Adherence to single inhaler triple therapy and digital inhalers in Chronic Obstructive Pulmonary Disease: a literature review and protocol for a randomized controlled trial (TRICOLON study).

BACKGROUND: Medication non-adherence is a significant problem in patients with Chronic Obstructive Pulmonary Disease (COPD). Efforts to address this issue are receiving increased attention. Simplifying treatment by prescribing single-inhaler triple therapy (SITT) as an alternative to multi-inhaler triple therapy (MITT) or with smart inhalers are often considered potential solutions. However, the actual impact of these innovations on adherence and clinical outcomes is unclear. METHODS: To address this knowledge gap we first conducted a literature review focusing on two research questions: 1) the difference in adherence between SITT and MITT users in COPD, and 2) the effect of smart inhalers on adherence in COPD. Separate searches were conducted in PubMed and two authors independently assessed the articles. In addition, we present a protocol for a study to acquire knowledge for the gaps identified. RESULTS: To address the first research question, 8 trials were selected for further review. All trials were observational, i.e. randomized controlled trials were lacking. Seven of these trials showed higher adherence and/or persistence in patients on SITT compared with patients on MITT. In addition, four studies showed a positive effect of SITT on various clinical outcomes. For the second research question, 11 trials were selected for review. While most of the studies showed a positive effect of smart inhalers on adherence, there was considerable variation in the results regarding their effect on other clinical outcomes. The TRICOLON (TRIple therapy COnvenience by the use of one or multipLe Inhalers and digital support in ChrONic Obstructive Pulmonary Disease) trial aims to improve understanding regarding the effectiveness of SITT and smart inhalers in enhancing adherence. This open-label, randomized, multi-center study will enroll COPD patients requiring triple therapy at ten participating hospitals. In total, 300 patients will be randomized into three groups: 1) MITT; 2) SITT; 3) SITT with digital support through a smart inhaler and an e-health platform. The follow-up period will be one year, during which three methods of measuring adherence will be used: smart inhaler data, self-reported data using the Test of Adherence to Inhalers (TAI) questionnaire, and drug analysis in scalp hair samples. Finally, differences in clinical outcomes between the study groups will be compared. DISCUSSION: Our review suggests promising results concerning the effect of SITT, as opposed to MITT, and smart inhalers on adherence. However, the quality of evidence is limited due to the absence of randomized controlled trials and/or the short duration of follow-up in many studies. Moreover, its impact on clinical outcomes shows considerable variation. The TRICOLON trial aims to provide solid data on these frequently mentioned solutions to non-adherence in COPD. Collecting data in a well-designed randomized controlled trial is challenging, but the design of this trial addresses both the usefulness of SITT and smart inhalers while ensuring minimal interference in participants' daily lives. TRIAL REGISTRATION: NCT05495698 (Clinicaltrials.gov), registered at 08-08-2022. Protocol version: version 5, date 27-02-2023.

Production and Characterization of Nanocellulose from Maguey (Agave cantala) Fiber.

Plant fibers have been studied as sources of nanocellulose due to their sustainable features. This study investigated the effects of acid hydrolysis parameters, reaction temperature, and acid concentration on nanocellulose yield from maguey (Agave cantala) fiber. Nanocellulose was produced from the fibers via the removal of non-cellulosic components through alkali treatment and bleaching, followed by strong acid hydrolysis for 45 min using sulfuric acid (H2SO4). The temperature during acid hydrolysis was 30, 40, 50, and 60 °C, and the H2SO4 concentration was 40, 50, and 60 wt. % H2SO4. Results showed that 53.56% of raw maguey fibers were isolated as cellulose, that is, 89.45% was α-cellulose. The highest nanocellulose yield of 81.58 ± 0.36% was achieved from acid hydrolysis at 50 °C using 50 wt. % H2SO4, producing nanocellulose measuring 8-75 nm in diameter and 72-866 nm in length, as confirmed via field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) analysis. Fourier-transform infrared spectroscopy (FTIR) analysis indicated the chemical transformation of fibers throughout the nanocellulose production process. The zeta potential analysis showed that the nanocellulose had excellent colloidal stability with a highly negative surface charge of -37.3 mV. Meanwhile, X-ray diffraction (XRD) analysis validated the crystallinity of nanocellulose with a crystallinity index of 74.80%. Lastly, thermogravimetric analysis (TGA) demonstrated that the inflection point attributed to the cellulose degradation of the produced nanocellulose is 311.41 °C.

