Tag: pubmed

Adv Ther. 2022 Aug 12. doi: 10.1007/s12325-022-02290-3. Online ahead of print.

ABSTRACT

INTRODUCTION: We sought to identify and characterize distinct responder profiles among osteoarthritis (OA) subjects treated with tanezumab, nonsteroidal anti-inflammatory drugs (NSAIDs), or placebo.

METHODS: Subject-level data were derived from three randomized, double-blind, placebo- or NSAID-controlled trials of tanezumab in subjects with moderate-to-severe OA. Subjects received subcutaneous tanezumab (2.5 mg, n = 1527; 5 mg, n = 1279) every 8 weeks, oral NSAIDs (n = 994) daily, or placebo (n = 513). Group-based trajectory modeling (GBTM, an application of finite mixture statistical modeling that uses response trajectory to identify and summarize complex patterns in longitudinal data) was used to identify subgroups of subjects following similar patterns of response in each treatment arm, based on daily pain intensity scores from baseline through Week 16. We then examined whether subject-related variables were associated with any of the subgroups using multinomial logistic regression.

RESULTS: A three-subgroup/four-inflection point trajectory model was selected based on clinical and statistical considerations. The subgroups were high responders (substantial pain improvement and a large majority of members achieved ≥ 30% improvement before Week 16), medium responders (gradual pain improvement and a majority of members achieved ≥ 30% improvement by Week 16), and non-responders (little to no pain improvement over 16 weeks). Across all treatments, fluctuation in pain intensity in the week prior to treatment was consistently associated with treatment response. Other variables were positively (age, body mass index, days of rescue medication use) or negatively (severity of disease based on Kellgren-Lawrence grading) associated with response but effects were small and/or varied across treatments.

CONCLUSIONS: Across all treatments, GBTM identified three subgroups of subjects that were characterized by extent of treatment response (high, medium, and non-responders). Similar analyses (e.g., grouping of subjects based on response trajectory and identification of subgroup-related variables) in other studies of OA could inform clinical trial design and/or treatment approaches. (NCT02697773; NCT02709486; NCT02528188).

PMID:35960482 | DOI:10.1007/s12325-022-02290-3

Ann Surg Oncol. 2022 Aug 12. doi: 10.1245/s10434-022-12361-y. Online ahead of print.

ABSTRACT

BACKGROUND: Ductal carcinoma in situ (DCIS) is uncommon and understudied in young women. The objective of this study is to describe clinicopathologic features, treatment, and oncologic outcomes in a modern cohort of women aged ≤ 40 years with DCIS.

PATIENTS AND METHODS: Patients with DCIS were identified from the Young Women’s Breast Cancer Study, a multisite prospective cohort of women diagnosed with stage 0-IV breast cancer at age ≤ 40 years, enrolled from 2006 to 2016. Clinical data were collected from patient surveys and medical records. Pathologic features were examined by central review. Data were summarized with descriptive statistics and groups were compared with χ² and Fisher’s exact tests.

RESULTS: Among the 98 patients included, median age of diagnosis was 38 years; 36 (37%) patients were symptomatic on presentation. DCIS nuclear grade was high in 35%, intermediate in 50%, and low in 15% of lesions; 36% of lesions had comedonecrosis. The majority of patients underwent bilateral mastectomy (57%), 16 (16%) underwent unilateral mastectomy, and 26 (27%) underwent lumpectomy, most of whom received radiation. Few (13%) patients were receiving tamoxifen therapy 1 year postdiagnosis. Over a median follow-up of 8.4 years, six patients (6%) had disease recurrence, including five locoregional and one distant event.

CONCLUSIONS: A high proportion of young women with DCIS underwent mastectomy with or without contralateral prophylactic mastectomy. Although DCIS was frequently symptomatic on presentation and exhibited unfavorable pathologic factors, clinicopathologic features were overall heterogeneous and few recurrences occurred. This underscores the need for careful consideration of treatment options in young women with DCIS.

PMID:35960452 | DOI:10.1245/s10434-022-12361-y

J Genet Eng Biotechnol. 2022 Aug 12;20(1):121. doi: 10.1186/s43141-022-00390-9.

ABSTRACT

BACKGROUND: The production of industrial enzymes such as xylanase using sufficient cost-effective substrates from potent microorganisms is considered economically feasible. Studies have reported castor cake (Ricinus communis) as the most potent and inexpensive alternative carbon source for production of xylanase C by using Aspergillus terreus (A. terreus).

