Dual-targeting tigecycline nanoparticles for treating intracranial infections caused by multidrug-resistant Acinetobacter baumannii.

Multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) is a formidable pathogen responsible for severe intracranial infections post-craniotomy, exhibiting a mortality rate as high as 71%. Tigecycline (TGC), a broad-spectrum antibiotic, emerged as a potential therapeutic agent for MDR A. baumannii infections. Nonetheless, its clinical application was hindered by a short in vivo half-life and limited permeability through the blood-brain barrier (BBB). In this study, we prepared a novel core-shell nanoparticle encapsulating water-soluble tigecycline using a blend of mPEG-PLGA and PLGA materials. This nanoparticle, modified with a dual-targeting peptide Aß11 and Tween 80 (Aß11/T80@CSs), was specifically designed to enhance the delivery of tigecycline to the brain for treating A. baumannii-induced intracranial infections. Our findings demonstrated that Aß11/T80@CSs nanocarriers successfully traversed the BBB and effectively delivered TGC into the cerebrospinal fluid (CSF), leading to a significant therapeutic response in a model of MDR A. baumannii intracranial infection. This study offers initial evidence and a platform for the application of brain-targeted nanocarrier delivery systems, showcasing their potential in administering water-soluble anti-infection drugs for intracranial infection treatments, and suggesting promising avenues for clinical translation.

H2S donor S-propargyl-cysteine for skin wound healing improvement via smart transdermal delivery.

Hydrogen sulfide for wound healing has drawn a lot of attention recently. In this research, the S-propargyl-cysteine (SPRC), an endogenous H2S donor, was loaded on carbomer hydrogel, and a copper sheet rat burn model was developed. Pathological changes in rat skin tissue were examined using hematoxylin-eosin (HE) and Masson staining. The immunohistochemistry (IHC) staining was performed to detect the expression of Collagen I (Col I) and Collagen III (Col III). The mRNA levels of interleukin (IL)-6, Col Iα2, Col IIIα1, tissue inhibitors of metalloproteinase (TIMP)-1, matrix metalloproteinase (MMP)-9, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)-ß1 were examined by quantitative real-time chain polymerase reaction. The findings demonstrated that the collagen layer was thicker in the SPRC group during the proliferative phase, SPRC hydrogel promoted VEGF expression. In the late stage of wound healing, the expression of IL-6, TIMP-1, MMP-9, and TGF-ß1 was inhibited, and the Col I content was closer to that of normal tissue. These results surface that SPRC hydrogel can promote wound healing and play a positive role in reducing scar formation. Our results imply that SPRC can facilitate wound healing and play a positive role in reducing scar formation.

Gastrointestinal manifestations of critical ill heatstroke patients and their associations with outcomes: A multicentre, retrospective, observational study.

BACKGROUND: Extreme heat exposure is a growing health problem, and the effects of heat on the gastrointestinal (GI) tract is unknown. This study aimed to assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes. AIM: To assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes. METHODS: Patients admitted to the intensive care unit (ICU) due to heatstroke were included from 83 centres. Patient history, laboratory results, and clinically relevant outcomes were recorded at ICU admission and daily until up to day 15, ICU discharge, or death. GI symptoms, including nausea/vomiting, diarrhoea, flatulence, and bloody stools, were recorded. The characteristics of patients with heatstroke concomitant with GI symptoms were described. Multivariable regression analyses were performed to determine significant predictors of GI symptoms. RESULTS: A total of 713 patients were included in the final analysis, of whom 132 (18.5%) patients had at least one GI symptom during their ICU stay, while 26 (3.6%) suffered from more than one symptom. Patients with GI symptoms had a significantly higher ICU stay compared with those without. The mortality of patients who had two or more GI symptoms simultaneously was significantly higher than that in those with one GI symptom. Multivariable logistic regression analysis revealed that older patients with a lower GCS score on admission were more likely to experience GI symptoms. CONCLUSION: The GI manifestations of heatstroke are common and appear to impact clinically relevant hospitalization outcomes.

