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Conducting polymer hydrogels with electrically-tuneable mechanical properties as dynamic cell culture substrates

Mater Sci Eng C Mater Biol Appl. 2021 Nov 23:112559. doi: 10.1016/j.msec.2021.112559. Online ahead of print.

ABSTRACT

Hydrogels are a popular substrate for cell culture due to their mechanical properties closely resembling natural tissue. Stimuli-responsive hydrogels are a good platform for studying cell response to dynamic stimuli. Poly(N-isopropylacrylamide) (pNIPAM) is a thermo-responsive polymer that undergoes a volume-phase transition when heated to 32 °C. Conducting polymers can be incorporated into hydrogels to introduce electrically responsive properties. The conducting polymer, polypyrrole (PPy), has been widely studied as electrochemical actuators due to its electrochemical stability, fast actuation and high strains. We determine the volume-phase transition temperature of pNIPAM hydrogels with PPy electropolymerised with different salts as a film within the hydrogel network. We also investigate the electro-mechanical properties at the transition temperature (32 °C) and physiological temperature (37 °C). We show statistically significant differences in the Young’s modulus of the hybrid hydrogel at elevated temperatures upon electrochemical stimulation, with a 5 kPa difference at the transition temperature. Furthermore, we show a three-fold increase in actuation at transition temperature compared to room temperature and physiological temperature, attributed to the movement of ions in/out of the PPy film that induce the volume-phase transition of the pNIPAM hydrogel. Furthermore, cell adhesion to the hybrid hydrogel was demonstrated with mouse articular chondrocytes.

PMID:35527144 | DOI:10.1016/j.msec.2021.112559

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Pregnancy Associated Breast Cancer Among Israeli BRCA1/BRCA2 Carriers in a High-Risk Clinic

Acad Radiol. 2022 May 5:S1076-6332(22)00207-0. doi: 10.1016/j.acra.2022.03.030. Online ahead of print.

ABSTRACT

RATIONALE AND OBJECTIVES: Female carriers of pathogenic sequence variants (PSVs) in the BRCA1 /BRCA2 (Breast Cancer gene – BRCA) genes are at a substantially high-risk for developing breast cancer (BC), hence are offered active surveillance scheme based on semiannual breast exam and imaging from age 25 years to facilitate BC early detection (mammography/breast ultrasound depending on the age, and MRI). However, there are not specific guidelines for screening in case of pregnancy or lactation. In the current study, we summarize the experience at the largest high-risk clinic in Israel.

MATERIALS AND METHODS: Data of consecutive BRCA-PSV carriers undergoing surveillance as well as diagnostic ultrasound at the Meirav high-risk clinic from January 2014 to 2021 who were pregnant and/or breastfeeding at time of follow-up were identified. Relevant clinical data including results of breast exam, breast ultrasonography, biopsies and histological results were retrieved. Percentage of biopsies with malignancy, cancer detection rate and positive predictive values were calculated. Data is presented in descriptive statistics.

RESULTS: A total of 263 BRCA-carriers were included. Of these, 593 breast-ultrasonograms were performed in 263 BRCA-carriers for 292 pregnancies and 409 breast-ultrasonograms for 175 breastfeeding carriers. Of 36 breast biopsies in 292 pregnancies, 4 (PPV = 11%) had BC diagnosed (high grade invasive). Of 175 breastfeeding women, 25 biopsies were performed and 2 (PPV = 8%) were high grade invasive BC. Five of 6 BC were diagnosed in BRCA1 carriers, and 4/6 were screen detected. The rate of pregnancy-associated breast cancer was 6/292 (2.05%).

CONCLUSION: The overall detection rate of pregnancy-associated BC in BRCA-carriers is relatively low (2.05%), but still much higher than that in the general population. Two thirds of the BC were detected by screening. Therefore, despite the changes of the glandular breast tissue at time of pregnancy and breastfeeding, screening plays an important role in early detection. Ultrasound should be considered as a screening tool during this period of life of high-risk patients.