High refill-adherence to adalimumab is associated with low disease activity in patients with inflammatory bowel disease.

PURPOSE: Adalimumab has evolved to one of the more affordable first-line biologics for the treatment of inflammatory bowel disease (IBD), since its patent expired. However, poor adherence to adalimumab is a concern and may limit its effectiveness. It is plausible that good adherence improves treatment outcomes in IBD patients, but evidence is scarce. The aim of this study was to assess whether high refill-adherence (medication possession ratio (MPR) ≥ 80%) to adalimumab is associated with less active disease in IBD patients. METHODS: In this retrospective study, the MPR was used to assess refill-adherence of IBD patients using adalimumab. Disease activity was defined as a composite endpoint determined by endoscopy findings, laboratory results, validated questionnaires and clinical assessment by a gastroenterologist. Logistic regression was used to determine the association between high refill-adherence (MPR ≥ 80%) and disease activity. RESULTS: IBD was in remission in 72 of the 113 included patients and 41 had active disease at the time of the most recent prescription. Out of the patients who were in remission, 86.1% were adherent vs. 75.6% in patients with active disease. High refill-adherence was significantly associated with lower odds of active disease after adjustment for confounders: adjusted odds ratio 0.297, 95% confidence interval 0.099-0.892. CONCLUSION: High refill-adherence to adalimumab therapy was associated with less active disease in IBD patients. Our results confirm the relevance of good adherence to adalimumab for achieving optimal treatment results, which may limit the need for switching to more expensive biologics.

A review of antibody, aptamer, and nanomaterials synergistic systems for an amplified electrochemical signal.

The synergy between biomolecules with inorganic nanomaterials and nanoparticles has been investigated over the past years, primarily to improve biomarker reception, generate signals, and amplify the signals generated. In this paper, several articles on aptamer-based and antibody-based electrochemical biosensors that target antigens were examined. Among the key characteristics identified were the electrochemical platform development, which includes the usage of nanomaterials as electroactive or electrocatalytic labels, crosslinking of the biological agent with inorganic compounds, and electrode coating to provide an electronic source and support efficient electron transfer. A single approach using labeled or unlabeled biological receptors has become advantageous due to its simple architecture and more straightforward application method. However, the dual system approach allows the incorporation of more nanomaterials to boost the signal and add more features to the electrochemical system. The dual system approach uses a capture and reporter probe in a competitive or sandwich detection format. The reporter probe is often labeled by an electroactive or electrocatalytic compound or immobilized in a nanocarrier, resulting in an increase in measured peak current in proportion to the target's concentration. The reported limit of detection and linear range for each platform is presented to assess its efficiency. Generally, the dual system aptasensor showed higher sensitivity, stability, and reproducibility than the immunosensor in comparable settings. The aptasensor showed promising results for the development of point-of-care type applications.

The sodium does not affect joint pain and functional activity of knee osteoarthritis patients.

