The Making of a Flight Feather: Bio-architectural Principles and Adaptation.

The evolution of flight in feathered dinosaurs and early birds over millions of years required flight feathers whose architecture features hierarchical branches. While barb-based feather forms were investigated, feather shafts and vanes are understudied. Here, we take a multi-disciplinary approach to study their molecular control and bio-architectural organizations. In rachidial ridges, epidermal progenitors generate cortex and medullary keratinocytes, guided by Bmp and transforming growth factor ß (TGF-ß) signaling that convert rachides into adaptable bilayer composite beams. In barb ridges, epidermal progenitors generate cylindrical, plate-, or hooklet-shaped barbule cells that form fluffy branches or pennaceous vanes, mediated by asymmetric cell junction and keratin expression. Transcriptome analyses and functional studies show anterior-posterior Wnt2b signaling within the dermal papilla controls barbule cell fates with spatiotemporal collinearity. Quantitative bio-physical analyses of feathers from birds with different flight characteristics and feathers in Burmese amber reveal how multi-dimensional functionality can be achieved and may inspire future composite material designs. VIDEO ABSTRACT.

Facioscapulohumeral Muscular Dystrophy is Associated With Altered Myoblast Proteome Dynamics.

Proteomic studies in facioscapulohumeral muscular dystrophy (FSHD) could offer new insight into disease mechanisms underpinned by post-transcriptional processes. We used stable isotope (deuterium oxide; D2O) labeling and peptide mass spectrometry to investigate the abundance and turnover rates of proteins in cultured muscle cells from two individuals affected by FSHD and their unaffected siblings (UASb). We measured the abundance of 4420 proteins and the turnover rate of 2324 proteins in each (n = 4) myoblast sample. FSHD myoblasts exhibited a greater abundance but slower turnover rate of subunits of mitochondrial respiratory complexes and mitochondrial ribosomal proteins, which may indicate an accumulation of "older" less viable mitochondrial proteins in myoblasts from individuals affected by FSHD. Treatment with a 2'-O-methoxyethyl modified antisense oligonucleotide targeting exon 3 of the double homeobox 4 (DUX4) transcript tended to reverse mitochondrial protein dysregulation in FSHD myoblasts, indicating the effect on mitochondrial proteins may be a DUX4-dependent mechanism. Our results highlight the importance of post-transcriptional processes and protein turnover in FSHD pathology and provide a resource for the FSHD research community to explore this burgeoning aspect of FSHD.

Microbiome of periodontitis and peri-implantitis before and after therapy: Long-read 16S rRNA gene amplicon sequencing.

AIMS: The microbial profiles of peri-implantitis and periodontitis (PT) are inconclusive. The controversies mainly arise from the differences in sampling sites, targeted gene fragment, and microbiome analysis techniques. The objective of this study was to explore the microbiomes of peri-implantitis (PI), control implants (CI), PT and control teeth (CT), and the microbial change of PI after nonsurgical treatment (PIAT). METHODS: Twenty-two patients diagnosed with both PT and peri-implantitis were recruited. Clinical periodontal parameters and radiographic bone levels were recorded. In each patient, the subgingival and submucosal plaque samples were collected from sites with PI, CI, PT, CT, and PIAT. Microbiome diversity was analyzed by high-throughput amplicon sequencing using full-length of 16S rRNA gene by next generation sequencing. RESULTS: The 16S rRNA gene sequencing analysis revealed 512 OTUs in oral microbiome and 377 OTUs reached strain levels. The PI and PT groups possessed their own unique core microbiome. Treponema denticola was predominant in PI with probing depth of 8-10 mm. Interestingly, Thermovirga lienii DSM 17291 and Dialister invisus DSM 15470 were found to associate with PI. Nonsurgical treatment for peri-implantitis did not significantly alter the microbiome, except Rothia aeria. CONCLUSION: Our study suggests Treponemas species may play a pivotal role in peri-implantitis. Nonsurgical treatment did not exert a major influence on the peri-implantitis microbiome in short-term follow-up. PT and peri-implantitis possess the unique microbiome profiles, and different therapeutic strategies may be suggested in the future.

