in ancient China and to treat FGIDs such as functional dyspepsia and irritable bowel syndrome in modern times. Previous studies have shown that PLWNT can reduce fatigue in patients with CFS. But it is unclear whether the effect of PLWNT on CFS fatigue is related to gastrointestinal function. The aim of this study was to explore the relationship between PLWNT and fatigue and gastrointestinal function in patients with CFS.

METHODS: This study is a non-inferiority randomized controlled trial (RCT). The whole study period is 38 weeks, including 2 weeks of baseline evaluation, 12 weeks of intervention and 6 months of follow-up. Ninety-six CFS patients will be stratified random assigned to the intervention group (PLWNT) and the control group (cognitive behavior treatment) in the ratio of 1:1 through the random number table generated by SPSS. In the evaluation of results, Multidimensional Fatigue Inventory-20 (MFI-20), Gastrointestinal Symptom Rating Scale (GSRS), Bristol Stool Form Scale (BSFS), and Short Form 36 item health survey (SF-36) will be evaluated at week 0 (baseline), week 6 (midterm), week 12 (endpoint) and month 9 (follow up). The intestinal flora will be evaluated at week 0 (baseline) and week 12 (endpoint). The data results will be processed by statistical experts. The data analysis will be based on the intention to treat principle and per-protocol analysis. In the efficacy evaluation, repeated measurement analysis of variance will be used for data conforming to normal distribution or approximate normal distribution. The data which do not conform to the analysis of repeated measurement variance will be analyzed by the generalized estimation equation Linear discriminant analysis will be used to clarify the difference species of intestinal flora. The significance level sets as 5%. The safety of interventions will be evaluated after each treatment session.

DISCUSSION: This trial will provide evidence to PLWNT exerting positive effects on fatigue and gastrointestinal function of CFS. It will further explore whether the improvement of PLWNT on CFS fatigue is related to gastrointestinal function.

TRIAL REGISTRATION: The trial was registered at Chinese Clinical Trial Registry http://www.chictr.org.cn/showproj.aspx?proj=151456 (Registration No.: ChiCTR2200056530). Date: 2022-02-07.

PMID:37922308 | DOI:10.1371/journal.pone.0287287