pH-dependent water permeability switching and its memory in MoS2 membranes.

Intelligent transport of molecular species across different barriers is critical for various biological functions and is achieved through the unique properties of biological membranes1-4. Two essential features of intelligent transport are the ability to (1) adapt to different external and internal conditions and (2) memorize the previous state5. In biological systems, the most common form of such intelligence is expressed as hysteresis6. Despite numerous advances made over previous decades on smart membranes, it remains a challenge to create a synthetic membrane with stable hysteretic behaviour for molecular transport7-11. Here we demonstrate the memory effects and stimuli-regulated transport of molecules through an intelligent, phase-changing MoS2 membrane in response to external pH. We show that water and ion permeation through 1T' MoS2 membranes follows a pH-dependent hysteresis with a permeation rate that switches by a few orders of magnitude. We establish that this phenomenon is unique to the 1T' phase of MoS2, due to the presence of surface charge and exchangeable ions on the surface. We further demonstrate the potential application of this phenomenon in autonomous wound infection monitoring and pH-dependent nanofiltration. Our work deepens understanding of the mechanism of water transport at the nanoscale and opens an avenue for the development of intelligent membranes.

Determinants of Staff Intent to Leave Health Care During the COVID-19 Pandemic.

Objectives. To identify potential drivers of health care worker attrition. Methods. We conducted a survey of 1083 nonphysician health care workers in a large urban health system in New York City from September to October 2022. Results. The results of a multivariable logistic regression analysis revealed that higher odds of intending to leave health care were significantly associated with male gender, registered nurse profession, burnout, self-perceived mental health service need, and verbal abuse from patients or visitors, whereas lower odds were seen among those reporting greater emotional well-being and a better workplace culture. A relative importance analysis indicated that burnout was the strongest correlate of intention to leave (22.5% relative variance explained [RVE]), followed by subjective emotional well-being (16.7% RVE), being a registered nurse (12.3% RVE), poorer perceived workplace culture (9.5% RVE), and male gender (5.9% RVE). Conclusions. Overall, our findings suggest the need for well-coordinated interventions that address both individual- and system-level factors in an effort to improve retention. Public Health Implications. Our results indicate a need for interventions targeting workplace culture, staff burnout, and mental health service provision. (Am J Public Health. 2024;114(S2):S200-S203. https://doi.org/10.2105/AJPH.2024.307574).

Population-based analysis of POT1 variants in a cutaneous melanoma case-control cohort.

Pathogenic germline variants in the protection of telomeres 1 gene (POT1) have been associated with predisposition to a range of tumour types, including melanoma, glioma, leukaemia and cardiac angiosarcoma. We sequenced all coding exons of the POT1 gene in 2928 European-descent melanoma cases and 3298 controls, identifying 43 protein-changing genetic variants. We performed POT1-telomere binding assays for all missense and stop-gained variants, finding nine variants that impair or disrupt protein-telomere complex formation, and we further define the role of variants in the regulation of telomere length and complex formation through molecular dynamics simulations. We determine that POT1 coding variants are a minor contributor to melanoma burden in the general population, with only about 0.5% of melanoma cases carrying germline pathogenic variants in this gene, but should be screened in individuals with a strong family history of melanoma and/or multiple malignancies.

EuroGuiderm guideline on lichen sclerosus-introduction into lichen sclerosus.

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness. It may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are redness and oedema, typically followed by whitening of the genital skin; sometimes fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS, highlight important aspects in the care of LS patients (part 1), generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

EuroGuiderm guideline on lichen sclerosus-Treatment of lichen sclerosus.

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness; it may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are usually a whitening of the genital skin, sometimes preceded by redness and oedema; fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS (part 1), highlight important aspects in the care of LS patients, generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

Measurement of Direct-Photon Cross Section and Double-Helicity Asymmetry at sqrt[s]=510 GeV in p[over →]+p[over →] Collisions.

We present measurements of the cross section and double-helicity asymmetry A_{LL} of direct-photon production in p[over →]+p[over →] collisions at sqrt[s]=510 GeV. The measurements have been performed at midrapidity (|η|<0.25) with the PHENIX detector at the Relativistic Heavy Ion Collider. At relativistic energies, direct photons are dominantly produced from the initial quark-gluon hard scattering and do not interact via the strong force at leading order. Therefore, at sqrt[s]=510 GeV, where leading-order-effects dominate, these measurements provide clean and direct access to the gluon helicity in the polarized proton in the gluon-momentum-fraction range 0.02

Low Body Mass Index at Treatment Initiation and Rifampicin-Resistant Tuberculosis Treatment Outcomes: An Individual Participant Data Meta-Analysis.

