Tag: pubmed

J Math Biol. 2024 May 19;89(1):6. doi: 10.1007/s00285-024-02104-w.

ABSTRACT

Multiple infections enable the recombination of different strains, which may contribute to viral diversity. How multiple infections affect the competition dynamics between the two types of strains, the wild and the immune escape mutant, remains poorly understood. This study develops a novel mathematical model that includes the two strains, two modes of viral infection, and multiple infections. For the representative double-infection case, the reproductive numbers are derived and global stabilities of equilibria are obtained via the Lyapunov direct method and theory of limiting systems. Numerical simulations indicate similar viral dynamics regardless of multiplicities of infections though the competition between the two strains would be the fiercest in the case of quadruple infections. Through sensitivity analysis, we evaluate the effect of parameters on the set-point viral loads in the presence and absence of multiple infections. The model with multiple infections predict that there exists a threshold for cytotoxic T lymphocytes (CTLs) to minimize the overall viral load. Weak or strong CTLs immune response can result in high overall viral load. If the strength of CTLs maintains at an intermediate level, the fitness cost of the mutant is likely to have a significant impact on the evolutionary dynamics of mutant viruses. We further investigate how multiple infections alter the viral dynamics during the combination antiretroviral therapy (cART). The results show that viral loads may be underestimated during cART if multiple-infection is not taken into account.

PMID:38762831 | DOI:10.1007/s00285-024-02104-w

Am J Orthod Dentofacial Orthop. 2024 May 18:S0889-5406(24)00149-5. doi: 10.1016/j.ajodo.2024.04.011. Online ahead of print.

ABSTRACT

INTRODUCTION: The objective of this study was to identify the soft-tissue profile changes and the potential pretreatment cephalometric parameters that clinicians could use to predict the lip response after premolar extraction treatment in adult patients.

METHODS: Pretreatment and posttreatment lateral cephalograms of 75 white patients treated with premolar extractions were analyzed. The following initial cephalometric measurements were recorded: upper and lower lip to E-plane, vermilion thickness, lip length, maxillary and mandibular incisor inclination, and mentolabial and nasolabial angle. Pretreatment and posttreatment radiographs were superimposed using the Björk structural method to record lip retraction and incisor/lip retraction ratio. Pearson correlation and Kruskal-Wallis tests were used to compare lip retraction and incisor/lip retraction ratio with the cephalometric variables. The sample was divided according to different extraction patterns.

RESULTS: The mean upper and lower lip retraction values were 1.4 mm and 1.7 mm, respectively. Vermilion thickness showed a negative and statistically significant correlation (P <0.05) with lip retraction and incisor/lip retraction ratio. In addition, the mean incisor/lip retraction ratio was 61% and 98% for the upper and lower thin lip, respectively, whereas the mean incisor/lip retraction ratio was 17% and 44% for the upper and lower thick lip, respectively. The comparison among extraction patterns did not highlight any noticeable difference.

CONCLUSIONS: The choice of a specific extraction pattern did not impact lip response. The vermilion thickness was the key factor influencing lip retraction: an increase in this parameter was related to a decrease in lip retraction and vice versa.

PMID:38762811 | DOI:10.1016/j.ajodo.2024.04.011

Australas J Dermatol. 2024 May 19. doi: 10.1111/ajd.14306. Online ahead of print.

ABSTRACT

BACKGROUND: Female-pattern hair loss (FPHL) is characterized by decreased scalp hair density, thinning of hair shafts, and progressive miniaturization of hair follicles.

OBJECTIVE: To compare the safety and efficacy of spironolactone versus bicalutamide in female pattern hair loss [FPHL].

METHODS: The study design was retrospective, and all eligible females aged between 18 years and 50 years with FPHL were included. We identified 120 patients from our database who fulfilled the inclusion and exclusion criteria, and patients were then categorized into two groups, Group A comprising patients who were taking 100 mg of spironolactone once daily and Group B comprising patients who were taking 50 mg of bicalutamide once daily along with topical minoxidil 2% in both groups. Patient were analysed at approximately at 24 weeks from the commencement of the treatment.

RESULTS: Mean reduction in hair loss severity score on Sinclair scale was 19.51% in spironolactone group compared to 28.20% in bicalutamide group at 24 weeks, which was statistically significant. On global photographic assessment, marked improvement was seen in bicalutamide group compared to spironolactone group (p = 0.139).

CONCLUSIONS: Our study, though limited by its retrospective design and small sample size, showed that bicalutamide has greater efficacy and better safety profile in comparison to spironolactone in the treatment of FPHL.

