Induction of protective immune responses at respiratory mucosal sites.

Many pathogens enter the host through mucosal sites. Thus, interfering with pathogen entry through local neutralization at mucosal sites therefore is an effective strategy for preventing disease. Mucosally administered vaccines have the potential to induce protective immune responses at mucosal sites. This manuscript delves into some of the latest developments in mucosal vaccination, particularly focusing on advancements in adjuvant technologies and the role of these adjuvants in enhancing vaccine efficacy against respiratory pathogens. It highlights the anatomical and immunological complexities of the respiratory mucosal immune system, emphasizing the significance of mucosal secretory IgA and tissue-resident memory T cells in local immune responses. We further discuss the differences between immune responses induced through traditional parenteral vaccination approaches vs. mucosal administration strategies, and explore the protective advantages offered by immunization through mucosal routes.

Standard Versus Rapid Inpatient Methadone Titration for Pregnant Patients With Opioid Use Disorder: A Retrospective Cohort Study.

OBJECTIVES: Our study evaluated if rapid inpatient titration of methadone for pregnant patients with opioid use disorder (OUD) improved outcomes without increasing the risk for overdose. METHODS: This is a retrospective cohort study of pregnant patients admitted for inpatient methadone titration from January 2020 to June 2022. Outcomes were compared between standard versus rapid titration protocols. Standard titration involved an initial methadone dose with additional doses every 6 hours if clinical opiate withdrawal score (COWS) is >9. Rapid titration involved an initial methadone dose with additional doses every 4 hours if COWS is >9. The primary outcome was time required to achieve stable dose. Secondary outcomes included elopement prior to achieving stable dose, methadone-related readmission, opioid overdose, and final dose. RESULTS: There were 97 patients in the standard titration (STP) and 97 patients in the rapid titration (RTP) groups. Demographic characteristics and substance use history did not differ between the 2 groups. Time to stable dose did not differ between the 2 groups (RTP, 5.0 days ±4.0; STP, 4.0 days ±3.0; P = 0.08). Patients in the rapid titration group were less likely to elope from the hospital prior to stabilization (RTP 23.0% vs STP 37.9%, P = 0.03) and had fewer methadone-related readmissions (P < 0.001). One patient (1.0%) in the RTP group required naloxone treatment while inpatient for concern for overdose, while none did in the STP group (P = 0.32). There was no difference in median final stable dose between the 2 groups (P = 0.07). CONCLUSIONS: Rapid titration of methadone for pregnant patients with OUD was associated with decreased medical elopement and methadone-related readmission, without increasing the risk for overdose.

Intravenous versus oral acetaminophen for pain and quality of recovery after ambulatory spine surgery: a randomized controlled trial.

INTRODUCTION: As ambulatory spine surgery increases, efficient recovery and discharge become essential. Multimodal analgesia is superior to opioids alone. Acetaminophen is a central component of multimodal protocols and both intravenous and oral forms are used. While some advantages for intravenous acetaminophen have been touted, prospective studies with patient-centered outcomes are lacking in ambulatory spine surgery. A substantial cost difference exists. We hypothesized that intravenous acetaminophen would be associated with fewer opioids and better recovery. METHODS: Patients undergoing ambulatory spine surgery were randomized to preoperative oral placebo and intraoperative intravenous acetaminophen or preoperative oral acetaminophen. All patients received general anesthesia and multimodal analgesia. The primary outcome was 24-hour opioid use in intravenous morphine milligram equivalents (MMEs), beginning with arrival to the postanesthesia care unit (PACU). Secondary outcomes included pain, Quality of Recovery (QoR)-15 scores, postoperative nausea and vomiting, recovery time, and correlations between pain catastrophizing, QoR-15, and pain. RESULTS: A total of 82 patients were included in final analyses. Demographics were similar between groups. For the primary outcome, the median 24-hour MMEs did not differ between groups (12.6 (4.0, 27.1) vs 12.0 (4.0, 29.5) mg, p=0.893). Postoperative pain ratings, PACU MMEs, QoR-15 scores, and recovery time showed no differences. Spearman's correlation showed a moderate negative correlation between postoperative opioid use and QoR-15. CONCLUSION: Intravenous acetaminophen was not superior to the oral form in ambulatory spine surgery patients. This does not support routine use of the more expensive intravenous form to improve recovery and accelerate discharge. TRIAL REGISTRATION NUMBER: NCT04574778.

