Fleaborne Typhus-Associated Deaths - Los Angeles County, California, 2022.

Fleaborne typhus (also known as murine typhus), a widely distributed vectorborne zoonosis caused by Rickettsia typhi, is a moderately severe, but infrequently fatal illness; among patients who receive doxycycline, the case-fatality rate is <1%. Fleaborne typhus is a mandated reportable condition in California. Reported fleaborne typhus cases in Los Angeles County have been increasing since 2010, with the highest number (171) reported during 2022. During June-October 2022, Los Angeles County Department of Public Health learned of three fleaborne typhus-associated deaths. This report describes the clinical presentation, illness course, and methods used to diagnose fleaborne typhus in these three cases. Severe fleaborne typhus manifestations among these cases included hemophagocytic lymphohistiocytosis, a rare immune hyperactivation syndrome that can occur in the infection setting; myocarditis; and septic shock with disseminated intravascular coagulation. Increased health care provider and public health awareness of the prevalence and severity of fleaborne typhus and of the importance of early doxycycline therapy is essential for prevention and treatment efforts.

Results from the Survey of Antibiotic Resistance (SOAR) 2016-18 in Vietnam, Cambodia, Singapore and the Philippines: data based on CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.

OBJECTIVES: To determine antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates collected from community-acquired respiratory tract infections (CA-RTIs) in 2016-18 in four Asian countries. METHODS: MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. RESULTS: In total, 260 S. pneumoniae and 258 H. influenzae isolates were tested. Pneumococci from Vietnam (n = 161) were the least susceptible, with rates of susceptibility >90% for fluoroquinolones by CLSI breakpoints, ∼60% for amoxicillin, amoxicillin/clavulanic acid and ceftriaxone but <14% for most other agents. Pneumococcal isolates from Cambodia (n = 48) and Singapore (n = 34) showed susceptibilities ranging from ∼30% for trimethoprim/sulfamethoxazole and oral penicillin to 100% for fluoroquinolones. Among isolates of H. influenzae from Cambodia (n = 30), the Philippines (n = 59) and Singapore (n = 80), rates of susceptibility using CLSI breakpoints were >90% for amoxicillin/clavulanic acid, cephalosporins [except cefaclor in Singapore (77.5%)], macrolides and fluoroquinolones; for isolates from Vietnam (n = 89) the rates of susceptibility were >85% only for amoxicillin/clavulanic acid (95.5%), ceftriaxone (100%) and macrolides (87.6%-89.9%). Susceptibility to other antibiotics ranged from 7.9% (trimethoprim/sulfamethoxazole) to 57.3%-59.6% (fluoroquinolones) and 70.8% (cefixime). The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. A limitation of the study was the small sample sizes and only one or two sites participating per country; however, since susceptibility data are scarce in some of the participating countries any information concerning antibiotic susceptibility is of value. CONCLUSIONS: Antibiotic susceptibility varied across countries and species, with isolates from Vietnam demonstrating the lowest susceptibility. Knowledge of resistance patterns can be helpful for clinicians when choosing empirical therapy options for CA-RTIs.

Nonequilibrium thermodynamics: emergent and fundamental.

How can we derive the evolution equations of dissipative systems? What is the relation between the different approaches? How much do we understand the fundamental aspects of a second law based framework? Is there a hierarchy of dissipative and ideal theories at all? How far can we reach with the new methods of nonequilibrium thermodynamics? This article is part of the theme issue 'Fundamental aspects of nonequilibrium thermodynamics'.

Variational principles and nonequilibrium thermodynamics.

Variational principles play a fundamental role in deriving the evolution equations of physics. They work well in the case of non-dissipative evolution, but for dissipative systems, the variational principles are not unique and not constructive. With the methods of modern nonequilibrium thermodynamics, one can derive evolution equations for dissipative phenomena and, surprisingly, in several cases, one can also reproduce the Euler-Lagrange form and symplectic structure of the evolution equations for non-dissipative processes. In this work, we examine some demonstrative examples and compare thermodynamic and variational techniques. Then, we argue that, instead of searching for variational principles for dissipative systems, there is another viable programme: the second law alone can be an effective tool to construct evolution equations for both dissipative and non-dissipative processes. This article is part of the theme issue 'Fundamental aspects of nonequilibrium thermodynamics'.

