Efficacy of microchips and 3D sensors for orthodontic force measurement: A systematic review of in vitro studies.

OBJECTIVE: To evaluate the efficacy of microchips and 3D microsensors in the measurement of orthodontic forces. METHODS: Through September 2023, comprehensive searches were conducted on PubMed/MEDLINE, SCOPUS and SCIELO without restrictions. RESULTS: After removing duplicate entries and applying the eligibility criteria, 23 studies were included for analysis. All the studies were conducted in vitro, and slightly more than half of them were centred on evaluating orthodontic forces exerted by aligners. Eight utilized microchips as measurement tools, while the remaining studies made use of 3D microsensors for their assessments. In the context of fixed appliances, key findings included a high level of agreement in 3-dimensional orthodontic force detection between simulation results and actual applied forces. Incorporating critical force-moment combinations during smart bracket calibration reduced measurement errors for most components. Translational tooth movement revealed a moment-to-force ratio, aligning with the bracket's centre of resistance. The primary findings in relation to aligners revealed several significant factors affecting the forces exerted by them. Notably, the foil thickness and staging were found to have a considerable impact on these forces, with optimal force transmission occurring at a layer height of 150 µm. Furthermore, the type of material used in 3D-printing aligners influenced the force levels, with attachments proving effective in generating extrusive forces. Deliberate adjustments in aligner thickness were observed to alter the forces and moments generated. CONCLUSIONS: Microchips and 3D sensors provide precise and quantitative measurements of orthodontic forces in in vitro studies, enabling accurate monitoring and control of tooth movement.

Infectious Diseases Consultation Associated With Reduced Mortality in Gram-Negative Bacteremia.

Gram-negative bacteremia (GN-BSI) can cause significant morbidity and mortality, but the benefit of infectious diseases consultation (IDC) is not well defined. A 24-site observational cohort study of unique hospitalized patients with 4861 GN-BSI episodes demonstrated a 40% decreased risk of 30-day mortality in patients with IDC compared to those without IDC.

Oral lesions in patients with human monkeypox: A systematic scoping review.

OBJECTIVES: To describe the clinical features and location of oral lesions in patients with human monkeypox. METHODS: A systematic scoping review was accomplished by implementing the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews. The analysis incorporated varied databases and the gray literature. Keywords were implemented to search publications in all languages until July 2022. RESULTS: The initial electronic exploration included 889 reports, of which 843 studies were eliminated. Reading the full text occasioned the omission of 27 additional investigations. Finally, 19 publications were included. These reports analyzed 1256 patients with monkeypox, mostly described in Europe. Most of them were men who have sex with men. The study population consisted mainly of adults but children were also infected. The oral lesions of monkeypox patients were observed in different parts of the oral mucosa, including lips and tongue, but mainly in the tonsils (15 cases). The oral lesions manifested as papules, vesicles, pustules, and ulcers. Erythema, edema, enanthema, and severe pain were also observed, accompanied by tonsillar enlargement. Sore throat was also reported. Monkeypox is accompanied by a significant number of systemic manifestations, mainly including multiple skin lesions throughout the body, as well as lymphadenopathy, fever, headache, myalgia, and fatigue, among others. The symptoms associated with monkeypox were managed with different antiretroviral and antimicrobial therapies and medications to control pain and fever principally. Seventeen deaths were informed. CONCLUSION: Most monkeypox-associated oral lesions are seen in different parts of the oral mucosa, mainly in the tonsils manifested as papules, vesicles, pustules, and ulcers.

Antibiotic resistance in periodontitis patients: A systematic scoping review of randomized clinical trials.