Titanium Surfaces with a Laser-Produced Microchannel Structure Enhance Pre-Osteoblast Proliferation, Maturation, and Extracellular Mineralization In Vitro.

The clinical success of dental titanium implants is profoundly linked to implant stability and osseointegration, which comprises pre-osteoblast proliferation, osteogenic differentiation, and extracellular mineralization. Because of the bio-inert nature of titanium, surface processing using subtractive or additive methods enhances osseointegration ability but limits the benefit due to accompanying surface contamination. By contrast, laser processing methods increase the roughness of the implant surface without contamination. However, the effects of laser-mediated distinct surface structures on the osteointegration level of osteoblasts are controversial. The role of a titanium surface with a laser-mediated microchannel structure in pre-osteoblast maturation remains unclear. This study aimed to elucidate the effect of laser-produced microchannels on pre-osteoblast maturation. Pre-osteoblast human embryonic palatal mesenchymal cells were seeded on a titanium plate treated with grinding (G), sandblasting with large grit and acid etching (SLA), or laser irradiation (L) for 3-18 days. The proliferation and morphology of pre-osteoblasts were evaluated using a Trypan Blue dye exclusion test and fluorescence microscopy. The mRNA expression, protein expression, and protein secretion of osteogenic differentiation markers in pre-osteoblasts were evaluated using reverse transcriptase quantitative polymerase chain reaction, a Western blot assay, and a multiplex assay, respectively. The extracellular calcium precipitation of pre-osteoblast was measured using Alizarin red S staining. Compared to G- and SLA-treated titanium surfaces, the laser-produced microchannel surfaces enhanced pre-osteoblast proliferation, the expression/secretion of osteogenic differentiation markers, and extracellular calcium precipitation. Laser-treated titanium implants may enhance the pre-osteoblast maturation process and provide extra benefits in clinical application.

Individual differences in the positive outcome from adolescent ketamine treatment in a female mouse model of anorexia nervosa involve drebrin A at excitatory synapses of the medial prefrontal cortex.

Anorexia nervosa (AN) is a mental illness with the highest rates of mortality and relapse, and no approved pharmacological treatment. Using an animal model of AN, called activity-based anorexia (ABA), we showed earlier that a single intraperitoneal injection of ketamine at a dose of 30 mg/kg (30mgKET), but not 3 mg/kg (3mgKET), has a long-lasting effect upon adolescent females of ameliorating anorexia-like symptoms through the following changes: enhanced food consumption and body weight; reduced running and anxiety-like behavior. However, there were also individual differences in the drug's efficacy. We hypothesized that individual differences in ketamine's ameliorative effects involve drebrin A, an F-actin-binding protein known to be required for the activity-dependent trafficking of NMDA receptors (NMDARs). We tested this hypothesis by electron microscopic quantifications of drebrin A immunoreactivity at excitatory synapses of pyramidal neurons (PN) and GABAergic interneurons (GABA-IN) in deep layer 1 of prefrontal cortex (PFC) of these mice. Results reveal that (1) the areal density of excitatory synapses on GABA-IN is greater for the 30mgKET group than the 3mgKET group; (2) the proportion of drebrin A+ excitatory synapses is greater for both PN and GABA-IN of 30mgKET than 3mgKET group. Correlation analyses with behavioral measurements revealed that (3) 30mgKET's protection is associated with reduced levels of drebrin A in the cytoplasm of GABA-IN and higher levels at extrasynaptic membranous sites of PN and GABA-IN; (5) altogether pointing to 30mgKET-induced homeostatic plasticity that engages drebrin A at excitatory synapses of both PN and GABA-IN.

Third-generation sequencing-selected Scardovia wiggsiae promotes periodontitis progression in mice.