Reliability and Failure Modes of a Hybrid Ceramic Abutment Prototype.

PURPOSE: A ceramic and metal abutment prototype was fatigue tested to determine the probability of survival at various loads. MATERIALS AND METHODS: Lithium disilicate CAD-milled abutments (n = 24) were cemented to titanium sleeve inserts and then screw attached to titanium fixtures. The assembly was then embedded at a 30° angle in polymethylmethacrylate. Each (n = 24) was restored with a resin-cemented machined lithium disilicate all-ceramic central incisor crown. Single load (lingual-incisal contact) to failure was determined for three specimens. Fatigue testing (n = 21) was conducted employing the step-stress method with lingual mouth motion loading. Failures were recorded, and reliability calculations were performed using proprietary software. Probability Weibull curves were calculated with 90% confidence bounds. Fracture modes were classified with a stereomicroscope, and representative samples imaged with scanning electron microscopy. RESULTS: Fatigue results indicated that the limiting factor in the current design is the fatigue strength of the abutment screw, where screw fracture often leads to failure of the abutment metal sleeve and/or cracking in the implant fixture. Reliability for completion of a mission at 200 N load for 50K cycles was 0.38 (0.52% to 0.25 90% CI) and for 100K cycles was only 0.12 (0.26 to 0.05)-only 12% predicted to survive. These results are similar to those from previous studies on metal to metal abutment/fixture systems where screw failure is a limitation. No ceramic crown or ceramic abutment initiated fractures occurred, supporting the research hypothesis. The limiting factor in performance was the screw failure in the metal-to-metal connection between the prototyped abutment and the fixture, indicating that this configuration should function clinically with no abutment ceramic complications. CONCLUSION: The combined ceramic with titanium sleeve abutment prototype performance was limited by the fatigue degradation of the abutment screw. In fatigue, no ceramic crown or ceramic abutment components failed, supporting the research hypothesis with a reliability similar to that of all-metal abutment fixture systems. A lithium disilcate abutment with a Ti alloy sleeve in combination with an all-ceramic crown should be expected to function clinically in a satisfactory manner.

Water Wicking and Droplet Spreading on Randomly Structured Thin Nanoporous Layers.

Growing thin, nanostructured layers on metallic surfaces is an attractive, new approach to create superhydrophilic coatings on heat exchangers that enhance spray cooling heat transfer. This paper presents results of an experimental study of enhanced droplet spreading on zinc oxide, nanostructured surfaces of this type that were thermally grown on copper substrates. The spreading rate data obtained from experimental high speed videos was used to develop a model specifically for this type of ultrathin, nanoporous layer. This investigation differs from previous related studies of droplet spreading on porous surfaces, which have generally considered either ordered, thin, moderately permeable layers, or thicker, microporous layers. Our layers are both very thin and have nanoscale porosity, making them low-permeability layers that exhibit strong wicking. An added benefit is that the thermally grown, stochastic nature of our surfaces make manufacturing easily scalable and particularly attractive for spray-cooled heat exchanger applications. The model presented here can predict the spreading rate for the wetted footprint of a deposited water droplet over two spreading stages: an early synchronous spreading stage, followed by hemispreading. The comparison of experimental data and model predictions confirms the presence of these two specific spreading stages. The model defines the transition conditions between synchronous and hemispreading regimes based on the change in spreading mechanisms, and we demonstrate that the model predictions of spreading rate are in good agreement with the experimental determinations of droplet footprint variation with time. The results indicate that the early synchronous spreading regime is characterized by flow in the porous layer that is primarily localized near the upper droplet contact line. The potential use of these experimental findings and model for optimizing superhydrophilic, nanostructured surface coatings is also discussed, as it pertains to the surface's ability to enhance water vaporization processes.