OBJECTIVES: The objective of the study was to evaluate the prevalence and proportions of antibiotic-resistant species in periodontitis patients. METHODS: A systematic scoping review of randomized clinical trials (RCTs) was conducted using the PRISMA extension for scoping reviews involving different databases. MeSH terms and keywords were provided to examine only RCTs with antibiotic-resistant results that included at least 3 months of follow-up of systematically healthy patients diagnosed with periodontitis and treated with systemic or local antibiotics adjunctive to subgingival debridement. RCTs that managed participants surgically, duplicate publications, and investigations implemented on animals were discarded. RESULTS: Six RCTs were chosen. These studies included 465 patients. Most investigations observed that while Aggregatibacter actinomycetemcomitans, Tannerella forsythia, and Porphyromonas gingivalis had low resistance to amoxicillin, microorganisms in many sites showed resistance to tetracycline, metronidazole, and azithromycin pretreatment. A. actinomycetemcomitans showed high resistance to tetracycline pre- and post-therapy. The proportion of antibiotic-resistant samples augmented rapidly after the prescription of antibiotics in all test groups. The percentage of antibiotic-resistant microorganisms decreased over time; at the end of the follow-up period, resistance levels were close to baseline levels. CONCLUSIONS: Adjunctive local and systemic antibiotic treatment temporarily increased the antibiotic resistance of subgingival microorganisms; nonetheless, many bacteria remained susceptible to antibiotics during their administration.

Pseudorandom number generator based on novel 2D Hénon-Sine hyperchaotic map with microcontroller implementation.

Recently, chaotic maps have been considered to design pseudorandom number generator (PRNG). However, some chaotic maps present security disadvantages, such as low uniformity and low randomness properties. Nowadays, chaos-based PRNGs are used as the main source for the development of cryptographic algorithms. In this work, to overcome such weaknesses, a novel 2D hyperchaotic map is proposed based on discrete-time feedback by using Hénon map and Sine map. In addition, the dynamics of the hyperchaotic map are enhanced by using the remainder after division function (rem), where better random statistical properties are obtained. A comparison is made between the enhanced Hénon-Sine hyperchaotic map (EHSHM) and the Hénon-Sine hyperchaotic map through Lyapunov exponent analysis, attractor trajectory, histograms and sensitivity at initialization. Then, 8-bit pseudorandom number generator based on the proposed hyperchaotic map (PRNG-EHSHM) is designed and the initial seed of the PRNG is calculated by a secret key of 60 hexadecimal characters. It is implemented in both MATLAB and Arduino Mega microcontroller for experimental results. A complete security analysis is presented from a cryptographic point of view, such as key space, floating frequency, histograms and entropy of the information. Moreover, the randomness is verified with the tests of the National Institute of Standards and Technology (NIST 800-22). Based on the security results obtained, the proposed PRNG-EHSHM can be implemented in embedded cryptographic applications based on chaos.

Secondary Cases of Delta Variant Coronavirus Disease 2019 Among Vaccinated Healthcare Workers With Breakthrough Infections is Rare.

In a retrospective, cohort study at 4 medical centers with high coronavirus disease 2019 vaccination rates, we evaluated breakthrough severe acute respiratory syndrome coronavirus 2 Delta variant infections in vaccinated healthcare workers. Few work-related secondary cases were identified. Breakthrough cases were largely due to unmasked social activities outside of work.

Mitigation of a Coronavirus Disease 2019 Outbreak in a Nursing Home Through Serial Testing of Residents and Staff.

Nursing homes and long-term care facilities represent highly vulnerable environments for respiratory disease outbreaks, such as coronavirus disease 2019 (COVID-19). We describe a COVID-19 outbreak in a nursing home that was rapidly contained by using a universal testing strategy of all residents and nursing home staff.

Molecular and epidemiological characterization of imported malaria cases in Chile.

BACKGROUND: Chile is one of the South American countries certified as malaria-free since 1945. However, the recent increase of imported malaria cases and the presence of the vector Anopheles pseudopunctipennis in previously endemic areas in Chile require an active malaria surveillance programme. METHODS: Specimens from 268 suspected malaria cases-all imported-collected between 2015 and 2018 at the Public Health Institute of Chile (ISP), were diagnosed by microscopy and positive cases were included for epidemiological analysis. A photo-induced electron transfer fluorogenic primer real-time PCR (PET-PCR) was used to confirm the presence of malaria parasites in available blood samples. Sanger sequencing of drug resistance molecular markers (pfk13, pfcrt and pfmdr1) and microsatellite (MS) analysis were performed in confirmed Plasmodium falciparum samples and results were related to origin of infection. RESULTS: Out of the 268 suspected cases, 65 were Plasmodium spp. positive by microscopy. A total of 63% of the malaria patients were male and 37% were female; 43/65 of the patients acquired infections in South American endemic countries. Species confirmation of available blood samples by PET-PCR revealed that 15 samples were positive for P. falciparum, 27 for Plasmodium vivax and 4 were mixed infections. The P. falciparum samples sequenced contained four mutant pfcrt genotypes (CVMNT, CVMET, CVIET and SVMNT) and three mutant pfmdr1 genotypes (Y184F/S1034C/N1042D/D1246Y, Y184F/N1042D/D1246Y and Y184F). MS analysis confirmed that all P. falciparum samples presented different haplotypes according to the suspected country of origin. Four patients with P. vivax infection returned to the health facilities due to relapses. CONCLUSION: The timely detection of polymorphisms associated with drug resistance will contribute to understanding if current drug policies in the country are appropriate for treatment of imported malaria cases and provide information about the most frequent resistant genotypes entering Chile.