Background: The sodium may aggravate synovial inflammation and cartilage thinning. This incidence can cause joint pain and reduce functional activity. Not many people know the effect of sodium on the incidence of osteoarthritis. Objective: This study aims to determine the relationship between sodium in the body and knee joint pain which results in functional activity. Methods: The quantitative descriptive study used accidental sampling. The study was conducted at three outpatient polyclinic orthopedics of hospitals and was approved by the Health Ethics Committee. All data were collected during the interview. The Semi-Quantitative Food Frequency Questionnaire and the Nutrisurvey Indonesia 2007 application were used as a tool to collect daily sodium intake (mg). Knee joint pain score was measured using the Visual Analog Scale (VAS), while functional body activity was measured using the Western Ontario McMaster Osteoarthritis Index (WOMAC). The Pearson and Spearman test (P<0.05) were used as a correlation test. Results: 80 subjects were recruited according to the inclusion criteria. Characteristics of the subjects were pre-elderly (32, 40%), women (74, 92.5%), body mass index ≥30 kg/m2 (54, 67.5%) and occupation (43, 53.75%). Average sodium intake = 2090.78±1084.33 mg, VAS score = 6.28±1.95 and WOMAC score = 32.65±14.88. The correlation sodium, VAS, and WOMAC were not significant (P=0.196, P=0.372). Conclusions: Increased sodium intake is not associated with knee joint pain and functional body activity.

Large-mode-area soliton fiber oscillator mode-locked using NPE in an all-PM self-stabilized interferometer.

In this work, we investigate an approach to scale up the output pulse energy in an all-polarization-maintaining 17.3 MHz Yb-doped fiber oscillator via implementation of a 25 µm core-diameter large-mode-area fiber. The artificial saturable absorber is based on a Kerr-type linear self-stabilized fiber interferometer, enabling non-linear polarization rotation in polarization-maintaining fibers. Highly stable mode-locked steady states in the soliton-like operation regime are demonstrated with 170 mW average output power and a total output pulse energy of ∼10n J distributed between two output ports. An experimental parameter comparison with a reference oscillator constructed with 5.5 µm core-sized standard fiber components reveals an increase of pulse energy by a factor of 36 with simultaneously reduced intensity noise in the high-frequency range >100k H z.

What Are the Predictors of Self-Reported Change in Physical Activity in Older Adults with Knee or Hip Osteoarthritis?

BACKGROUND: Although physical activity (PA) has been shown to be beneficial in older adults with osteoarthritis (OA), most show low levels of PA. This study evaluated if self-efficacy, attitude, social norm, and coping styles predicted change in PA in older adults with OA in the knee and/or hip. METHODS: Prospective study following 105 participants in a self-management intervention with baseline, post-test (6 weeks), and follow-up (6 months). Univariate associations and multivariate regression with self-reported change in PA as the dependent variable were measured. Potential predictors in the model: demographic, illness-related, and behavioral variables (attitude, self-efficacy, social norm, and intention), coping style, and pain coping. RESULTS: Forty-eight percent of participants reported increased PA at 6 weeks and 37% at 6 months which corresponded with registered PA levels. At 6 weeks, use of the pain coping style "resting," intention, and participation in the intervention was univariately and multivariately, positively associated with more self-reported change, whereas being single and less use of the pain coping style "distraction" predicted less change. Higher pain severity only predicted less change multivariately. At 6 months, univariate associations for age, general coping style "seeking support," and participation in the intervention were found; higher age was associated multivariately with less self-reported change. CONCLUSION: At short term, self-reported change of PA was predicted by the behavioral factors intention and several pain coping styles. Together with other predictors of self-reported change (pain severity, higher age, being single), these could be addressed in future interventions for enhancing PA in older adults with OA.

The Aer2 chemoreceptor from Vibrio vulnificus is a tri-PAS-heme oxygen sensor.

The marine pathogen Vibrio vulnificus senses and responds to environmental stimuli via two chemosensory systems and 42-53 chemoreceptors. Here, we present an analysis of the V. vulnificus Aer2 chemoreceptor, VvAer2, which is the first V. vulnificus chemoreceptor to be characterized. VvAer2 is related to the Aer2 receptors of other gammaproteobacteria, but uncharacteristically contains three PAS domains (PAS1-3), rather than one or two. Using an E. coli chemotaxis hijack assay, we determined that VvAer2, like other Aer2 receptors, senses and responds to O2 . All three VvAer2 PAS domains bound pentacoordinate b-type heme and exhibited similar O2 affinities. PAS2 and PAS3 both stabilized O2 via conserved Iß-Trp residues, but PAS1, which was easily oxidized in vitro, was unaffected by Iß-Trp replacement. Our results support a model in which PAS1 is largely dispensable for O2 -mediated signaling, whereas PAS2 modulates PAS3 signaling, and PAS3 signals to the downstream domains. Each PAS domain appeared to be positionally optimized, because PAS swapping caused altered signaling properties, and neither PAS1 nor PAS2 could replace PAS3. Our findings strengthen previous conclusions that Aer2 receptors are O2 sensors, but with distinct N-terminal domain arrangements that facilitate, modulate and tune responses based on environmental signals.

