Consensus on rapid screening for prodromal Alzheimer's disease in China.

Alzheimer's disease (AD) is a common cause of dementia, characterised by cerebral amyloid-ß deposition, pathological tau and neurodegeneration. The prodromal stage of AD (pAD) refers to patients with mild cognitive impairment (MCI) and evidence of AD's pathology. At this stage, disease-modifying interventions should be used to prevent the progression to dementia. Given the inherent heterogeneity of MCI, more specific biomarkers are needed to elucidate the underlying AD's pathology. Although the uses of cerebrospinal fluid and positron emission tomography are widely accepted methods for detecting AD's pathology, their clinical applications are limited by their high costs and invasiveness, particularly in low-income areas in China. Therefore, to improve the early detection of Alzheimer's disease (AD) pathology through cost-effective screening methods, a panel of 45 neurologists, psychiatrists and gerontologists was invited to establish a formal consensus on the screening of pAD in China. The supportive evidence and grades of recommendations are based on a systematic literature review and focus group discussion. National meetings were held to allow participants to review, vote and provide their expert opinions to reach a consensus. A majority (two-thirds) decision was used for questions for which consensus could not be reached. Recommended screening methods are presented in this publication, including neuropsychological assessment, peripheral biomarkers and brain imaging. In addition, a general workflow for screening pAD in China is established, which will help clinicians identify individuals at high risk and determine therapeutic targets.

[A Novel Three-minute Game-based Cognitive Risk Screening Tool-WeChat Mini-program-based Design and Large-sample Feasibility Studies].

OBJECTIVE: To develop a novel cognitive screening tool for older adults in China. METHODS: "Game-based Cognitive Assessment-3 Minute Version"(G3) was designed and developed based on WeChat mini-program. And its feasibility was analyzed. RESULTS: G3 mini-program contains three one-minute mini digital games and supports users' self-assessment of cognitive functions with instant access to reports. G3 had a good correlation with Montreal Cognitive Assessment Basic (MoCA-B) with Pearson's r =0.611 (P<0.001). Among natural users aged 50 and older (71 179), the G3 initiation and completion rates were 99.55% and 92.28%, respectively. The average time to complete G3 assessments was (278.5±73.73) seconds. CONCLUSIONS: The novel G3 mini-program has good feasibility and usability for older Chinese adults, and can be used for cognitive screening and home self-assessment.

Two-point fixation enhanced the outcome of laparoscopy-assisted ventriculoperitoneal shunt in adult patients with hydrocephalus: a retrospective study.

Objective: In patients with hydrocephalus, laparoscopy significantly improved ventriculoperitoneal shunt (VPS) outcomes. However, abdominal complications still occur, which require revision surgeries. In this study, we aimed to examine whether laparoscopy-assisted VPS with two-point fixation (LAVPS-TPF) has better outcomes than those of VPS (open-VPS) and laparoscopy-assisted VPS with no fixation (LAVPS-NF). Methods: We retrospectively reviewed clinical records of 105 open-VPS, 40 LAVPS-NF, and 49 LAVPS-TPF cases from 2015 to 2020. Data including body mass index, etiology, abdominal surgery history, Glasgow coma scale (GCS), operation time, in-hospital days, shunt failure, complications, and modified Rankin scores were analyzed, as well as subgroups of patients with history of abdominal surgery, GCS scores, and revision surgeries. Results: The LAVPS-TPF group demonstrated decreased shunt failure rates at 12 months (2.04%) compared to those of the open-VPS group (14.29%, P = 0.020) and reduced abdominal shunt-related complications (P = 0.004 vs. open-VPS and LAVPS-NF) and shunt revisions. In the LAVPS-TPF group with abdominal history (n = 51), 12-month shunt failure rates (P = 0.020 vs. open-VS), repair frequency (P = 0.020 vs. open-VS), and abdominal complications (P = 0.003 and 0.006 vs. open-VS and LAVPS-NF) were reduced. In the LAVPS-TPF group with GCS scores of 13-15 (n = 152), shunt failure rates at 12 months, abdominal complications, and revision frequency were decreased (P < 0.05 vs. other groups). Compared to the LAVPS-NF group, neurological complications were also reduced (P = 0.001). Among revision surgeries (n = 28), fixed shunts resulted in improved shunt survival rates at 12 months, reduced abdominal complications, and secondary revisions (P < 0.05). Moreover, a more optimal recovery without neurological sequelae was achieved by shunt fixation than that by LAVPS-NF (P < 0.01). Conclusions: LAVPS-TPF significantly improved shunt survival rates at 12 months and reduced the incidence of abdominal shunt-related complications compared to open-VPS and LAVPS-NF, especially in patients with history of abdominal surgery, higher GCS scores, and revision surgeries. However, further studies are required to confirm these benefits.