RESULTS: A. terreus strain RGS Eg-NRC, a local isolate from agro-wastes, was first identified by sequencing the internal transcribed spacer region of a nuclear DNA encoding gene cluster deposited in GenBank (accession number MW282328). Before optimization of xylanase production, A. terreus produced 20.23 U/g of xylanase after 7 days using castor cake as a substrate in a solid-state fermentation (SSF) system that was employed to achieve ricin detoxification and stimulate xylanase production. Physicochemical parameters for the production of xylanase were optimized by using a one-variable-at-a-time approach and two statistical methods (two-level Plackett-Burman design and central composite design, CCD). The maximum xylanase yield after optimization was increased by 12.1-fold (245 U/g). A 60-70% saturation of ammonium sulfate resulted in partially purified xylanase with a specific activity of 3.9 IU/mg protein. At 60 °C and pH 6, the partially purified xylanase had the highest activity, and the activation energy (Ea) was 23.919 kJmol. Subsequently, antioxidant capacity and cytotoxicity tests in normal Ehrlich ascites carcinoma human cells demonstrated xylooligosaccharides produced by the xylanase degradation of xylan as a potent antioxidant and moderate antitumor agent. Further investigations with sodium dodecyl sulfate polyacrylamide gel electrophoresis then determined the molecular weight of partially purified xylanase C to be 36 kDa. Based on the conserved regions, observations revealed that xylanase C belonged to the glycosyl hydrolase family 10. Next, the xylanase-encoding gene (xynC), which has an open reading frame of 981 bp and encodes a protein with 326 amino acids, was isolated, sequenced, and submitted to the NCBI GenBank database (accession number LC595779.1). Molecular docking analysis finally revealed that Glu156, Glu262, and Lys75 residues were involved in the substrate-binding and protein-ligand interaction site of modeled xylanase, with a binding affinity of -8.7 kcal. mol^-1. CONCLUSION: The high production of safe and efficient xylanase could be achieved using economical materials such as Ricinus communis.

PMID:35960448 | DOI:10.1186/s43141-022-00390-9

J Racial Ethn Health Disparities. 2022 Aug 12. doi: 10.1007/s40615-022-01357-9. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: The Dysfunctional Voiding and Incontinence Scoring System (DVISS) is a validated tool to evaluate lower urinary tract dysfunction (LUTD) severity in children. DVISS provides a quantitative score (0-35) including a quality-of-life measure, with higher values indicating more/worse symptoms. Clinically, variability exists in symptom severity when patients present to pediatric urology with LUTD. We hypothesized that symptom severity at consultation varied based on race, gender, and/or socioeconomic status.

METHODS: All urology encounters at a single institution with completed modified DVISS scores 6/2015-3/2018 were reviewed. Initial visits for patients 5-21 years old with non-neurogenic LUTD were included. Patients with neurologic disorders or genitourinary tract anomalies were excluded. Wilcoxon rank sum tests compared scores between White and Black patients and between male and female patients. Multiple regression models examined relationships among race, gender, estimated median household income, and insurance payor type. All statistics were performed using Stata 15.

RESULTS: In total, 4086 initial patient visits for non-neurogenic LUTD were identified. Median DVISS scores were higher in Black (10) versus White (8) patients (p < 0.001). Symptom severity was higher in females (9) versus males (8) (p < 0.001). When estimated median income and insurance payer types were introduced into a multiple regression model, race, gender, and insurance payer type were significantly associated with symptom severity at presentation.

CONCLUSIONS: Race, gender, and socioeconomic status significantly impact LUTS severity at the time of urologic consultation. Future studies are needed to clarify the etiologies of these disparities and to determine their clinical significance.

PMID:35960437 | DOI:10.1007/s40615-022-01357-9

Ann Biomed Eng. 2022 Aug 12. doi: 10.1007/s10439-022-03040-w. Online ahead of print.