High performance polyvinyl alcohol/lignin fibers with excellent mechanical and water resistance properties.

To address the shortcoming of Polyvinyl alcohol (PVA) fibers for food or medical packaging materials including low mechanical strength and poor water resistance, lignin (LN) was used as raw material, acetone/H2O as solvent to self-assemble into lignin nanoparticles (LNP) by adverse solvent precipitation approach, and then PVA/LNP composite fibers with different LNP contents were fabricated successfully by wet and dry spinning. Herein, vast hydrophilic hydroxyl groups in PVA decreased owing to the hydrogen bond between LN and PVA, Especially, with only 0.5 wt% loading of LNP into the PVA/LNP fibers, the diameter was 94.4 dtex, tensile strength was 10.1 cN/dtex (1279.8 MPa), initial modulus was 94.7 cN/dtex (12.0 GPa), the crystallinity was 56.7 %, the orientation was 97.1 %, and water contact angle was 103.1°. Compared with pure PVA fibers, the tensile strength of PVA/LNP-0.5 fibers was increased by 44.2 % and the contact angle was increased 37°. This work provides novel insights into obtaining lignin-reinforced PVA composite fibers with strong mechanical properties and excellent water resistance properties, indicating the potential of the PVA/LNP fibers for food or medical packaging application.

Transcranial pulse stimulation in the treatment of mild neurocognitive disorders.

OBJECTIVE: There are limited effectiveness and potential side effects of existing pharmacological approach in treating mild neurocognitive disorder (NCD). Transcranial pulse stimulation (TPS) applies repetitive single high-pressure ultrashort shockwave pulses to stimulate the brain, which has been shown to effectively improve cognition in major NCD. However, the effectiveness of TPS in mild NCD patients remained unknown. This study aims to assess the effectiveness and tolerability of TPS with neuro-navigation in old-age adults with mild NCD by both clinical and biochemical assessments. METHODS: An open-label study recruited older adults with mild NCD to receive neuro-navigated TPS intervention for two weeks with three sessions per week. Assessments included detailed cognitive assessments, APOE genotype, and brain-derived neurotrophic factor (BDNF). RESULTS: Nineteen participants (12 females and 7 males) completed the whole TPS interventions with no serious adverse effects reported. Repeated measures ANOVA showed statistically significant effects of time on HK-MoCA (F (3, 54) = 4.99, P = 0.004), 30-sec interval of Verbal Fluency Test (F (3, 54) = 2.94, P = 0.041), Stroop interference (F (3, 54) = 3.46, P = 0.023), and Chinese IADL (F (3, 54) = 2.78, P = 0.050) after receiving the intervention. Bonferroni post hoc comparisons on HK-MoCA showed a significant improvement after intervention. There was no significant change in serum BDNF level. INTERPRETATION: TPS has brought significant improvement in cognition of elderly with mild NCD. It has a great potential to delay the deterioration of cognition in older adults. The long-term effect of TPS in cognition would benefit from further large-scale, randomized, sham-controlled trials.

A novel colorimetric biosensor for detecting SARS-CoV-2 by utilizing the interaction between nucleocapsid antibody and spike proteins.