Shanghai Cognitive Screening: A Mobile Cognitive Assessment Tool Using Voice Recognition to Detect Mild Cognitive Impairment and Dementia in the Community.

BACKGROUND: A rapid digital instrument is needed to facilitate community-based screening of mild cognitive impairment (MCI) and Alzheimer's disease (AD) in China. OBJECTIVE: We developed a voice recognition-based cognitive assessment (Shanghai Cognitive Screening, SCS) on mobile devices and evaluated its diagnostic performance. METHODS: Participants (N = 251) including healthy controls (N = 98), subjective cognitive decline (SCD, N = 42), MCI (N = 80), and mild AD (N = 31) were recruited from the memory clinic at Shanghai Sixth People's Hospital. The SCS is fully self-administered, takes about six minutes and measures the function of visual memory, language, and executive function. Participants were instructed to complete SCS tests, gold-standard neuropsychological tests and standardized structural 3T brain MRI. RESULTS: The Cronbach's alpha was 0.910 of the overall scale, indicating high internal consistency. The SCS total score had an AUC of 0.921 to detect AD (sensitivity = 0.903, specificity = 0.945, positive predictive value = 0.700, negative predictive value = 0.986, likelihood ratio = 16.42, number needed for screening utility = 0.639), and an AUC of 0.838 to detect MCI (sensitivity = 0.793, specificity = 0.671, positive predictive value = 0.657, negative predictive value = 0.803, likelihood ratio = 2.41, number needed for screening utility = 0.944). The subtests demonstrated moderate to high correlations with the gold-standard tests from their respective cognitive domains. The SCS total score and its memory scores all correlated positively with relative volumes of the whole hippocampus and almost all subregions, after controlling for age, sex, and education. CONCLUSION: The SCS has good diagnostic accuracy for detecting MCI and AD dementia and has the potential to facilitate large-scale screening in the general community.

On the Conformation of Dimeric Acceptors and Their Polymer Solar Cells with Efficiency over 18 .

The determination of molecular conformations of oligomeric acceptors (OAs) and their impact on molecular packing are crucial for understanding the photovoltaic performance of their resulting polymer solar cells (PSCs) but have not been well studied yet. Herein, we synthesized two dimeric acceptor materials, DIBP3F-Se and DIBP3F-S, which bridged two segments of Y6-derivatives by selenophene and thiophene, respectively. Theoretical simulation and experimental 1D and 2D NMR spectroscopic studies prove that both dimers exhibit O-shaped conformations other than S- or U-shaped counter-ones. Notably, this O-shaped conformation is likely governed by a distinctive "conformational lock" mechanism, arising from the intensified intramolecular π-π interactions among their two terminal groups within the dimers. PSCs based on DIBP3F-Se deliver a maximum efficiency of 18.09 %, outperforming DIBP3F-S-based cells (16.11 %) and ranking among the highest efficiencies for OA-based PSCs. This work demonstrates a facile method to obtain OA conformations and highlights the potential of dimeric acceptors for high-performance PSCs.

Impact of vitamin D on the prognosis after spinal cord injury: A systematic review.