Whence the Maryland Bridge? The evolution of the adhesive bridge.

The evolution of the adhesive bridge technique from perforated retainers in the anterior to its application in the posterior and how this led to development of methods to bond directly to metal are detailed below. The parallel nature of bonded bridges evolution in the US and Japan are noted.

Results from the Survey of Antibiotic Resistance (SOAR) 2009-11 in Vietnam.

OBJECTIVES: To investigate the susceptibility of respiratory tract infection pathogens collected between 2009 and 2011 from the SOAR study in Vietnam. METHODS: MICs were determined using Etest(®) and susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. RESULTS: Two hundred and eighty-nine Streptococcus pneumoniae and 195 Haemophilus influenzae were collected from 11 centres. Overall, 4.8% of S. pneumoniae were penicillin susceptible (CLSI oral and EUCAST breakpoints). Using CLSI intravenous breakpoints, 86.9% were penicillin susceptible. Susceptibility to high-dose amoxicillin/clavulanic acid (or amoxicillin) using PK/PD breakpoints, cefuroxime (using CLSI or PK/PD breakpoints), cefaclor (CLSI breakpoint) and azithromycin (CLSI breakpoint) was 96.9%, 18.7%, 8% and 4.2%, respectively. Ofloxacin susceptibility was 93.4% by CLSI but 0% by EUCAST. All S. pneumoniae were fully vancomycin susceptible. S. pneumoniae from children were significantly less susceptible to most antimicrobials than those from the elderly. For ofloxacin, however, the reverse was true.Among H. influenzae isolates, 40.5% produced ß-lactamase and 13.8% were ß-lactamase negative but ampicillin resistant (BLNAR) by CLSI. H. influenzae were highly susceptible (97.4%) in vitro to amoxicillin/clavulanic acid and also to ceftriaxone by CLSI and PK/PD breakpoints but not EUCAST breakpoints. However, BLNAR isolates should be considered clinically resistant, with susceptibility reduced to 84.1%. With EUCAST breakpoints, amoxicillin/clavulanic acid susceptibility was lower, at 63.1%. Azithromycin susceptibility was 79.5% (CLSI). CONCLUSIONS: Resistance to antibacterials in Vietnam was high, with amoxicillin/clavulanic acid being the most active agent. Ceftriaxone was highly active against H. influenzae while ofloxacin appeared highly active against S. pneumoniae using CLSI but not by EUCAST breakpoints. Ongoing surveillance through SOAR will further assist in understanding susceptibility trends over time.

Short- and Long-term Evaluation of Dentin-Resin Interfaces Formed by Etch-and-Rinse Adhesives on Plasma-treated Dentin.

PURPOSE: To investigate the influence of atmospheric pressure plasma (APP) treatment on the microtensile dentin bond strength of two etch-and-rinse adhesive systems, after one week and one year of water storage, and additionally to observe the micromorphology of resin/dentin interfaces under scanning electronic microscopy (SEM). MATERIALS AND METHODS: The occlusal enamel was removed from third human molars to expose a flat dentin surface. The teeth were then randomly divided into six groups (n = 7), according to two adhesives (Optibond FL and XP-Bond) and three APP treatments (untreated dentin [control], APP application before or after acid etching). After performing the composite resin buildup on bonded dentin, the teeth were sectioned perpendicularly to the bonded interface to obtain beam-shaped specimens (cross-sectional area of ~0.9 mm2). The specimens were tested in tension until failure after one week and one year of water storage (1.0 mm/min rate). Bond strength data were analyzed by three-way ANOVA and Tukey's post-hoc test (α = 0.05%). Bonded beam specimens from each tooth were also prepared for interfacial SEM investigation. RESULTS: At one week, APP treatment applied after acid etching increased the dentin bond strength for XP Bond, while no effect was observed for Optibond FL. After one year, the bond strength of XP Bond decreased in groups where APP was applied after etching. The evaluation time did not influence the bond strength for Optibond FL. CONCLUSION: One-year evaluation did not show any sign of degradation of interfacial structures in any group. Application of APP to etched dentin combined with a two-step etch-and-rinse adhesive significantly increased bond strength at one week, but the effect was not stable after one year and was adhesive dependent.

