Nanoscale borosilicate bioactive glass for regenerative therapy of full-thickness skin defects in rabbit animal model.

Bioactive glass (BG) occupies a significant position in the field of hard and soft tissue regeneration. Different processing techniques and formulas have been introduced to expand their regenerative, angiogenic, and antibacterial properties. In the present study, a new formula of bborosilicate bioactive glass nanofibers was prepared and tested for its wound-healing efficacy in a rabbit animal model. The glass formula ((1-2) mol% of B2O3 (68-69) mol% of SiO2, and (29-30) mol% of CaO) was prepared primarily by the sol-gel technique followed by the electrospinning technique. The material was characterized for its ultrastructure using scanning electron microscopy, chemical composition using FTIR, and its dynamic in vitro biodegradability using ICP-AES. Twelve rabbits were subjected to surgical induction of full-thickness skin defects using a 1 cm2 custom-made stainlessteel skin punch. The bioactive glass nanofibers were used as a grafting material in 6 experimental rabbits, while the defects in the remaining rabbits were considered as the negative control samples. All defects were assessed clinically for the decrease in wound size and clinical signs of healing and histologically for angiogenesis, collagen density, inflammatory response, cell recruitment, epithelial lining, and appendages at 1,2 and 3 weeks following the intervention. Structural analysis of the glass fibers confirmed their nano-size which ranged from 150 to 700 nm. Moreover, the chemical analysis confirmed the presence of SiO2 and B2O3 groups within the structure of the nanofibers. Additionally, dynamic biodegradation analysis confirmed the rapid degradation of the material starting from the first 24 h and rapid leaching of calcium, silicon, and boron ions confirming its bioactivity. The wound healing study of the nanofibrous scaffold confirmed its ability to accelerate wound healing and the closure rate in healthy rabbits. Histological analysis of the defects confirmed the angiogenic, regenerative and antibacterial ability of the material throughout the study period. The results unveil the powerful therapeutic properties of the formed nanofibers and open a new gate for more experimental and clinical applications.

Heterocyclic Electrochemistry: Renewable Electricity in the Construction of Heterocycles.

Numerous applications in the realm of biological exploration and drug synthesis can be found in heterocyclic chemistry, which is a vast subject. Many efforts have been developed to further improve the reaction conditions to access this interesting family to prevent employing hazardous ingredients. In this instance, it has been stated that green and environmentally friendly manufacturing methodologies have been introduced to create N-, S-, and O-heterocycles. It appears to be one of the most promising methods to access these types of compounds avoiding use of stoichiometric amounts of oxidizing/reducing species or precious metal catalysts, in which only catalytic amounts are sufficient, and it represent an ideal way of contributing toward the resource economy. Thus, renewable electricity provides clean electrons (oxidant/reductant) that initiate a reaction cascade via producing reactive intermediates that facilitate in building new bonds for valuable chemical transformations. Moreover, electrochemical activation using metals as catalytic mediators has been identified as a more efficient strategy toward selective functionalization. Thus, indirect electrolysis makes the potential range more practical, and less side reactions can occur. The latest developments in using an electrolytic strategy to create N-, S-, and O-heterocycles are the main topic of this mini review, which was documented over the last five years.

Frequency and Risk Factors for Difficult Intubation in Women Undergoing General Anesthesia for Cesarean Delivery: A Multicenter Retrospective Cohort Analysis.