Dental manifestations and treatment of hypophosphatemic rickets: A case report and review of literature.

BACKGROUND: The treatment and management of patients suffering from hypophosphatemic rickets (HR) remain a major challenge for dental practitioners and affected patients. OBJECTIVES: To report a case of HR presenting with specific dental findings and to review the dental manifestations and treatment of HR patients. METHODS: Case: A 32-year-old male presented with multiple dental abscesses and short stature. A thorough history was taken followed by clinical oral examination, and relevant radiological investigation was done. Literature research: In 2020, electronic literature searches were carried out in PubMed and complemented by a careful assessment of the reference lists of the identified relevant papers. Articles and reports fulfilled the inclusion criteria: indexed reviews, case series and case reports in English and restricted to human studies were considered. RESULTS: The intraoral examination revealed multiple dental abscesses and general periodontal disease; the radiographic examination showed poorly defined lamina dura, large pulp chambers and periapical lesions. Based on the contents of the 43 articles identified in the search, the current knowledge of dental manifestations, treatment and management of HR was summarized. CONCLUSIONS: As HR is a multisystem disease, multidisciplinary care is needed. By summarizing current evidences, we proposed an evidence-based dental management and provided recommendations on diagnosis and treatment of the disease. It is of profound clinical significance to acquire knowledge of the dental manifestations and provide optimal treatment options for patients.

Effects of an orthodontic primer containing amorphous fluorinated calcium phosphate nanoparticles on enamel white spot lesions.

OBJECTIVES: The study investigated the effects of an orthodontic primer containing amorphous fluorinated calcium phosphate (AFCP) nanoparticles on enamel white spot lesions (WSLs). MATERIALS AND METHODS: The AFCP nanoparticles were prepared and incorporated into Transbond XT Primer. Thirty-two human enamel slices were highly polished and randomly divided into four groups: no part covered (control), half covered with a primer containing 0 wt%, 25 wt%, and 35 wt% AFCP. Subsequently, samples were challenged by a modified pH-cycling and characterized by color measurement, micro-computed tomography, and scanning electron microscope (SEM). The bonding properties of the primers containing AFCP were assessed using shear bond strength test, and the mouse fibroblasts (L929) were employed to evaluate the cytotoxicity. RESULTS: When the enamel was challenged by pH cycling, 25 wt% and 35 wt% AFCP groups exhibited less color change (ΔE) and less mineral loss than the control and 0 wt% AFCP groups. The SEM images showed that the original microstructural integrity and mineral deposition rate of the enamel surface were better in the 25 wt% and 35 wt% AFCP groups. In particular, the 35 wt% AFCP group exhibited the best performance after 3 weeks of pH cycling. The shear bond strength and cell viability revealed no significant difference among the tested groups (P > 0.05). CONCLUSION: Using the primer containing 35 wt% AFCP might be a promising strategy for preventing the occurrence and development of WSLs during orthodontic treatment.

Cytosine-guanine-guanine repeats of FMR1 gene negatively affect ovarian reserve and response in Chinese women.

RESEARCH QUESTION: Do cytosine-guanine-guanine (CGG) repeats of the FMR1 gene affect ovarian function, ovarian response and assisted reproductive technology (ART) outcomes in Chinese women? DESIGN: A retrospective cohort study of 5869 women who underwent 8932 ART cycles at Women's Hospital, School of Medicine, Zhejiang University between January 2018 and June 2021. Basic hormone level, oocyte yield, embryo quality and the rate of live birth were considered as main outcome measures to evaluate the effects of CGG repeats on ovarian function, ovarian response and ART outcomes. RESULTS: The CGG repeats were negatively related to serum anti-Müllerian hormone (AMH), oestradiol, antral follicle count (AFC) and oocyte yield. A significant association was found between serum AMH, oestradiol and AFC even after age was controlled for. No statistically significant association, however, was found between CGG repeats and embryo quality or live birth rate. Ovarian function mediated the association between CGG repeats and ovarian response. CONCLUSION: Increased CGG repeats on the FMR1 gene were associated with diminished ovarian function and poor ovarian response, and ovarian function played an intermediary role in the relationship between CGG repeats and ovarian response.

