Should blastocyst transfer be performed in patients with 1-3 embryos available on day 3?

RESEARCH QUESTION: In patients with 1-3 embryos available on day 3, does blastocyst transfer reduce the chances of a clinical pregnancy by cancelling transfer cycles compared with cleavage transfer? DESIGN: This retrospective observational study included 423 IVF cycles performed from 1 January 2019 to 31 December 2020 at the Center for Reproduction and Fertility of the Second Affiliated Hospital of Kunming Medical University. Cleavage transfer was performed in 267 cycles and blastocyst transfer was performed in 156 cycles. The primary outcome was the ongoing pregnancy rate, and the secondary outcomes were clinical pregnancy rate and embryo cessation rate. Univariate analysis was performed to compare outcomes. A logistic regression analysis was performed to explore the association between transfer stage and ongoing pregnancy rate. RESULTS: No differences were observed in the ongoing pregnancy rate (25.84% versus 26.92%; odds ratio [OR] 0.95; 95% confidence interval [CI] 0.61-1.50; P = 0.82) and embryo cessation rate (83.48% versus 85.75%; OR 1.19; 95% CI 0.82-1.75; P = 0.40) between the two groups. Logistic regression analysis showed no association between transfer stage and ongoing pregnancy rate (OR 1.06; 95% CI 0.64-1.73). CONCLUSIONS: Blastocyst transfer does not reduce the chances of a clinical pregnancy. These results support the proposal of blastocyst transfer in patients with 1-3 embryos available on day 3.

What is the impact of granulocyte colony-stimulating factor (G-CSF) in subcutaneous injection or intrauterine infusion and during both the fresh and frozen embryo transfer cycles on recurrent implantation failure: a systematic review and meta-analysis?

BACKGROUND: Among recurrent implantation failure (RIF) patients, the rate of successful implantation remains relatively low due to the complex etiology of the condition, including maternal, embryo and immune factors. Effective treatments are urgently needed to improve the outcomes of embryo transfer for RIF patients. In recent years, many researchers have focused on immunotherapy using granulocyte colony-stimulating factor (G-CSF) to regulate the immune environment. However, the study of the G-CSF for RIF patients has reached conflicting conclusions. The aim of this systematic review and meta-analysis was performed to further explore the effects of G-CSF according to embryo transfer cycle (fresh or frozen) and administration route (subcutaneous injection or intrauterine infusion) among RIF patients. METHOD: The PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for literature published from the initial to October 2020. The meta-analysis, random-effects model and heterogeneity of the studies with I2 index were analyzed. Stata 15 was used for statistical analysis. RESULTS: A total of 684 studies were obtained through the databases mentioned above. Nine RCTs included 976 RIF patients were enrolled in this meta-analysis. Subgroup analysis indicated that G-CSF improved the clinical pregnancy rate for both the fresh and frozen embryo transfer cycles (fresh RR: 1.74, 95% CI: 1.27-2.37, I2 = 0.0%, n = 410; frozen RR: 1.44, 95% CI: 1.14-1.81, I2 = 0.0.%, n = 366), and for both subcutaneous injection and intrauterine infusion (subcutaneous RR: 1.73, 95% CI: 1.33-2.23, I2 = 0.0%, n = 497; intrauterine RR: 1.39, 95% CI: 1.09-1.78, I2 = 0.0%, n = 479), but the biochemical pregnancy rate of the RIF group was also higher than that of the control group (RR: 1.85, 95% CI: 1.28-2.68; I2 = 20.1%, n = 469). There were no significant differences in the miscarriage rate (RR: 1.13, 95% CI: 0.25-5.21: I2 = 63.2%, n = 472) and live birth rate (RR: 1.43, 95% CI: 0.86-2.36; I2 = 52.5%; n = 372) when a random-effects model was employed. CONCLUSION: The administration of G-CSF via either subcutaneous injection or intrauterine infusion and during both the fresh and frozen embryo transfer cycles for RIF patients can improve the clinical pregnancy rate. However, whether G-CSF is effective in improving livebirth rates of RIF patients is still uncertain, continued research on the utilization and effectiveness of G-CSF is recommended before G-CSF can be considered mainstream treatment for RIF patients.

Health Benefits and Costs of Clean Heating Renovation: An Integrated Assessment in a Major Chinese City.

