Children With Special Health Care Needs: An Analysis of National Survey of Children's Health Database.

Background Children with Special Health Care Needs (CSHCN) represent a diverse pediatric population requiring healthcare services beyond typical childhood needs. This study analyzes data from the 2016-2020 National Survey of Children's Health Database to elucidate demographic patterns, prevalence rates, and nuanced factors influencing the health and well-being of CSHCN. Methods This retrospective observational study focuses on children aged 0-17 who are identified as CSHCN based on Maternal and Child Health Bureau criteria. A comprehensive analysis of the National Survey of Children's Health (NSCH) database examines key variables, including health outcomes, healthcare utilization, parental-reported health status, and socio-demographic factors. Stratified random sampling ensures national representation. Results The study encompassed 40,335 patients, revealing that 14.6% (CI: 14.0-15.3, n=6,445) of CSHCN received care in a well-functioning system. Across age groups, 19.1% (CI: 14.0-15.3, n=6,445) of CSHCN aged 0-5 received ongoing treatment, contrasting with 5.7% (CI: 5.2-6.2, n=1,599) in the 12-17 years group. Males exhibited a prevalence of 15% (CI: 14.1-15.9, n=3,674), and females had 14.2% (CI: 13.2-15.2, n=2,771). Racial disparities were noted; non-Hispanic Native Hawaiian/Other Pacific Islander children had a 3% (CI: 1.1-8.1, n=6) prevalence. Across Federal Poverty Level categories, prevalence ranged from 12.5% (CI: 11.5-13.6, n=1,753) to 17.7% (CI: 16.6-18.9, n=2,856). Notably, 18.5% (CI: 17.4-19.7, n=3,515) of children without adverse experiences were CSHCN. Among CSHCN in two-parent currently married households, 15.9% (CI: 15.0-16.8, n=4,330) received treatment, while those in unmarried households had a prevalence of 12.9% (CI: 10.5-15.7, n=335). CSHCN with parents born in the United States showed a prevalence of 15.4% (CI: 14.7-16.1, n=5,257). Conclusion This study provides valuable insights into the prevalence and demographic patterns of CSHCN. Limitations include potential recall bias and the retrospective study design. Despite these constraints, the findings lay a foundation for future research and targeted interventions, fostering a deeper understanding of the evolving landscape of pediatric healthcare in the United States.

Genetic profiles of oligometastatic non-small cell lung cancer and corresponding brain metastases.

OBJECTIVES: In patients with oligometastatic non-small cell lung cancer, systemic therapy in combination with local ablative treatment of the primary tumor and all metastatic sites is associated with improved prognosis. For patient selection and treatment allocation, further knowledge about the molecular characteristics of the oligometastatic state is necessary. Here, we performed a genetic characterization of primary non-small cell lung cancer and corresponding brain metastases. METHODS: We retrospectively identified patients with oligometastatic non-small cell lung cancer and synchronous (<3 months) or metachronous (>3 months) brain metastases who underwent surgical resection of both primary tumor and brain metastases. Mutation profiling of formalin-fixed paraffin-embedded tumor cell blocks was performed by targeted next generation sequencing using the oncomine focus assay panel. RESULTS: Sequencing was successful in 46 paired samples. An oncogenic alteration was present in 31 primary tumors (67.4%) and 40 brain metastases (86.9%). The alteration of the primary tumors was preserved in the corresponding brain metastases in 29 out of 31 cases (93.5%). The most prevalent oncogenic driver in both primary tumors and brain metastases was a KRAS mutation (n = 21). In 16 patients (34.8%), the brain metastasis harbored additional oncogenic alterations. The presence of a private genetic alteration in the brain metastasis was an independent predictor of shorter overall survival. CONCLUSIONS: In oligometastatic non-small cell lung cancer, brain metastases retain the main genetic alterations of the primary tumors. Patients may profit from targeted inhibition of mutated KRAS. Additional private genetic alterations in the brain metastases are dismal.