Assessment of the American College of Surgeons National Surgical Quality Improvement Program Calculator in Predicting Outcomes and Length of Stay After Ivor Lewis Esophagectomy: A Single-Center Experience.

BACKGROUND: The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) calculator is a useful tool used by physicians to better inform patients on the surgical risk of postoperative complications. It makes use of the NSQIP database to derive the chance for several adverse outcomes to occur postoperatively given certain patient's factors. The aim of this study was to assess its applicability in a series of patients undergoing an Ivor Lewis esophagectomy. METHODS: Data from 100 consecutive patients who underwent an Ivor Lewis esophagectomy between September 2013 and November 2017 at our institution were reviewed. Each patient was assessed using the ACS NSQIP surgical risk calculator. Actual events in this group were compared with their particular NSQIP-assessed risk. Logistic regression models were used to compare surgical risk calculator estimates binary outcomes such as incidence of postoperative complications such as cardiac events, renal events, surgical site infection, and death. Mixed linear model was used for length of stay (LOS) duration versus observed LOS. C-statistic was for predictive accuracy each binary outcome and intraclass correlation was used for LOS. RESULTS: C-statistic values were higher than the cutoff (0.75) for surgical site infection and death. The ACS NSQIP risk calculator was poorly predictive of other reported outcomes by the calculator such as cardiac or renal complications. Corroboration between observed LOS and predicted LOS was weak (8 d versus 11 d, respectively, intraclass coefficient 0.04). CONCLUSIONS: This study suggests that the risk calculator is useful for identifying risk of death or surgical site infection but poor at discriminating likelihood of other reported outcomes occurring, such as pneumonia, acute renal failure and cardiac complications for patients who underwent an Ivor Lewis esophagectomy. Estimations for procedure-specific complications for esophagectomy may need reevaluated.

Development and analytical validation of real-time PCR for the detection of Streptococcus agalactiae in pregnant women.

BACKGROUND: Group B Streptococcus (GBS) is the leading cause of invasive neonatal infection. In this study, we aimed to evaluate the analytical validation of qualitative real-time polymerase chain reaction (qPCR) as a means to detect GBS. METHODS: Genomic DNA (gDNA) was purified from 12 ATCC bacterial strains, two belonging to GBS and the remainder acting as negative controls. Additionally, gDNA was isolated from 21 strains of GBS from various serotypes (Ia, Ib and II-VIII). All gDNA was used to evaluate the analytical validation of the qPCR method employing a specific Taqman probe. Inclusivity, exclusivity, anticipated reportable range, the limit of detection and robustness were evaluated. The methods used are described in international guidelines and other existing reports. The performance of this qPCR method for detecting GBS was compared to other microbiological methods used with vaginal-rectal samples from pregnant women. RESULTS: Our qPCR method for detecting GBS was analytically validated. It has a limit of detection of 0.7 GE/µL and 100% analytical specificity. It detects all strains of GBS with the same level of performance as microbiological methods. CONCLUSION: Data suggest that this qPCR method performs adequately as a means to detect GBS in vaginal-rectal swabs from pregnant women.

Emerging Biorecognition and Transduction Schemes for Rapid Detection of Pathogenic Bacteria in Food.