BACKGROUNDS: Periodontitis is an oral-bacteria-directed disease that occurs worldwide. Currently, periodontal pathogens are mostly determined using traditional culture techniques, next-generation sequencing, and microbiological screening system. In addition to the well-known and cultivatable periodontal bacteria, we aimed to discover a novel periodontal pathogen by using DNA sequencing and investigate its role in the progression of periodontitis. OBJECTIVE: This study identified pathogens from subgingival dental plaque in patients with periodontitis by using the Oxford Nanopore Technology (ONT) third-generation sequencing system and validated the impact of selected pathogen in periodontitis progression by ligature-implanted mice. METHODS: Twenty-five patients with periodontitis and 25 healthy controls were recruited in this study. Subgingival plaque samples were collected for metagenomic analysis. The ONT third-generation sequencing system was used to confirm the dominant bacteria. A mouse model with ligature implantation and bacterial injection verified the pathogenesis of periodontitis. Neutrophil infiltration and osteoclast activity were evaluated using immunohistochemistry and tartrate-resistant acid phosphatase assays in periodontal tissue. Gingival inflammation was evaluated using pro-inflammatory cytokines in gingival crevicular fluids. Alveolar bone destruction in the mice was evaluated using micro-computed tomography and hematoxylin and eosin staining. RESULTS: Scardovia wiggsiae (S. wiggsiae) was dominant in the subgingival plaque of the patients with periodontitis. S. wiggsiae significantly deteriorated ligature-induced neutrophil infiltration, osteoclast activation, alveolar bone destruction, and the secretion of interleukin-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α in the mouse model. CONCLUSION: Our metagenome results suggested that S. wiggsiae is a dominant flora in patients with periodontitis. In mice, the induction of neutrophil infiltration, proinflammatory cytokine secretion, osteoclast activation, and alveolar bone destruction further verified the pathogenic role of S. wiggsiae in the progress of periodontitis. Future studies investigating the metabolic interactions between S. wiggsiae and other periodontopathic bacteria are warranted.

Enhancing the Performance of Electret-Free Phototransistor Memory by Using All-Conjugated Block Copolymer.

Conjugated polymers are of great interest owing to their potential in stretchable electronics to function under complex deformation conditions. To improve the performance of conjugated polymers, various structural designs have been proposed and these conjugated polymers are specially applied in exotic optoelectronics. In this work, a series of all-conjugated block copolymers (PII2T-b-PNDI2T) comprising poly(isoindigo-bithiophene) (PII2T) and poly(naphthalenediimide-bithiophene) (PNDI2T) are developed with varied compositions and applied to electret-free phototransistor memory. Accordingly, these memory devices present p-type transport capability and electrical-ON/photo-OFF memory behavior. The efficacy of the all-conjugated block copolymer design in improving the memory-photoresponse properties in phototransistor memory is revealed. By optimizing the composition of the block copolymer, the corresponding device achieves a wide memory window of 36 V and a high memory ratio of 7 × 104 . Collectively, the results of this study indicate a new concept for designing electret-free phototransistor memory by using all-conjugated block copolymer heterojunctions to mitigate the phase separation of conjugated polymer blends. Meanwhile, the intrinsic optoelectronic properties of the constituent conjugated polymers can be well-maintained by using an all-conjugated block copolymer design.

Oral microbiome and serological analyses on association of Alzheimer's disease and periodontitis.

OBJECTIVE: To investigate the association between Alzheimer's disease (AD) and periodontitis in the aspects of periodontal status, serological markers, and oral microbiome. MATERIALS AND METHODS: Twenty AD and 20 healthy subjects were enrolled in this age- and gender-matched case-control study. Clinical periodontal parameters and serum biomarkers, including amyloid ß42 (Aß42 ), Tau, phosphorylated Tau (pTau), triglyceride, pro-inflammatory cytokines, and anti-Porphyromonas gingivalis lipopolysaccharide (LPS) antibody were examined. The saliva samples were analyzed for oral microbiome composition. RESULTS: Alzheimer's disease patients with Clinical Dementia Rating (CDR) ≥1 exhibited significantly more clinical attachment loss (CAL) than those with lower CDR. The levels of serum Tau protein, hsCRP and anti-P. gingivalis LPS antibody were markedly elevated in the AD group compared with the control group. Serum pTau protein level was positively correlated with anti-P. gingivalis LPS antibody titer. Moreover, the increased abundances of Capnocytophaga sp ora clone DZ074, Eubacterium infirmum, Prevotella buccae, and Selenomonas artemidis were detected in the AD group. Interestingly, serum levels of Aß42, pTau, and anti-P. gingivalis LPS antibody were strongly related to the gene upregulation in human pathogen septicemia. CONCLUSIONS: Our study suggested the association of periodontal infection and oral microbiome with AD. Further large-scale studies with longitudinal follow-up are warranted.