Using non-invasive behavioral and physiological data to measure biological age in wild baboons.

Biological aging is near-ubiquitous in the animal kingdom, but its timing and pace vary between individuals and over lifespans. Prospective, individual-based studies of wild animals-especially non-human primates-help identify the social and environmental drivers of this variation by indicating the conditions and exposure windows that affect aging processes. However, measuring individual biological age in wild primates is challenging because several of the most promising methods require invasive sampling. Here, we leverage observational data on behavior and physiology, collected non-invasively from 319 wild female baboons across 2402 female-years of study, to develop a composite predictor of age: the non-invasive physiology and behavior (NPB) clock. We found that age predictions from the NPB clock explained 51% of the variation in females' known ages. Further, deviations from the clock's age predictions predicted female survival: females predicted to be older than their known ages had higher adult mortality. Finally, females who experienced harsh early-life conditions were predicted to be about 6 months older than those who grew up in more benign conditions. While the relationship between early adversity and NPB age is noisy, this estimate translates to a predicted 2-3 year reduction in mean adult lifespan in our model. A constraint of our clock is that it is tailored to data collection approaches implemented in our study population. However, many of the clock's components have analogs in other populations, suggesting that non-invasive data can provide broadly applicable insight into heterogeneity in biological age in natural populations.

Nickel-Catalyzed Atroposelective Cross-Electrophile Coupling of Aryl Halides: A General and Practical Route to Diverse MOP-Type Ligands.

We report a highly cross- and atroposelective coupling between ortho-(chloro)arylphosphine oxides and ortho-(bromo)aryl ethers. This previously unknown asymmetric nickel-catalyzed reaction offers a direct route to highly enantioenriched axially chiral biaryl monophosphine oxides that are difficult to access by other means. These products can be readily reduced to generate chiral MOP-type ligands bearing complex skeletal backbones. The utility of these chiral ligands in asymmetric catalysis is also demonstrated.

Rehabilitation and Return to Play Protocols After Anterior Cruciate Ligament Reconstruction in Soccer Players: A Systematic Review.

BACKGROUND: Rehabilitation after anterior cruciate ligament ACL reconstruction (ACLR) is crucial for safe return to play (RTP) and reducing the chances of a reinjury. Yet, there is no consensus on the ideal functional tests to assess rehabilitation progress in soccer players after ACLR. PURPOSE: The primary objective was to highlight the existing gap in the literature concerning the most effective standardized rehabilitation protocols and testing for facilitating successful RTP among soccer players. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review using PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) was conducted. Inclusion criteria encompassed original studies (level of evidence 1-4) that examined rehabilitation protocols, metrics of knee rehabilitation, and clinical outcomes after ACLR in soccer players. RESULTS: This review incorporated 23 studies, predominantly retrospective case series, with a total number of 874 soccer players who underwent ACLR and rehabiliation. 5 (21.7%) studies utilized an accelerated rehabilitation protocol, while 7 (30.4%) of studies utilized a criterion-based rehabilitation. A wide heterogeneity of data was extracted including functional tests of rehabilitation and RTP such as strength test batteries, hop test batteries, and movement quality assessments. Of the 23 selected studies, 2 (8.7%) used all 3 test batteries, 8 (34.8%) used 2 test batteries, 12 (52.2%) used 1 test battery, and 1 (4.3%) used 0 of the test batteries. The mean time between surgery and RTP ranged from 3 to 8 months with only 2 (8.7%) studies reporting complications after ACLR. Lastly, out of the total studies examined, 9 (39.1%) assessed patient-reported outcome measures (PROMs), all of which demonstrated significant improvement from the initial assessment to the final follow up. CONCLUSION: Soccer-specific rehabilitation after ACLR lacks standardization. Even though many studies have assessed protocols for optimal RTP and reduced secondary ACL injuries, there is a gap in the literature regarding the most effective protocols and RTP testing. The methodology reported by Kyritsis et al could serve as a foundation for future prospective randomized multicenter studies to establish a standard rehabilitation protocol and enable a successful return to soccer.