The presence of unsafe levels of microorganisms in food constitutes a growing economic and public health problem that necessitates new technology for their rapid detection along the food continuum from production to consumption. While traditional techniques are reliable, there is a need for more sensitive, selective, rapid, and cost-effective approaches for food safety evaluation. Methods such as microbiological counts are sufficiently accurate and inexpensive, and are capable of determining presence and viability for most pathogens. However, these techniques are time consuming, involve destructive sampling, and require trained personnel and biosafety-certified facilities for analysis. Molecular techniques such as the polymerase chain reaction have greatly improved analytical capability over the last decade, achieving shorter analysis time with quantitative data and strain specificity, and in some cases the ability to discriminate cell viability. The emerging field of nanosensors/biosensors has demonstrated a variety of devices that hold promise to bridge the gap between traditional plate counting and molecular techniques. Many nanosensors/biosensors are rapid, portable, accurate devices that can be used as an additional screening tool for identifying unsafe levels of microorganisms in food products with no need for pre-enrichment. In this review, we provide a brief overview of available biorecognition-transduction techniques for detecting bacteria in food. We then discuss the advantages and disadvantages of each technique, and describe some recent biosensor or nanosensor technologies that are under development. We conclude by summarizing the opportunities and challenges in the field of pathogen monitoring in food systems and we focus the discussion on the strengths/weaknesses of the most popular biorecognition agents and transducer nanomaterials for biosensing.

Factors associated with hysterectomy among older women from Latin America and the Caribbean.

To identify factors associated with hysterectomy, data collected from 1999-2000 were assessed from seven cities of the Health, Well-Being and Aging in Latin America and the Caribbean Study on 6,549 women, aged 60 years and older. Hysterectomy prevalence ranged from 12.8% in Buenos Aires (Argentina) to 30.4% in Bridgetown (Barbados). The median age for having had a hysterectomy ranged from 45 to 50 years across the cities and was 47 years in the pooled sample. Ethnic differences in hysterectomy rates were partially explained by differences across cities. Factors significantly associated with lower odds for hysterectomy included older age, household crowding conditions, and having public/military or no health insurance, compared to having private health insurance. Women who had three or more children were less likely to have had a hysterectomy, a finding that differs from most previous studies. Socioeconomic position related to rates of hysterectomy in late life rather than hysterectomies earlier in life. However, the nature of these differences varied across birth cohorts. The findings suggested that adverse socioeconomic factors were most likely related to hysterectomy risk by affecting access to health care, whereas parity was most likely acting through an effect on decision-making processes.

Inhaled, nebulized sodium nitrite protects in murine and porcine experimental models of hemorrhagic shock and resuscitation by limiting mitochondrial injury.

OBJECTIVE: The cellular injury that occurs in the setting of hemorrhagic shock and resuscitation (HS/R) affects all tissue types and can drive altered inflammatory responses. Resuscitative adjuncts hold the promise of decreasing such injury. Here we test the hypothesis that sodium nitrite (NaNO2), delivered as a nebulized solution via an inhalational route, protects against injury and inflammation from HS/R. METHODS: Mice underwent HS/R to a mean arterial pressure (MAP) of 20 or 25 mmHg. Mice were resuscitated with Lactated Ringers after 90-120 min of hypotension. Mice were randomized to receive nebulized NaNO2 via a flow through chamber (30 mg in 5 mL PBS). Pigs (30-35 kg) were anesthetized and bled to a MAP of 30-40 mmHg for 90 min, randomized to receive NaNO2 (11 mg in 2.5 mL PBS) nebulized into the ventilator circuit starting 60 min into the hypotensive period, followed by initial resuscitation with Hextend. Pigs had ongoing resuscitation and support for up to four hours. Hemodynamic data were collected continuously. RESULTS: NaNO2 limited organ injury and inflammation in murine hemorrhagic shock. A nitrate/nitrite depleted diet exacerbated organ injury, as well as mortality, and inhaled NaNO2 significantly reversed this effect. Furthermore, NaNO2 limited mitochondrial oxidant injury. In porcine HS/R, NaNO2 had no significant influence on shock induced hemodynamics. NaNO2 limited hypoxia/reoxia or HS/R-induced mitochondrial injury and promoted mitochondrial fusion. CONCLUSION: NaNO2 may be a useful adjunct to shock resuscitation based on its limitation of mitochondrial injury.

Adenosine monophosphate-activated protein kinase activation protects against sepsis-induced organ injury and inflammation.