China has been promoting one of the world's largest campaigns for clean heating renovation since 2017. Here, we present an integrated cost-benefit analysis in a major prefecture-level city by combining a large-scale household energy survey and PM2.5 exposure measurement, high-resolution chemical transport simulation, and health impact assessment. We find that the completed renovation decreases the share of solid fuels in the heating energy mix from 96 to 6% and achieves a concomitant reduction of cooking solid-fuel use by 70%. The completed renovation decreases the ambient PM2.5 concentration in Linfen by 0.5-5 µg m-3 (2.4 µg m-3 on average) and decreases the integrated PM2.5 exposure by 4.2 (3.5-5.0) µg m-3. The renovation is estimated to avoid 162 (125-225) and 328 (254-457) premature deaths annually based on two health impact assessment methods. The ratios of monetized health benefits to cost are 1.51 (0.73-2.59) and 3.06 (1.49-5.23) based on the above two methods. The benefit-to-cost ratio is projected to remain high if the renovation is further expanded. More polluted and less wealthy households enjoy larger health benefits but also experience a higher expense increase, suggesting that a more carefully designed subsidy policy is needed to protect low-income households.

Interleukin 6 in follicular fluid reduces embryo fragmentation and improves the clinical pregnancy rate.

PURPOSE: The aim of this study was to evaluate the role of interleukin 6 in embryo development in the in vitro fertilization cycles. METHODS: This was a retrospective cohort study. One hundred and three women undergoing in vitro fertilization and embryo transfer due to a tubal factor were included in the study. The follicular fluid IL-6 levels on oocyte retrieval day from each patient were determined by ELISA. The relationships between follicular fluid IL-6 levels and IVF cycle parameters were investigated. RESULTS: The levels of follicular fluid IL-6 were not affected by the use of drugs for superovulation or by estrogen. In addition, follicular fluid IL-6 levels did not affect the number of oocytes retrieved or the MII oocyte rate. High levels of follicular fluid IL-6 correlated with a significant increase in the rates of clinical pregnancy. Follicular fluid IL-6 levels did not affect the cell number or the blastomere symmetry of day 3 embryos, but it did significantly reduce the embryo fragmentation rate. CONCLUSIONS: High levels of follicular fluid IL-6 improved the rates of clinical pregnancy and reduce embryo fragmentation.

Position- and region-isomerized derivatives of a V-shaped fluorophore: the unique solution-state dual emission and the unusual force-induced solid-state turn-on emission.

A V-shaped parent fluorophore as well as its position- and region-isomerized derivatives with a phenyl introduced on either the electron-donating or the electron-withdrawing moiety in the ortho-, meta- or para-linkage is prepared. Compared with the parent, these derivatives exhibit unique solvent-dependent dual emission in solutions presumably due to the considerably enhanced rotation energy barrier triggered by the insertion of the phenyl, which results in competitive relaxation between the LE and the TICT states. The intrinsically differentiated electron effect induced by the linkage position, which is strengthened by the twisted conformations, should be responsible for the faint or fully quenched fluorescence of the ortho- and meta-isomers in both solution and solid states. The rare turn-on solid-state emission of such isomers under force stimuli is caused by the enhanced π-conjugation effect on excited molecules, which are released from broken lattices to possess more planarized geometries. Moreover, the red shifts of emission wavelengths before and after force application are remarkably reduced from the parent to the derivatives. X-ray crystallography helps us gain a deep insight on the reasons for such a reduction.

Protection of ischemic post conditioning against transient focal ischemia-induced brain damage is associated with inhibition of neuroinflammation via modulation of TLR2 and TLR4 pathways.