Inhibition of DUX4 expression with antisense LNA gapmers as a therapy for facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD), characterized by progressive muscle weakness and deterioration, is genetically linked to aberrant expression of DUX4 in muscle. DUX4, in its full-length form, is cytotoxic in nongermline tissues. Here, we designed locked nucleic acid (LNA) gapmer antisense oligonucleotides (AOs) to knock down DUX4 in immortalized FSHD myoblasts and the FLExDUX4 FSHD mouse model. Using a screening method capable of reliably evaluating the knockdown efficiency of LNA gapmers against endogenous DUX4 messenger RNA in vitro, we demonstrate that several designed LNA gapmers selectively and effectively reduced DUX4 expression with nearly complete knockdown. We also found potential functional benefits of AOs on muscle fusion and structure in vitro. Finally, we show that one of the LNA gapmers was taken up and induced effective silencing of DUX4 upon local treatment in vivo. The LNA gapmers developed here will help facilitate the development of FSHD therapies.

Vapor-Induced Pore-Forming Atmospheric-Plasma-Sprayed Zinc-, Strontium-, and Magnesium-Doped Hydroxyapatite Coatings on Titanium Implants Enhance New Bone Formation-An In Vivo and In Vitro Investigation.

OBJECTIVES: Titanium implants are regarded as a promising treatment modality for replacing missing teeth. Osteointegration and antibacterial properties are both desirable characteristics for titanium dental implants. The aim of this study was to create zinc (Zn)-, strontium (Sr)-, and magnesium (Mg)-multidoped hydroxyapatite (HAp) porous coatings, including HAp, Zn-doped HAp, and Zn-Sr-Mg-doped HAp, on titanium discs and implants using the vapor-induced pore-forming atmospheric plasma spraying (VIPF-APS) technique. METHODS: The mRNA and protein levels of osteogenesis-associated genes such as collagen type I alpha 1 chain (COL1A1), decorin (DCN), osteoprotegerin (TNFRSF11B), and osteopontin (SPP1) were examined in human embryonic palatal mesenchymal cells. The antibacterial effects against periodontal bacteria, including Porphyromonas gingivalis and Prevotella nigrescens, were investigated. In addition, a rat animal model was used to evaluate new bone formation via histologic examination and micro-computed tomography (CT). RESULTS: The ZnSrMg-HAp group was the most effective at inducing mRNA and protein expression of TNFRSF11B and SPP1 after 7 days of incubation, and TNFRSF11B and DCN after 11 days of incubation. In addition, both the ZnSrMg-HAp and Zn-HAp groups were effective against P. gingivalis and P. nigrescens. Furthermore, according to both in vitro studies and histologic findings, the ZnSrMg-HAp group exhibited the most prominent osteogenesis and concentrated bone growth along implant threads. SIGNIFICANCE: A porous ZnSrMg-HAp coating using VIPF-APS could serve as a novel technique for coating titanium implant surfaces and preventing further bacterial infection.

Long-read single-molecule maps of the functional methylome.