PMID:35527100 | DOI:10.1016/j.acra.2022.03.030

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Analysis of reinjection periodicity in knee osteoarthritis with different types of hyaluronic acids

Rehabilitacion (Madr). 2022 May 5:S0048-7120(22)00012-3. doi: 10.1016/j.rh.2022.02.008. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the periodicity of hyaluronic acid (HA) reinjection in patients with knee osteoarthritis. Secondary aim: To relate the degree of arthrosis with the time between infiltrations and the possible study by subgroups between the different commercial preparations.

DESIGN: Retrospective observational study.

MATERIALS AND METHOD: Review of medical records and X-rays of patients with knee osteoarthritis that had been treated with intra-articular HA at the Rehabilitation Service in the period between January 2017 and June 2019.

VARIABLES: Socio-demographic, Laterality, Intervention Date, Degree of Arthrosis according to Kellgren and Lawrence, HA used, Time between filtrations. Statistical analysis carried out by Kaplan-Meier curves, taking into account the reinfiltration as final event, and Kruskal-Wallis test for non-parametric quantitative data.

RESULTS: We analysed 110 infiltration acts in 67 patients: average age at the time of infiltration 72.12 years, 85.1% women, 59.1% right knee. 4 types of HA: 33 cases at 1%. MW: 0.9MDa (HA1), 12 at 1.5%. MW: 1.5-2MDa (HA2), 42 at 2%. MW: 1.2MDa (HA3) and 6 Hylan G-F20. MW: 6MDa (HA4). We reinfiltrated in 31 occasions (28.2%). Average of months (IC 95%) between infiltrations: HA1 6.9 (5.7-8.16), HA2 12.5 (0-35), HA3 9.3 (5.5-13.1), HA4 5 (3-6.9). In 2 cases where it was not possible to establish the type of infiltrated formulations, the mean value between reinfiltrations was 8.5 (5.6-11.4) There were no statistically significant results by relating the HA type or the degree of arthrosis with the reinfiltration time.

CONCLUSIONS: In our study, we observe that the HA3 presented a longer time between infiltrations in comparison with other types, with no possibility to detect significant differences.

PMID:35527076 | DOI:10.1016/j.rh.2022.02.008

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Challenges for Peritoneal Dialysis Centers Before and During the COVID-19 Pandemic in Mexico

Arch Med Res. 2022 Apr 29:S0188-4409(22)00047-9. doi: 10.1016/j.arcmed.2022.04.005. Online ahead of print.

ABSTRACT

AIM: We aimed at performing a situation analysis to identify challenges that Mexico’s peritoneal dialysis centers (PDCs) have faced before and during the COVID-19 pandemic.

METHODS: From May-August 2021, we conducted a cross-sectional nationwide online survey with the heads of 136 PDCs at the Mexican Institute of Social Security. The survey gathered information about PDCs characteristics and the adaptations and challenges they faced before and during the COVID-19 pandemic. The response rate to the survey was 79.5% (136 out of 171 PDCs). We used descriptive statistics to analyze the data.

RESULTS: The survey responses suggest wide variations between PDCs regarding their number of patients, healthcare staff availability, and compliance with the International Society for Peritoneal Dialysis recommendations. In the pre-pandemic period, PDCs faced staff shortages (71.3%); scarcity of supplies (39.0%); catheter dysfunctions (29.4%); poor patient adherence to peritoneal dialysis (PD) (28.6%); and lack of patient support networks (25.7%). During the pandemic, PDCs faced emergent challenges, such as losing designated PDC areas within hospitals (61.0%), and staff and supply shortages (60.2%, 41.1%, respectively) because of a reallocation of human and physical resources towards the COVID-19 response. The pandemic prompted 86.7% of PDCs to implement preventive public health measures, delay non-urgent consultations and procedures (63.6%), and introduce telemedicine (37.3%). Additionally, fewer patients visited PDCs because of their fear of COVID-19 contagion (36.0%).