Nanoparticle elasticity affects systemic circulation lifetime by modulating adsorption of apolipoprotein A-I in corona formation.

Nanoparticle elasticity is crucial in nanoparticles' physiological fate, but how this occurs is largely unknown. Using core-shell nanoparticles with a same PEGylated lipid bilayer shell yet cores differing in elasticity (45 kPa - 760 MPa) as models, we isolate the effects of nanoparticle elasticity from those of other physiochemical parameters and, using mouse models, observe a non-monotonic relationship of systemic circulation lifetime versus nanoparticle elasticity. Incubating our nanoparticles in mouse plasma provides protein coronas varying non-monotonically in composition depending on nanoparticle elasticity. Particularly, apolipoprotein A-I (ApoA1) is the only protein whose relative abundance in corona strongly correlates with our nanoparticles' blood clearance lifetime. Notably, similar results are observed when above nanoparticles' PEGylated lipid bilayer shell is changed to be non-PEGylated. This work unveils the mechanisms by which nanoparticle elasticity affects nanoparticles' physiological fate and suggests nanoparticle elasticity as a readily tunable parameter in future rational exploiting of protein corona.

Disinfection methods of dental unit waterlines contamination: a systematic review.

Background. Severe contamination of dental unit waterlines was found in healthcare settings. The benefits of decontamination methods are controversial. The aim of this review was to systematically evaluate disinfection methods in contamination control of dental unit waterlines.Methods. The terms 'dental unit waterline(s) or DUWL(s) or dental unit water line(s)' were searched through PubMed, Cochrane Library, Embase, Web of Science and Scopusup to 31 May 2021. The DUWLs' output water was incubated on R2A agar at 20-28 °C for 5-7 days to evaluate heterotrophic mesophilic bacteria. The risk of bias was evaluated by a modified Newcastle-Ottawa quality assessment scale.Results. Eighteen papers from the literature were included. One study indicated that water supply played a crucial role in disinfecting DUWLs. Three studies indicated that flushing decreased bacteria counts but did not meet the American CDC standard (500 c.f.u. ml-1). All chlorine- and peroxide-containing disinfectants except sodium hypochlorite in one of 15 studies as well as three mouthrinses and citrus botanical extract achieved the standard (≤500 c.f.u. ml-1). The included studies were of low (1/18), moderate (6/18) and high (11/18) quality.Conclusion. Independent water reservoirs are recommended for disinfecting DUWLs using distilled water. Flushing DUWLs should be combined with disinfections. Nearly all the chlorine-, chlorhexidine- and peroxide-containing disinfectants, mouthrinses and citrus botanical extract meet the standard for disinfecting DUWLs. Alkaline peroxide would lead to tube blockage in the DUWLs. Regularly changing disinfectants can reduce the risk of occurrence of disinfectant-resistant strains of microbes.

How to Make Personal Protective Equipment Spontaneously and Continuously Antimicrobial (Incorporating Oxidase-like Catalysts).

The inability of commercial personal protective equipment (PPE) to inactivate microbes in the droplets/aerosols they intercept makes used PPE a potential source of cross-contamination. To make PPE spontaneously and continuously antimicrobial, we incorporate PPE with oxidase-like catalysts, which efficiently convert O2 into reactive oxygen species (ROS) without requiring any externally applied stimulus. Using a single-atom catalyst (SAC) nanoparticle containing atomically dispersed copper atoms as the reactive centers (Cu-SAC) and a silver-palladium bimetallic alloy nanoparticle (AgPd0.38) as models for oxidase-like catalysts, we show that the incorporation of oxidase-like catalysts enables PPE to inactivate bacteria in the droplets/aerosols they intercept without requiring any externally applied stimulus. Notably, this approach works both for PPE that are fibrous and woven such as a commercial KN95 facial respirator and for those made of solid plastics such as an apron. This work suggests a feasible and global approach for preventing PPE from spreading infectious diseases.