We report on the development of a methylation analysis workflow for optical detection of fluorescent methylation profiles along chromosomal DNA molecules. In combination with Bionano Genomics genome mapping technology, these profiles provide a hybrid genetic/epigenetic genome-wide map composed of DNA molecules spanning hundreds of kilobase pairs. The method provides kilobase pair-scale genomic methylation patterns comparable to whole-genome bisulfite sequencing (WGBS) along genes and regulatory elements. These long single-molecule reads allow for methylation variation calling and analysis of large structural aberrations such as pathogenic macrosatellite arrays not accessible to single-cell second-generation sequencing. The method is applied here to study facioscapulohumeral muscular dystrophy (FSHD), simultaneously recording the haplotype, copy number, and methylation status of the disease-associated, highly repetitive locus on Chromosome 4q.

Long reads capture simultaneous enhancer-promoter methylation status for cell-type deconvolution.

MOTIVATION: While promoter methylation is associated with reinforcing fundamental tissue identities, the methylation status of distant enhancers was shown by genome-wide association studies to be a powerful determinant of cell-state and cancer. With recent availability of long reads that report on the methylation status of enhancer-promoter pairs on the same molecule, we hypothesized that probing these pairs on the single-molecule level may serve the basis for detection of rare cancerous transformations in a given cell population. We explore various analysis approaches for deconvolving cell-type mixtures based on their genome-wide enhancer-promoter methylation profiles. RESULTS: To evaluate our hypothesis we examine long-read optical methylome data for the GM12878 cell line and myoblast cell lines from two donors. We identified over 100 000 enhancer-promoter pairs that co-exist on at least 30 individual DNA molecules. We developed a detailed methodology for mixture deconvolution and applied it to estimate the proportional cell compositions in synthetic mixtures. Analysis of promoter methylation, as well as enhancer-promoter pairwise methylation, resulted in very accurate estimates. In addition, we show that pairwise methylation analysis can be generalized from deconvolving different cell types to subtle scenarios where one wishes to resolve different cell populations of the same cell-type. AVAILABILITY AND IMPLEMENTATION: The code used in this work to analyze single-molecule Bionano Genomics optical maps is available via the GitHub repository https://github.com/ebensteinLab/Single_molecule_methylation_in_EP.

Clinical Implications of HBV PreS/S Mutations and the Effects of PreS2 Deletion on Mitochondria, Liver Fibrosis, and Cancer Development.

BACKGROUND AND AIMS: PreS mutants of HBV have been reported to be associated with HCC. We conducted a longitudinal study of the role of HBV preS mutations in the development of HCC, particularly in patients with chronic hepatitis B (CHB) having low HBV DNA or alanine aminotransferase (ALT) levels, and investigated the effects of secretion-defective preS2 deletion mutant (preS2ΔMT) on hepatocyte damage in vitro and liver fibrosis in vivo. APPROACH AND RESULTS: Association of preS mutations with HCC in 343 patients with CHB was evaluated by a retrospective case-control follow-up study. Effects of preS2ΔMT on HBsAg retention, endoplasmic reticulum (ER) stress, calcium accumulation, mitochondrial dysfunction, and liver fibrosis were examined. Multivariate analysis revealed a significant association of preS mutations with HCC (HR, 3.210; 95% CI, 1.072-9.613; P = 0.037) including cases with low HBV DNA or ALT levels (HR, 2.790; 95% CI, 1.133-6.873; P = 0.026). Antiviral therapy reduced HCC risk, including cases with preS mutations. PreS2ΔMT expression promoted HBsAg retention in the ER and unfolded protein response (UPR). Transmission electron microscopic examination, MitoTracker staining, real-time ATP assay, and calcium staining of preS2ΔMT-expressing cells revealed aberrant ER and mitochondrial ultrastructure, reduction of mitochondrial membrane potential and ATP production, and calcium overload. Serum HBV secretion levels were ~100-fold lower in preS2ΔMT-infected humanized Fah-/-/ Rag2-/-/Il2rg-/- triple knockout mice than in wild-type HBV-infected mice. PreS2ΔMT-infected mice displayed up-regulation of UPR and caspase-3 and enhanced liver fibrosis. CONCLUSIONS: PreS mutations were significantly associated with HCC development in patients with CHB, including those with low HBV DNA or ALT levels. Antiviral therapy reduced HCC occurrence in patients with CHB, including those with preS mutations. Intracellular accumulation of mutated HBsAg induced or promoted ER stress, calcium overload, mitochondrial dysfunction, impaired energy metabolism, liver fibrosis, and HCC.