CONCLUSIONS: Actions are urgently needed to ensure adherence to evidence-based PD guidelines and sufficient resources, including trained staff, supplies, and designated spaces to strengthen PDCs and provide safe and effective PD.

PMID:35527074 | DOI:10.1016/j.arcmed.2022.04.005

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Evaluation of the flexural strength of metal frameworks fabricated by sintering-based computer-aided manufacturing methods

J Prosthet Dent. 2022 May 5:S0022-3913(22)00220-7. doi: 10.1016/j.prosdent.2022.04.003. Online ahead of print.

ABSTRACT

STATEMENT OF PROBLEM: Sintering-based computer-aided metal manufacturing strategies have been proposed as an alternative to hard metal milling. While these fabrication methods have been evaluated in terms of marginal and internal discrepancies and bond strength to porcelain, limited information on metal frameworks is available regarding their flexural yield strength.

PURPOSE: The purpose of this in vitro study was to evaluate the flexural yield strength of 3-unit cobalt-chromium (Co-Cr) metal frameworks fabricated by hard metal milling (HMM), presintered soft metal milling (PSMM), and direct metal laser melting (DMLM) with 25-μm and 50-μm layer thicknesses.

MATERIAL AND METHODS: Three-unit master metal die models were prepared. A total of 40 metal frameworks (n=10) were fabricated by using HMM (group HM), PSMM (group PSM), and DMLM with 25-μm (group LM25) and 50-μm layer thicknesses (group LM50). Metal frameworks were cemented to the master die and then subjected to a 3-point bend test. The flexural yield force was used to calculate the flexural yield strength. The data were statistically analyzed (α=.05). One metal framework from each group was evaluated with scanning electron microscopy for microstructural analysis.

RESULTS: The group LM50 exhibited the lowest significant (P<.001) flexural yield strength values. The group HM exhibited higher flexural yield strength values than the other groups. No significant difference was found between the groups LM25 and PSM (P=.954) or between the groups PSM and HM (P=.111).

CONCLUSIONS: The fabrication method significantly affected the flexural yield strength of metal frameworks. Metal frameworks fabricated by DMLM with a 50-μm layer thickness exhibited considerably lower flexural yield strength values.

PMID:35527067 | DOI:10.1016/j.prosdent.2022.04.003

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Characterizing the impact of verbal communication and health literacy in the patient-surgeon encounter

Am J Surg. 2022 Apr 30:S0002-9610(22)00296-3. doi: 10.1016/j.amjsurg.2022.04.034. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with limited health literacy (HL) have difficulty understanding written/verbal information. The quality of verbal communication is not well understood. Therefore, our aim was to characterize patient-surgeon conversations and identify opportunities for improvement.

METHODS: New colorectal patient-surgeon encounters were audio-recorded and transcribed. HL was measured. Primary outcomes were rates-of-speech, understandability of words, patient-reported understanding, and usage of medical jargon/statistics. Secondary outcomes included length-of-visit (LOV), conversation possession time, patient-surgeon exchanges, and speech interruptions.

RESULTS: Significant variations existed between surgeons in rates-of-speech and understandability of words (p < 0.05). Faster rates-of-speech were associated with significantly less understandable words (p < 0.05). Patient-reported understanding varied by HL and by surgeon. Conversation possession time and usage of medical jargon/statistics varied significantly by surgeon (p < 0.05) in addition to patient-surgeon exchanges and interruptions. Patients with limited HL had shorter LOV.

CONCLUSIONS: Significant variations exist in how surgeons talk to patients. Opportunities to improve verbal communication include slowing speech and using more understandable words.

