Radiofrequency atrial flutter and atrial fibrillation ablation in a patient with deep brain stimulation.

Radiofrequency ablation for atrial fibrillation or atrial flutter is feasible in patients with deep brain stimulation but with extreme caution given the possibility of life-threatening complications.

Evidence-based brief interventions targeting acute mental health presentations for children and adolescents: systematic review.

BACKGROUND: Brief intervention services provide rapid, mobile and flexible short-term delivery of interventions to resolve mental health crises. These interventions may provide an alternative pathway to the emergency department or in-patient psychiatric services for children and young people (CYP), presenting with an acute mental health condition. AIMS: To synthesise evidence on the effectiveness of brief interventions in improving mental health outcomes for CYP (0-17 years) presenting with an acute mental health condition. METHOD: A systematic literature search was conducted, and the studies' methodological quality was assessed. Five databases were searched for peer-reviewed articles between January 2000 and September 2022. RESULTS: We synthesised 30 articles on the effectiveness of brief interventions in the form of (a) crisis intervention, (b) integrated services, (c) group therapies, (d) individualised therapy, (e) parent-child dyadic therapy, (f) general services, (g) pharmacotherapy, (h) assessment services, (i) safety and risk planning and (j) in-hospital treatment, to improve outcomes for CYP with an acute mental health condition. Among included studies, one study was rated as providing a high level of evidence based on the National Health and Medical Research Council levels of evidence hierarchy scale, which was a crisis intervention showing a reduction in length of stay and return emergency department visits. Other studies, of moderate-quality evidence, described multimodal brief interventions that suggested beneficial effects. CONCLUSIONS: This review provides evidence to substantiate the benefits of brief interventions, in different settings, to reduce the burden of in-patient hospital and readmission rates to the emergency department.

Evidence-based long term interventions targeting acute mental health presentations for children and adolescents: systematic review.

Background: Long term intervention services have proven to be effective in improving mental health (MH) outcomes and the quality of life for children and young people (CYP). Aim: To synthesize evidence on the effectiveness of long-term interventions in improving MH outcomes for CYP, 0-17 years, presenting with MH conditions. Methods: A systematic search was carried out and the methodological quality of included long term MH intervention studies were assessed. Six databases were searched for peer-reviewed articles between January 2000 and September 2022. Results: We found 30 studies that reported on the effectiveness of a range of long-term MH interventions in the form of (i) group therapy, (ii) multisystemic behavior therapy, (iii) general services, (iv) integrated services, (v) psychotherapy, (vi) intensive intervention services, (vii) comprehensive collaborative care, (viii) parent training, and (ix) home outreach service. Among the included studies, seven were rated as high level of evidence based on the National Health and Medical Research Council (NHMRC) levels of evidence hierarchy scale and seven were of moderate quality evidence. Others were rated as lower-quality evidence. Among the studies providing high quality evidence, most were reported for group therapy, general services, and psychotherapy studies demonstrating beneficial effects. Conclusion: This systematic review provides evidence to demonstrate the benefits of a range of long-term interventions, in a range of settings, can be effective in improving MH outcomes for CYP and their families. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022323324.

Cross-streamline migration and near-wall depletion of elastic fibers in micro-channel flows.

The complex dynamics of elastic fibers in viscous fluids are central to many biological and industrial systems. Fluid-structure interactions underlying these dynamics govern the shape and transport of flexible fibers, and understanding these interactions can help tune flow properties in applications such as microfluidic separation, printing and clogging. In this work, we use slender-body theory to study micromechanical dynamics that arise from the coupling between the elastic backbone of a fiber and the local straining flow that contributes to filament flipping and cross-streamline migration. The resulting transverse drift is unbiased in either direction in simple shear flow. However, a non-uniform shear rate results in bias towards regions of high shear, which we connect to the shape transitions during flips. We discover a depletion layer that forms near the boundaries of pressure-driven channel flow due to the competition between such a cross-streamline drift and steric exclusion from the walls. Finally, we develop scaling laws for the curvature of filaments during flip events, demonstrating the origin of the drift bias in non-uniform flows, and confirm this behavior from our simulations. Put together, these results shed light on the role of a local and dominant coupling between elasticity and viscous resistance in dictating long-term dynamics and transport of elastic fibers in confined flows.