A pilot study of dentists' assessment of caries detection and staging systems applied to early caries: PEARL Network findings.

The International Caries Detection and Assessment System (ICDAS II) and the Caries Classification System (CCS) are caries stage description systems proposed for adoption into clinical practice. This pilot study investigated clinicians' training in and use of these systems for detection of early caries and recommendations for individual tooth treatment. Patient participants (N = 8) with a range of noncavitated lesions (CCS ranks 2 and 4 and ICDAS II ranks 2-4) identified by a team of calibrated examiners were recruited from the New York University College of Dentistry clinic. Eighteen dentists-8 from the Practitioners Engaged in Applied Research and Learning (PEARL) Network and 10 recruited from the Academy of General Dentistry-were randomly assigned to 1 of 3 groups: 5 dentists used only visual-tactile (VT) examination, 7 were trained in the ICDAS II, and 6 were trained in the CCS. Lesion stage for each tooth was determined by the ICDAS II and CCS groups, and recommended treatment was decided by all groups. Teeth were assessed both with and without radiographs. Caries was detected in 92.7% (95% CI, 88%-96%) of the teeth by dentists with CCS training, 88.8% (95% CI, 84%-92%) of the teeth by those with ICDAS II training, and 62.3% (95% CI, 55%-69%) of teeth by the VT group. Web-based training was acceptable to all dentists in the CCS group (6 of 6) but fewer of the dentists in the ICDAS II group (5 of 7). The modified CCS translated clinically to more accurate caries detection, particularly compared to detection by untrained dentists (VT group). Moreover, the CCS was more accepted than was the ICDAS II, but dentists in both groups were open to the application of these systems. Agreement on caries staging requires additional training prior to a larger validation study.

Long-term Adhesion Study of Self-etching Systems to Plasma-treated Dentin.

PURPOSE: To determine the influence of atmospheric pressure plasma (APP) treatment on the microtensile dentin bond strength of two self-etching adhesive systems after one year of water storage as well as observe the contact angle changes of dentin treated with plasma and the micromorphology of resin/dentin interfaces using SEM. MATERIALS AND METHODS: For contact angle measurements, 6 human molars were sectioned to remove the occlusal enamel surface, embedded in PMMA resin, and ground to expose a flat dentin surface. Teeth were divided into two groups: 1) argon APP treatment for 30 s, and 2) blown air (control). For the microtensile test, 28 human third molars were used and prepared similarly to contact angle measurements. Teeth were randomly divided into 4 groups (n = 7) according to two self-etching adhesives and APP treatment (with/without). After making the composite resin buildup, teeth were sectioned perpendicular to the bonded interface to obtain beam specimens. The specimens were tested after 24 h and one year of water storage until failure. Bond strength data were analyzed by three-way ANOVA and Tukey's post-hoc test (α = 0.05%). Three beam specimens per group that were not used in the bond strength test were prepared for interfacial SEM analysis. RESULTS: APP application decreased the contact angle, but increased the bond strength only for one adhesive tested. SEM evaluation found signs of degradation within interfacial structures following 1-year aging in water. APP increased the dentin surface energy, but the effects of APP and 1-year water storage on dentin bond strength were product dependent. CONCLUSION: APP increased the dentin surface energy. It also increased the bond strength for Scotchbond Universal, but storage for one year negated the positive effect of APP treatment.

Liver-on-chip model and application in predictive genotoxicity and mutagenicity of drugs.