SARS-CoV-2 is a pandemic coronavirus that causes severe respiratory disease (COVID-19) in humans and is responsible for millions of deaths around the world since early 2020. The virus affects the human respiratory cells through its spike (S) proteins located at the outer shell. To monitor the rapid spreading of SARS-CoV-2 and to reduce the deaths from the COVID-19, early detection of SARS-CoV-2 is of utmost necessity. This report describes a flexible colorimetric biosensor capable of detecting the S protein of SARS-CoV-2. The colorimetric biosensor is made of polyurethane (PU)-polydiacetylene (PDA) nanofiber composite that was chemically functionalized to create a binding site for the receptor molecule-nucleocapsid antibody (anti-N) protein of SARS-CoV-2. After the anti-N protein conjugation to the functionalized PDA fibers, the PU-PDA-NHS-anti fiber was able to detect the S protein of SARS-CoV-2 at room temperature via a colorimetric transition from blue to red. The PU-PDA nanofiber-based biosensors are flexible and lightweight and do not require a power supply such as a battery when the colorimetric detection to S protein occurs, suggesting a sensing platform of wearable devices and personal protective equipment such as face masks and medical gowns for real-time monitoring of virus contraction and contamination. The wearable biosensors could significantly power mass surveillance technologies to fight against the COVID-19 pandemic. Supplementary Information: The online version contains supplementary material available at 10.1007/s44164-022-00022-z.

Mechanical Considerations of Electrospun Scaffolds for Myocardial Tissue and Regenerative Engineering.

Biomaterials to facilitate the restoration of cardiac tissue is of emerging importance. While there are many aspects to consider in the design of biomaterials, mechanical properties can be of particular importance in this dynamically remodeling tissue. This review focuses on one specific processing method, electrospinning, that is employed to generate materials with a fibrous microstructure that can be combined with material properties to achieve the desired mechanical behavior. Current methods used to fabricate mechanically relevant micro-/nanofibrous scaffolds, in vivo studies using these scaffolds as therapeutics, and common techniques to characterize the mechanical properties of the scaffolds are covered. We also discuss the discrepancies in the reported elastic modulus for physiological and pathological myocardium in the literature, as well as the emerging area of in vitro mechanobiology studies to investigate the mechanical regulation in cardiac tissue engineering. Lastly, future perspectives and recommendations are offered in order to enhance the understanding of cardiac mechanobiology and foster therapeutic development in myocardial regenerative medicine.

Protective activity of geraniol against acetic acid and Helicobacter pylori- induced gastric ulcers in rats.

Geraniol, an active constituent of rose and palmarosa essential oils, possesses several pharmacological properties, including antioxidant, antibacterial and antiulcer activity. Geraniol was therefore investigated for its antiulcer and anti-Helicobacter pylori activity in rats. Ulcers were induced by injecting acetic acid into the sub-serosal layer of the stomach followed by orogastric inoculation of H. pylori for 7 days. Geraniol (15 and 30 mg/kg), vehicle and a standard drug combination (amoxicillin, 50 mg/kg; clarithromycin, 25 mg/kg and omeprazole, 20 mg/kg) were administered twice daily for 14 days. All the parameters were measured at the end of treatment. The ulcer index was significantly (P < 0.05) lowered in geraniol and standard drug-treated rats as compared to the H. pylori control group (4.13 ±â€¯0.43). Treatment with geraniol (30 mg/kg) significantly (P < 0.01) increased the gastric pH along with a reduction in total acidity and gastric juice volume. Geraniol significantly (P < 0.05) attenuated the myeloperoxidase activity and augmented the total glutathione level in gastric mucosa. The extent of damage in the stomach was measured using a histopathological score. The score in H. pylori control, geraniol (30 mg/kg) and standard drugs was 9, 3.5 and 2.0 respectively. In the rapid urease test, treatment with geraniol (30 mg/kg) and the standard drugs produced a 33% and 67% cure respectively from H. pylori infection. Further, the reduction in bacterial load in the gastric mucosa was confirmed using modified Giemsa staining. Geraniol was observed to exhibit significant antiulcer and anti-H. pylori activity in a rodent model.

Novel ZnO/NiO Janus-like nanofibers for effective photocatalytic degradation.