PMID:38762801 | DOI:10.1111/ajd.14306

JAMA. 2024 May 19. doi: 10.1001/jama.2024.8771. Online ahead of print.

ABSTRACT

IMPORTANCE: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Observational studies report that β-blocker use may be associated with reduced risk of COPD exacerbations. However, a recent trial reported that metoprolol did not reduce COPD exacerbations and increased COPD exacerbations requiring hospital admission.

OBJECTIVE: To test whether bisoprolol decreased COPD exacerbations in people with COPD at high risk of exacerbations.

DESIGN, SETTING, AND PARTICIPANTS: The Bisoprolol in COPD Study (BICS) was a double-blind placebo-controlled randomized clinical trial conducted in 76 UK sites (45 primary care clinics and 31 secondary clinics). Patients with COPD who had at least moderate airflow obstruction on spirometry (ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity <0.7; FEV1 <80% predicted) and at least 2 COPD exacerbations treated with oral corticosteroids, antibiotics, or both in the prior 12 months were enrolled from October 17, 2018, to May 31, 2022. Follow-up concluded on April 18, 2023.

INTERVENTIONS: Patients were randomly assigned to bisoprolol (n = 261) or placebo (n = 258). Bisoprolol was started at 1.25 mg orally daily and was titrated as tolerated during 4 sessions to a maximum dose of 5 mg/d, using a standardized protocol.

MAIN OUTCOMES AND MEASURES: The primary clinical outcome was the number of patient-reported COPD exacerbations treated with oral corticosteroids, antibiotics, or both during the 1-year treatment period. Safety outcomes included serious adverse events and adverse reactions.

RESULTS: Although the trial planned to enroll 1574 patients, recruitment was suspended from March 16, 2020, to July 31, 2021, due to the COVID-19 pandemic. Two patients in each group were excluded postrandomization. Among the 515 patients (mean [SD] age, 68 [7.9] years; 274 men [53%]; mean FEV1, 50.1%), primary outcome data were available for 514 patients (99.8%) and 371 (72.0%) continued taking the study drug. The primary outcome of patient-reported COPD exacerbations treated with oral corticosteroids, antibiotics, or both was 526 in the bisoprolol group, with a mean exacerbation rate of 2.03/y, vs 513 exacerbations in the placebo group, with a mean exacerbation rate of 2.01/y. The adjusted incidence rate ratio was 0.97 (95% CI, 0.84-1.13; P = .72). Serious adverse events occurred in 37 of 255 patients in the bisoprolol group (14.5%) vs 36 of 251 in the placebo group (14.3%; relative risk, 1.01; 95% CI, 0.62-1.66; P = .96).

CONCLUSIONS AND RELEVANCE: Among people with COPD at high risk of exacerbation, treatment with bisoprolol did not reduce the number of self-reported COPD exacerbations requiring treatment with oral corticosteroids, antibiotics, or both.

TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN10497306.

PMID:38762800 | DOI:10.1001/jama.2024.8771

JAMA. 2024 May 19. doi: 10.1001/jama.2024.8693. Online ahead of print.

ABSTRACT

IMPORTANCE: Current treatments for idiopathic pulmonary fibrosis slow the rate of lung function decline, but may be associated with adverse events that affect medication adherence. In phase 2 trials, pamrevlumab (a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity) attenuated the progression of idiopathic pulmonary fibrosis without substantial adverse events.

OBJECTIVE: To assess the efficacy and safety of pamrevlumab for patients with idiopathic pulmonary fibrosis.

DESIGN, SETTING, AND PARTICIPANTS: Phase 3 randomized clinical trial including 356 patients aged 40 to 85 years with idiopathic pulmonary fibrosis who were not receiving antifibrotic treatment with nintedanib or pirfenidone at enrollment. Patients were recruited from 117 sites in 9 countries between July 18, 2019, and July 29, 2022; the last follow-up encounter occurred on August 28, 2023.

INTERVENTIONS: Pamrevlumab (30 mg/kg administered intravenously every 3 weeks; n = 181) or placebo (n = 175) for 48 weeks.

MAIN OUTCOMES AND MEASURES: The primary outcome was absolute change in forced vital capacity (FVC) from baseline to week 48. There were 5 secondary outcomes (including time to disease progression, which was defined as a decline of ≥10% in predicted FVC or death). The exploratory outcomes included patient-reported symptoms. Adverse events were reported.