BACKGROUND: Estimates for the incidence of difficult intubation in the obstetric population vary widely, although previous studies reporting rates of difficult intubation in obstetrics are older and limited by smaller samples. The goals of this study were to provide a contemporary estimate of the frequency of difficult and failed intubation in women undergoing general anesthesia for cesarean delivery and to elucidate risk factors for difficult intubation in women undergoing general anesthesia for cesarean delivery. METHODS: This is a multicenter, retrospective cohort study utilizing the Multicenter Perioperative Outcomes Group database. The study population included women aged 15 to 44 yr undergoing general anesthesia for cesarean delivery between 2004 and 2019 at 1 of 45 medical centers. Coprimary outcomes included the frequencies of difficult and failed intubation. Difficult intubation was defined as Cormack-Lehane view of 3 or greater, three or more intubation attempts, rescue fiberoptic intubation, rescue supraglottic airway, or surgical airway. Failed intubation was defined as any attempt at intubation without successful endotracheal tube placement. The rates of difficult and failed intubation were assessed. Several patient demographic, anatomical, and obstetric factors were evaluated for potential associations with difficult intubation. RESULTS: This study identified 14,748 cases of cesarean delivery performed under general anesthesia. There were 295 cases of difficult intubation, with a frequency of 1:49 (95% CI, 1:55 to 1:44; n = 14,531). There were 18 cases of failed intubation, with a frequency of 1:808 (95% CI, 1:1,276 to 1:511; n = 14,537). Factors with the highest point estimates for the odds of difficult intubation included increased body mass index, Mallampati score III or IV, small hyoid-to-mentum distance, limited jaw protrusion, limited mouth opening, and cervical spine limitations. CONCLUSIONS: In this large, multicenter, contemporary study of more than 14,000 general anesthetics for cesarean delivery, an overall risk of difficult intubation of 1:49 and a risk of failed intubation of 1:808 were observed. Most risk factors for difficult intubation were nonobstetric in nature. These data demonstrate that difficult intubation in obstetrics remains an ongoing concern.

Opioid deaths involving concurrent benzodiazepine use: Assessing risk factors through the analysis of prescription drug monitoring data and postmortem toxicology.

BACKGROUND: A high proportion of opioid drug deaths involve concurrent benzodiazepine use. To reduce the risk of drug overdose, various prescription drug monitoring programs have been implemented. This study examined the impact of concurrent benzodiazepine use on opioid-related deaths, and the utility of the Michigan Automated Prescription System (MAPS) in predicting risk of opioid death. METHODS: Wayne County Medical Examiner's Office cases from 2018 were examined in terms of MAPS data and MAPS-derived drug risk scores, as well as postmortem toxicology. Opioid death cases with concurrent benzodiazepine use were compared to non-drug deaths. RESULTS: For cases with a MAPS history for 6 months preceding death, the incidence of opioid prescriptions filled did not differ between groups. In contrast, significantly more opioid death cases had filled a benzodiazepine prescription; alprazolam prescription was the single best predictor of opioid drug death. Groups differed in MAPS-calculated drug risk scores, though these were less predictive of opioid death than some individual measures of prescription drug use. In terms of postmortem toxicology, fentanyl was the best discriminator between cohorts, with significant associations seen for morphine, benzodiazepine, or cocaine use. Similar results were obtained in the subset of subjects filling a prescription within a month of death, except that MAPS risk scores no longer predicted drug deaths. CONCLUSION: MAPS scores did not adequately predict risk of opioid-related death. Contrary to expectations, prescription opioid use was not correlated with opioid-related death, whereas concurrent use of opioids and benzodiazepines represented a highly significant risk factor.

Efficacy of Bioactive Glass Nanofibers Tested for Oral Mucosal Regeneration in Rabbits with Induced Diabetes.

The healing of oral lesions that are associated with diabetes mellitus is a matter of great concern. Bioactive glass is a highly recommended bioceramic scaffold for bone and soft tissue regeneration. In this study, we aimed to assess the efficacy of a novel formula of bioactive glass nanofibers in enhancing oral mucosal wound regeneration in diabetes mellitus. Bioactive glass nanofibres (BGnf) of composition (1-2) mol% of B2O3, (68-69) mol% of SiO2, and (29-30) mol% of CaO were synthesized via the low-temperature sol-gel technique followed by mixing with polymer solution, then electrospinning of the glass sol to produce nanofibers, which were then subjected to heat treatment. X-Ray Diffraction analysis of the prepared nanofibers confirmed its amorphous nature. Microstructure of BGnf simulated that of the fibrin clot with cross-linked nanofibers having a varying range of diameter (500-900 nm). The in-vitro degradation profile of BGnf confirmed its high dissolution rate, which proved the glass bioactivity. Following fibers preparation and characterization, 12 healthy New Zealand male rabbits were successfully subjected to type I diabetic induction using a single dose of intravenous injection of alloxan monohydrate. Two weeks after diabetes confirmation, the rabbits were randomly divided into two groups (control and experimental groups). Bilateral elliptical oral mucosal defects of 10 × 3.5 mm were created in the maxillary mucobuccal fold of both groups. The defects of the experimental group were grafted with BGnf, while the other group of defects considered as a control group. Clinical, histological, and immune-histochemical assessment of both groups of wounds were performed after one, two and three weeks' time interval. The results of the clinical evaluation of BGnf treated defects showed complete wound closure with the absence of inflammation signs starting from one week postoperative. Control defects, on the other hand, showed an open wound with suppurative exudate. On histological and immunohistochemical level, the BGnf treated defects revealed increasing in cell activity and vascularization with the absence of inflammation signs starting from one week time interval, while the control defects showed signs of suppurative inflammation at one week time interval with diminished vascularization. The results advocated the suitability of BGnf as bioscaffold to be used in a wet environment as the oral cavity that is full of microorganisms and also for an immune-compromised condition as diabetes mellitus.