Machine Learning-Led Optimization of Combination Therapy: Confronting the Public Health Threat of Extensively Drug Resistant Gram-Negative Bacteria.

Developing optimized regimens for combination antibiotic therapy is challenging and often performed empirically over many clinical studies. Novel implementation of a hybrid machine-learning pharmacokinetic/pharmacodynamic/toxicodynamic (ML-PK/PD/TD) approach optimizes combination therapy using human PK/TD data along with in vitro PD data. This study utilized human population PK (PopPK) of aztreonam, ceftazidime/avibactam, and polymyxin B along with in vitro PDs from the Hollow Fiber Infection Model (HFIM) to derive optimal multi-drug regimens de novo through implementation of a genetic algorithm (GA). The mechanism-based PD model was constructed based on 7-day HFIM experiments across 4 clinical, extensively drug resistant Klebsiella pneumoniae isolates. GA-led optimization was performed using 13 different fitness functions to compare the effects of different efficacy (60%, 70%, 80%, or 90% of simulated subjects achieving bacterial counts of 102 CFU/mL) and toxicity (66% of simulated subjects having a target polymyxin B area under the concentration-time curve [AUC] of 100 mg·h/L and aztreonam AUC of 1,332 mg·h/L) on the optimized regimen. All regimens, except those most heavily weighted for toxicity prevention, were able to achieve the target efficacy threshold (102 CFU/mL). Overall, GA-based regimen optimization using preclinical data from animal-sparing in vitro studies and human PopPK produced clinically relevant dosage regimens similar to those developed empirically over many years for all three antibiotics. Taken together, these data provide significant insight into new therapeutic approaches incorporating ML to regimen design and treatment of resistant bacterial infections.

A mechanism-based pathway toward administering highly active N-phage cocktails.

Bacteriophage (phage) therapy is being explored as a possible response to the antimicrobial resistance public health emergency. Administering a mixture of different phage types as a cocktail is one proposed strategy for therapeutic applications, but the optimal method for formulating phage cocktails remains a major challenge. Each phage strain has complex pharmacokinetic/pharmacodynamic (PK/PD) properties which depend on the nano-scale size, target-mediated, self-dosing nature of each phage strain, and rapid selection of resistant subpopulations. The objective of this study was to explore the pharmacodynamics (PD) of three unique and clinically relevant anti-Pseudomonas phages after simulation of dynamic dosing strategies. The Hollow Fiber Infection Model (HFIM) is an in vitro system that mimics in vivo pharmacokinetics (PK) with high fidelity, providing an opportunity to quantify phage and bacteria concentration profiles over clinical time scales with rich sampling. Exogenous monotherapy-bolus (producing max concentrations of Cmax = 7 log10 PFU/mL) regimens of phages LUZ19, PYO2, and E215 produced Pseudomonas aeruginosa nadirs of 0, 2.14, or 2.99 log10 CFU/mL after 6 h of treatment, respectively. Exogenous combination therapy bolus regimens (LUZ19 + PYO2 or LUZ19 + E215) resulted in bacterial reduction to <2 log10 CFU/mL. In contrast, monotherapy as a continuous infusion (producing a steady-state concentration of Css,avg = 2 log10PFU/mL) was less effective at reducing bacterial densities. Specifically, PYO2 failed to reduce bacterial density. Next, a mechanism-based mathematical model was developed to describe phage pharmacodynamics, phage-phage competition, and phage-dependent adaptive phage resistance. Monte Carlo simulations supported bolus dose regimens, predicting lower bacterial counts with bolus dosing as compared to prolonged phage infusions. Together, in vitro and in silico evaluation of the time course of phage pharmacodynamics will better guide optimal patterns of administration of individual phages as a cocktail.