DUX4 Transcript Knockdown with Antisense 2'-O-Methoxyethyl Gapmers for the Treatment of Facioscapulohumeral Muscular Dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder characterized by a progressive, asymmetric weakening of muscles, starting with those in the upper body. It is caused by aberrant expression of the double homeobox protein 4 gene (DUX4) in skeletal muscle. FSHD is currently incurable. We propose to develop a therapy for FSHD using antisense 2'-O-methoxyethyl (2'-MOE) gapmers, to knock down DUX4 mRNA expression. Using immortalized patient-derived muscle cells and local intramuscular injections in the FLExDUX4 FSHD mouse model, we showed that our designed 2'-MOE gapmers significantly reduced DUX4 transcript levels in vitro and in vivo, respectively. Furthermore, in vitro, we observed significantly reduced expression of DUX4-activated downstream targets, restoration of FSHD signature genes by RNA sequencing, significant improvements in myotube morphology, and minimal off-target activity. This work facilitates the development of a promising candidate therapy for FSHD and lays down the foundation for in vivo systemic treatment studies.

Effect of Hypertonic Dextrose Injection on Pain and Shoulder Disability in Patients with Chronic Supraspinatus Tendinosis: A Randomized Double-Blind Controlled Study.

OBJECTIVES: To investigate the effect of hypertonic dextrose injection on pain and disability in patients with chronic supraspinatus tendinosis. The secondary aim was to evaluate its effect on the tendon range of motion (ROM) and morphology. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Outpatient clinic. PARTICIPANTS: Individuals (N=57) with symptomatic chronic supraspinatus tendinosis. INTERVENTIONS: Participants were randomly administered ultrasound-guided injections of 20% hypertonic dextrose (study group, n=29) or 5% normal saline (control group, n=28). MAIN OUTCOME MEASURES: The primary outcome measure was visual analog scale (VAS) scores for pain and Shoulder Pain and Disability Index (SPADI) scores. Secondary outcomes included the ROM and ultrasound examination findings of the supraspinatus tendon at baseline and at 2, 6, and 12 weeks postintervention. RESULTS: The study group exhibited significant improvements in the VAS (mean difference [MD], -2.1; 95% confidence interval [CI], -2.7 to -1.4; P<.001) and SPADI (MD, -11.6; 95% CI, -16.5 to -6.7; P<.001) scores compared with baseline scores at week 2. However, the effect was not sustained to week 6. Flexion ROM increased at weeks 2 (MD, 14.1; 95% CI, 5.7-22.5; P<.001) and 6 (MD, 8.9; 95% CI, 2.4-15.4; P=.003) compared with baseline. The thickness of the supraspinatus tendon improved at weeks 6 (MD, .50; 95% CI, .26-.74; P<.001) and 12 (MD, .61; 95% CI, .37-.84; P<.001) compared with baseline. The ratio of histograms also improved at weeks 6 (MD, .19; 95% CI, .06-.32; P=.002) and 12 (MD, .26; 95% CI, .10-.41; P<.001) compared with baseline. CONCLUSION: Hypertonic dextrose injection could provide short-term pain and disability relief in patients with chronic supraspinatus tendinosis. Ultrasound imaging at week 6 revealed changed tendon morphology.

Effectiveness, Compliance, and Safety of Dextrose Prolotherapy for Knee Osteoarthritis: A Meta-Analysis and Metaregression of Randomized Controlled Trials.