RESULTS: Among 356 patients (mean age, 70.5 years; 258 [72.5%] were men; 221 [62.1%] were White), 277 (77.8%) completed the trial. There was no significant between-group difference for absolute change in FVC from baseline to week 48 (least-squares mean, -260 mL [95% CI, -350 to -170 mL] in the pamrevlumab group vs -330 mL [95% CI, -430 to -230 mL] in the placebo group; mean between-group difference, 70 mL [95% CI, -60 to 190 mL], P = .29). There were no significant between-group differences in any of the secondary outcomes or in the patient-reported outcomes. In the pamrevlumab group, there were 160 patients (88.4%) with treatment-related adverse events and 51 patients (28.2%) with serious adverse events vs 151 (86.3%) and 60 (34.3%), respectively, in the placebo group. During the study, 23 patients died in each group (12.7% in the pamrevlumab group vs 13.1% in the placebo group).

CONCLUSIONS AND RELEVANCE: Among patients with idiopathic pulmonary fibrosis treated with pamrevlumab or placebo, there was no statistically significant between-group difference for the primary outcome of absolute change in FVC from baseline to week 48.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03955146.

PMID:38762797 | DOI:10.1001/jama.2024.8693

Semin Ophthalmol. 2024 May 19:1-5. doi: 10.1080/08820538.2024.2354692. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the incidence and cost of intraocular lens(IOL) waste during IOL implantation, as well as the reasons for it.

METHODS: A retrospective analysis was conducted on the data of 485 patients from the IOL waste registers of a single tertiary eye hospital in China during 2016-2020. The primary outcomes were the incidence, cost, and reasons for different IOL properties. Cases were examined to ascertain IOL material, design, procedural details, and causes of waste.

RESULTS: IOL waste occurred in 485 (6.62‰) of the 73,246 IOL implantations during the study period. The total cost of IOL waste was 429, 850.26 Chinese Yuan (CNY) related to waste with an average cost of 2, 442.33 CNY per procedure during the study period. Comparisons between IOL properties showed that polymethyl methacrylate (PMMA) material (39, 2.05%), three-piece design (142, 1.49%), and secondary IOL implantation (26, 2.16%) were associated with IOL wastage, and the difference was statistically significant. The causes of IOL waste were damage (107, 60.80%), patient reasons (37, 21.26%), aseptic errors (22, 12.50%), IOL quality problems (8, 4.55%), and loss (2, 1.14%).

CONCLUSIONS: The incidence of IOL waste is low, but still leads to a significant cost burden due to a large number of cataract surgeries. PMMA material, three-piece design, and secondary implantation were identified as factors increasing IOL waste. Damage emerged as the primary reason for waste, largely attributed to human error. Therefore, the development of strategies to mitigate IOL waste is imperative.

PMID:38762793 | DOI:10.1080/08820538.2024.2354692

Am J Reprod Immunol. 2024 May;91(5):e13858. doi: 10.1111/aji.13858.

ABSTRACT

PROBLEM: In the current study we aimed to investigate Syndecan 1 (SDC1) levels in pregnant women diagnosed with fetal growth restriction (FGR) and the relationship between SDC1 levels and clinical and doppler parameters in FGR cases associated with endothelial dysfunction, angiogenesis and uteroplacental insufficiency METHOD OF STUDY: A total of 90 pregnant women included in the study, (45 with FGR, 45 healthy control) matched by week of gestation and maternal age. Venous blood samples were collected and plasma concentrations of SDC1 were determined by a specific immunoassay. Doppler examination was performed to evaluate the relationship between the SDC1 levels and placental blood supply.

RESULTS: Doppler parameters; mean UtA-PI (p < .001), CPR (p = .002) and CPUR (p < .001) were different between the groups, however MCA PI, umbilical artery PI and umbilical artery S/D were not (p > .05). While gestational age at delivery, birth weight, APGAR score at 1 and 5 min were significantly lower (all, p < .001) in the study group, non-reassure fetal heart rate tracing (p = .09) and NICU admission (p = .02) were significantly higher. SDC 1 level was 2,00 ± 1,47 ng/mL and 2,34 ± 1,12 ng/mL in the FGR and control groups, respectively (p = .008). In the study group SDC 1 level was 1,69 ± 2,00 in those with gestational age below 32 weeks and 2,13 ± 1,18 in those with gestational age above 32 weeks and there was a statistically significant difference between the groups (p = .015). Plasma SDC 1 concentration of 2,1850 ng/mL or less had a sensitivity of 70%, a specificity of 72%, area under the ROC curve .65 (p < .005).

CONCLUSIONS: Low maternal plasma SDC1 level may be associated with placental insufficiency and FGR. Low levels of SDC1 may be helpful as a predictor for the development of FGR during gestation.