Early-onset juvenile nasopharyngeal angiofibroma (JNA): a systematic review.

BACKGROUND: Juvenile Nasopharyngeal Angiofibroma (JNA) is a fibrovascular tumor of the nasopharynx that classically presents in adolescent males. The reported mean age of onset is between 13 and 22 years old [1-6]. Significant androgen stimulation is hypothesized to explain the strong predisposition for JNA to present in young adolescent males. However, considerable variability in age at diagnosis exists with rare involvement of very young patients incongruent with typical male pubertal growth patterns. OBJECTIVE: The purpose of this systematic review is to identify cases of early-onset JNA (EOJNA), (defined as age < 10 years) in the literature and to examine the disease characteristics and treatments used in this patient group. A case of a 7 year old boy with EOJNA at our institution is also described and presented. METHODS: We searched Embase, Cochrane database and MEDLINE from 1996 to February 2021 for studies that reported cases of EOJNA. Relevant clinico-demographic data, disease severity and treatment outcomes were recorded and analyzed using descriptive statistics. We compared our findings with reported means for JNA in all ages. RESULTS: We identified 29 studies containing a total of 34 cases of EOJNA. The vast majority (31/34) of patients were males and the mean age of diagnosis was 8.15 years old. The most common presenting symptoms were nasal obstruction (65.2%) and epistaxis (60.9%). Patients were most commonly Radkowski stage II (39.4%) and III (39.4%). Primary treatment modalities included open surgery (66.7%), endoscopic surgery (24.2%), and radiotherapy (9.1%). Recurrence was evident in 30%. Radkowski stage and type of treatment did not differ significantly within the EOJNA group (p = 0.440 and p = 0.659, respectively). CONCLUSION: This systematic review suggests that rare cases of EOJNA have distinct disease characteristics. Patients in this cohort appeared to have more advanced disease and higher recurrence rates when compared with reported averages. We hope that this review prompts increased clinical awareness of this potentially more aggressive subtype of JNA. As more cases of EOJNA are reported, a more powered statistical analysis of this cohort would be feasible.

Persistent Brain Connectivity Changes in Healthy Volunteers Following Nitrous Oxide Inhalation.

Background: Nitrous oxide holds promise in the treatment of major depressive disorder. Its psychotropic effects and NMDA receptor antagonism have led to comparisons with ketamine. Despite longstanding use, persistent effects of nitrous oxide on the brain have not been characterized. Methods: Sixteen healthy volunteers were recruited in a double-blind crossover study. In randomized order, individuals underwent a 1-hour inhalation of either 50% nitrous oxide/oxygen or air/oxygen mixtures. At least two 7.5-minute echo-planar resting-state functional magnetic resonance imaging scans were obtained before and at 2 and 24 hours after each inhalation (average 130 min/participant). Using the time series of preprocessed, motion artifact-scrubbed, and nuisance covariate-regressed imaging data, interregional signal correlations were measured and converted to T scores. Hierarchical clustering and linear mixed-effects models were employed. Results: Nitrous oxide inhalation produced changes in global brain connectivity that persisted in the occipital cortex at 2 and 24 hours postinhalation (p < .05, false discovery rate-corrected). Analysis of resting-state networks demonstrated robust strengthening of connectivity between regions of the visual network and those of the dorsal attention network, across 2 and 24 hours after inhalation (p < .05, false discovery rate-corrected). Weaker changes in connectivity were found between the visual cortex and regions of the frontoparietal and default mode networks. Parallel analyses following air/oxygen inhalation yielded no significant changes in functional connectivity. Conclusions: Nitrous oxide inhalation in healthy volunteers revealed persistent increases in global connectivity between regions of primary visual cortex and dorsal attention network. These findings suggest that nitrous oxide inhalation induces neurophysiological cortical changes that persist for at least 24 hours.

A novel phosphorylation site involved in dissociating RAF kinase from the scaffolding protein 14-3-3 and disrupting RAF dimerization.