S1PR3 agonism and S1P lyase inhibition rescue mice in the severe state of experimental sepsis.

Sepsis is characterized as life-threatening organ dysfunction caused by a dysregulated host response to an infection. Despite numerous clinical trials that addressed this syndrome, there is still no causative treatment available to dampen its severity. Curtailing the infection at an early stage with anti-infectives is the only effective treatment regime besides intensive care. In search for additional treatment options, we recently discovered the inhibition of the sphingosine 1-phosphate (S1P) lyase and subsequent activation of the S1P receptor type 3 (S1PR3) in pre-conditioning experiments as promising targets for sepsis prevention. Here, we demonstrate that treatment of septic mice with the direct S1P lyase inhibitor C31 or the S1PR3 agonist CYM5541 in the advanced phase of sepsis resulted in a significantly increased survival rate. A single dose of each compound led to a rapid decline of sepsis severity in treated mice and coincided with decreased cytokine release and increased lung barrier function with unaltered bacterial load. The survival benefit of both compounds was completely lost in S1PR3 deficient mice. Treatment of the murine macrophage cell line J774.1 with either C31 or CYM5541 resulted in decreased protein kinase B (Akt) and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) phosphorylation without alteration of the mitogen-activated protein kinase (MAPK) p38 and p44/42 phosphorylation. Thus, activation of S1PR3 in the acute phase of sepsis by direct agonism or S1P lyase inhibition dampened Akt and JNK phosphorylation, resulting in decreased cytokine release, improved lung barrier stability, rapid decline of sepsis severity and better survival in mice.

Triple-induction treatment for locally advanced non-small cell lung cancer: a case report of pathological complete response.

BACKGROUND: In patients with resectable stage III non-small cell lung cancer (NSCLC), induction chemoimmunotherapy followed by surgical resection has shown unprecedented rates of pathological response and event-free survival. However, a triple-induction including radiochemotherapy and immunotherapy followed by surgical resection has not been routinely established in clinical practice. CASE PRESENTATION: We report the case of a 47-year-old patient with stage IIIA NSCLC who was treated in a combined concept including induction concurrent radiochemotherapy, followed by 4 cycles of pembrolizumab and subsequent intrapericardial left-sided pneumonectomy. Histological analysis revealed a pathological complete response. CONCLUSIONS: The case demonstrates that the combination of neoadjuvant chemo-, radio- and immunotherapy in advanced NSCLC may lead to a relevant down-staging and may enable a R0-resection of a borderline resectable tumor. However, the combination of four different treatment modalities requires resilience and a good performance status. A triple induction treatment may be a promising option for selected patients with locally advanced NSCLC and good performance status.

Coping as a resource to allow for psychosocial adjustment in fatal disease: results from patients with amyotrophic lateral sclerosis.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal disorder, which imposes a severe emotional burden on patients. Appropriate coping mechanisms may alleviate this burden and facilitate wellbeing, with social support known to be a successful coping strategy. This observational study aimed to determine the interplay of general coping traits of hope for success and fear of failure, coping behavior of social activity, and patients' wellbeing. Methods: In this cross-sectional study, patients with ALS from a clinical-epidemiological registry in Southwestern Germany were interviewed regarding coping traits (achievement-motivated behavior: hope for success and fear of failure), coping behavior of social activity, and psychosocial adjustment, determined using measures of depressiveness, anxiety [both measured by Hospital Anxiety and Depression Scale (HADS)], and quality of life [Anamnestic Comparative Self-Assessment (ACSA)]. Demographics, clinical [ALS Functional Rating Scale revised version (ALSFRS-R)], and survival data were recorded. Results: A total of 868 patients [60.70% male patients, mean age: 64.70 (±10.83) years, mean ALSFRS-R: 37.36 ± 7.07] were interviewed. Anxiety in patients was found to be associated with a high fear of failure. In contrast, a generally positive attitude in patients exemplified in high hopes for success was associated with better wellbeing. Finally, coping behavior of social activity explained up to 65% of the variance of depressiveness among the patients with ALS. Conclusion: In this study, we present evidence that the wellbeing of patients with ALS is not an immediate fatalistic consequence of physical degradation but rather determined by coping traits and behavior, which may be trained to substantially increase the wellbeing of patients with ALS.