BACKGROUND: Mortality in sepsis is most often attributed to the development of multiple organ failure. In sepsis, inflammation-mediated endothelial activation, defined as a proinflammatory and procoagulant state of the endothelial cells, has been associated with severity of disease. Thus, the objective of this study was to test the hypothesis that adenosine monophosphate-activated protein kinase (AMPK) activation limits inflammation and endothelium activation to protect against organ injury in sepsis. 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), which is an adenosine monophosphate analog, has been used to upregulate activity of AMPK. Compound C is a cell-permeable pyrrazolopyrimidine compound that inhibits AMPK activity. METHODS: Wild-type mice underwent cecal ligation and puncture (CLP) or sham surgery. Mice were randomized to vehicle, AICAR, or compound C. Mouse kidney endothelial cells were used for in vitro experiments. Renal and liver function were determined by serum cystatin C, blood urea nitrogen (BUN), creatinine, and alanine aminotransferase. Serum cytokines were measured by enzyme-linked immunosorbent assay. Microvascular injury was determined using Evans blue dye and electron microscopy. Immunohistochemistry was used to measure protein levels of phospho-AMPK (p-AMPK), microtubule-associated protein 1A/1B-light chain 3 (LC3), and intracellular adhesion molecule. LC3 levels were used as a measure of autophagosome formation. RESULTS: AICAR decreased liver and kidney injury induced by CLP and minimized cytokine elevation in vivo and in vitro. CLP increased renal and hepatic phosphorylation of AMPK and autophagic signaling as determined by LC3. Inhibition of AMPK with compound C prevented CLP-induced autophagy and exacerbated tissue injury. Additionally, CLP led to endothelial injury as determined by electron microscopy and Evans blue dye extravasation, and AICAR limited this injury. Furthermore, AICAR limited CLP and lipopolysaccharide (LPS)-induced upregulation of intracellular adhesion molecule in vivo and in vitro and decreased LPS-induced neutrophil adhesion in vitro. CONCLUSIONS: In this model, activation of AMPK was protective, and AICAR minimized organ injury by decreasing inflammatory cytokines and endothelial activation. These data suggest that AMPK signaling influences sepsis or LPS-induced endothelial activation and organ injury.

Effects of inhalation of low-dose nitrite or carbon monoxide on post-reperfusion mitochondrial function and tissue injury in hemorrhagic shock swine.

INTRODUCTION: Tissue reperfusion following hemorrhagic shock may paradoxically cause tissue injury and organ dysfunction by mitochondrial free radical expression. Both nitrite and carbon monoxide (CO) may protect from this reperfusion injury by limiting mitochondrial free radial production. We explored the effects of very small doses of inhaled nitrite and CO on tissue injury in a porcine model of hemorrhagic shock. METHODS: Twenty pigs (mean wt. 30.6 kg, range 27.2 to 36.4 kg) had microdialysis catheters inserted in muscle, peritoneum, and liver to measure lactate, pyruvate, glucose, glycerol, and nitrite. Nineteen of the pigs were bled at a rate of 20 ml/min to a mean arterial pressure of 30 mmHg and kept between 30 and 40 mmHg for 90 minutes and then resuscitated. One pig was instrumented but not bled (sham). Hemorrhaged animals were randomized to inhale nothing (control, n = 7), 11 mg nitrite (nitrite, n = 7) or 250 ppm CO (CO, n = 5) over 30 minutes before fluid resuscitation. Mitochondrial respiratory control ratio was measured in muscle biopsies. Repeated measures from microdialysis catheters were analyzed in a random effects mixed model. RESULTS: Neither nitrite nor CO had any effects on the measured hemodynamic variables. Following inhalation of nitrite, plasma, but not tissue, nitrite increased. Following reperfusion, plasma nitrite only increased in the control and CO groups. Thereafter, nitrite decreased only in the nitrite group. Inhalation of nitrite was associated with decreases in blood lactate, whereas both nitrite and CO were associated with decreases in glycerol release into peritoneal fluid. Following resuscitation, the muscular mitochondrial respiratory control ratio was reduced in the control group but preserved in the nitrite and CO groups. CONCLUSIONS: We conclude that small doses of nebulized sodium nitrite or inhaled CO may be associated with intestinal protection during resuscitation from severe hemorrhagic shock.

Polymicrobial sepsis is associated with decreased hepatic oxidative phosphorylation and an altered metabolic profile.