Comparison of Low-Value Services Among Medicare Advantage and Traditional Medicare Beneficiaries.

Importance: Low-value care in the Medicare program is prevalent, costly, potentially harmful, and persistent. Although Medicare Advantage (MA) plans can use managed care strategies not available in traditional Medicare (TM), it is not clear whether this flexibility is associated with lower rates of low-value care. Objectives: To compare rates of low-value services between MA and TM beneficiaries and explore how elements of insurance design present in MA are associated with the delivery of low-value care. Design, Setting, and Participants: This cross-sectional study analyzed beneficiaries enrolled in MA and TM using claims data from a large, national MA insurer and a random 5% sample of TM beneficiaries. The study period was January 1, 2017, through December 31, 2019. All analyses were conducted from July 2021 to March 2022. Exposures: Enrollment in MA vs TM. Main Outcomes and Measures: Low-value care was assessed using 26 claims-based measures. Regression models were used to estimate the association between MA enrollment and rates of low-value services while controlling for beneficiary characteristics. Stratified analyses explored whether network design, product design, value-based payment, or utilization management moderated differences in low-value care between MA and TM beneficiaries and among MA beneficiaries. Results: Among a study population of 2 470 199 Medicare beneficiaries (mean [SD] age, 75.6 [7.0] years; 1 346 777 [54.5%] female; 229 107 [9.3%] Black and 2 126 353 [86.1%] White individuals), 1 527 763 (61.8%) were enrolled in MA and 942 436 (38.2%) were enrolled in TM. Beneficiaries enrolled in MA received 9.2% (95% CI, 8.5%-9.8%) fewer low-value services in 2019 than TM beneficiaries (23.1 vs 25.4 total low-value services per 100 beneficiaries). Although MA beneficiaries enrolled in health management organization and preferred provider organization products received fewer low-value services than TM beneficiaries, the difference was largest for those enrolled in health management organization products (2.6 fewer [95% CI, 2.4-2.8] vs 2.1 fewer [95% CI, 1.9-2.3] services per 100 beneficiaries, respectively). Across primary care payment arrangements, MA beneficiaries received fewer low-value services than TM beneficiaries, with the largest difference observed for MA beneficiaries whose primary care physicians were reimbursed within 2-sided risk arrangements. Conclusions and Relevance: In this cross-sectional study of Medicare beneficiaries, those enrolled in MA had lower rates of low-value care than those enrolled in TM; elements of insurance design present in the MA program and absent in TM were associated with reduction in low-value care.

Comparison of Health Care Utilization by Medicare Advantage and Traditional Medicare Beneficiaries With Complex Care Needs.