Rapidly accelerated fibrosarcoma (ARAF, BRAF, CRAF) kinase is central to the MAPK pathway (RAS-RAF-MEK-ERK). Inactive RAF kinase is believed to be monomeric, autoinhibited, and cytosolic, while activated RAF is recruited to the membrane via RAS-GTP, leading to the relief of autoinhibition, phosphorylation of key regulatory sites, and dimerization of RAF protomers. Although it is well known that active and inactive BRAF have differential phosphorylation sites that play a crucial role in regulating BRAF, key details are still missing. In this study, we report the characterization of a novel phosphorylation site, BRAFS732 (equivalent in CRAFS624), located in proximity to the C-terminus binding motif for the 14-3-3 scaffolding protein. At the C terminus, 14-3-3 binds to BRAFpS729 (CRAFpS621) and enhances RAF dimerization. We conducted mutational analysis of BRAFS732A/E and CRAFS624A/E and revealed that the phosphomimetic S→E mutant decreases 14-3-3 association and RAF dimerization. In normal cell signaling, dimerized RAF phosphorylates MEK1/2, which is observed in the phospho-deficient S→A mutant. Our results suggest that phosphorylation and dephosphorylation of this site fine-tune the association of 14-3-3 and RAF dimerization, ultimately impacting MEK phosphorylation. We further characterized the BRAF homodimer and BRAF:CRAF heterodimer and identified a correlation between phosphorylation of this site with drug sensitivity. Our work reveals a novel negative regulatory role for phosphorylation of BRAFS732 and CRAFS624 in decreasing 14-3-3 association, dimerization, and MEK phosphorylation. These findings provide insight into the regulation of the MAPK pathway and may have implications for cancers driven by mutations in the pathway.

Trajectories of psychological distress and social integration in newly resettled refugees: findings from the Building a New Life in Australia longitudinal study.

PURPOSE: Refugees are at greater risk of mental illness due to stressors encountered post-resettlement. However, few longitudinal studies have examined the within-person effects of these stressors, especially with respect to social integration. This study aims to examine what factors are associated with psychological distress in a longitudinal sample of refugees resettled in Australia. METHODS: This study used data from three Waves of the Building a New Life in Australia study, collected between 2013 and 2018. The eligible sample included 1881 adult respondents, clustered in 1175 households. We conducted multilevel mixed-effects growth modelling incorporating time-variant and time-invariant covariates with psychological distress, using the Kessler Psychological Distress Scale (K6). RESULTS: Rates of high psychological distress increased across the 5-year follow-up period. Social integration stressors (e.g. discrimination, lower sense of belonging, loneliness, lower English proficiency) were associated with higher levels of psychological distress over time. Refugees reporting loneliness not only had a greater risk of elevated psychological distress at each time point, but the difference in risk increased over each time point. Refugees who were exposed to traumatic events, older, female and of Middle Eastern background were also more likely to report higher levels of psychological distress over time. CONCLUSIONS: These findings highlight the importance of identifying refugees who may encounter difficulties with social integration in the early years of resettlement. Newly arrived refugees may benefit from longer-term resettlement programmes that address post-migratory stressors, particularly with regards to loneliness, to reduce the prevalence of elevated psychological distress during the early years of resettlement.

Novel series of tunable µOR modulators with enhanced brain penetration for the treatment of opioid use disorder, pain and neuropsychiatric indications.

Structural optimization of a previously reported agonist of µOR, PZM21 is described resulting in the discovery of a novel series of amides with at least 4-folds enhanced CNS penetration in rat. Furthermore, these efforts yielded compounds with varying levels of efficacy on the receptor ranging from high efficacy agonists such as compound 20 to antagonists, such as 24. The correlation between in vitro activation of µOR and relative activity in models of analgesia for these compounds is discussed. The compelling results obtained in these studies demonstrate the potential utility of these newly discovered compounds in the treatment of pain and opioid use disorder.

Bayesian optimization of tacrolimus exposure in stable kidney transplant patients.