BACKGROUND: The impact of low body mass index (BMI) at initiation of rifampicin-resistant tuberculosis (RR-TB) treatment on outcomes is uncertain. We evaluated the association between BMI at RR-TB treatment initiation and end-of-treatment outcomes. METHODS: We performed an individual participant data meta-analysis of adults aged ≥18 years with RR-TB whose BMI was documented at treatment initiation. We compared odds of any unfavorable treatment outcome, mortality, or failure/recurrence between patients who were underweight (BMI <18.5 kg/m2) and not underweight. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using logistic regression, with matching on demographic, clinical, and treatment-related factors. We evaluated effect modification by human immunodeficiency virus (HIV) status and other variables using likelihood ratio tests. We also estimated cumulative incidence of mortality during treatment stratified by HIV. RESULTS: Overall, 5148 patients were included; 1702 (33%) were underweight at treatment initiation. The median (interquartile range) age was 37 years (29 to 47), and 455 (9%) had HIV. Compared with nonunderweight patients, the aOR among underweight patients was 1.7 (95% CI, 1.4-1.9) for any unfavorable outcome, 3.1 (2.4-3.9) for death, and 1.6 (1.2-2.0) for failure/recurrence. Significant effect modification was found for World Health Organization region of treatment. Among HIV-negative patients, 24-month mortality was 14.8% (95% CI, 12.7%-17.3%) for underweight and 5.6% (4.5%-7.0%) for not underweight patients. Among patients with HIV, corresponding values were 33.0% (25.6%-42.6%) and 20.9% (14.1%-27.6%). CONCLUSIONS: Low BMI at treatment initiation for RR-TB is associated with increased odds of unfavorable treatment outcome, particularly mortality.

A Specific CNOT1 Mutation Results in a Novel Syndrome of Pancreatic Agenesis and Holoprosencephaly through Impaired Pancreatic and Neurological Development.

We report a recurrent CNOT1 de novo missense mutation, GenBank: NM_016284.4; c.1603C>T (p.Arg535Cys), resulting in a syndrome of pancreatic agenesis and abnormal forebrain development in three individuals and a similar phenotype in mice. CNOT1 is a transcriptional repressor that has been suggested as being critical for maintaining embryonic stem cells in a pluripotent state. These findings suggest that CNOT1 plays a critical role in pancreatic and neurological development and describe a novel genetic syndrome of pancreatic agenesis and holoprosencephaly.

Self-management processes, sedentary behavior, physical activity and dietary self-management behaviors: impact on muscle outcomes in continuing care retirement community residents.

BACKGROUND: Despite the known benefits of non-sedentary behavior, physical activity, and protein and caloric intake to health and muscle mass, strength, and function, many older adults do not meet physical activity and dietary recommendations. A better understanding of the factors associated with sedentary behavior, physical activity and dietary self-management behaviors, and muscle outcomes (muscle mass, strength, and function) is needed, particularly among continuing care retirement community residents. The objective of this study was to examine the factors associated with sedentary behavior, physical activity and dietary self-management behaviors, and muscle outcomes among continuing care retirement community residents. It also aimed to determine whether sedentary behavior and physical activity and dietary self-management behaviors mediate the relationships between self-efficacy, goal congruence, aging expectations, social support, and muscle outcomes. METHODS: A sample of 105 continuing care retirement community residents (age > 70 years) participated in this correlational, cross-sectional study. Questionnaires on pain, self-efficacy, goal congruence, aging expectation, social support, and daily protein and caloric intake were administered. Physical activity and sedentary behavior (ActiGraph wGT3X-BT), muscle mass (ImpediMed SFB7), muscle strength (Jamar Smart Digital Hand Dynamometer), and muscle function (Short Physical Performance Battery) were measured. Multiple regression, logistic regression, and mediation analyses were performed. RESULTS: Low goal congruence predicted engagement in sedentary behavior and light physical activity. Higher levels of self-efficacy and social support were associated with increased likelihoods of achieving greater moderate physical activity and meeting daily recommendations for caloric intake, respectively. Self-efficacy and goal congruence predicted muscle function and strength. Moreover, sedentary behavior and achieving greater moderate physical activity were found to partially but significantly mediate the relationship between self-efficacy and muscle function. CONCLUSION: Future research should evaluate whether attempts to reduce sedentary behavior and promote physical activity and dietary self-management behaviors and muscle outcomes are more successful when modifications to the self-management process factors are also targeted.