Importance: Medicare beneficiaries with co-occurring chronic conditions and complex care needs experience high rates of acute care utilization and poor outcomes. These patterns are well described among traditional Medicare (TM) beneficiaries, but less is known about outcomes among Medicare Advantage (MA) beneficiaries. Compared with TM, MA plans have additional levers to potentially address beneficiary needs, such as network design, care management, supplemental benefits, and value-based contracting. Objective: To compare health care utilization for MA and TM beneficiaries with complex care needs. Design, Setting, and Participants: This cross-sectional study analyzed beneficiaries enrolled in MA and TM using claims data from a large, national MA insurer and a random 5% sample of TM beneficiaries. Beneficiaries were segmented into the following cohorts: frail elderly, major complex chronic, and minor complex chronic. Regression models estimated the association between MA enrollment and health care utilization in 2018, using inverse probability of treatment weighting to balance the MA and TM cohorts on observable characteristics. The study period was January 1, 2017, through December 31, 2018. All analyses were conducted from December 2020 to August 2022. Exposures: Enrollment in MA vs TM. Main Outcomes and Measures: Hospital stays (inpatient admissions and observation stays), emergency department (ED) visits, and 30-day readmissions. Results: Among a study population of 1 844 326 Medicare beneficiaries (mean [SD] age, 75.6 [7.1] years; 1 021 479 [55.4%] women; 1 524 458 [82.7%] White; 223 377 [12.1%] with Medicare-Medicaid dual eligibility), 1 177 896 (63.9%) were enrolled in MA and 666 430 (36.1%) in TM. Beneficiary distribution across cohorts was as follows: frail elderly, 116 047 with MA (10.0% of the MA sample) and 104 036 with TM (15.6% of the TM sample); major complex chronic, 320 954 (27.2%) and 158 811 (23.8%), respectively; and minor complex chronic, 740 895 (62.9%) and 403 583 (60.6%), respectively. Beneficiaries enrolled in MA had lower rates of hospital stays, ED visits, and 30-day readmissions. The largest relative differences were observed for hospital stays, which ranged from -9.3% (95% CI, -10.9% to -7.7%) for the frail elderly cohort to -11.9% (95% CI, -13.2% to -10.7%) for the major complex chronic cohort. Conclusions and Relevance: In this cross-sectional study of Medicare beneficiaries with complex care needs, those enrolled in MA had lower rates of hospital stays, ED visits, and 30-day readmissions than similar beneficiaries enrolled in TM, suggesting that managed care activities in MA may influence the nature and quality of care provided to these beneficiaries.

Hydroxypicolinic acid tethered on magnetite core-silica shell (HPCA@SiO2@Fe3O4) as an effective and reusable adsorbent for practical Co(II) recovery.

The soaring demand and future supply risk for cobalt (Co) necessitate more efficient adsorbents for its recycling from electronic wastes, as a cheaper and less hazardous option for its production. Herein, a magnetic adsorbent covalently tethered with 5-hydroxypicolinic acid (HPCA) as Co(II) ligand was developed. The magnetic component (Fe3O4) was protected with silica (SiO2), then silanized with chloroalkyl linker and subsequently functionalized with HPCA via SN2 nucleophilic substitution (HPCA@SiO2@Fe3O4). Results from FTIR, TGA, EA, and XPS confirm the successful adsorbent preparation with high HPCA loading of 2.62 mmol g-1. TEM-EDS reveal its imperfect spherical morphology with ligands well-distributed on its surface. HPCA@SiO2@Fe3O4 is hydrophilic, water-dispersible and magnetically retrievable, which is highly convenient for its recovery. The Co(II) capture on HPCA@SiO2@Fe3O4 involves monodentate coordination with carboxylate (COO-) and lone pair acceptance from pyridine (aromatic -N = ) moiety of HPCA, with minor interaction from acidic silanols (Si-O-). The binding occurs at 2 HPCA: 1 Co(II) ratio, that follows the Sips isotherm model with competitive Qmax = 92.35 mg g-1 and pseudo-second order kinetics (k2 = 0.0042 g mg-1 min-1). In a simulated LIB liquid waste, HPCA@SiO2@Fe3O4 preferentially captures Co(II) over Li(I) with αLi(I)Co(II)=166 and Mn(II) with αMn(II)Co(II)=55, which highlights the importance of HPCA for Co(II) recovery. Silica protection of Fe3O4 rendered the adsorbent chemically stable in acidic thiourea solution for its regeneration by preventing the deterioration of the magnetic component. Covalent functionalization averted ligand loss, which allowed HPCA@SiO2@Fe3O4 to deliver consistent and reversible adsorption/desorption performance. Overall results demonstrate the potential of HPCA@SiO2@Fe3O4 as a competitive and practical adsorbent for Co(II) recovery in liquid waste sources.