BACKGROUND: Organ failure in sepsis accounts for significant mortality worldwide. Mitochondrial and metabolic responses are central to the overall response of the cell, and thus of the organ and organism. Adaptive responses in metabolism are critical to the recovery at the cellular level. The purpose of these investigations was to test the hypothesis that sepsis is associated with decreased aerobic respiration and significant metabolic changes in the liver. METHODS: C57BL/6 mice underwent cecal ligation and puncture (CLP) with a 21 gauge needle or an operation without CLP. Mice were euthanized from 0-24 h after the procedure and liver tissue was harvested. Tissue oxygen consumption and mitochondrial complex activity were measured. Global biochemical profiles of 311 metabolites were performed at the 8-h time point (n = 8/group) and analyzed by gas chromatography-mass spectrometry and liquid chromatography tandem mass spectrometry platforms by Metabolon (Durham, North Carolina). The influence of lipopolysaccharide (LPS) on aerobic and anaerobic respiration in primary mouse hepatocytes was also investigated. RESULTS: CLP in vivo or LPS in vitro resulted in a significant decrease in hepatic oxygen consumption. There was a significant decrease in oxidative phosphorylation measured at 12 h. LPS also resulted in a significant increase in anaerobic respiration in hepatocytes. Interestingly, the metabolomic analysis resulted in a metabolic shift in the liver from carbohydrate-based energy to utilization of fatty acids and amino acids. This included an increase in every tricarboxylic acid cycle intermediate and derivative, suggesting an increased flux into the cycle from fatty acid beta-oxidation and anaplerotic contributions from amino acids. CONCLUSIONS: Sepsis results in a metabolic response and profile consistent with increased anaerobic respiration, which occurs prior to significant changes in hemodynamics. The metabolic responses of cells and organs may be important adaptive responses to prevent organ failure and death.

Booster Vaccination with BNT162b2 Improves Cellular and Humoral Immune Response in the Pediatric Population Immunized with CoronaVac.

The SARS-CoV-2 Omicron variant and its sublineages continue to cause COVID-19-associated pediatric hospitalizations, severe disease, and death globally. BNT162b2 and CoronaVac are the main vaccines used in Chile. Much less is known about the Wuhan-Hu-1 strain-based vaccines in the pediatric population compared to adults. Given the worldwide need for booster vaccinations to stimulate the immune response against new Omicron variants of SARS-CoV-2, we characterized the humoral and cellular immune response against Omicron variant BA.1 in a pediatric cohort aged 10 to 16 years who received heterologous vaccination based on two doses of CoronaVac, two doses of CoronaVac (2x) plus one booster dose of BNT162b2 [CoronaVac(2x) + BNT162b2 (1x)], two doses of CoronaVac plus two booster doses of BNT162b2 [CoronaVac(2x) + BNT162b2 (2x)], and three doses of BNT162b2. We observed that the [CoronaVac(2x) + BNT162b2 (2x)] vaccination showed higher anti-S1 and neutralizing antibody titers and CD4 and CD8 T cell immunity specific to the Omicron variant compared to immunization with two doses of CoronaVac alone. Furthermore, from all groups tested, immunity against Omicron was highest in individuals who received three doses of BNT162b2. We conclude that booster vaccination with BNT162b2, compared to two doses of CoronaVac alone, induces a greater protective immunity.

A common regulatory switch controls a suite of C4 traits in multiple cell types.

The C4 photosynthetic pathway provided a major advantage to plants growing in hot, dry environments, including the ancestors of our most productive crops. Two traits were essential for the evolution of this pathway: increased vein density and the functionalization of bundle sheath cells for photosynthesis. Although GRAS transcriptional regulators, including SHORT ROOT (SHR), have been implicated in mediating leaf patterning in both C3 and C4 species, little is known about what controls the specialized features of the cells that mediate C4 metabolism and physiology. We show in the model monocot, Setaria viridis, that SHR regulates components of multiple cell identities, including chloroplast biogenesis and photosynthetic gene expression in bundle sheath cells, a central feature of C4 plants. Furthermore, we found that it also contributes to the two-cell compartmentalization of the characteristic four-carbon shuttle pathway. Disruption of SHR function clearly reduced photosynthetic capacity and seed yield in mutant plants under heat stress. Together, these results show how cell identities are remodeled by SHR to host the suite of traits characteristic of C4 regulation, which are a main engineering target in non-C4 crops to improve climate resilience.