STUDY OBJECTIVE: The objective was to compare tacrolimus AUC0-12 determined by Non-Compartmental Analysis (NCA) using intensive sampling to Maximum a Posteriori-Bayesian (MAP-Bayesian) estimates from robust (n = 9 samples/subject) and sparse (n = 2 samples/subject) sampling in 67 stable KTRs and a validation group of similar patients. DESIGN: This open-label, prospective, single center 12-h PK study included nine serial samples collected in KTRs to determine steady-state NCA tacrolimus AUC0-12 . SETTING: This study was conducted at a single site within a large, urban hospital in the western New York area. PATIENTS: This study described tacrolimus pharmacokinetics in stable kidney transplant recipients on maintenance tacrolimus therapy. INTERVENTION: Robust and sparse AUC0-12 estimates by a MAP-Bayesian approach were obtained using the Advanced Dosing Solutions (AdDS) and ADAPT5 freeware. Limited sampling strategies were evaluated using the original population PK model (n = 67), which was also assessed using a validation group (n = 15). AUC0-12 agreement was tested by paired t-tests with intraclass correlation coefficient (ICC) and Bland Altman analysis. MEASUREMENTS AND MAIN RESULTS: A total of 35 Black and 32 White stable KTRs (estimated glomerular filtration rate [eGFR] = 55.2 ± 15.7 mL/min/1.73m2 ) received the tacrolimus dose of 3.4 ± 1.7 mg/study with troughs of 6.8 ± 1.8 ng/mL. The NCA-AUC0-12 was 123.8 ± 33.6 µg·h/L compared to MAP-Bayesian estimates for Robust-AUC0-12 of 124.7 ± 33.3 µg·h/L and optimal 2-specimen Sparse-AUC0-12 of 119.7 ± 32.7 µg·h/L for the training group. Comparison of Robust-AUC0-12 to NCA-AUC0-12 had an ICC of 0.96 (p = 0.99) while comparison of Robust-AUC0-12 to Sparse-AUC0-12 using Pre-dose trough [C(t0h )] and 1 h [C(t1h )] resulted in an ICC of 0.93 (p = 0.014). In the validation group, 5 Black and 10 White KTRs (eGFR = 56.4 ± 16.8 mL/min/1.73m2 ) received a mean tacrolimus dose of 1.9 ± 1.2 mg/study with a trough of 6.0 ± 1.7 ng/mL. The validation group's NCA-AUC0-12 (88.4 ± 33.1 µg·h/L) was comparable to Robust-AUC0-12 (85.1 ± 33.8 µg·h/L, ICC = 0.93; p = 0.12) and Sparse-AUC0-12 determined from C(t0h ) and C(t4h ) (86.7 ± 33.9 µg·h/L, ICC = 0.91; p = 0.61). CONCLUSION: MAP-Bayesian estimation for patient-specific AUC0-12 using sparse, two-specimen sampling is comparable to NCA and may enhance tacrolimus TDM in stable KTRs.

Tranexamic acid in endoscopic sinus and skull base surgery: A systematic review and meta-analysis.

OBJECTIVE: Endoscopic sinus surgery (ESS) and endoscopic skull base surgery (ESBS) approaches have revolutionized the management of sinonasal and intracranial pathology. Maintaining surgical hemostasis is essential as bleeding can obscure the visibility of the surgical field, thus increasing surgical duration, risk of complications, and procedural failure. Tranexamic acid (TXA) acts to reduce bleeding by inhibiting fibrin degradation. This review aims to assess whether TXA improves surgical field quality and reduces intraoperative blood loss compared with control. METHODS: We searched PubMed, MEDLINE, Embase, Web of Science, and Cochrane Library from inception until September 1, 2022. Two reviewers independently screened citations, extracted data, and assessed methodological quality using the Cochrane risk-of-bias tool for randomized trials. Data were pooled using a random-effect model, with continuous data presented as mean differences and dichotomous data presented as odds ratios. RESULTS: Seventeen ESS randomized controlled trials (n = 1377) and one ESBS randomized controlled trial (n = 50) were reviewed. Significant improvement in surgical field quality was achieved with both systemic TXA (six studies, p < 0.00001) and topical TXA (six studies, p = 0.01) compared with the control. Systemic TXA (eight studies) and topical TXA (three studies) both achieved a significant reduction in intraoperative blood loss compared with the control (p < 0.00001). There were significant differences in operative times (p < 0.001) but no significant difference in perioperative outcomes (p = 0.30). CONCLUSION: This meta-analysis demonstrated that the administration of TXA in ESS can improve surgical field quality and reduce intraoperative blood loss. TXA use did not result in increased perioperative complications including thrombotic events.