Assessment of vancomycin utilization among Lebanese hospitals.

OBJECTIVES: To assess the appropriateness of vancomycin dosing and monitoring at Lebanese hospitals. METHODS: This was a multicenter retrospective study conducted at 3 Lebanese hospitals between January and March 2018. Patients 18 years of age and older treated with vancomycin for a systemic infection or prophylaxis were eligible for study enrollment. Consistency with the Infectious Diseases Society of America guidelines was evaluated to determine whether the dose of vancomycin was appropriate, as well as for the time of trough measurement, and the target concentration obtained. RESULTS: From a total of 120 patients who met the inclusion criteria, only 11 (12%) were given the appropriate maintenance dose of vancomycin with respect to actual body weight. The trough levels were monitored for 67 (55.8%) patients, with 20 (29.9%) of these patients achieving appropriate therapeutic trough levels of 15-20 mg/l. The trough concentration time measurement before the fourth dose was only carried out in 28 (41.8%) of the 67 patients. CONCLUSION: This study reveals a gap between the appropriate utilization of vancomycin with respect to the international guidelines in the studied Lebanese hospitals. It highlights the need for dosing and monitoring protocols suitable for vancomycin utilization in these hospitals.

Differentially expressed gene networks, biomarkers, long noncoding RNAs, and shared responses with cocaine identified in the midbrains of human opioid abusers.

Opioid abuse is now the most common cause of accidental death in the US. Although opioids and most other drugs of abuse acutely increase signaling mediated by midbrain dopamine (DA)-synthesizing neurons, little is known about long-lasting changes in DA cells that may contribute to continued opioid abuse, craving, and relapse. A better understanding of the molecular and cellular bases of opioid abuse could lead to advancements in therapeutics. This study comprises, to our knowledge, the first unbiased examination of genome-wide changes in midbrain gene expression associated with human opioid abuse. Our analyses identified differentially expressed genes and distinct gene networks associated with opioid abuse, specific genes with predictive capability for subject assignment to the opioid abuse cohort, and genes most similarly affected in chronic opioid and cocaine abusers. We also identified differentially expressed long noncoding RNAs capable of regulating known drug-responsive protein-coding genes. Opioid-regulated genes identified in this study warrant further investigation as potential biomarkers and/or therapeutic targets for human substance abuse.

Opioid Deaths: Trends, Biomarkers, and Potential Drug Interactions Revealed by Decision Tree Analyses.

Opioid abuse is now the primary cause of accidental deaths in the United States. Studies over several decades established the cyclical nature of abused drugs of choice, with a current resurgence of heroin abuse and, more recently, fentanyl's emergence as a major precipitant of drug-related deaths. To better understand abuse trends and to explore the potential lethality of specific drug-drug interactions, we conducted statistical analyses of forensic toxicological data from the Wayne County Medical Examiner's Office from 2012-2016. We observed clear changes in opioid abuse over this period, including the rapid emergence of fentanyl and its analogs as highly significant causes of lethality starting in 2014. We then used Chi-square Automatic Interaction Detector (CHAID)-based decision tree analyses to obtain insights regarding specific drugs, drug combinations, and biomarkers in blood most predictive of cause of death or circumstances surrounding death. The presence of the non-opioid drug acetaminophen was highly predictive of drug-related deaths, likely reflecting the abuse of various combined acetaminophen-opioid formulations. The short-lived cocaine adulterant levamisole was highly predictive of a short post-cocaine survival time preceding sudden non-drug-related death. The combination of the opioid methadone and the antidepressant citalopram was uniformly linked to drug death, suggesting a potential drug-drug interaction at the level of a pathophysiological effect on the heart and/or drug metabolism. The presence of fentanyl plus the benzodiazepine midazolam was diagnostic for in-hospital deaths following serious medical illness and interventions that included these drugs. These data highlight the power of decision tree analyses not only in the determination of cause of death, but also as a key surveillance tool to inform drug abuse treatment and public health policies for combating the opioid crisis.