PMID:35527045 | DOI:10.1016/j.amjsurg.2022.04.034

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Neurodevelopmental outcomes of preterm infants with very low birth weight conceived with the assistance of in vitro fertilization

Fertil Steril. 2022 May 5:S0015-0282(22)00190-X. doi: 10.1016/j.fertnstert.2022.03.006. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the neurodevelopmental outcomes at 18-24 months of corrected age between preterm (<32 weeks of gestational age) infants with very low birth weight (VLBW) conceived with and without the assistance of in vitro fertilization (IVF).

DESIGN: Prospective cohort study.

SETTING: Not applicable.

PATIENT(S): In total, 4,940 infants with VLBW were born before 32 weeks of gestational age from January 2013 to December 2015.

INTERVENTION(S): In vitro fertilization.

MAIN OUTCOME MEASURE(S): Neuromotor or sensory disability (primary outcome) and developmental delay assessed using the Bayley Scales of Infant and Toddler Development (secondary outcome) at 18-24 months of corrected age.

RESULT(S): Of the 4,940 infants with VLBW enrolled, 2,818 surviving infants who were followed up for neurodevelopmental assessment at 18-24 months of corrected age were included in the study. Of these 2,818 infants, 630 (22.4%) were conceived with the assistance of IVF, and 2,188 (77.6%) were not. After adjustment for potential confounders, no statistically significant differences were found in the rate of neuromotor or sensory disability at 18-24 months of corrected age between infants conceived with and without the assistance of IVF. After excluding infants with neuromotor or sensory disability, the rate of developmental delay was also comparable between those conceived with and without the assistance of IVF.

CONCLUSION(S): This study showed comparable neurodevelopmental outcomes at 18-24 months of corrected age between preterm infants with VLBW conceived with and without the assistance of IVF.

PMID:35527036 | DOI:10.1016/j.fertnstert.2022.03.006

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Perceptions of a virtual interview process for pharmacy residents during the COVID-19 pandemic: A multisite survey of residency candidates, preceptors, and residency program directors

Am J Health Syst Pharm. 2022 May 8:zxac130. doi: 10.1093/ajhp/zxac130. Online ahead of print.

ABSTRACT

DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

PURPOSE: To describe the perceptions of residency candidates, residency practitioners (current residents and preceptors), and residency program directors (RPDs) regarding a virtual interview process for pharmacy residency programs across multiple institutions.

METHODS: In May 2021, an anonymous web-based questionnaire characterizing perceptions of the virtual interview process used during the coronavirus disease 2019 (COVID-19) pandemic was distributed to residency candidates, residency practitioners, and RPDs across 13 institutions. Quantitative responses measured on a 5-point Likert scale were summarized with descriptive statistics, and open-ended questions were analyzed using thematic qualitative methods.

RESULTS: 236 residency candidates and 253 residency practitioners/RPDs completed the questionnaire, yielding response rates of 27.8% (236 of 848), and 38.1% (253 of 663), respectively. Overall, both groups perceived the virtual interview format positively. When asked whether virtual interviews should replace in-person interviews moving forward, 60.0% (18 of 30) of RPDs indicated they agreed or strongly agreed, whereas only 30.5% (61 of 200) of current preceptors/residents and 28.7% (66 of 230) of residency candidates agreed or strongly agreed. Thematic analysis of qualitative responses revealed that while virtual interviews were easier logistically, the lack of in-person interactions was a common concern for many stakeholders. Lastly, the majority (65.0%) of residency candidates reported greater than $1,000 in savings with virtual interviews.

CONCLUSION: Virtual interviews offered logistical and financial benefits. The majority of RPDs were in favor of offering virtual interviews to replace in-person interviews, whereas the majority of residency candidates and practitioners preferred on-site interviews. As restrictions persist with the ongoing pandemic, our results provide insight into best practices for virtual pharmacy residency interviews.