ABSTRACT

Continuous monitoring of both hemodynamic and respiratory parameters would be beneficial to patients, e.g., those in intensive care unit. The objective of this exploratory animal study was to test the feasibility of simultaneous measurements of relative tidal volume (rTV) and relative stroke volume (rSV) using an electrical impedance tomography (EIT) device equipped with a new real-time source separation algorithm implemented as two spatial filters. Five pigs were anesthetized and mechanically ventilated. The supplied tidal volume from a mechanical ventilator was reduced to 70, 50 and 30% from the 100% normal volume to simulate hypoventilation. The respiratory volume signal and cardiac volume signal were generated by applying the spatial filters to the acquired EIT data, from which values of rTV and rSV were extracted. The measured rTV values were compared with the TV values from the mechanical ventilator using the four-quadrant concordance analysis method. For changes in TV, the concordance rate in each animal ranged from 81.8% to 100%, while it was 92.5% when the data from all five animals were pooled together. When the measured rTV values for each animal were scaled to the absolute TV_EIT values in mL using the TV_Vent data from the mechanical ventilator, the smallest 95% limits of agreement (LoA) were – 6.04 and 7.44 mL for the 70% ventilation level, and the largest 95% LoA were – 18.1 and 19.4 mL for the 50% ventilation level. The percentage error between TV_EIT and TV_Vent was 10.3%. Although similar statistical analyses on rSV data could not be performed due to limited intra-animal variability, changes in rSV values measured by the EIT device were comparable to those measured by an invasive hemodynamic monitor. In this animal study, we were able to demonstrate the feasibility of an EIT device for noninvasive and simultaneous measurements of rTV and rSV in real time. However, the performance of the real-time source separation method needs to be further validated on animals and human subjects, particularly over a wide range of SV values. Future clinical studies are needed to assess the potential usefulness of the new method in dynamic cardiopulmonary monitoring and explore other clinical applications.

PMID:35960417 | DOI:10.1007/s10439-022-03040-w

Matern Child Health J. 2022 Aug 12. doi: 10.1007/s10995-022-03465-8. Online ahead of print.

ABSTRACT

INTRODUCTION: The 2030 health agenda for the United Nations Sustainable Development Goals promote exclusive breastfeeding (EBF) for the first 6 months of life as a central step towards ensuring the survival of infants. As Jamaica attempts to achieve this goal, monitoring the rates of EBF is desirable. Currently, EBF rate is measured by questionnaires which are subject to recall and social desirability biases. We determined the rate of EBF using the Deuterium-oxide dose-to-mother (DTM) method and 24-h recall. The concordance of both methods and urban-rural differences of EBF were evaluated. Additionally, the growth of infants who were exclusively breastfed was compared to the infants who were mixed-fed.

METHODS: Sixty-one healthy mother-child pairs were followed from birth. EBF was measured at 6 weeks. Growth was determined using standard anthropometric measurements. Differences in means were assessed by independent t-test or ANOVA. The agreement between the DTM and 24-h recall method was assessed with the kappa statistic. Differences in anthropometry and location were determined using a repeated measure model approach.

RESULTS: Thirty (49%) women exclusively breastfed their infants with mean breast milk intake of 1024.3 ± 256.9 g/day. There was moderate agreement between the methods (Agreement 69%, kappa 0.37, p = 0.002). Rural women (65%) were more likely to practice exclusive breastfeeding. There was no significant difference between the growth of the exclusively breastfed infant and mixed-fed infants.

CONCLUSION: EBF rate was successfully measured using the DTM method. Women from urban settings are less likely to practice EBF. Further research may be needed to gain an in-depth understanding of the factors affecting breastfeeding practices in urban Jamaica.

PMID:35960420 | DOI:10.1007/s10995-022-03465-8

Mol Biol Rep. 2022 Aug 12. doi: 10.1007/s11033-022-07754-x. Online ahead of print.

ABSTRACT

BACKGROUND: Early and intermediate serological screening cannot detect sex chromosome abnormalities. Currently, noninvasive prenatal testing (NIPT) is the only procedure available for screening such disorders; however, its use is controversial.

METHODS AND RESULTS: A total of 47,855 pregnant women underwent NIPT at our referral center from January 2014 to December 2020. Of the 314 patients with a positive NIPT indicating sex chromosome abnormalities, 260 were screened via karyotype analysis and single nucleotide polymorphism (SNP) array after amniotic fluid extraction; 96 cases were confirmed. Karyotype analysis and SNP array were consistent in the diagnosis of 88 out of the 96 fetuses. The positive predictive value (PPV) for sex chromosome abnormalities was found to be 36.9%. The PPV in patients aged 30-34 years was significantly higher than that in patients aged < 30 years. No statistically significant difference was observed on the PPV among patients with or without previous adverse pregnancy outcomes. Moreover, 83 women carrying fetuses were diagnosed with a sex chromosome abnormality terminated their pregnancy.