Retrospective study on the effectiveness of a prevention strategy in a dental hospital during the COVID-19 pandemic.

OBJECTIVES: To evaluate the effectiveness of a prevention strategy against the spread of SARS-CoV-2 infection among dental hospital staff over a 3-month period. MATERIALS AND METHODS: The effectiveness of the prevention strategy, which adopted healthcare staff protective measures, including patient triage and correct usage of personal preventive equipment, was evaluated by SARS-CoV-2 detection and serological testing. Patients who visited the Affiliated Stomatology Hospital, Zhejiang University School of Medicine, Hangzhou, China, between January 31 and March 1 (lockdown period) and March 2 and April 27 (reopening period) in 2020 and in the same period in 2019 were included in the study. Patients' diagnosis, age, gender, and several undergoing aerosol-generating procedures during the study period were collected from the hospital's database. Corresponding data were compared year-on-year (2020-on-2019). A total of 757 hospital staff underwent SARS-CoV-2 detection and serological testing on April 28-29, 2020. RESULTS: During the lockdown and reopening period in 2020, the number of hospital visits was dramatically decreased to about 6% and 58%, respectively, compared with the same period in 2019. However, emergency visits were increased 16- and 6.4-fold. A total of at least 6654 patients (13.58%) underwent aerosol-generating procedures during the study period in the year 2020. All hospital staff were negative according to SARS-CoV-2 detection and serological testing (IgG, IgM) data. CONCLUSION: During the study period in 2020, the total number of hospital visits dramatically reduced but emergency visits significantly increased. The prevention strategy implemented successfully prevented SARS-CoV-2 infection spread among healthcare workers in a dental hospital. CLINICAL RELEVANCE: The prevention strategy indicated patient triage and how to adopt preventive measures for controlling SARS-CoV-2 spread among healthcare workers. These data can be used as a reference for other sectors suffering from the COVID-19 pandemic.

Biomimetic fabrication and application of fibrous-like nanotubes.

AIMS: To investigate the biomimetic fabrication of fibrous-like organic-inorganic hybrid structures via a simple bottom-up approach, viz. self-assembly of simple molecules, and apply fibrous-like composites as a novel primer to improve dentin bond strengths of self-etch adhesives. MATERIALS AND METHODS: The resultants of commercial amorphous calcium phosphate (ACP) nanoparticles and 10-methacryloyloxydecyl dihydrogen phosphate (MDP) ethanol-aqueous solution were analyzed by TEM, SEM, XRD, DLS and AFM. The acid and alkali resistance of abovementioned self-assembled composites were analyzed with TEM. Micro-tensile bond strengths (MTBS) tests were performed after polished dentin surfaces were pretreated with self-assembled composites. The pretreated dentin surfaces and dentin-resin interfaces were characterized by SEM/TEM. KEY FINDINGS: ACP nanoparticles in MDP solution could self-assemble into fibrous-like nanotube structures in 8 nm diameter. Self-assembly and self-proliferation process went from ACP nanoparticles, dissolved ACP nanoparticles (less than 50 nm), twig-like structures and fibrous-like nanotubes to cellular networks. The fibrous-like nanotubes were only detected when the amount of ACP in reaction system were more than 0.01 g. The more ACP interacted with MDP, the more fibrous-like nanotubes were formed. After the dentin surfaces were treated with fibrous-like nanotube composites, MTBS could be significantly improved. Moreover, the fibrous-like nanotube structures could be resistant to acidic challenge, and were stable at least for 3 months. SIGNIFICANCE: The fibrous-like nanotube structures could be self-assembled via a bottom-up approach at certain ratio of MDP and commercial ACP nanoparticles. The application of fibrous-like nanotube composites as a novel primer prior to self-etch adhesives greatly improved dentin bond strengths.