BACKGROUND AND PURPOSE: Ischemic postconditioning has been demonstrated to be a protective procedure to brain damage caused by transient focal ischemia/reperfusion. However, it is elusive whether the protection of postconditioning against brain damage and neuroinflammation is via regulating TLR2 and TLR4 pathways. In the present study, we examined the protection of ischemic postconditioning performed immediately prior to the recovery of cerebral blood supply on brain damage caused by various duration of ischemia and tested the hypothesis that its protection is via inhibition of neuroinflammation by modulating TLR2/TLR4 pathways. METHODS: Brain damage in rats was induced by using the middle cerebral artery occlusion (MCAO) model. Ischemic postconditioning consisting of fivecycles of ten seconds of ischemia and reperfusion was performed immediately following theischemic episode Theduration of administration of ischemic postconditioning was examined by comparing its effects on infarction volume, cerebral edema and neurological function in 2, 3, 4, 4.5and 6 hour ischemia groups. The protective mechanism of ischemic postconditioning was investigated by comparing its effects on apoptosis, production of the neurotoxic cytokine IL-1ß and the transcription and expression of TLR2, TLR4 and IRAK4 in the 2 and 4.5 hour ischemia groups. RESULTS: Ischemic postconditioning significantly attenuated cerebral infarction, cerebral edema and neurological dysfunction in ischemia groups of up to 4 hours duration, but not in 4.5and 6 hour ischemia groups. It also inhibited apoptosis, production of IL-1ß, abnormal transcription and expression of TLR2, TLR4 and IRAK4 in the 2 hour ischemia group, but not in the 4.5 hour ischemia group. CONCLUSIONS: Ischemic postconditioning protected brain damage caused by 2, 3 and 4 hours of ischemia, but not by 4.5 and 6 hours of ischemia. The protection of ischemic postconditioning is associated with its inhibition of neuroinflammation via inhibition of TLR2 and TLR4 pathways.

Anti-inflammatory effects of Edaravone and Scutellarin in activated microglia in experimentally induced ischemia injury in rats and in BV-2 microglia.

BACKGROUND: In response to cerebral ischemia, activated microglia release excessive inflammatory mediators which contribute to neuronal damage. Therefore, inhibition of microglial over-activation could be a therapeutic strategy to alleviate various microglia-mediated neuroinflammation. This study was aimed to elucidate the anti-inflammatory effects of Scutellarin and Edaravone given either singly, or in combination in activated microglia in rats subjected to middle cerebral artery occlusion (MCAO), and in lipopolysaccharide (LPS)-induced BV-2 microglia. Expression of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and inducible nitric oxide synthase (iNOS) was assessed by immunofluorescence staining and Western blot. Reactive oxygen species (ROS) and nitric oxide (NO) levels were determined by flow cytometry and fluorescence microscopy, respectively. RESULTS: In vivo, both Edaravone and Scutellarin markedly reduced the infarct cerebral tissue area with the latter drug being more effective with the dosage used; furthermore, when used in combination the reduction was more substantial. Remarkably, a greater diminution in distribution of activated microglia was observed with the combined drug treatment which also attenuated the immunoexpression of TNF-α, IL-1ß and iNOS to a greater extent as compared to the drugs given separately. In vitro, both drugs suppressed upregulated expression of inflammatory cytokines, iNOS, NO and ROS in LPS-induced BV-2 cells. Furthermore, Edaravone and Scutellarin in combination cumulatively diminished the expression levels of the inflammatory mediators being most pronounced for TNF-α as evidenced by Western blot. CONCLUSION: The results suggest that Edaravone and Scutellarin effectively suppressed the inflammatory responses in activated microglia, with Scutellarin being more efficacious within the dosage range used. Moreover, when both drugs were used in combination, the infarct tissue area was reduced more extensively; also, microglia-mediated inflammatory mediators notably TNF-α expression was decreased cumulatively.

Inhibition of histone deacetylase promotes a neuroprotective mechanism in an experimental model of Parkinson's disease.

Introduction: Therapies targeting histone deacetylase (HDAC) have gained wider attention in the treatment of various clinical conditions. However, the use of HDAC inhibitors in pre-clinical trials in the case of Parkinson's disease (PD) is very limited. In the present study, the HDAC inhibitor, entinostat, was tested in animals induced with Parkinson's disease experimentally. Material and methods: Wistar male rats (150 ±10 g) were administered with rotenone (2 mg/kg/day, s.c.) for 21 days to induce PD, while entinostat (20 mg/kg) was given intraperitoneally. Then, the neurological functions, PD markers, and HDACs were analysed in the control and experimental animals. Results: The results demonstrated that rats that received entinostat displayed progressive motor, behavioural, and neurological function with attenuated α-synuclein and improved tyrosine-hydroxylase compared to control cells. Moreover, the induction of PD in rats demonstrated reduced levels of H2S, dopamine, 3, and 4-dihydroxyphenylacetic acid (DOPAC), and increased monoamine oxidase activity in PD rats. However, the rats that received entinostat demonstrated progressive levels of dopa and DOPAC, with attenuated levels of HDAC-2, -4, and -6 mRNA in the PD rats compared to controls. On the other hand, elevated (p < 0.01) levels of PD marker genes such as GDF3 and NMDA2b were reduced, with a significant increase in neuroprotective genes such as VDAC3 and CBX5 in entinostat-supplemented rats. Conclusions: The study results suggest that inhibition of HDAC systematically improves the neurological functions, and hence treatments, emphasizing that HDACI, as the speculated mechanism, will be a promising mode of treatment in PD.