Post-COVID syndrome and work ability 9-12 months after a SARS-CoV-2 infection among over 9000 employees from the general population.

Objectives: Evidence on the work-related societal impact of long-term health-related consequences following SARS-CoV-2 is emerging. We characterize the modified work ability index (mWAI) of employees 6 to 12 months after an acute infection compared to pre-infection. Methods: Analyses were based on a population-based, multi-center cross-sectional study including employees aged 18-65 years with positive SARS-CoV-2 polymerase chain reaction (tested between October 2020-April 2021 in defined geographic regions in Germany). Prevalences and results of adjusted logistic regression analyses were given. Results: In 9752 employees (mean age 45.6 years, 58% females, response 24%), n = 1217 (13.1%) participants were regarded as having low mWAI compared to pre-infection. Outpatient medical treatment, inpatient treatment, and admission to intensive care during infection were associated with mWAI <15th percentile (P15, each odds ratio [OR] >3.0). Post-COVID symptom clusters most strongly linked to mWAI

Microbially conjugated bile salts found in human bile activate the bile salt receptors TGR5 and FXR.

BACKGROUND: Bile salts of hepatic and microbial origin mediate interorgan cross talk in the gut-liver axis. Here, we assessed whether the newly discovered class of microbial bile salt conjugates (MBSCs) activate the main host bile salt receptors (Takeda G protein-coupled receptor 5 [TGR5] and farnesoid X receptor [FXR]) and enter the human systemic and enterohepatic circulation. METHODS: N-amidates of (chenodeoxy) cholic acid and leucine, tyrosine, and phenylalanine were synthesized. Receptor activation was studied in cell-free and cell-based assays. MBSCs were quantified in mesenteric and portal blood and bile of patients undergoing pancreatic surgery. RESULTS: MBSCs were activating ligands of TGR5 as evidenced by recruitment of Gsα protein, activation of a cAMP-driven reporter, and diminution of lipopolysaccharide-induced cytokine release from macrophages. Intestine-enriched and liver-enriched FXR isoforms were both activated by MBSCs, provided that a bile salt importer was present. The affinity of MBSCs for TGR5 and FXR was not superior to host-derived bile salt conjugates. Individual MBSCs were generally not detected (ie, < 2.5 nmol/L) in human mesenteric or portal blood, but Leu-variant and Phe-variant were readily measurable in bile, where MBSCs comprised up to 213 ppm of biliary bile salts. CONCLUSIONS: MBSCs activate the cell surface receptor TGR5 and the transcription factor FXR and are substrates for intestinal (apical sodium-dependent bile acid transporter) and hepatic (Na+ taurocholate co-transporting protein) transporters. Their entry into the human circulation is, however, nonsubstantial. Given low systemic levels and a surplus of other equipotent bile salt species, the studied MBSCs are unlikely to have an impact on enterohepatic TGR5/FXR signaling in humans. The origin and function of biliary MBSCs remain to be determined.

Thyroid hormone concentrations in female baboons: Metabolic consequences of living in a highly seasonal environment.