CONCLUSIONS: Improvements in detection and analytical technologies are needed to increase the accuracy of sex chromosome abnormalities detection. Pregnant women with a positive NIPT for these abnormalities may require invasive diagnostic procedures such as karyotype analysis and SNP array for better genetic counseling.

PMID:35960415 | DOI:10.1007/s11033-022-07754-x

J Clin Psychol Med Settings. 2022 Aug 12. doi: 10.1007/s10880-022-09904-6. Online ahead of print.

ABSTRACT

This is a retrospective study conducted in Vlora from January 2016 to April 2017 and the aim was to report the prevalence of depression in cardiovascular (CVD) patients. Depression assessment was done using the Patient Health Questionnaire (PHQ)-9 (PHQ-9). Data were derived from the patient records and the standard recommended cut-off point of PHQ-9 ≥ 10 was used. In total, data of 300 patients were analyzed. Depressive symptoms (PHQ-9 ≥ 10) were observed at 6% of the participants. Trouble falling asleep or staying asleep or sleeping too much, feeling tired or having little energy and having little interest or pleasure in doing things were the most common symptoms reported. In multivariate analysis, only family status showed statistical significance. Unmarried (mean rank = 207.22) are more likely to have moderate or severe depression level (OR 3.529; C.I. 95% 1.017-12.238). Future research should focus on the needed actions after depression screening (i.e. referral, treatment etc.).

PMID:35960399 | DOI:10.1007/s10880-022-09904-6

Eur J Nutr. 2022 Aug 12. doi: 10.1007/s00394-022-02978-w. Online ahead of print.

ABSTRACT

PURPOSE: To assess the cross-sectional association between dietary indexes (DI) that underlie, respectively, the Nutri-score (NS), the proposed Canadian ‘High In’ Symbol (CHIL) and the Diabetes Canada Clinical Practice Guidelines (DCCP) with food consumption, nutrient intakes and metabolic markers.

METHODS: 1836 adults (18-74 years) participating in the representative ESTEBAN study, conducted in mainland France in 2014-2016, were included in the analysis. Food consumption was assessed with three repeated 24 h dietary recalls. Anthropometric measurements and biomarkers of metabolic risk (cholesterol-total, LDL (Low Density Lipoprotein), HDL (High Density Lipoprotein)-triglycerides, glucose) were obtained through a clinical examination and fasting blood draw. The DI were assessed for their association with food consumption, dietary intakes and metabolic biomarkers as quintiles and continuous variables using multi-adjusted linear regression. Heathier diets were assigned to lower scores.

RESULTS: Correlations between scores ranged from + 0.62 between CHIL-DI and NS-DI to + 0.75 between NS-DI and DCCP-DI. All DIs discriminated individuals according to the nutritional quality of their diets through food consumption and nutrient intakes (healthier diets were associated with lower intakes of energy, added sugars and saturated fat; and with higher intakes of fiber, vitamins and minerals). NS-DI was associated with blood glucose (adjusted mean in Q1 = 5 vs. Q5 = 5.46 mmol/dl, p_trend = 0.001) and DCCP-DI was associated with BMI (Q1 = 24.8 kg/m² vs. Q5 = 25.8 kg/m², p_trend = 0.025), while CHIL showed no significant association with any anthropometric measures or biomarkers.

CONCLUSIONS: This study provides elements supporting the validity of the nutrient profiling systems underlying front-of-package nutrition labellings (FOPLs) to characterize the healthiness of diets.

PMID:35960367 | DOI:10.1007/s00394-022-02978-w

J Math Biol. 2022 Aug 12;85(3):20. doi: 10.1007/s00285-022-01783-7.

ABSTRACT

Although ecological networks are typically constructed based on a single type of interaction, e.g. trophic interactions in a food web, a more complete picture of ecosystem composition and functioning arises from merging networks of multiple interaction types. In this work, we consider tripartite networks constructed by merging two bipartite networks, one mutualistic and one antagonistic. Taking the interactions within each sub-network to be distributed randomly, we consider the stability of the dynamics of the network based on the spectrum of its community matrix. In the asymptotic limit of a large number of species, we show that the spectrum undergoes an eigenvalue phase transition, which leads to an abrupt destabilisation of the network as the ratio of mutualists to antagonists is increased. We also derive results that show how this transition is manifest in networks of finite size, as well as when disorder is introduced in the segregation of the two interaction types. Our random-matrix results will serve as a baseline for understanding the behaviour of merged networks with more realistic structures and/or more detailed dynamics.

PMID:35960362 | DOI:10.1007/s00285-022-01783-7