Interleukin-6 Concentration in Single-Embryo Medium Is Associated with Blastocyst Formation.

IL-6 plays an important role in oogenesis in humans. However, at the preimplantation stage, IL-6 production and the role in embryo development remain unclear. In this study, IL-6 concentrations in single-embryo media were analyzed. In addition, the association between IL-6 production and blastocyst formation was investigated. Single-embryo culture media from 194 embryos were collected on day 6 after fertilization and divided into four groups according to the developmental stage of the corresponding embryo, as follows: cleavage stage group, morula-early blastocyst group, unavailable full blastocyst group, and available full blastocyst group. IL-6 concentrations were significantly lower in the cleavage stage group than in the morula-early blastocyst group (p = 0.009), in the unavailable full blastocyst group (p = 0.003), and in the available full blastocyst group (p < 0.001). Logistic regression analysis showed that IL-6 concentration in single-embryo medium was significantly associated with blastocyst formation (odds ratios ß1 = 1.876, 95% CI 1.433 to 2.644, p < 0.0001). Therefore, IL-6 was produced by human preimplantation embryos throughout the preimplantation stage and may play a role in embryo development.

Intramolecular dynamic coupling slows surface relaxation of polymer glasses.

Over the past three decades, studies have indicated a mobile surface layer with steep gradients on glass surfaces. Among various glasses, polymers are unique because intramolecular interactions - combined with chain connectivity - can alter surface dynamics, but their fundamental role has remained elusive. By devising polymer surfaces occupied by chain loops of various penetration depths, combined with surface dissipation experiments and Monte Carlo simulations, we demonstrate that the intramolecular dynamic coupling along surface chains causes the sluggish bulk polymers to suppress the fast surface dynamics. Such effect leads to that accelerated segmental relaxation on polymer glass surfaces markedly slows when the surface polymers extend chain loops deeper into the film interior. The surface mobility suppression due to the intramolecular coupling reduces the magnitude of the reduction in glass transition temperature commonly observed in thin films, enabling new opportunities for tailoring polymer properties at interfaces and under confinement and producing glasses with enhanced thermal stability.

Expression of angiotensin II and its receptors in activated microglia in experimentally induced cerebral ischemia in the adult rats.

Expression of angiotensin II (Ang II) and its receptors (AT1/AT2) is undetected in the mature microglia in normal brain. We report here that the immunoexpression of Ang II and AT1/AT2 was altered in activated microglia notably at 1 week in rats subjected to middle cerebral artery occlusion (MCAO). Immunolabeled activated microglia were widely distributed in the infarcted cerebral tissue after MCAO. By enzyme immunoassay, Ang II protein expression levels of the ischemic tissues were decreased drastically at 12 h after ischemia, then rose rapidly at 3 days and 1 week after MCAO when compared with the control. On the other hand, AT1 and AT2 receptor mRNA and protein levels were up-regulated after MCAO, peaking at 12 h, but declined thereafter. Expression of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) mRNA and protein levels was concomitantly increased. Edaravone significantly suppressed Ang II and AT1/AT2 receptor expression as well as that of TNF-α and IL-1ß suggesting that microglia-derived Ang II can act through an autocrine manner via its receptor that may be linked partly to the production of proinflammatory cytokines. We conclude that neuroinflammation in MCAO may be attenuated by Edaravone which acts through suppression of expression of Ang II and its receptors and proinflammatory cytokines in activated microglia.

A panel dataset of COVID-19 vaccination policies in 185 countries.