OBJECTIVES: This study assessed the effectiveness, compliance, and safety of dextrose prolotherapy for patients with knee osteoarthritis. DATA SOURCES: PubMed, EMBASE, the Cochrane Library Database, and the Scopus database from their inception to December 31, 2021. METHODS: This study was conducted in accordance with the guidelines recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Randomized controlled trials regarding the effectiveness of dextrose prolotherapy in knee osteoarthritis were identified. The included trials were subjected to meta-analysis. Risk of bias was assessed using the Cochrane risk of bias tool. Subgroup and random-effects metaregression analyses were performed to explore any heterogeneity (I2) of treatment effects across studies. RESULTS: A total of 14 trials enrolling 978 patients were included in the meta-analysis. Compared with placebo injection and noninvasive control therapy, dextrose prolotherapy had favorable effects on pain, global function, and quality of life during the overall follow-up. Dextrose prolotherapy yielded greater reductions in pain score over each follow-up duration than did the placebo. Compared with other invasive therapies, dextrose prolotherapy generally achieved comparable effects on pain and functional outcomes for each follow-up duration.Subgroup results indicated that combined intra-articular and extra-articular injection techniques may have stronger effects on pain than a single intra-articular technique. CONCLUSIONS: Dextrose prolotherapy may have dose-dependent and time-dependent effects on pain reduction and function recovery, respectively, in patients with knee osteoarthritis. Due to remarkable heterogeneity and the risk of biases across the included trials, the study results should be cautiously interpreted.

Quantitative Assessment of Lung Ultrasound Grayscale Images Based on Shannon Entropy for the Detection of Pulmonary Aeration: An Animal Study.

OBJECTIVE: Lung ultrasound (LUS) is a radiation-free, affordable, and bedside monitoring method that can detect changes in pulmonary aeration before hypoxic damage. However, visual scoring methods of LUS only enable subjective diagnosis. Therefore, quantitative analysis of LUS is necessary for obtaining objective information on pulmonary aeration. Because raw data are not always available in conventional ultrasound systems, Shannon entropy (ShanEn) of information theory without the requirement of raw data is valuable. In this study, we explored the feasibility of ShanEn estimated through grayscale histogram (GSH) analysis of LUS images for the quantification of pulmonary aeration. METHODS: Different degrees of pulmonary aeration caused by edema was induced in 32 male New Zealand rabbits intravenously injected with 0.1 mL/kg saline (the control group) and 0.025, 0.05, and 0.1 mL/kg oleic acid (mild, moderate, and severe groups, respectively). In vivo grayscale LUS images were acquired using a commercial point-of-care ultrasound system for estimation of GSH and corresponding ShanEn. Both lungs of each rabbit were dissected, weighed, and dried to determine the wet weight-to-dry weight ratio (W/D) through gravimetry. RESULTS: The determination coefficients of linear correlations between ShanEn and W/D increased from 0.0487 to 0.7477 with gain and dynamic range (DR). In contrast to visual scoring methods of pulmonary aeration that use median gain and low DR, ShanEn for quantifying pulmonary aeration requires high gain and DR. CONCLUSION: The current findings indicate that ShanEn estimated through GSH analysis of LUS images acquired using conventional ultrasonic imaging systems has great potential to provide objective information on pulmonary aeration.

Court decisions in criminal proceedings for dental malpractice in Taiwan.

BACKGROUND/PURPOSE: Malpractice claims place heavy economic and emotional burdens on both dentists and patients. Recently, medical malpractice lawsuits are decreasing in prevalence but increasing in severity. The percentage of dental malpractice payments is also growing among the health profession. The present study aimed to explore criminal convictions in dental malpractice litigation and to analyze the factors affecting the judgment in dental disputes in Taiwan. METHODS: The keywords "dentist," "professional negligence," "medical malpractice," and "professional liability" were used to search Taiwan's Law and Regulations Retrieving System for criminal dental malpractice cases in all district courts from January 1, 2000 to June 30, 2021. The eligible judgments were summarized and analyzed. RESULTS: Overall, 425 cases were identified, with 28 dental disputes included in the final analysis. The dentists lost in 10 cases (35.7%). The average claim time was 36.75 ± 16.34 months. Taipei and Taichung dealt with more lawsuit cases (n = 8). Local clinics were the most common institution of the defendants (75%) and had the highest number of convictions (n = 9). Implant dentistry was the most common specialty involved. Expert testimony of the Medical Review Committee (MRC) had a high K coefficient of agreement with court judgments regarding professional negligence (p < 0.001). CONCLUSION: The overall criminal conviction rate was 35.7%. Implant therapy and local clinics had the highest rate of lawsuits and a considerably higher conviction rate. All guilty dentists were fined or given probation. The court judgments were highly consistent with the expert testimony of the MRC.