Currently, there is no test system, whether in vitro or in vivo, capable of examining all endpoints required for genotoxicity evaluation used in pre-clinical drug safety assessment. The objective of this study was to develop a model which could assess all the required endpoints and possesses robust human metabolic activity, that could be used in a streamlined, animal-free manner. Liver-on-chip (LOC) models have intrinsic human metabolic activity that mimics the in vivo environment, making it a preferred test system. For our assay, the LOC was assembled using primary human hepatocytes or HepaRG cells, in a MPS-T12 plate, maintained under microfluidic flow conditions using the PhysioMimix® Microphysiological System (MPS), and co-cultured with human lymphoblastoid (TK6) cells in transwells. This system allows for interaction between two compartments and for the analysis of three different genotoxic endpoints, i.e. DNA strand breaks (comet assay) in hepatocytes, chromosome loss or damage (micronucleus assay) and mutation (Duplex Sequencing) in TK6 cells. Both compartments were treated at 0, 24 and 45 h with two direct genotoxicants: methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS), and two genotoxicants requiring metabolic activation: benzo[a]pyrene (B[a]P) and cyclophosphamide (CP). Assessment of cytochrome activity, RNA expression, albumin, urea and lactate dehydrogenase production, demonstrated functional metabolic capacities. Genotoxicity responses were observed for all endpoints with MMS and EMS. Increases in the micronucleus and mutations (MF) frequencies were also observed with CP, and %Tail DNA with B[a]P, indicating the metabolic competency of the test system. CP did not exhibit an increase in the %Tail DNA, which is in line with in vivo data. However, B[a]P did not exhibit an increase in the % micronucleus and MF, which might require an optimization of the test system. In conclusion, this proof-of-principle experiment suggests that LOC-MPS technology is a promising tool for in vitro hazard identification genotoxicants.

Association of levofloxacin resistance with mortality in adult patients with invasive pneumococcal diseases: a post hoc analysis of a prospective cohort.

OBJECTIVE: This study was conducted to identify risk factors for mortality and to evaluate the impact of antimicrobial resistance on outcome in adult patients with invasive pneumococcal disease (IPD). METHODS: A post hoc analysis of an observational cohort study on community-acquired pneumococcal infections was conducted and a total of 136 adult patients with IPD were analyzed in this study. RESULTS: Pneumonia was the most common type of infection (n = 84, 61.8 %), followed by primary bacteremia (n = 15, 11.0 %) and meningitis (n = 15, 11.0 %). One hundred and three patients (75.7 %) had concomitant pneumococcal bacteremia. The overall 30-day mortality rate was 26.5 % (36/136), and factors associated with 30-day mortality were corticosteroid use, presentation with septic shock, and development of acute respiratory distress syndrome (ARDS) (all P < 0.05). While penicillin and erythromycin resistance were associated with a lower mortality, an association between levofloxacin resistance and increased mortality was found in the univariate analysis; however, statistical significance was not reached (P = 0.083). Multivariable analysis showed that presentation with septic shock, corticosteroid use, development of ARDS, and levofloxacin resistance were independent factors associated with 30-day mortality. Of the five patients with IPD caused by levofloxacin-resistant Streptococcus pneumoniae, three (60 %) died within 30 days of diagnosis. CONCLUSION: Levofloxacin resistance was associated with increased mortality, along with septic shock, prior use of corticosteroids, and development of ARDS, in adult patients with IPD. Our data suggest that the emergence of levofloxacin resistance among invasive pneumococcal isolates is now becoming a challenge for clinicians managing community-acquired bacterial infections.

Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR Dental PBRN.