Short-term exposure to an obesogenic diet during adolescence elicits anxiety-related behavior and neuroinflammation: modulatory effects of exogenous neuregulin-1.

Childhood obesity leads to hippocampal atrophy and altered cognition. However, the molecular mechanisms underlying these impairments are poorly understood. The neurotrophic factor neuregulin-1 (NRG1) and its cognate ErbB4 receptor play critical roles in hippocampal maturation and function. This study aimed to determine whether exogenous NRG1 administration reduces hippocampal abnormalities and neuroinflammation in rats exposed to an obesogenic Western-like diet (WD). Lewis rats were randomly divided into four groups (12 rats/group): (1) control diet+vehicle (CDV); (2) CD + NRG1 (CDN) (daily intraperitoneal injections: 5 µg/kg/day; between postnatal day, PND 21-PND 41); (3) WD + VEH (WDV); (4) WD + NRG1 (WDN). Neurobehavioral assessments were performed at PND 43-49. Brains were harvested for MRI and molecular analyses at PND 49. We found that NRG1 administration reduced hippocampal volume (7%) and attenuated hippocampal-dependent cued fear conditioning in CD rats (56%). NRG1 administration reduced PSD-95 protein expression (30%) and selectively reduced hippocampal cytokine levels (IL-33, GM-CSF, CCL-2, IFN-γ) while significantly impacting microglia morphology (increased span ratio and reduced circularity). WD rats exhibited reduced right hippocampal volume (7%), altered microglia morphology (reduced density and increased lacunarity), and increased levels of cytokines implicated in neuroinflammation (IL-1α, TNF-α, IL-6). Notably, NRG1 synergized with the WD to increase hippocampal ErbB4 phosphorylation and the tumor necrosis alpha converting enzyme (TACE/ADAM17) protein levels. Although the results did not provide sufficient evidence to conclude that exogenous NRG1 administration is beneficial to alleviate obesity-related outcomes in adolescent rats, we identified a potential novel interaction between obesogenic diet exposure and TACE/ADAM17-NRG1-ErbB4 signaling during hippocampal maturation. Our results indicate that supraoptimal ErbB4 activities may contribute to the abnormal hippocampal structure and cognitive vulnerabilities observed in obese individuals.

Hyper-crosslinked tetraphenylborate as a regenerable sorbent for Cs+ sequestration in aqueous media through cation-π interactions.

Practical adsorbents that could efficiently collect radioactive Cesium (Cs+) are critically important in achieving proper management and treatment measures for nuclear wastes. Herein, a hyper-crosslinked tetraphenylborate-based adsorbent (TPB-X) was prepared by reacting TPB anions as Cs+ binding sites with dimethoxymethane (DMM) as crosslinker. The most efficient TPB-X synthesis was attained at 1:4 TPB/DMM mole ratio with sorbent yield of 81.75%. Various techniques such as FTIR, TGA-DTG, N2 adsorption/desorption and SEM-EDS reveal that TPB-X is a water-insoluble, thermally stable and highly porous granular sorbent. Its hierarchical pore structure explains its very high BET surface area (1030 m2 g-1). Sequestration of Cs+ by TPB-X involves its exchange with H+ followed by its binding with the phenyl rings of TPB through cation-π interactions. The Cs+ adsorption in TPB-X is endothermic and spontaneous, which adheres to the Hill isotherm model (qm = 140.58 mg g-1) and follows pseudo-second order kinetics (k2 = 0.063 g mg-1 h-1). Calculations from the density functional theory reveal that the binding of TPB anion is strongest for Cs+. Thus, TPB-X was able to selectively capture Cs+ in simulated surface water containing Na+, K+, Mg2+, and Ca2+ and in HLLW containing Na+, Rb+, Sr2+, and Ba2+. Hyper-crosslinking was found beneficial in rendering TPB-X reusable as the sorbent was easily retrieved from the feed after Cs+ capture and was able to withstand the acid treatment for its regeneration. TPB-X exhibited consistent performance with no sign of chemical or physical deterioration. TPB-X offers a practical approach in handling Cs+ contaminated streams as it can be repeatedly used to enrich Cs+ in smaller volume of media, which can then be purified for Cs+ reuse or stored for long-term natural Cs+ decay process.