A prospective cohort study of the psychological consequences of the COVID-19 pandemic on frontline healthcare workers in New York City.

OBJECTIVES: We sought to describe the course and correlates of psychological distress in frontline healthcare workers (FHCWs) during the COVID-19 pandemic in New York City (NYC). METHODS: A prospective cohort study of FHCWs at the Mount Sinai Hospital was conducted during the initial 2020 surge (T1) and 7 months later (T2). Psychological distress [i.e., positive screen for pandemic-related post-traumatic stress disorder (PTSD), major depressive disorder (MDD), and/or generalized anxiety disorder (GAD)], occupational and personal exposures to COVID-19, coping strategies, and psychosocial characteristics were assessed. Four courses of psychological distress response were identified: no/minimal, remitted, persistent, and new-onset. Multinomial logistic regression and relative importance analyses were conducted to identify factors associated with courses of distress. RESULTS: Of 786 FHCWs, 126 (16.0%) FHCWs had persistent distress; 150 (19.1%) remitted distress; 35 (4.5%) new-onset distress; and 475 (60.4%) no/minimal distress. Relative to FHCWs with no/minimal distress, those with persistent distress reported greater relationship worries [19.8% relative variance explained (RVE)], pre-pandemic burnout (18.7% RVE), lower dispositional optimism (9.8% RVE), less emotional support (8.6% RVE), and feeling less valued by hospital leadership (8.4% RVE). Relative to FHCWs with remitted symptoms, those with persistent distress reported less emotional support (29.7% RVE), fewer years in practice (28.3% RVE), and psychiatric history (23.6% RVE). CONCLUSIONS: One-fifth of FHCWs in our study experienced psychological distress 7 months following the COVID-19 surge in NYC. Pandemic-related worries, pre-pandemic burnout, emotional support, and feeling valued by leaders were linked to persistent distress. Implications for prevention, treatment, and organizational efforts to mitigate distress in FHCWs are discussed.

Association of vitiligo with high-frequency sensorineural hearing loss: a systematic review and meta-analysis.

The association between vitiligo and hearing loss has been noted but the specific frequencies and degrees of hearing impairment remain unclear. The objective of this systematic review was to investigate the relationship between vitiligo and hearing thresholds at various specific frequencies. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched MEDLINE and Embase for relevant studies from inception to 10th April 2021. Case-control studies, cross-sectional, or cohort studies that compared the frequency-specific hearing thresholds between vitiligo patients and age-matched non-vitiligo controls were included. There were neither language nor geographic limitations. We used the Newcastle-Ottawa Scale to assess the risk of bias of included studies. The DerSimonian and Laird random-effects model was utilized in meta-analyses due to expected clinical heterogeneity. We included 9 case-control studies with 371 vitiligo patients and 349 controls, which were rated with low or unclear risk. We found neither relevant cross-sectional nor cohort studies. The meta-analysis showed that when compared with controls, vitiligo patients had significantly higher pure-tone hearing thresholds at 2000, 4000, and 8000 Hz. In conclusions, vitiligo patients are prone to high-frequency sensorineural hearing loss.

Factors Associated With Burnout Among Nurses Providing Direct Patient Care During the COVID-19 Pandemic.

OBJECTIVE: This study aimed to identify factors associated with burnout in nurses and nurses' opinions regarding interventions to promote well-being during crisis conditions such as those experienced during the COVID-19 pandemic. BACKGROUND: Burnout among nurses is prevalent under usual conditions and may increase during crises such as COVID-19. METHODS: Researchers conducted a survey of 1103 frontline nurses in a single New York City hospital during the first (spring 2020) and second (fall 2020/winter 2021) local waves of COVID-19. RESULTS: Burnout prevalence increased from 45% to 52% between the first and second wave. Younger age, female gender, posttraumatic stress, anxiety or depressive symptoms, history of burnout, feeling less valued by hospital leadership, less informed of responsibilities, less certain about duration of enhanced workload, and prepared by prepandemic experience were predictive of burnout in multivariable analyses. CONCLUSIONS: Although some identified risk factors for burnout were nonmodifiable, others may be modifiable by hospital leadership.

Parenting styles and dimensions in parents of children with developmental disabilities.