Partial Extraction Therapy (Part 2): Complication Management in Full-Arch Dental Implant Therapy.

Partial extraction therapy (PET) is a group of surgical techniques that preserve the periodontium and peri-implant tissues during restorative and implant therapy by conserving a portion of the patient's own root structure to maintain the blood supply, derived from the periodontal ligament complex. PET includes the socket shield technique (SST), proximal shield technique (PrST), pontic shield technique (PtST), and root submergence technique (RST). Although their clinical success and benefits have been demonstrated, several studies report possible complications. The focus of this article is to highlight management strategies for the most common complications associated with PET, including internal root fragment exposure, external root fragment exposure, and root fragment mobility.

Multiple Subperiosteal Sling Sutures for Connective Tissue Graft Stabilization in the Treatment of Multiple Recession Defects Utilizing Subperiosteal Tunnels via VISTA and Intrasulcular Access.

This report describes the utilization of multiple subperiosteal sling (SPS) sutures to stabilize connective tissue grafts in the treatment of multiple recession defects using subperiosteal tunnels via vestibular and intrasulcular accesses. The SPS sutures engage only the graft and stabilize it against teeth inside the subperiosteal tunnel without engaging the overlying soft tissue, which is neither sutured nor coronally advanced. At sites with deep recessions, the graft is left exposed over the denuded root surfaces and allowed to epithelialize, which results in root coverage and increased attached keratinized tissue. Further controlled studies are required to investigate the predictability of this treatment approach.

RNA Polymerase II transcription independent of TBP in murine embryonic stem cells.

Transcription by RNA Polymerase II (Pol II) is initiated by the hierarchical assembly of the pre-initiation complex onto promoter DNA. Decades of research have shown that the TATA-box binding protein (TBP) is essential for Pol II loading and initiation. Here, we report instead that acute depletion of TBP in mouse embryonic stem cells has no global effect on ongoing Pol II transcription. In contrast, acute TBP depletion severely impairs RNA Polymerase III initiation. Furthermore, Pol II transcriptional induction occurs normally upon TBP depletion. This TBP-independent transcription mechanism is not due to a functional redundancy with the TBP paralog TRF2, though TRF2 also binds to promoters of transcribed genes. Rather, we show that the TFIID complex can form and, despite having reduced TAF4 and TFIIA binding when TBP is depleted, the Pol II machinery is sufficiently robust in sustaining TBP-independent transcription.

Developing a Culturally Competent Neuropsychological Assessment Battery for Vietnamese-speaking Patients with Suspected Dementia.

OBJECTIVES: To assemble a core battery of culturally and linguistically appropriate neuropsychological measures that can be administered to Vietnamese-speaking patients with suspected dementia. METHODS: Test instruments in Vietnamese were identified through systematic searches of PubMed, PsychInfo, and Google Scholar, and in consultation with two Vietnamese-speaking cultural brokers. RESULTS: A battery assessing the domains of attention, executive function, verbal and visual episodic memory, basic language abilities, visuospatial/visuoconstruction abilities, and mood/anxiety was assembled that included core measures developed either specifically for a Vietnamese-speaking population, or were validated/normed with a Vietnamese-speaking sample either in Vietnam or Vietnamese-speaking persons in the U.S. Supplemental measures were selected that can be administered using translated instructions with U.S. English normative data. The rationale for test selection and caveats for their clinical use are presented. CONCLUSIONS: The number of neuropsychological measures identified in Vietnamese and/or with Vietnamese normative data was sparse. Given the large and growing population of Vietnamese-speaking residents in the U.S. and the aging of these communities, it is imperative to develop additional, appropriately designed and normed instruments to provide culturally competent assessments to better serve these individuals.