PMID:38762781 | DOI:10.1111/aji.13858

Clin Gerontol. 2024 May 19:1-11. doi: 10.1080/07317115.2024.2346906. Online ahead of print.

ABSTRACT

OBJECTIVES: To describe nursing home (NH) characteristics associated with antipsychotic use and test whether associations changed after implementation of the National Partnership to Improve Dementia Care’s antipsychotic reduction initiative (ARI).

METHODS: Longitudinal quasi-experimental design using data from multiple sources and piecewise linear mixed models were used for statistical analyses.

RESULTS: There was a significant decrease in monthly antipsychotic use across the study period (pre-ARI b = -0.0003, p <.001; post-ARI b = -0.0012, p <.001), which held after adjusting for NH characteristics. Registered nurse hours (b = -0.0026, p <.001), licensed practical nurse hours (b = -0.0019, p <.001), facility chain membership (b = -0.0013, p <.01), and health inspection ratings (b = -0.0003, p >.01) were associated with decreased antipsychotic use. Post-ARI changes in associations between NH characteristics and antipsychotic use were small and not statistically significant.

CONCLUSIONS: Decreases in antipsychotic use were associated with most NH characteristics, and associations persisted post-ARI. Further research is warranted to examine the interactions between ARI policy and NH characteristics on antipsychotic prescribing, as well as other NH factors, such as facility prescribing cultures and clinical specialty of staff.

CLINICAL IMPLICATIONS: Decreases in monthly antipsychotic use were observed following the ARI. The decreases in monthly antipsychotic use were associated with most NH characteristics, and these associations persisted during the post-ARI period.

PMID:38762776 | DOI:10.1080/07317115.2024.2346906

Med Sci Monit. 2024 May 19;30:e944553. doi: 10.12659/MSM.944553.

ABSTRACT

BACKGROUND Scaphoid nonunion (SN) is a challenging condition in wrist pathology, often resulting in severe consequences if left untreated. Surgical intervention, particularly using vascularized bone grafts (VBGs), is a promising but uncertain approach. The 4+5 extensor compartment artery (ECA) pedicled graft, less commonly used for SN, has potential benefits due to its vascular supply and accessibility to the scaphoid. This study aimed to evaluate the effectiveness of the 4+5 ECA pedicled graft combined with headless compression screw fixation in treating avascular necrosis (AVN)-induced proximal pole SN. Radiological results, functional outcomes, and complications related to this method were assessed. MATERIAL AND METHODS This was a retrospective analysis of 19 proximal pole SN cases with AVN treated using the 4+5 ECA-VBG technique from 2016 to 2022. Patients underwent preoperative evaluation and postoperative follow-up for at least 1 year. Data on surgery, demographics, radiological assessments, and functional outcomes were recorded and analyzed statistically. RESULTS All patients achieved radiographic union within 8.5 weeks postoperatively, with revascularization of proximal pole necrosis. Significant improvements in functional outcomes were observed, including pain reduction, increased wrist range of motion, improved grip and pinch strength, and enhanced wrist scores. No major complications were reported. CONCLUSIONS The 4+5 ECA-VBG technique, with headless compression screw fixation, showed high success rates in treating AVN-induced proximal pole SN. This method offers comprehensive restoration of wrist function and minimal complications, making it a viable option for SN management, especially in AVN cases. Further research is needed to confirm these results and establish standardized protocols for SN treatment.

PMID:38762751 | DOI:10.12659/MSM.944553

Autophagy. 2024 May 18:1-8. doi: 10.1080/15548627.2024.2353458. Online ahead of print.

ABSTRACT

Segmenting autophagic bodies in yeast TEM images is a key technique for measuring changes in autophagosome size and number in order to better understand macroautophagy/autophagy. Manual segmentation of these images can be very time consuming, particularly because hundreds of images are needed for accurate measurements. Here we describe a validated Cellpose 2.0 model that can segment these images with accuracy comparable to that of human experts. This model can be used for fully automated segmentation, eliminating the need for manual body outlining, or for model-assisted segmentation, which allows human oversight but is still five times as fast as the current manual method. The model is specific to segmentation of autophagic bodies in yeast TEM images, but researchers working in other systems can use a similar process to generate their own Cellpose 2.0 models to attempt automated segmentations. Our model and instructions for its use are presented here for the autophagy community.Abbreviations: AB, autophagic body; AvP, average precision; GUI, graphical user interface; IoU, intersection over union; MVB, multivesicular body; ROI, region of interest; TEM, transmission electron microscopy; WT,wild type.

PMID:38762750 | DOI:10.1080/15548627.2024.2353458