Platelet rich plasma enhances osteoconductive properties of a hydroxyapatite-ß-tricalcium phosphate scaffold (Skelite) for late healing of critical size rabbit calvarial defects.

The use of platelet rich plasma (PRP) in bone repair remains highly controversial. In this work, we evaluated the effect of lyophilized PRP on bone regeneration when associated with a silicon stabilized hydroxyapatite tricalcium phosphate scaffold in a rabbit calvarial defect (Skelite). Critical defects were created in the calvaria of twenty-four rabbits. The periosteum was removed and the defects were either left empty or filled with allogeneic PRP gel; Skelite particles; Skelite and PRP gel. Four animals were killed after 4 weeks, 10 animals after 8 and 10 after 16 weeks. Specimens were processed for X-ray microtomography (µCT) and for resin embedded histology. µCT analysis revealed significant osteoid-like matrix and new bone deposition in PRP + Skelite group at both 8 and 16 weeks in respect to Skelite alone. Histologically, PRP + Skelite defects were highly cellular with more abundant osteoid deposition and more regular collagen fibres. Moreover, in vitro migration assays confirmed the chemotactic effect of PRP to endothelial and osteoprogenitor cells. We conclude that the addition of PRP influenced the local tissue microenvironment by providing key cryptic factors for regeneration, thereby enhancing progenitor cell recruitment, collagen and bone matrix deposition, and by creating a bridging interface between the scaffold and bone.

Cultured keratinocytes on urinary bladder matrix scaffolds increase angiogenesis and help in rapid healing of wounds.

INTRODUCTION: Urinary Bladder Matrix (UBM) is an extracellular matrix (ECM) scaffold. It is now used in wound care management of partial and full-thickness wounds where conventional methods for wound care usually fail to give satisfactory results. OBJECTIVE: In this study, the authors are comparing the healing of full-thickness excisional wounds in New Zealand rabbits using either UBM scaffolds alone or in combination with cultured keratinocytes. The wounds were compared grossly and histologically. MATERIALS AND METHODS: It is a comparative controlled study including 40 full-thickness wounds in 2 groups. Group (A) wounds: treated with UBM scaffolds, Group (B) wounds: treated with UBM scaffolds with cultured keratinocytes. The wounds were examined grossly after 1, 2, and 3 weeks, and were examined histologically at the end of the 3rd week using ordinary hematoxylin-eosin staining techniques. RESULTS: All the wounds healed completely by the end of the 3rd week. Early wound contraction was significantly less in group B. More angiogenic response was evident in all specimens of group B. CONCLUSION: This study shows that adding cultured keratinocytes to the rough surface of the UBM scaffold may be beneficial in reducing early wound contraction and improving wound vascularity in treatment of full-thickness wounds.

Immediate- and medium-term effects of balloon pulmonary valvuloplasty in infants with critical pulmonary stenoses during the first year of life: A prospective single center study.

BACKGROUND: Balloon pulmonary valvuloplasty (BPV) represents the standard of management for all patients with severe pulmonary stenosis (PS) irrespective of their age. Nevertheless neonates and infants with critical PS represent a high-risk group that needs to be studied. METHODS: The study population included 72 infants with severe congenital valvular PS and four infants with imperforate pulmonary valve (PV) who were subjected to detailed history taking, full clinical examination, resting 12-lead ECG, Chest roentgenogram and transthoracic echocardiography. BPV was attempted in all infants with a peak-to-peak gradient across the PV of 50 mmHg or greater at catheterization-laboratory. Full echocardiographic evaluation was done 24 hours after the procedure as well as 3 and 6 months later. RESULTS: Seventy-six infants with severe PS or imperforate PV with a mean age of 5.63 ± 2.99 months were subjected to BPV with or without wire perforation. Immediately after the procedure patients had a significant reduction of the right ventricular systolic pressure (RVSP) (104.69 ± 24.98 mm Hg Vs 43.6 ± 13 mm Hg, p < 0.001) and RV-PA systolic pressure gradient (PG) (82.5 ± 23.76 mm Hg Vs 17.35 ± 8.96 mm Hg, p < 0.001). The immediate success rate defined as the drop in the RVSP to less than or equal to 50% of the baseline measurement was achieved in 85% of the cases. There was a progressive drop in the PG across the PV by Doppler echocardiogram throughout a follow-up period of six months from a mean of 93.3 ± 28.2 mm Hg to a mean of 17.4 ± 10.42 mm Hg (p < 0.001). There was a significant increase of the mean PV annulus diameter after balloon dilatation (p < 0.001). There was also a highly significant inverse correlation between the growth of the pulmonary annulus and the annular size at the baseline before dilatation (r = -0.74, p value <0.001). The incidence of PR significantly increased immediately after BPV to 64% followed by a progressive decline over a 6 months period of follow-up to 20%. There was a significant decrease in the incidence of tricuspid regurgitation (TR) over the same period of follow-up (from 55.6% at baseline to less than 20% at follow-up). CONCLUSION: BPV is safe and effective to relieve critical PS in infants during the first year of life. The balloon promotes advantageous changes in both, pulmonary annulus and PG across the RVOT. In addition, the Doppler gradient observations during the follow-up support the expectation that BPV is a "curative" therapy.