Severity of periodontitis and salivary interleukin-1ß are associated with psoriasis involvement.

BACKGROUND/PURPOSE: Both psoriasis and periodontal diseases are characterized by an exaggerated immune response to the microbiota residing on epithelial surfaces. This study aimed to explore the associations between the severity of psoriasis and periodontal destruction in patients with psoriasis. METHODS: Thirty-three patients diagnosed with psoriasis were referred from the dermatology clinic of National Taiwan University Hospital. Full-mouth periodontal examination was performed and saliva was collected after patients signed informed consent forms. The Psoriasis Area Severity Index (PASI) as well as clinical periodontal parameters including probing depth (PD), plaque index (PI), gingival index (GI), and clinical attachment level (CAL) were evaluated. Salivary cytokines including interleukin (IL)-1ß, IL-12, IL-17, interferon-γ, and tumor necrosis factor (TNF)-α were tested with the Luminex Bio-Plex system. Anti-inflammatory medication, tobacco use, and underlying comorbidities were included in the analysis. RESULTS: Baseline PASI was significantly associated with PI. PASI at follow-up was positively correlated with CAL ≥ 4 mm (%) and saliva IL-1ß levels. Psoriasis patients who used non-steroidal anti-inflammatory drugs or topical steroids had significantly lower GI, PD ≥ 4 mm (%), and saliva IL-1ß and TNF-α levels. Moreover, a history of tobacco use was associated with higher PD ≥ 4 mm (%). CONCLUSION: PI, CAL, and salivary IL-1ß were associated with PASI. Periodontal severity was associated with psoriasis involvement. Periodontal inflammation in psoriasis may be modified by anti-inflammatory medication and tobacco use. Additional large-scale longitudinal and mechanistic studies are needed.

Posterior-Stabilized Antibiotic Cement Articulating Spacer With Endoskeleton-Reinforced Cam Reduces Rate of Post-Cam Mechanical Complications in Prosthetic Knee Infection: A Preliminary Study.

BACKGROUND: Posterior-stabilized antibiotic cement articulating spacers (PS spacers) reduce spacer mechanical complications in prosthetic knee infections (PKIs); however, joint dislocation after femoral cam fracture has been reported. We hypothesized that the rate of post-cam mechanical complications is lower in PS spacers with an endoskeleton-reinforced cam. METHOD: A retrospective study of PKIs using PS spacers with or without a Kirschner wire-reinforced cam (K-PS or nK-PS spacers, respectively) was conducted between 2015 and 2019. The rates of post-cam mechanical complications and reoperation, as well as risk factors for post or cam failure, were analyzed. RESULTS: The cohort included 118 nK-PS and 49 K-PS spacers. All patients were followed up for 2 years. The rate of joint subluxation/dislocation after femoral cam fracture was lower in K-PS (0%) than in nK-PS spacers (17.8%; P = .002). The reoperation rate for spacer mechanical complications was lower in K-PS (0%) than in nK-PS spacers (11.9%; P = .008). The identified risk factors for femoral cam fractures were body mass index ≥25 kg/m2, femoral spacer size ≤2, and surgical volume ≤12 resection arthroplasties per year. CONCLUSION: This preliminary study highlights that K-PS spacers have a lower rate of post-cam mechanical complications than nK-PS spacers. We recommend the use of PS spacers with endoskeleton-reinforced cam when treating PKIs performed by surgeons with lower surgical volumes, especially in patients with higher body mass index and smaller femoral spacer sizes.