Long-read sequencing-based in silico phage typing of vancomycin-resistant Enterococcus faecium.

BACKGROUND: Vancomycin-resistant enterococci (VRE) are successful nosocomial pathogens able to cause hospital outbreaks. In the Netherlands, core-genome MLST (cgMLST) based on short-read sequencing is often used for molecular typing. Long-read sequencing is more rapid and provides useful information about the genome's structural composition but lacks the precision required for SNP-based typing and cgMLST. Here we compared prophages among 50 complete E. faecium genomes belonging to different lineages to explore whether a phage signature would be usable for typing and identifying an outbreak caused by VRE. As a proof of principle, we investigated if long-read sequencing data would allow for identifying phage signatures and thereby outbreak-related isolates. RESULTS: Analysis of complete genome sequences of publicly available isolates showed variation in phage content among different lineages defined by MLST. We identified phage present in multiple STs as well as phages uniquely detected within a single lineage. Next, in silico phage typing was applied to twelve MinION sequenced isolates belonging to two different genetic backgrounds, namely ST117/CT24 and ST80/CT16. Genomic comparisons of the long-read-based assemblies allowed us to correctly identify isolates of the same complex type based on global genome architecture and specific phage signature similarity. CONCLUSIONS: For rapid identification of related VRE isolates, phage content analysis in long-read sequencing data is possible. This allows software development for real-time typing analysis of long-read sequencing data, which will generate results within several hours. Future studies are required to assess the discriminatory power of this method in the investigation of ongoing outbreaks over a longer time period.

The Management of Pulmonary Fibrosis in COVID-19.

Pulmonary fibrosis due to COVID-19 is recognized as sequel of ARDS characterized by failed alveolar re-epithelization, fibroblast activation, excessive collagen deposition and other extracellular matrix components that disrupt the normal lung architecture. There are risk factor for pulmonary fibrosis namely advanced age, severe ARDS infection, mechanical ventilation due to ventilator-induced lung injury, smoking and chronic alcoholism. Diagnosis of post-COVID pulmonary fibrosis can be made by clinical symptoms and characteristic finding from lung CT scan. To date, there is no definitive treatment for post-inflammatory pulmonary fibrosis after COVID-19 infection, however some of antifibrotic therapies may be considered. Beside medical treatment, pulmonary rehabilitation program and long-term oxygen treatment should be included as part of comprehensive treatment for pulmonary fibrosis due to COVID-19.

When face masks signal social identity: Explaining the deep face-mask divide during the COVID-19 pandemic.

With the COVID-19 pandemic still raging and the vaccination program still rolling out, there continues to be an immediate need for public health officials to better understand the mechanisms behind the deep and perpetual divide over face masks in America. Using a random sample of Americans (N = 615), following a pre-registered experimental design and analysis plan, we first demonstrated that mask wearers were not innately more cooperative as individuals than non-mask wearers in the Prisoners' Dilemma (PD) game when information about their own and the other person's mask usage was not salient. However, we found strong evidence of in-group favouritism among both mask and non-mask wearers when information about the other partner's mask usage was known. Non-mask wearers were 23 percentage points less likely to cooperate than mask wearers when facing a mask-wearing partner, and 26 percentage points more likely to cooperate than mask wearers when facing a non-mask-wearing partner. Our analysis suggests social identity effects as the primary reason behind people's decision whether to wear face masks during the pandemic.

CHECKLIST USE FOR ASSESSMENT OF SATISFACTION WITH TRANS-TIBIAL PROSTHESES.