We present a panel dataset of COVID-19 vaccine policies, with data from 01 January 2020 for 185 countries and a number of subnational jurisdictions, reporting on vaccination prioritization plans, eligibility and availability, cost to the individual and mandatory vaccination policies. For each of these indicators, we recorded who is targeted by a policy using 52 standardized categories. These indicators document a detailed picture of the unprecedented scale of international COVID-19 vaccination rollout and strategy, indicating which countries prioritized and vaccinated which groups, when and in what order. We highlight key descriptive findings from these data to demonstrate uses for the data and to encourage researchers and policymakers in future research and vaccination planning. Numerous patterns and trends begin to emerge. For example: 'eliminator' countries (those that aimed to prevent virus entry into the country and community transmission) tended to prioritize border workers and economic sectors, while 'mitigator' countries (those that aimed to reduce the impact of community transmission) tended to prioritize the elderly and healthcare sectors for the first COVID-19 vaccinations; high-income countries published prioritization plans and began vaccinations earlier than low- and middle-income countries. Fifty-five countries were found to have implemented at least one policy of mandatory vaccination. We also demonstrate the value of combining this data with vaccination uptake rates, vaccine supply and demand data, and with further COVID-19 epidemiological data.

Development of a compact linear accelerator to generate ultrahigh dose rate high-energy X-rays for FLASH radiotherapy applications.

PURPOSE: In recent years, the FLASH effect, in which ultrahigh dose rate (UHDR) radiotherapy (RT) can significantly reduce toxicity to normal tissue while maintaining antitumor efficacy, has been verified in many studies and even applied in human clinical cases. This work evaluates whether a room-temperature radio-frequency (RF) linear accelerator (linac) system can produce UHDR high-energy X-rays exceeding a dose rate of 40 Gy/s at a clinical source-surface distance (SSD), exploring the possibility of a compact and economical clinical FLASH RT machine suitable for most hospital treatmentrooms. METHODS: A 1.65 m long S-band backward-traveling-wave (BTW) electron linac was developed to generate high-current electron beams, supplied by a commercial klystron-based power source. A tungsten-copper electron-to-photon conversion target for UHDR X-rays was designed and optimized with Monte Carlo (MC) simulations using Geant4 and thermal finite element analysis (FEA) simulations using ANSYS. EBT3 and EBT-XD radiochromic films, which were calibrated with a clinical machine Varian VitalBeam, were used for absolute dose measurements. A PTW ionization chamber detector was used to measure the relative total dose and a plane-parallel ionization chamber detector was used to measure the relative normalized dose of each pulse. RESULTS: The BTW linac generated 300-mA-pulse-current 11 MeV electron beams with 29 kW mean beam power, and the conversion target could sustain this high beam power within a maximum irradiation duration of 0.75 s. The mean energy of the produced X-rays was 1.66 MeV in the MC simulation. The measured flat-filter-free (FFF) maximum mean dose rate of the room-temperature linac exceeded 80 Gy/s at an SSD of 50 cm and 45 Gy/s at an SSD of 67.9 cm, both at a 2.1 cm depth of the water phantom. The FFF radiation fields at 50 cm and 67.9 cm SSD at a 2.1 cm depth of the water phantom showed Gaussian-like distributions with 14.3 and 20 cm full-width at half-maximum (FWHM) values, respectively. CONCLUSION: This work demonstrated the feasibility of UHDR X-rays produced by a room-temperature RF linac, and explored the further optimization of system stability. It shows that a simple and compact UHDR X-ray solution can be facilitated for both FLASH-RT scientific research and clinical applications.

Neuroimaging for differential diagnosis of transient neurological attacks.

BACKGROUND: Rapid yet comprehensive neuroimaging protocols are required for patients with suspected acute stroke. However, stroke mimics can account for approximately one in five clinically diagnosed acute ischemic strokes and the rate of thrombolyzed mimics can be as high as 17%. Therefore, to accurately determine the diagnosis and differentiate mimics from true transient ischemic attacks, acute ischemic stroke is a challenge to every clinician. DISCUSSION: Medical history and neurological examination, noncontract head computed tomography, and routine magnetic resonance imaging play important roles in the assessment and management of patients with transient neurological attacks in the emergency department. This review attempts to summarize how neuroimaging can be utilized to help differentiate the most common mimics from transient ischemic attack and acute ischemic stroke. CONCLUSION: Although imaging can help direct critical triage decisions for intravenous thrombolysis or endovascular therapy, more detailed medical history and neurological examination are crucial for making a prompt and accurate diagnosis for transient neurological attack patients.

Autophagy protects against cerebral ischemic reperfusion injury by inhibiting neuroinflammation.