Parenting influences child development. There is limited research, however, related to parenting children who have developmental disabilities. The aims of this study were to: (1) describe the parenting styles and dimensions of parents of children with developmental disabilities and (2) assess differences in parenting styles and dimensions among parents of children with autism spectrum disorder (ASD), Down syndrome (DS), and spina bifida (SB). Secondary data analysis was conducted from a nationwide cross-sectional study of 496 parents of children aged 5-16 years with ASD (n = 180), DS (n = 156), or SB (n = 160). Parent scores indicated high use of the authoritative parenting style and associated parenting dimensions, mid-to-low use of the permissive parenting style, and low use of the authoritarian parenting style and associated dimensions. Variation in parenting styles and dimensions among parents was primarily related to the child's diagnosis and family income. An unanticipated but positive finding was that parents with lower family incomes had significantly higher scores for the authoritative parenting style. Results from this study can inform future research that might inform clinical practice.

[Impact of bicuspid aortic valve or tricuspid aortic valve on hemodynamics and left ventricular reverse remodeling in patients after transcatheter aortic valve replacement].

Objective: To compare the impact of bicuspid aortic valve (BAV) or tricuspid aortic valve (TAV) on hemodynamics and left ventricular reverse remodeling after transcatheter aortic valve replacement (TAVR). Methods: We retrospectively analyzed the clinical data of patients who underwent TAVR in our hospital from January 2019 to March 2021. Patients were divided into BAV group and TAV group according to aortic contrast-enhanced CT. Each patient was followed up by N-terminal pro B-type natriuretic peptide (NT-proBNP) and echocardiography at four time points, namely before TAVR, 24 hours, 1 month and 6 months after TAVR. Echocardiographic data, including mean pressure gradient (MPG), aortic valve area (AVA), left ventricular ejection fraction (LVEF), left ventricle mass (LVM) and LV mass index (LVMi) were evaluated. Results: A total of 41 patients were included. The age was (75.0±8.6) years, and male patients accounted for 53.7%. There were 19 BAV patients and 22 TAV patients in this cohort. All patients undergoing TAVR using a self-expandable prosthesis Venus-A valve. MPG was (54.16±21.22) mmHg(1 mmHg=0.133 kPa) before TAVR, (21.11±9.04) mmHg at 24 hours after TAVR, (18.84±7.37) mmHg at 1 month after TAVR, (17.68±6.04) mmHg at 6 months after TAVR in BAV group. LVEF was (50.42±13.30)% before TAVR, (53.84±10.59)% at 24 hours after TAVR, (55.68±8.71)% at 1 month after TAVR and (57.42±7.78)% at 6 months after TAVR in BAV group. MPG and LVEF substantially improved at each time point after operation, and the difference was statistically significant (all P<0.05) in BAV group. MPG in TAV group improved at each time point after operation, and the difference was statistically significant (all P<0.05). LVMi was (164.13±49.53), (156.37±39.11), (146.65±38.84) and (134.13±39.83) g/m2 at the 4 time points and the value was significantly reduced at 1 and 6 months post TAVR compared to preoperative level(both P<0.05). LVEF in the TAV group remained unchanged at 24 hours after operation, but it was improved at 1 month and 6 months after operation, and the difference was statistically significant (all P<0.05). LVMi in TAV group substantially improved at each time point after operation, and the difference was statistically significant (all P<0.05). NT-proBNP in both two groups improved after operation, at 1 month and 6 months after operation, and the difference was statistically significant (all P<0.05). MPG in TAV group improved better than in BAV group during the postoperative follow-up (24 hours after TAVR: (11.68±5.09) mmHg vs. (21.11±9.04) mmHg, P<0.001, 1 month after TAVR: (10.82±3.71) mmHg vs. (18.84±7.37) mmHg, P<0.001, 6 months after TAVR: (12.36±4.42) mmHg vs. (17.68±6.04) mmHg, P=0.003). There was no significant difference in NT-proBNP between BAV group and TAV group at each time point after operation (all P>0.05). There was no significant difference in paravalvular regurgitation and second prosthesis implantation between the two groups (all P>0.05). Conclusions: AS patients with BAV or TAV experience hemodynamic improvement and obvious left ventricular reverse remodeling after TAVR, and the therapeutic effects of TAVR are similar between BAV and TAV AS patients in the short-term post TAVR.