Case reports and cohort studies have linked bisphosphonate therapy and osteonecrosis of the jaws (ONJ), but neither causality nor specific risks for lesion development have been clearly established. We conducted a 1:3 case-control study with 3 dental practice-based research networks, using dentist questionnaires and patient interviews for collection of data on bisphosphonate therapy, demographics, co-morbidities, and dental and medical treatments. Multivariable logistic regression analyses tested associations between bisphosphonate use and other risk factors with ONJ. We enrolled 191 ONJ cases and 573 controls in 119 dental practices. Bisphosphonate use was strongly associated with ONJ (odds ratios [OR] 299.5 {95% CI 70.0-1282.7} for intravenous [IV] use and OR = 12.2 {4.3-35.0} for oral use). Risk markers included local suppuration (OR = 7.8 {1.8-34.1}), dental extraction (OR = 7.6 {2.4-24.7}), and radiation therapy (OR = 24.1 {4.9-118.4}). When cancer patients (n = 143) were excluded, bisphosphonate use (OR = 7.2 {2.1-24.7}), suppuration (OR = 11.9 {2.0-69.5}), and extractions (OR = 6.6 {1.6-26.6}) remained associated with ONJ. Higher risk of ONJ began within 2 years of bisphosphonate initiation and increased 4-fold after 2 years. Both IV and oral bisphosphonate use were strongly associated with ONJ. Duration of treatment >2 years; suppuration and dental extractions were independent risk factors for ONJ.

Residual thermal stress simulation in three-dimensional molar crown systems: a finite element analysis.

PURPOSE: To simulate coefficient of thermal expansion (CTE)-generated stress fields in monolithic metal and ceramic crowns, and CTE mismatch stresses between metal, alumina, or zirconia cores and veneer layered crowns when cooled from high temperature processing. MATERIALS AND METHODS: A 3D computer-aided design model of a mandibular first molar crown was generated. Tooth preparation comprised reduction of proximal walls by 1.5 mm and of occlusal surfaces by 2.0 mm. Crown systems were monolithic (all-porcelain, alumina, metal, or zirconia) or subdivided into a core (metallic, zirconia, or alumina) and a porcelain veneer layer. The model was thermally loaded from 900°C to 25°C. A finite element mesh of three nodes per edge and a first/last node interval ratio of 1 was used, resulting in approximately 60,000 elements for both solids. Regions and values of maximum principal stress at the core and veneer layers were determined through 3D graphs and software output. RESULTS: The metal-porcelain and zirconia-porcelain systems showed compressive fields within the veneer cusp bulk, whereas alumina-porcelain presented tensile fields. At the core/veneer interface, compressive fields were observed for the metal-porcelain system, slightly tensile for the zirconia-porcelain, and higher tensile stress magnitudes for the alumina-porcelain. Increasingly compressive stresses were observed for the metal, alumina, zirconia, and all-porcelain monolithic systems. CONCLUSIONS: Variations in residual thermal stress levels were observed between bilayered and single-material systems due to the interaction between crown configuration and material properties.

Abutment design for implant-supported indirect composite molar crowns: reliability and fractography.

PURPOSE: To investigate the reliability of titanium abutments veneered with indirect composites for implant-supported crowns and the possibility to trace back the fracture origin by qualitative fractographic analysis. MATERIALS AND METHODS: Large base (LB) (6.4-mm diameter base, with a 4-mm high cone in the center for composite retention), small base (SB-4) (5.2-mm base, 4-mm high cone), and small base with cone shortened to 2 mm (SB-2) Ti abutments were used. Each abutment received incremental layers of indirect resin composite until completing the anatomy of a maxillary molar crown. Step-stress accelerated-life fatigue testing (n = 18 each) was performed in water. Weibull curves with use stress of 200 N for 50,000 and 100,000 cycles were calculated. Probability Weibull plots examined the differences between groups. Specimens were inspected in light-polarized and scanning electron microscopes for fractographic analysis. RESULTS: Use level probability Weibull plots showed Beta values of 0.27 for LB, 0.32 for SB-4, and 0.26 for SB-2, indicating that failures were not influenced by fatigue and damage accumulation. The data replotted as Weibull distribution showed no significant difference in the characteristic strengths between LB (794 N) and SB-4 abutments (836 N), which were both significantly higher than SB-2 (601 N). Failure mode was cohesive within the composite for all groups. Fractographic markings showed that failures initiated at the indentation area and propagated toward the margins of cohesively failed composite. CONCLUSIONS: Reliability was not influenced by abutment design. Qualitative fractographic analysis of the failed indirect composite was feasible.