In recent years, Janus materials have become a research hotspot in the field of materials science; however, fabricating inorganic Janus-like nanofibers (NFs) is still a challenge. Herein, we report novel ZnO/NiO Janus-like NFs with efficient photocatalytic performance via an electrospinning method followed by calcination treatment. The morphology, structure, chemical composition and crystallinity of ZnO/NiO Janus-like NFs were studied in detail via SEM, TEM, HRTEM, EDS, FT-IR, XPS and XRD, indicating that the NFs had a perfect Janus-like structure composed of ZnO and NiO. A series of photocatalytic experiments were carried out in aqueous organic dye solutions under 365 nm UV radiation for 1 h, with the degradation rate of malachite green able to reach 96%, proving that the NFs have great potential in the field of organic dye degradation. Furthermore, a reasonable catalytic mechanism for the ZnO/NiO Janus-like NFs was proposed, which was discussed from the view of electron-hole pairs and p-n junctions. In short, the method in our work is expected to become a new way of effectively preparing functional inorganic Janus-like NFs.

Independent association of serum vitamin D with anti-Mullerian hormone levels in women with polycystic ovary syndrome.

OBJECTIVE: This study aimed at investigating the association of serum vitamin D (25(OH)D) and anti-Mullerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) as well as non-PCOS healthy ovulatory women and the possible confounding effects of adiposity and androgen. METHOD: This was a cross-sectional study conducted on serum samples collected from 451 women diagnosed with PCOS as well as 244 age-matched healthy ovulatory women in a tertiary gynaecology out-patient clinic and a family planning clinic. RESULTS: Serum 25(OH)D level was significantly higher in women recruited during summer and autumn than those recruited in winter and spring. Both serum 25(OH)D and AMH levels peaked during summer in women with PCOS. In ovulatory women, only serum 25(OH)D but not AMH level showed such seasonal variation. Serum 25(OH)D level in women with PCOS significantly correlated positively with AMH, AMH/antral follicle count (AFC) ratio, serum total testosterone, sex-hormone-binding globulin and quantitative insulin-sensitivity check index and inversely with body mass index (BMI), insulin, triglycerides and homeostatic model assessment of insulin resistance. After controlling for BMI, 25(OH)D level remained significantly correlated positively with serum AMH, AMH/AFC and total testosterone, and inversely with triglycerides. 25(OH)D level was an independent predictor of serum AMH level after controlling for age, BMI and free androgen index in women with PCOS. CONCLUSION: Serum 25(OH)D level is an independent factor significantly associated with AMH level in women with PCOS but not in ovulatory women.

An asymmetric graphene oxide film for developing moisture actuators.

Although Janus films of different compositions have been commonly utilized to develop moisture actuators due to the different capabilities of swelling in materials, a sole material with a distinct structural design is also able to provide moisture-actuation. In this study, we simply used graphene oxide (GO) to fabricate a sole GO film with an asymmetric structure which consisted of a wavy layer and a smooth layer. Due to the asymmetric structure and excellent hygroscopicity of the GO material, the asymmetric graphene oxide (AGO) film (2.5 × 0.5 cm2) was responsive to moisture and showed a maximum bending angle change of ≈1800° as the relative humidity (RH) changed. Compared with other reports about moisture actuators, the AGO film exhibited a superior bending capability. Furthermore, we propose a novel mechanism for moisture actuation of the AGO film based on our detailed observations, and a wavy structure has been introduced for showing great potential in bending deformation. Finally, the AGO film was used as a grabber to grab a leaf and it exhibited good capability to twine around a plastic rod. This work provides a novel pathway for the development of moisture-responsive materials for potential applications in robotics, artificial muscles and switches.

Polydiacetylene Nanofiber Composites as a Colorimetric Sensor Responding To Escherichia coli and pH.