Vitamin D (VitD) insufficiency is a worldwide health problem and affects billions of people. Spinal cord injury (SCI) patients seem more susceptible to developing suboptimal levels of VitD. However, the literature regarding its impact on the prognosis of SCI is limited. Thus, in this review, we systematically investigated the published studies via a combination of keywords associated with SCI and VitD in four medical databases (Medline, Embase, Scopus, and Web of Science). All included studies were analyzed, and selected clinical data on the prevalence of VitD insufficiency (serum 25-hydroxyvitamin D < 30 ng/ml) and deficiency (serum 25-hydroxyvitamin D < 20 ng/ml) were collected for further meta-analysis via random effects. Through literature review, a total of 35 studies were eligible and included. The meta-analysis of VitD status (13 studies, 1,962 patients) indicated high prevalence of insufficiency (81.6% [75.7, 87.5]) and deficiency (52.5% [38.1, 66.9]) after SCI. Besides, low levels of VitD were reported to be associated with a higher risk of skeletal diseases, venous thromboembolism, psychoneurological syndromes, and chest illness after injury. Existing literature suggested that supplemental therapy might act as an adjuvant treatment to facilitate post-injury rehabilitation. Non-human experimental studies highlighted the neuroprotective effect of VitD, which was associated with enhancing axonal and neuronal survival, suppressing neuroinflammation, and modulating autophagy. Therefore, the current evidence suggests that the prevalence of VitD insufficiency is high in the SCI population, and low-level VitD may impair functional restoration after SCI. VitD supplemental treatment may have potential benefits to accelerate rehabilitation in mechanistically related processes after SCI. However, due to the limitation of the available evidence, more well-designed randomized controlled trials and mechanism experimental research are still needed to validate its therapeutic effect, elucidate its neuroprotective mechanism, and develop novel treatments.

Challenging PM6-like donor polymers for pairing with a Y-type state-of-the-art acceptor in binary blends for bulk heterojunction solar cells.

Being fluorine-free and a high performance material as a small organic acceptor molecule, BTP-eC9 has been well mixed with BDT-based PM6 donor polymers for providing satisfactory photovoltaic properties, especially towards future large scale/large area solar cell production. However, as one of the key electrical outputs from such binary active layer materials, the open circuit voltage (VOC) was limited to ca. 0.84 V, which needs to be further improved for BTP-eC9 to have a bright future. This paper focuses on the molecular design of alkylthio- and alkoxy-phenyl flanked benzo[1,2-b:4,5-b']dithiophene-based conjugated polymers (PBDT-PS-ttTPD or P10 for short and PBDT-PO-ttTPD or P11), which were successfully synthesized and applied as donor materials for pairing with BTP-eC9 in organic photovoltaic (OPV) devices. By fine-tuning the side chains of the benzodithiophene (BDT) moiety, such non-fullerene OPV devices with normal configuration demonstrate an attractively high open circuit voltage (VOC) of 0.89 and 0.87 V in P10/BTP-eC9 and P11/BTP-eC9 based binary single bulk heterojunction OPV devices, while still maintaining an excellent JSC of 22.7 and 20.0 mA cm-2 with a final power conversion efficiency (PCE) of 12.93% and 9.37%, respectively. The alkylthio-phenyl chain substituted BDT polymer exhibits better photovoltaic performance in all aspects than the alternative with alkoxy chains due to the synergistic effect of the alkylthio-phenyl flanked BDT, TPD, and π-bridge (thieno[3,2-b]thiophene).

Fine-Tuned Morphology Based on Two Well-Miscible Polymer Donors Enables Higher Open-Circuit Voltage and Enhanced Stability for Highly Efficient Ternary All-Polymer Solar Cells.

Developing organic solar cells based on a ternary active layer is one of the most effective approaches to improve their photovoltaic performance. However, limited success has been achieved in all-polymer solar cells (all-PSCs). In this study, a ternary all-PSC with improved efficiency and stability is realized by using J71 as the third component to adjust the host system of PBDB-T:PG1. The deeper highest occupied molecular orbital (HOMO) energy level of J71 downshifts the mixed HOMO energy levels of donors. The two polymer donors (PD s) have good miscibility and present Förster resonance energy transfer. When blended with PG1, the optimized morphology is obtained, showing enhanced crystallinity but meanwhile slightly reduced phase separation with improved exciton dissociation and collection efficiency, suppressed charge recombination, and reduced energy loss (0.55 eV). Combining the benefits mentioned above, the ternary all-PSC exhibits an excellent efficiency of 12.8% with simultaneously elevated open-circuit voltage (0.96 V), short-circuit current density (18.4 mA cm-2 ), and fill factor (72.2%). Moreover, the optimized ternary all-PSC shows improved storage and thermal stability. This study demonstrates that the utilization of a ternary all-polymer system based on two well-miscible PD s is an effective strategy to enhance the photovoltaic performance and stability of all-PSCs.