OBJECTIVE: To examine the effect of autophagy on cerebral damage caused by different models and test the hypothesis that its protection mechanism acts via inhibiting expression of neuroinflammatory mediators. METHODS: Autophagy was induced by rapamycin treatment. Cerebral damage was induced using models of IL-6 treatment, oxygen glucose deprivation/reoxygenation (OGD/R) in vitro, and middle cerebral artery occlusion (MCAO) in vivo. The effect and mechanism of autophagy was examined and assessed in terms of cell viability, infarction size in brain tissue, neurological score, production of inflammatory mediators IL-1ß and IL-6, transcription and protein expression of autophagy markers beclin-1 and LC-3II in different experimental groups. RESULTS: Autophagy triggered by rapamycin could protect neurons from IL-6-induced injury and astrocytes from OGD/R-induced injury in vitro and in rat brain tissue from MCAO in vivo. Autophagy significantly increased cell viability, attenuated cerebral infarction and improved neurological scores. It also inhibited production of the IL-1ß and IL-6 and elevated the expression of beclin-1 and LC-3II. CONCLUSIONS: Autophagy can inhibit the inflammatory response and reduce cerebral I/R injury. There was a relationship between the extent of protection and (i) the level of the autophagic response, (ii) the stage of the cerebral I/R injury, and (iii) the time of intervention.

Remote ischaemic perconditioning reduces the infarct volume and improves the neurological function of acute ischaemic stroke partially through the miR-153-5p/TLR4/p65/IkBa signalling pathway.

Remote ischemic perconditioning (RIPerC) could improve neuronal damage and inhibit inflammation and apoptosis. We conducted an in-depth exploration of the protective mechanism of RIPerC in cerebral ischaemia injury. In this study, a middle cerebral artery occlusion (MCAO) mouse model was built. According to whether to undergo RIPerC treatment and the duration of cerebral infarction, mice were divided into 5 groups: Sham group, MCAO 3.0 h group, MCAO 4.5 h group, MCAO 3.0 h + RIPerC group, and MCAO 4.5 h + RIPerC group. Overexpressed or silenced miR-153-5p was transfected into the cells to analyse the effects of oxygen-glucose deprivation (OGD) treatment on Neuro-2a cell viability, apoptosis, and related gene expressions by performing quantitative real-time polymerase chain reaction (qRT-PCR), MTT assay, flow cytometry, and Western blot. Bioinformatics analysis, qRT-PCR, dual-luciferase experiment, and RNA immunoprecipitation (RIP) were used to screen and verify the miRNA and downstream mRNA-targeted Toll-like receptor 4 (TLR4). The rescue test further verified the effects of the above target genes and miR-153-5p on the apoptosis of OGD-injured cells, apoptosis-related proteins, and the p65/IkBa pathway. The plasma levels of miR-153-5p in 68 patients with ischaemic stroke were detected within 6 hours of onset, and the patients were followed up for 3 months. We found that, in in vivo studies, RIPerC treatment inhibits cerebral infarction volume and neurological damage, and promotes the expression of miR-153-5p in the MCAO animal model. The expression of miR-153-5p in OGD cells was inhibited, and its upregulation protected Neuro-2a cells. TLR4 was predicted to be the target gene of miR-153-5p and could offset the effect of miR-153-5p mimic on OGD cell protection after up-regulating TLR4. TLR4 overexpression promoted the activation of OGD on the p65/IkBa pathway. Compared with the high plasma miR-153-5p group, the 3-month overall survival rate of patients with ischaemic stroke in the low plasma miR-153-5p group was significantly lower (c2 = 5.095, p = 0.024). In conclusion, RIPerC intervention inhibits the damage caused by cerebral ischaemia partially through the miR-153-5p/TLR4/p65/IkBa signalling pathway.

Local Disorder Facilitates Chain Stretching in Crowded Polymer Brushes.

Intermolecular crowding of densely tethered polymers promotes chain extension and anisotropy that induces many unique properties. In this study, we used conformation-sensitive infrared spectroscopy to determine that chain extension in a polymer brush is associated with local conformation rearrangements, i.e., contraction of side groups and increased proportion of gauche twists in the backbone, which served to increase molecular disorder at or below the segmental scale. This conformational transition points to a particular molecular mechanism for chain extension in densely tethered polymers, wherein increased local disorder facilitates global chain ordering (i.e., chain extension) and therefore supplements our current understanding of chain orientation at a molecular level.