Probing Gluon Spin-Momentum Correlations in Transversely Polarized Protons through Midrapidity Isolated Direct Photons in p

Studying spin-momentum correlations in hadronic collisions offers a glimpse into a three-dimensional picture of proton structure. The transverse single-spin asymmetry for midrapidity isolated direct photons in p^{↑}+p collisions at sqrt[s]=200 GeV is measured with the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). Because direct photons in particular are produced from the hard scattering and do not interact via the strong force, this measurement is a clean probe of initial-state spin-momentum correlations inside the proton and is in particular sensitive to gluon interference effects within the proton. This is the first time direct photons have been used as a probe of spin-momentum correlations at RHIC. The uncertainties on the results are a 50-fold improvement with respect to those of the one prior measurement for the same observable, from the Fermilab E704 experiment. These results constrain gluon spin-momentum correlations in transversely polarized protons.

Is psoriasis associated with dementia or cognitive impairment? A Critically Appraised Topic.

CLINICAL QUESTION: Is psoriasis associated with dementia or cognitive impairment? BACKGROUND: Psoriasis is a multisystemic inflammatory disorder that has an unclear association with cognitive dysfunction. OBJECTIVES: To conduct a Critically Appraised Topic that synthesizes the results from relevant observational studies. METHODS: A systematic literature search of PubMed and Embase was conducted on 12 July 2019 to identify case-control, cross-sectional or cohort studies that investigated the association between psoriasis and cognitive impairment or dementia. Risk of bias was assessed for each study, and the results presented in a narrative synthesis. RESULTS: Eleven studies were included for critical appraisal. Of the 11 studies, 10 compared a total of 16 574 psoriasis cases with over 45 078 controls for risk of dementia or cognitive impairment. One of the 11 studies evaluated 7118 patients with dementia for odds of psoriasis compared with 21 354 controls. Six studies were assessed to have higher risk of bias. Nine of the 11 included studies found a significant positive association between the two diseases, one study a null association, and one study an inverse association. DISCUSSION AND RECOMMENDATION: Most of the 11 included studies found a positive association between psoriasis and either mild cognitive impairment or dementia. Brief cognitive assessments have been suggested to screen older patients with psoriasis who present with subjective cognitive complaints.

Global Guidelines in Dermatology Mapping Project (GUIDEMAP): a scoping review of dermatology clinical practice guidelines.

BACKGROUND: Clinical practice guidelines (CPGs) play a critical role in standardizing and improving treatment outcomes based on the available evidence. It is unclear how many CPGs are available globally to assist clinicians in the management of patients with skin disease. OBJECTIVES: To search for and identify CPGs for dermatological conditions with the highest burden globally. METHODS: We adapted a list of 12 dermatological conditions with the highest burden from the Global Burden of Disease (GBD) study 2019. A systematic literature search was done to identify CPGs published between October 2014 to October 2019. The scoping review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. RESULTS: A total of 226 CPGs were included. Melanoma had the greatest representation in the CPGs, followed by dermatitis and psoriasis. Skin cancers had a relatively high CPG representation but with lower GBD disease burden ranking. There was an uneven distribution by geographical region, with resource-poor settings being under-represented. The skin disease categories of the CPGs correlated weakly with the GBD disability-adjusted life-years metrics. Eighty-nine CPGs did not have funding disclosures and 34 CPGs were behind a paywall. CONCLUSIONS: The global production of dermatology CPGs showed wide variation in geographical representation, article accessibility and reporting of funding. The number of skin disease CPGs were not commensurate with its disease burden. Future work will critically appraise the methodology and quality of dermatology CPGs and lead to the production of an accessible online resource summarizing these findings.

Effects of solvation shell relaxation on chain association mechanisms in poly(3-hexylthiophene) solutions.

Using poly(3-hexylthiophene) (P3HT) as a model conjugated polymer and atomistic molecular dynamics simulations with carefully verified force fields, we performed in-depth investigations of solvation shell properties of P3HT chains (15 repeating units per chain) in two representative groups of non-polar (or aprotic) organic solvents (better solvents: ortho-dichlorobenzene, bromobenzene, and chlorobenzene; poorer solvents: chloroform, para-xylene, and toluene). We demonstrated that solvation shell relaxation properties in P3HT solutions dictate the formation of regular π-π associations and, hence, crystallinity through the initial chain association and subsequent chain sliding. In contrast, the mean features of polymer-solvent interactions, including solvation free energy and radial distribution function, present little or no difference for all solvent media investigated. Better-solvent media were revealed to bear relatively large values of the first solvation shell relaxation time (τ1 ≫ 100 ps) as well as larger ratios of relaxation times for the first two solvation shells (τ1/τ2 > 2), and vice versa for poorer-solvent media (τ1 ≪ 100 ps and τ1/τ2 < 2). The linear hexyl side-chain unit was noted to substantially enlarge both quantities while notably reducing the solvation free energy as well. As discussed herein, these findings shed new light on the mechanistic features by which solvent quality impacts the degree of π-π association crucial for modern applications with crystalline conjugated polymers.