Effects of different hydrocolloids on the water migration, rheological and 3D printing characteristics of ß-carotene loaded yam starch-based hydrogel.

The effects of guar gum (GG), xanthan gum (XG), carrageenan gum (CG), xanthan-guar gum blend (XG-GG), chitosan (CS), gum arabic (GA) on the water migration, rheological and 3D printing properties of ß-carotene loaded yam starch-based hydrogel (BCH) were investigated to expand product form of ß-carotene. The results showed that CS addition promoted the migration of weakly bound water to tightly bound water in BCH. Addition of GG, CG, XG-GG, CS and GA enhanced apparent viscosity, G', G'', hardness and gumminess of BCH. CG, XG-GG, CS and GA addition improved printing stability of BCH. The printed objects added with GG and CS displayed smooth lines with fine resolution and higher formability, which showed a more uniform pore distribution and thinner gel skeleton structure. The results of XRD showed that hydrocolloids addition decreased the relative crystallinity of BCH. A combination of physicochemical parameters could be used to discriminate samples through hierarchical cluster analysis.

Clinical Outcomes of Transcranial and Endoscopic Endonasal Surgery for Craniopharyngiomas: A Single-Institution Experience.

OBJECTIVE: Craniopharyngioma has always been a challenge for the neurosurgeon, and there is no consensus on optimal treatment. The objective of this study was to compare surgical outcomes and complications between transcranial surgery (TCS) and endoscopic endonasal surgery (EES) of craniopharyngiomas. METHODS: A retrospective review of patients who underwent craniopharyngioma resection at Wuhan Union Hospital between January 2010 and December 2019 was performed. A total of 273 patients were enrolled in this retrospective study. All patients were analyzed with surgical effects, endocrinologic outcomes, complications, and follow-up results. RESULTS: A total of 185 patients underwent TCS and 88 underwent EES. There were no significant differences in patient demographic data, preoperative symptoms, and tumor characteristics between the two groups. The mean follow-up was 30.5 months (range 8-51 months). The EES group had a greater gross total resection (GTR) rate (89.8% EES vs. 77.3% TCS, p < 0.05) and lower rate of hypopituitarism (53.4% EES vs. 68.1% TCS, p < 0.05) and diabetes insipidus (DI) (51.1% EES vs. 72.4% TCS, p < 0.05). More postoperative cerebrospinal fluid (CSF) leaks occurred in the EES group (4.5% EES vs. 0% TCS, p < 0.05). More patients in the EES group with preoperative visual deficits experienced improvement after surgery (74.5% EES vs. 56.3% TCS, p < 0.05). There were statistical differences in the recurrence rates (12.5% EES vs. 23.8% TCS, p < 0.05) between the 2 groups. CONCLUSION: These data support the view that EES is a safe and effective minimally invasive surgery compared to TCS. Compared to TCS, EES has fewer surgical complications and a lower recurrence rate.

Current Understanding of Hearing Loss in Sporadic Vestibular Schwannomas: A Systematic Review.