Ratio of carbon dioxide veno-arterial difference to oxygen arterial-venous difference is not associated with lactate decrease after fluid bolus in critically ill patients with hyperlactatemia: results from a prospective observational study.

BACKGROUND: High ratio of the carbon dioxide veno-arterial difference to the oxygen arterial-venous difference (PvaCO2/CavO2) is associated with fluid bolus (FB) induced increase in oxygen consumption (VO2). This study investigated whether PvaCO2/CavO2 was associated with decreases in blood-lactate levels FB in critically ill patients with hyperlactatemia. METHODS: This prospective observational study examined adult patients in the intensive care unit (ICU) with lactate levels > 1.5 mmol/L who received FBs. Blood-lactate levels were measured before and after FB under unchanged metabolic, respiratory, and hemodynamic conditions. The primary outcome was blood-lactate levels after FB. Significant decreases in blood-lactate levels were considered as blood-lactate levels < 1.5 mmol/L or a decrease of more than 10% compared to baseline. RESULTS: The study enrolled 40 critically ill patients, and their median concentration of blood lactate was 2.6 [IQR:1.9 - 3.8] mmol/L. There were 27 (68%) patients with PvaCO2/CavO2 ≥ 1.4 mmHg/ml, and 10 of them had an increase in oxygen consumption (dVO2) ≥ 15% after FB, while 13 (32%) patients had PvaCO2/CavO2 < 1.4 mmHg/ml before FB, and none of them had dVO2 ≥ 15% after FB. FB increased the cardiac index in patients with high and low preinfusion PvaCO2/CavO2 (13.4% [IQR: 8.3 - 20.2] vs. 8.8% [IQR: 2.9 - 17.4], p = 0.34). Baseline PvaCO2/CavO2 was not found to be associated with a decrease in blood lactate after FB (OR: 0.88 [95% CI: 0.39 - 1.98], p = 0.76). A positive correlation was observed between changes in blood lactate and baseline PvaCO2/CavO2 (r = 0.35, p = 0.02). CONCLUSIONS: In critically ill patients with hyperlactatemia, PvaCO2/CavO2 before FB cannot be used to predict decreases in blood-lactate levels after FB. Increased PvaCO2/CavO2 is associated with less decrease in blood-lactate levels.

Biomimicry and 3D-Printing of Mussel Adhesive Proteins for Regeneration of the Periodontium-A Review.

Innovation in the healthcare profession to solve complex human problems has always been emulated and based on solutions proven by nature. The conception of different biomimetic materials has allowed for extensive research that spans several fields, including biomechanics, material sciences, and microbiology. Due to the atypical characteristics of these biomaterials, dentistry can benefit from these applications in tissue engineering, regeneration, and replacement. This review highlights an overview of the application of different biomimetic biomaterials in dentistry and discusses the key biomaterials (hydroxyapatite, collagen, polymers) and biomimetic approaches (3D scaffolds, guided bone and tissue regeneration, bioadhesive gels) that have been researched to treat periodontal and peri-implant diseases in both natural dentition and dental implants. Following this, we focus on the recent novel application of mussel adhesive proteins (MAPs) and their appealing adhesive properties, in addition to their key chemical and structural properties that relate to the engineering, regeneration, and replacement of important anatomical structures in the periodontium, such as the periodontal ligament (PDL). We also outline the potential challenges in employing MAPs as a biomimetic biomaterial in dentistry based on the current evidence in the literature. This provides insight into the possible increased functional longevity of natural dentition that can be translated to implant dentistry in the near future. These strategies, paired with 3D printing and its clinical application in natural dentition and implant dentistry, develop the potential of a biomimetic approach to overcoming clinical problems in dentistry.