PMID:35526277 | DOI:10.1093/ajhp/zxac130

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Bridging Fixed Dose to Body Weight-Based Regimen of Adalimumab in Pediatric Ulcerative Colitis Using a Pharmacometric Modeling Approach: Case Study with the Phase 3 ENVISION I Trial

J Crohns Colitis. 2022 May 8:jjac066. doi: 10.1093/ecco-jcc/jjac066. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The Phase 3 study ENVISION I demonstrated efficacy and safety of adalimumab in pediatric patients with moderate to severe ulcerative colitis. The protocol-specified high dose adalimumab regimen was numerically more efficacious than the standard dose regimen. The objective of this work was to bridge a fixed dosing regimen to the protocol-specified high induction/high maintenance body weight-based dosing regimen studied in ENVISION I, using a pharmacometrics modeling and simulation approach.

METHODS: A stepwise strategy was implemented, including developing an adalimumab pediatric population pharmacokinetic model; using this model to determine a fixed dosing regimen in pediatric ulcerative colitis patients that achieves similar concentrations to those observed in ENVISION I patients; determining adalimumab exposure-response relationship using population pharmacokinetic/pharmacodynamic model and data from ENVISION I; simulating clinical remission rate in pediatric ulcerative colitis patients using the Markov exposure-response model and the dosing regimen determined to provide similar efficacy to that observed in ENVISION I.

RESULTS: Both developed population pharmacokinetic and pharmacokinetic/pharmacodynamic models adequately described the observed data. Adalimumab exposure was identified as a significant predictor of clinical remission at Week 8 based on logistic regression (p <0.01). Simulated efficacy suggested that the fixed dosing regimen performs similarly to the more efficacious dosing regimen used in ENVISION I by providing comparable clinical remission per Partial Mayo Score response rates over time. No relationship between adalimumab exposure and adverse events was identified.

CONCLUSIONS: The population pharmacokinetic/pharmacodynamic model supports the appropriateness of the use of fixed dosing regimen in the pediatric ulcerative colitis population.

PMID:35526272 | DOI:10.1093/ecco-jcc/jjac066

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Gene expression analysis of intestinal IL-8, IL-17 A and IL-10 in patients with celiac and inflammatory bowel diseases

Mol Biol Rep. 2022 May 8. doi: 10.1007/s11033-022-07397-y. Online ahead of print.

ABSTRACT

BACKGROUND: Celiac disease (CeD) and inflammatory bowel disease (IBD) are accompanied by impaired immune responses. To study the immune regulation of these diseases, we evaluated the expression levels of pro-inflammatory (IL-8 and IL-17 A) and anti-inflammatory (IL-10) cytokines in intestinal biopsy specimens of CeD and IBD patients in comparison to healthy subjects.

METHODS AND RESULTS: Intestinal biopsies were collected from 33 patients with IBD, 47 patients with CeD, and 20 healthy individuals. Total RNA was extracted and mRNA expression levels of IL-8, IL-17 A and IL-10 were assessed by qPCR. P-value < 0.05 was considered statistically significant. The expression levels of IL-8 and IL-17 A were higher in biopsies of IBD (UC and CD) and CeD patients compared to the control group (P < 0.05). IBD patients (UC and CD) had higher IL-8 intestinal level than CeD patients (P < 0.0001 and P = 0.0007, respectively). The expression of IL-10 was significantly down-regulated in intestinal biopsies of CeD and IBD patients compared with controls (P < 0.001). In addition, the expression level of this cytokine was significantly lower in IBD patients (P < 0.001 for UC patients and P < 0.0001 for CD patients) than CeD group.

CONCLUSIONS: The three selected pro- and anti-inflammatory cytokines showed a similar expression pattern in both IBD and CeD patients. As IBD and CeD are immune-mediated disorders and are accompanied by inflammatory events, the understanding of the similarities and differences among them can help researchers to find out useful candidate therapeutic protocols. We suggest that larger cohort studies be organized to achieve more insights into this regulation.

PMID:35526253 | DOI:10.1007/s11033-022-07397-y