OBJECTIVE: Hearing loss is the most common initial symptom in patients with sporadic vestibular schwannomas (SVS). Hearing preservation is an important goal of both conservative and surgical therapy. However, the mechanism of SVS-associated hearing loss remains unclear. Thus, we performed this systematic review to summarize the current understanding of hearing loss in the SVS and distill a testable hypothesis to further illuminate its underlying mechanism. METHODS: A systematic review querying four databases (PubMed, Medline, Embase, and Web of Science) was performed to identify studies evaluating hearing loss in patients with SVS and exploring the potential mechanisms of hearing impairment. RESULTS: A total of 50 articles were eligible and included in this review. After analysis, the retrieved studies could be categorized into four types: (1) 29 studies explore the relationship between hearing loss and the growth pattern of the tumor (e.g., tumor size/volume, growth rate, tumor location, etc.); (2) ten studies investigate the potential role of cochlear dysfunction in hearing deterioration, including structural abnormality, protein elevation in perilymph, and cochlear malfunctioning; (3) two studies looked into SVS-induced impairment of auditory pathway and cortex; (4) in the rest nine studies, researchers explored the molecular mechanism underlying hearing loss in SVS, which involves molecular and genetic alterations, inflammatory response, growth factors, and other tumor-associated secretions. CONCLUSIONS: Multiple factors may contribute to the hearing impairment in SVS, including the growth pattern of tumor, cochlear dysfunction, impairment of auditory pathway and cortex, genetic and molecular changes. However, our current understanding is still limited, and future studies are needed to explore this multifactorial hypothesis and dig deeper into its underlying mechanism.

Non-invasive approaches to functional recovery after spinal cord injury: Therapeutic targets and multimodal device interventions.

This paper is an interdisciplinary narrative review of efficacious non-invasive therapies that are increasingly used to restore function in people with chronic spinal cord injuries (SCI). First presented are the secondary injury cascade set in motion by the primary lesion and highlights in therapeutic development for mitigating the acute pathophysiologic process. Then summarized are current pharmacological strategies for modulation of noradrenergic, serotonergic, and dopaminergic neurotransmission to enhance recovery in bench and clinical studies of subacute and chronic SCI. Last examined is how neuromechanical devices (i.e., electrical stimulation, robotic assistance, brain-computer interface, and augmented sensory feedback) could be comprehensively engineered to engage efferent and afferent motosensory pathways to induce neuroplasticity-based neural pattern generation. Emerging evidence shows that computational models of the human neuromusculoskeletal system (i.e., human digital twins) can serve as functionalized anchors to integrate different neuromechanical and pharmacological interventions into a single multimodal prothesis. The system, if appropriately built, may cybernetically optimize treatment outcomes via coordination of heterogeneous biosensory, system output, and control signals. Overall, these rehabilitation protocols involved neuromodulation to evoke beneficial adaptive changes within spared supraspinal, intracord, and peripheral neuromuscular circuits to elicit neurological improvement. Therefore, qualitatively advancing the theoretical understanding of spinal cord neurobiology and neuromechanics is pivotal to designing new ways to reinstate locomotion after SCI. Future research efforts should concentrate on personalizing combination therapies consisting of pharmacological adjuncts, targeted neurobiological and neuromuscular repairs, and brain-computer interfaces, which follow multimodal neuromechanical principles.

Optimized Active Layer Morphologies via Ternary Copolymerization of Polymer Donors for 17.6 % Efficiency Organic Solar Cells with Enhanced Fill Factor.

Regulating molecular structure to optimize the active layer morphology is of considerable significance for improving the power conversion efficiencies (PCEs) in organic solar cells (OSCs). Herein, we demonstrated a simple ternary copolymerization approach to develop a terpolymer donor PM6-Tz20 by incorporating the 5,5'-dithienyl-2,2'-bithiazole (DTBTz, 20 mol%) unit into the backbone of PM6 (PM6-Tz00). This method can effectively tailor the molecular orientation and aggregation of the polymer, and then optimize the active layer morphology and the corresponding physical processes of devices, ultimately boosting FF and then PCE. Hence, the PM6-Tz20: Y6-based OSCs achieved a PCE of up to 17.1% with a significantly enhanced FF of 0.77. Using Ag (220 nm) instead of Al (100 nm) as cathode, the champion PCE was further improved to 17.6%. This work provides a simple and effective molecular design strategy to optimize the active layer morphology of OSCs for improving photovoltaic performance.

Visible light and temperature dual-responsive microgels by crosslinking of spiropyran modified prepolymers.