OBJECTIVE: To assess satisfaction of prosthesis users with their prostheses, and the problems they experience with the residual limb, using a checklist, in order to evaluate potential benefits of checklist use and to summarize issues and problems with the prosthesis and/or residual limb presented by prosthesis users. DESIGN: Cross-sectional study. SUBJECTS: Participants were adult trans-tibial prosthesis users (n = 82) and certified prosthetist orthotist (n = 19) experienced in fitting lower-limb prostheses. METHODS: Prosthesis users reported their reasons for consultation and factors concerning prosthesis (dis)satisfaction and residual limb problems, using a checklist. Checklist use was evaluated by certified prosthetist orthotists and prosthesis users and the significance of evaluation scores was determined. RESULTS: Checklist use identified 126 issues/problems, most of which concerned prosthesis fit (33%) and pressure points on the residual limb skin (26%). Evaluation scores were significantly higher than neutral regarding the checklist helping the certified prosthetist orthotist to gather more information and to make clear with which issues the prosthesis user was dissatisfied. Prosthesis users reported that checklist use made them feel more understood by the certified prosthetist orthotist. CONCLUSION: Checklist use in the assessment of trans-tibial prostheses is beneficial in identifying factors related to dissatisfaction, and improves the quality of certified prosthetist orthotists' consultation. The implementation of checklist use is, however, challenging.

Opinions on rehabilitation care of young adults with transversal upper limb reduction deficiency in their transition to adulthood.

PURPOSE: Young adults with transversal upper limb reduction deficiency experience limitations regarding education, employment and obtaining a driver's license. Contribution of rehabilitation care within these domains has been reported to be inadequate. This study evaluates the needs and suggestions of participants in rehabilitation care. METHODS: Two online focus groups with young adults and parents met during 4 consecutive days. Health care professionals joined a face-to-face focus group. Data analysis was based on framework analysis. RESULTS: The rehabilitation team was mainly consulted for problems with residual limb or for prostheses. Young adults and their parents were mostly unaware of resources regarding education, job selection or obtaining a driver's license. Professionals stated that these subjects were addressed during periodic appointments. Young adults didn't always attend these appointments due to limited perceived benefit. To improve rehabilitation care, participants suggested methods for providing relevant information, facilitating peer contact and offering dedicated training programs to practice work-related tasks, prepare for job interviews or enhance self-confidence. CONCLUSION: Periodic appointments do not fulfil needs of young adults with transversal upper limb reduction deficiency. To improve care, rehabilitation teams should offer age-relevant information, share peer stories, and create dedicated training programs.

PAS domains in bacterial signal transduction.

PAS domains are widespread, versatile domains found in proteins from all kingdoms of life. The PAS fold is composed of an antiparallel ß-sheet with several flanking α-helices, and contains a conserved cleft for cofactor or ligand binding. The last few years have seen a prodigious increase in identified PAS domains and resolved PAS structures, including structures with effector and other domains. New bacterial PAS ligands have been discovered, and structure-function studies have improved our understanding of PAS signaling mechanisms. The list of bacterial PAS functions has now expanded to include roles in signal sensing, modulation, transduction, dimerization, protein interaction, and cellular localization.

The Management of Cytokine Storm in COVID-19.

Cytokine storm in COVID-19 infection is an excessive immune response to external stimuli where the pathogenesis is complex. The disease progresses rapidly and the mortality is high. Certain evidence shows that the severe deterioration of some patients has been closely related to the strong upregulation of cytokine production in SARS-Co-V2 induced pneumonia with an associated cytokine storm syndrome. Identification of existing approaved therapy with proven safety profile to treat hyperinflammation is critical unmet need in order to reduce COVID-19 associated mortality. To date, no specific therapeutic drugs are available to treat COVID-19 infection. Preliminary studies have shown that immune-modulatory or immune suppressive treatments might be considered as treatment choices for COVID-19, particularly in severe disease. This article review the pathogenesis and treatment strategies of COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.