Surface immunogenic protein from Streptococcus agalactiae and Fissurella latimarginata hemocyanin are TLR4 ligands and activate MyD88- and TRIF dependent signaling pathways.

The development of vaccine adjuvants is of interest for the management of chronic diseases, cancer, and future pandemics. Therefore, the role of Toll-like receptors (TLRs) in the effects of vaccine adjuvants has been investigated. TLR4 ligand-based adjuvants are the most frequently used adjuvants for human vaccines. Among TLR family members, TLR4 has unique dual signaling capabilities due to the recruitment of two adapter proteins, myeloid differentiation marker 88 (MyD88) and interferon-ß adapter inducer containing the toll-interleukin-1 receptor (TIR) domain (TRIF). MyD88-mediated signaling triggers a proinflammatory innate immune response, while TRIF-mediated signaling leads to an adaptive immune response. Most studies have used lipopolysaccharide-based ligands as TLR4 ligand-based adjuvants; however, although protein-based ligands have been proven advantageous as adjuvants, their mechanisms of action, including their ability to undergo structural modifications to achieve optimal immunogenicity, have been explored less thoroughly. In this work, we characterized the effects of two protein-based adjuvants (PBAs) on TLR4 signaling via the recruitment of MyD88 and TRIF. As models of TLR4-PBAs, we used hemocyanin from Fissurella latimarginata (FLH) and a recombinant surface immunogenic protein (rSIP) from Streptococcus agalactiae. We determined that rSIP and FLH are partial TLR4 agonists, and depending on the protein agonist used, TLR4 has a unique bias toward the TRIF or MyD88 pathway. Furthermore, when characterizing gene products with MyD88 and TRIF pathway-dependent expression, differences in TLR4-associated signaling were observed. rSIP and FLH require MyD88 and TRIF to activate nuclear factor kappa beta (NF-κB) and interferon regulatory factor (IRF). However, rSIP and FLH have a specific pattern of interleukin 6 (IL-6) and interferon gamma-induced protein 10 (IP-10) secretion associated with MyD88 and TRIF recruitment. Functionally, rSIP and FLH promote antigen cross-presentation in a manner dependent on TLR4, MyD88 and TRIF signaling. However, FLH activates a specific TRIF-dependent signaling pathway associated with cytokine expression and a pathway dependent on MyD88 and TRIF recruitment for antigen cross-presentation. Finally, this work supports the use of these TLR4-PBAs as clinically useful vaccine adjuvants that selectively activate TRIF- and MyD88-dependent signaling to drive safe innate immune responses and vigorous Th1 adaptive immune responses.

Smile Aesthetics Assessment in Patients Undergoing the Finishing Phase of Orthodontic Treatment: An Observational Cross-Sectional Study.

Objective To describe the smile characteristics of patients entering the finishing phase of orthodontic treatment. Methods This observational study involved a non-probabilistic sample of 48 patients. Clinical records served as the basis for determining the type of treatment (with or without extractions). Photographs were analyzed to obtain smile variables. Dental casts and panoramic radiographs were evaluated to ascertain the cast-radiograph evaluation (CRE) index. Univariate and bivariate analyses were conducted at a significance level of 0.05. Results The study evaluated 24 men and 24 women, with an average age of 20.10 ± 6.78 years. Fifty percent of the patients did not undergo extractions, and the average CRE index for the sample was 34.83 ± 9.01. Regarding the smile, a medium smile line was prevalent in 66.7% of cases, and a non-consonant smile arc was observed in 58.3%. Significant differences in the smile arc were found between patients with and without extractions (p=0.019). Right and left buccal corridors measured 2.52 mm ± 1.52 and 2.43 mm ± 1.37, respectively. The upper dental midline deviated by 0.80 ± 0.91 mm and had an angulation of 1.65 ± 2.05º. Both variables showed significant differences between Class I and Class II patients (p=0.020; p=0.027). Symmetrical smiles were also observed (1.05 ± 0.17). Conclusions Based on our findings, clinicians should focus on the smile arc in patients who have not undergone extractions and on the midline inclination in Class II patients. These appear to be the most common areas for improvement in patients who are in the finishing phase of treatment. Additionally, considerable variability exists in the smile characteristics of patients still undergoing orthodontic treatment, leaving room for further enhancement of results.