HYPOTHESIS: Light-responsive microgels are interesting colloidal systems with potential applications in the biotechnology and medicine. However, synthesis of light-responsive microgels with high loading of photoswitchable molecules is still very challenging. EXPERIMENTS: Herein we developed a new method to synthesize light and temperature dual-responsive spiropyran-modified poly(N-vinylcaprolactam) microgels. The novel and straightforward microgels synthesis route involved: a) synthesis of poly(N-vinylcaprolactam-co-vinylformamide) copolymers via RAFT polymerization followed by the hydrolysis to obtain primary amine groups, b) attachment of carboxyl-modified spiropyran molecules to polymer chains via coupling, and c) crosslinking of spiropyran-modified polymer chains in W/O miniemulsion to form microgels. FINDINGS: Via this method, we successfully synthesized poly(N-vinylcaprolactam) microgels containing more than 10 mol% spiropyran. The reversible light responsiveness of the spiropyran-modified copolymers and microgels in aqueous solution, which originates from the spiropyran photoisomerization under irradiation with different wavelengths, was demonstrated by UV-Vis spectroscopy. Spiropyran-modified copolymers demonstrate shift of the lower critical solution temperature (LCST) due to the polarity change of spiropyran molecules under dark, UV and visible light. Surprisingly, dynamic light scattering (DLS) results show that the microgels based on the same copolymers are less affected by UV irradiation. Microgels are swollen in darkness when spiropyran molecules are in the polar, merocyanine form, and collapse after irradiation with visible light, due to the transformation of spiropyran to the relatively nonpolar, closed spirocyclic form. In addition, the spiropyran-modified microgels exhibit reversible temperature responsiveness by presenting a volume phase transition in water from a swollen state to a collapsed state with increasing temperature and the transition temperature decreased compared to the pristine microgels due to the hydrophobicity of spiropyran units.

RPP25 as a Prognostic-Related Biomarker That Correlates With Tumor Metabolism in Glioblastoma.

RPP25, a 25 kDa protein subunit of ribonuclease P (RNase P), is a protein-coding gene. Disorders associated with RPP25 include chromosome 15Q24 deletion syndrome and diffuse scleroderma, while systemic sclerosis can be complicated by malignancy. However, the functional role of RPP25 expression in glioblastoma multiforme (GBM) is unclear. In this study, comprehensive bioinformatics analysis was used to evaluate the impact of RPP25 on GBM occurrence and prognosis. Differential analysis of multiple databases showed that RPP25 was commonly highly expressed in multiple cancers but lowly expressed in GBM. Survival prognostic results showed that RPP25 was prognostically relevant in six tumors (CESC, GBM, LAML, LUAD, SKCM, and UVM), but high RPP25 expression was significantly associated with poor patient prognosis except for CESC. Analysis of RPP25 expression in GBM alone revealed that RPP25 was significantly downregulated in GBM compared with normal tissue. Receiver operating characteristic (ROC) combined with Kaplan-Meier (KM) analysis and Cox regression analysis showed that high RPP25 expression was a prognostic risk factor for GBM and had a predictive value for the 1-year, 2-year, and 3-year survival of GBM patients. In addition, the expression of RPP25 was correlated with the level of immune cell infiltration. The gene set enrichment analysis (GSEA) results showed that RPP25 was mainly associated with signalling pathways related to tumor progression and tumor metabolism.

Butterfly Effects Arising from Starting Materials in Fused-Ring Electron Acceptors.

We designed and synthesized a series of fused-ring electron acceptors (FREAs) based on naphthalene-fused octacyclic cores end-capped by 3-(1,1-dicyanomethylene)-5,6-difluoro-1- indanone (NOICs) using a bottom-up approach. The NOIC series shares the same end groups and side chains, as well as similar fused-ring cores. The butterfly effects, arising from different methoxy positions in the starting materials, impact the design of the final FREAs, as well as their molecular packing, optical and electronic properties, charge transport, film morphology, and performance of organic solar cells. The binary-blend devices based on this NOIC series show power conversion efficiencies varying from 7.15% to 14.1%, due to the different intrinsic properties of the NOIC series, morphologies of blend films, and voltage losses of devices.

Random terpolymer based on thiophene-thiazolothiazole unit enabling efficient non-fullerene organic solar cells.