Anaemia among intensive care unit survivors and association with days alive and at home: an observational study.

Anaemia is highly prevalent at the time of intensive care unit discharge and is persistent for a high proportion of intensive care unit survivors. Whether anaemia is a driver of impaired recovery after critical illness is uncertain. The aim of this study was to test the hypothesis that, in adult intensive care survivors, anaemia at the time of intensive care unit discharge independently predicts decreased days at home-90. This retrospective cohort study was conducted in a tertiary intensive care unit in Perth, Western Australia. All patients aged ≥ 16 years, discharged alive from their index intensive care unit admission and without documented treatment limitations were included. Median (IQR [range]) age of the 6358 participants was 61 (46-72 [16-95]) years and included 3385 (53.2%) unplanned admissions. Intensive care unit discharge with a haemoglobin concentration < 100 g.l-1 occurred in 2886 (45.4%) patients, a threshold that identified a cohort with significantly lower days at home-90 (median (IQR [range]) 80 (64-85 [0-90]) days vs. 85 (77-88 [0-90]) days (median difference 5 days, 95%CI 4.4-5.5, p < 0.0001). The association followed a severity-response relationship with more severe anaemia predicting lower days at home-90. When accounting for prespecified covariates including admission haemoglobin concentration and red blood cell transfusion, anaemia at intensive care unit discharge remained a significant predictor of decreased days at home-90, relative risk 0.96 (0.93-0.98), p < 0.002. These findings support the need for interventional trials investigating whether this risk is modifiable.

Blockade of fatty acid signalling inhibits lipopolysaccharide-induced macrophage recruitment and progression of apical periodontitis.

AIM: To examine the role of palmitic acid in lipopolysaccharide (LPS)-stimulated chemotaxis of macrophages and the potential contribution of saturated fatty acid in signalling during the pathogenesis of apical periodontitis. METHODOLOGY: J774, a mouse macrophage cell line, was used in the experiments. After treatment with LPS, proteolytic maturation of sterol regulatory element-binding protein-1c (SREBP-1c) and expression of fatty acid synthase (FASN) were examined by Western analysis. Levels of palmitic acid were measured by reverse phase-high performance liquid chromatography-mass spectrometry. Knockdown of SREBP-1c and FASN was accomplished by small interfering RNA technology. Secretion of CC-chemokine ligand 2 (CCL2) and cellular chemotaxis were assessed by enzyme-linked immunosorbent assay and transwell migration assay, respectively. Sulfo-N-succinimidyl oleate (SSO) treatment was used to inhibit fatty acid signalling in vitro and also in a rat model of apical periodontitis. All data were first subjected to Levene's test. In vitro data were then analysed using ANOVA followed by Tukey's multiple comparison test. Data from animal experiments were analysed by independent t-tests. The significant level was set at 0.05. RESULTS: LPS stimulated proteolytic maturation of SREBP-1c and FASN expression in macrophages and significantly enhanced palmitic acid synthesis (P < 0.05). Knockdown of SREBP-1c attenuated LPS-enhanced FASN expression. Knockdown of FASN significantly suppressed LPS-enhanced palmitic acid synthesis (P < 0.05). LPS and exogenous palmitic acid significantly enhanced CCL2 secretion and macrophage chemotaxis (all P < 0.05). Inhibition of FASN expression significantly alleviated LPS-augmented CCL2 secretion (P < 0.05). SSO significantly suppressed CCL2 secretion and macrophage chemotaxis augmented by LPS and palmitic acid (all P < 0.05). In a rat model of induced apical periodontitis, SSO treatment significantly attenuated progression of apical periodontitis and macrophage recruitment (all P < 0.05). CONCLUSIONS: LPS/SREBP-1c/FASN/palmitic acid signalling contributed to tissue destruction caused by bacterial infection. Modulation of lipid metabolism and signalling may be helpful for the management of apical periodontitis.