Experimental formation of periodontal structure around titanium implants utilizing bone marrow mesenchymal stem cells: a pilot study.

Tissue engineering in the head and neck area, presents numerous advantages. One of the most remarkable advantages is that regeneration of only a small amount of tissue can be highly beneficial to the patient, particularly in the field of periodontal tissue regeneration. For decades, successful osseointegration has provided thousands of restorations that maintain normal function. With the increasing need to utilize dental implants for growing patients and enhance their function to simulate normal tooth physiology and proprioception, there appears to be an urgent need for t concept of periodontal tissue regeneration around dental implants. In the present work, 5 goats wer used for immediate implant placement post canine teeth extraction. Each goat received 2 implan fixtures; the control side received a porous hollow root-form poly (DL-Lactide-co-Glycolide) scaf around the titanium fixture, and the experimental side received the same scaffold but seeded with autogenous bone marrow-derived mesenchymal stem cells. One animal was killed 10 days postoperatively, and the others were killed after 1 month. The results showed that on th experimental side, periodontal-like tissue with newly formed bone was demonstrated both at 1 days and after 1 month, while the control specimens showed early signs of connective tissue regeneration around the titanium fixture at 10 days, but was not shown in the 1 month specimens. I can be concluded that undifferentiated mesenchymal stem cells were capable of differentiating t provide the 3 critical tissues required for periodontal tissue regeneration: cementum, bone, a periodontal ligament. This work may provide a new approach for periodontal tissue regeneration.

Preservation and regeneration of alveolar bone by tissue-engineered implants.

Bone maintenance after dental extraction has a significant impact on the success of future treatment. The purpose of this study was to regenerate bone by implanting an engineered porous scaffold seeded with bone marrow mesenchymal stem cells (BMSCs) in a socket created by extraction of the lower left central incisor in rabbits, utilizing the principles of tissue engineering. It involved preparation and characterization of three-dimensional porous hollow root form scaffolds consisting of a poly-L-lactic acid:polyglycolic acid composite (PLG, 50:50), using a solvent casting/compression molding/particulate leaching technique. Porosity of the scaffolds was 83.71% with good interconnectivity and uniform distribution of the various pore sizes. The degraded scaffolds maintained their porosity and form for the first 2 weeks and their mass loss continued up to 6 weeks. The scaffolds developed viscoelastic behavior under dynamic compression; yet they lost their mechanical characteristics as they degraded. The scaffolds were seeded with BMSCs and examined by scanning electron microscopy. Cell proliferation and scaffold degradation were shown up to 2 weeks in vitro. The cultivated scaffolds were implanted in empty extraction sockets immediately after tooth removal. Four weeks later, bone regeneration was evaluated histologically in the healed sockets in three experimental groups: sockets left empty, sockets that received PLG without cells, and sockets that received PLG with cells. Radiographic evaluation, performed 4 weeks later for the three experimental groups, demonstrated preservation of alveolar bone walls in the extraction sockets that received PLG with cells as compared with the other two groups. The bone density profile for the healed sockets confirmed both histological and radiographic findings. The results of this study show promise in the area of dentoalveolar surgery, yet longitudinal studies under variable clinical situations would encourage the current application.