Developing a high-performance donor polymer is critical for achieving efficient non-fullerene organic solar cells (OSCs). Currently, most high-efficiency OSCs are based on a donor polymer named PM6, unfortunately, whose performance is highly sensitive to its molecular weight and thus has significant batch-to-batch variations. Here we report a donor polymer (named PM1) based on a random ternary polymerization strategy that enables highly efficient non-fullerene OSCs with efficiencies reaching 17.6%. Importantly, the PM1 polymer exhibits excellent batch-to-batch reproducibility. By including 20% of a weak electron-withdrawing thiophene-thiazolothiazole (TTz) into the PM6 polymer backbone, the resulting polymer (PM1) can maintain the positive effects (such as downshifted energy level and reduced miscibility) while minimize the negative ones (including reduced temperature-dependent aggregation property). With higher performance and greater synthesis reproducibility, the PM1 polymer has the promise to become the work-horse material for the non-fullerene OSC community.

Toward Drug Release Using Polymer Mechanochemical Disulfide Scission.

Traditional pharmacotherapy suffers from multiple drawbacks that hamper patient treatment, such as the buildup of antibiotic resistances or low drug selectivity and toxicity during systemic application. To overcome these challenges, drug activity can be controlled by employing delivery, targeting, or release solutions that mostly rely on the response to external physicochemical stimuli. Due to various technical limitations, mechanical force as a stimulus in the context of polymer mechanochemistry has so far not been used for this purpose, yet it has been proven to be a convenient and robust method to site-selectively rearrange or cleave bonds with submolecular precision in the realm of materials chemistry. Here, we present an unprecedented mechanochemically responsive system capable of successively releasing small furan-containing molecules, including the furylated fluorophore dansyl and the drugs furosemide as well as furylated doxorubicin, by ultrasound-induced selective scission of disulfide-centered polymers in solution. We show that mechanochemically generated thiol-terminated polymers undergo a Michael-type addition to Diels-Alder (DA) adducts of furylated drugs and acetylenedicarboxylate derivatives, initiating the downstream release of the small molecule drug by a retro DA reaction. We believe that this method can serve as a blueprint for the activation of many other small molecules.

Comparison of infection rate with tunneled vs standard external ventricular drainage: A prospective, randomized controlled trial.

OBJECTIVES: A prospective, blinded, randomized trial was performed to evaluate the incidence rates of external ventricular drainage (EVD)-related infection (ERI) after tunneled EVD (T-EVD) and standard EVD (S-EVD). PATIENTS AND METHODS: From February 2018 to February 2019, all adult patients admitted to the Union Hospital Neurosurgery Center for EVD placement were eligible for inclusion. After the application of strict exclusion criteria, all enrolled patients were randomly divided into two groups. The patients in Group A received S-EVD, and the remaining patients in Group B received T-EVD. A linear incision was made for T-EVD. The distal end of the catheter was inserted approximately 5 cm until cerebrospinal fluid was readily obtained, and then the catheter was tunneled approximately 4-5 cm from the insertion point. Finally, an external CSF drainage system was connected to the catheter. For the S-EVD patients, we secured the catheter at the original incision site after insertion, and an external CSF drainage system was also connected to the catheter. The rates of ERI were compared between the two patient groups. The odds ratios and χ² test were used to analyze the results. RESULTS: One hundred twenty patients were randomly divided into two groups and underwent EVD placement. Among them, 60 patients in Group A received S-EVD, and 60 patients in Group B received T-EVD. Finally, 51 patients in Group A and 50 patients in Group B met all of the study inclusion/exclusion criteria and were thus eligible for inclusion in the evaluation of ERI rates. All clinical features of the two groups were similar. A total of 12 patients' (11.9%) CSF cultures were positive for infection. Ten (19.6%) patients who underwent S-EVD had CSF-positive cultures, while only 2 (4.0%) patients who underwent T-EVD had CSF-positive cultures (P = 0.034). Additionally, 8 patients in Group A and 1 patient in Group B were complicated with CSF leakage (P = 0.039). CONCLUSIONS: Compared to S-EVD, T-EVD, when performed according to a previously established perioperative management protocol, resulted in lower infection and CSF leakage rates. We recommend that T-EVD should be preferentially performed when surgeons determine whether a catheter can be removed within 10 days, and the catheter used for EVD should be removed as soon as permitted by the clinical circumstances.