Polydiacetylenes (PDAs) are conjugative polymers that demonstrate color changes as a response to an external stimulus. In this study, 10,12-pentacosadiynoic acid (PCDA) was mixed with a supporting polymer including poly(ethylene oxide) (PEO) and polyurethane (PU), and the mixture solution was electrospun to construct fiber composites. The electrospun fibers were then photopolymerized using UV irradiation to produce PEO-PDA and PU-PDA nanofiber mats with a fiber diameter ranging from 130 nm to 2.5 µm. The morphologies of both PEO-PDA and PU-PDA nanofibers were dependent on electrospinning parameters such as the ratio of PCDA to PEO or PCDA to PU and the total polymer concentrations. Scanning electron microscopy images showed beaded fibers of PEO-PDA and PU-PDA at 2 and 18 w/v % concentrations, respectively. Smooth fibers were found when the solvent concentration was increased to 3.75 w/v % in PEO-PDA and 25 w/v % in PU-PDA fibers. Both PEO-PDA and PU-PDA nanofiber composites demonstrated excellent colorimetric responses to the presence of Escherichia coli ATCC25922 bacterial cells and the changes in pH as external stimuli. The nanofibers underwent a rapid colorimetric response when exposed directly to E. coli ATCC25922 grown on Luria-Bertani agar. The comparison between the PEO-PDA and PU-PDA suggested that the combination of PEO and PDA is favorable because it provides a sensitive response to the presence of E. coli. The results were compared with samples of a PDA polymer in the absence of a matrix polymer. The colorimetric response was similar when the PDA polymer and the PDA nanofiber composites were exposed to pH changes, and the color change was found to occur at pH 10 and enhanced at pH 11-13. The PDA-containing nanofiber composites showed stronger colorimetric responses than those of the PDA polymer only, suggesting their potential as biosensors and chemosensors.

Study of Polydiacetylene-Poly (Ethylene Oxide) Electrospun Fibers Used as Biosensors.

Polydiacetylene (PDA) is an attractive conjugated material for use in biosensors due to its unique characteristic of undergoing a blue-to-red color change in response to external stimuli. 10,12-Pentacosadiynoic acid (PCDA) and poly (ethylene oxide) (PEO) were used in this study to develop fiber composites via an electrospinning method at various mass ratios of PEO to PCDA, solution concentrations, and injection speeds. The PEO-PDA fibers in blue phase were obtained via photo-polymerization upon UV-light irritation. High mass ratios of PEO to PCDA, low polymer concentrations of spinning solution, and low injection speeds promoted fine fibers with small diameters and smooth surfaces. The colorimetric transition of the fibers was investigated when the fibers were heated at temperatures ranging from 25 °C to 120 °C. A color switch from blue to red in the fibers was observed when the fibers were heated at temperatures greater than 60 °C. The color transition was more sensitive in the fibers made with a low mass ratio of PEO to PCDA due to high fraction of PDA in the fibers. The large diameter fibers also promoted the color switch due to high reflectance area in the fibers. All of the fibers were analyzed using Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) and compared before and after the color change occurred. The colorimetric transitional mechanism is proposed to occur due to conformational changes in the PDA macromolecules.

Retention of silica nanoparticles on calcium carbonate sands immersed in electrolyte solutions.

Understanding nanoparticle-surface adhesion is necessary to develop inert tracers for subsurface applications. Here we show that nanoparticles with neutral surface charge may make the best subsurface tracers, and that it may be possible to used SiO2 nanoparticle retention to measure the fraction of solid surface that has positive charge. We show that silica nanoparticles dispersed in NaCl electrolyte solutions are increasingly retained in calcium carbonate (calcite) sand-packed columns as the solution ionic strength increases, but are not retained if they are injected in pure water or Na2SO4 electrolyte solutions. The particles retained in the NaCl experiments are released when the column is flushed with pure water or Na2SO4 solution. AFM measurements on calcite immersed in NaCl solutions show the initial repulsion of a silica colloidal probe as the surface is approached is reduced as the solution ionic strength increases, and that at high ionic strengths it disappears entirely and only attraction remains. These AFM measurements and their interpretation with Derjaguin-Landau-Verwey-Overbeek (DLVO) theory shows the calcite surface charge is always negative for Na2SO4 solutions, but changes from negative to positive in a patchy fashion as the ionic strength of the NaCl solution increases. Since mixed-charge (patchy) surfaces may be common in the subsurface, nanoparticles with near-zero charge may make the best tracers.