How female mammals adapt metabolically in response to environmental variation remains understudied in the wild, because direct measures of metabolic activity are difficult to obtain in wild populations. However, recent advances in the non-invasive measurement of fecal thyroid hormones, triiodothyronine (T3), an important regulator of metabolism, provide an opportunity to understand how female baboons living in the harsh Amboseli ecosystem in southern Kenya adapt to environmental variability and escape strict reproductive seasonality. Specifically, we assessed how a female's activity budget, diet, and concentrations of fecal T3 metabolites (mT3) changed over the course of the year and between years. We then tested which of several environmental variables (season, rainfall, and temperature) and behavioral variables (female activity budget and diet) best predicted mT3 concentrations. Finally, we determined if two important reproductive events - onset of ovarian cycling and conception of an offspring - were preceded by changes in female mT3 concentrations. We found female baboons' mT3 concentrations varied markedly across the year and between years as a function of environmental conditions. Further, changes in a female's behavior and diet only partially mediated the metabolic response to the environment. Finally, mT3 concentrations increased in the weeks prior to menarche and cycling resumption, regardless of the month or season in which cycling started. This pattern indicates that metabolic activation may be an indicator of reproductive readiness in female baboons as their energy balance is restored.

Taxogenomic analyses of Starmerella gilliamiae f.a, sp. nov. and Starmerella monicapupoae f.a., sp. nov., two novel species isolated from plant substrates and insects.

Four yeast isolates collected from flowers from different ecosystems in Brazil, one from fruit of Nothofagus alpina in Argentina, three from flowers of Neltuma chilensis in Chile and one obtained from the proventriculus of a female bumblebee in Canada were demonstred, by analysis of the sequences of the internal transcribed spacer (ITS) region and D1/D2 domains of the large subunit rRNA gene, to represent two novel species of the genus Starmerella. These species are described here as Starmerella gilliamiae f.a, sp. nov. (CBS 16166T; Mycobank MB 851206) and Starmerella monicapupoae f.a., sp. nov. (PYCC 8997T; Mycobank MB 851207). The results of a phylogenomic analysis using 1037 single-copy orthogroups indicated that S. gilliamiae is a member of a subclade that contains Starmerella opuntiae, Starmerella aceti and Starmerella apicola. The results also indicated that S. monicapupoae is phylogenetically related to Starmerella riodocensis. The two isolates of S. monicapupoae were obtained from flowers in Brazil and were probably vectored by insects that visit these substrates. Starmerella gilliamiae has a wide geographical distribution having been isolated in flowers from Brazil and Chile, fruit from Argentina and a bumblebee from Canada.

Pre-existing sleep problems as a predictor of post-acute sequelae of COVID-19.

Several months after COVID-19 many individuals still report persisting symptoms, the so-called 'post-COVID-19 syndrome'. An immunological dysfunction is one of the main pathophysiological hypotheses. As sleep is central to the functioning of the immune system, we investigated whether self-reported pre-existing sleep disturbance might be an independent risk factor for the development of post-COVID-19 syndrome. A total of 11,710 participants of a cross-sectional survey (all tested positive for severe acute respiratory syndrome coronavirus-2) were classified into probable post-COVID-19 syndrome, an intermediate group, and unaffected participants at an average of 8.5 months after infection. The case definition was based on newly occurring symptoms of at least moderate severity and ≥20% reduction in health status and/or working capacity. Unadjusted and adjusted odds ratios were calculated to investigate the association between pre-existing sleep disturbances and subsequent development of post-COVID-19 syndrome while controlling for a variety of demographic, lifestyle, and health factors. Pre-existing sleep disturbances were found to be an independent predictor of subsequent probable post-COVID-19 syndrome (adjusted odds ratio 2.7, 95% confidence interval 2.27-3.24). Sleep disturbances as part of the post-COVID-19 syndrome were reported by more than half of the participants and appeared to be a new symptom and to occur independent of a mood disorder in most cases. Recognition of disturbed sleep as an important risk factor for post-COVID-19 syndrome should promote improved clinical management of sleep disorders in the context of COVID-19. Further, it may stimulate further research on the effect of improving sleep on the prognosis of COVID-19 long-term sequelae and other post-viral conditions.

Cystatin C based estimation of chronic kidney disease and amyotrophic lateral sclerosis in the ALS registry Swabia: associated risk and prognostic value.

Kidney function as part of metabolic changes could be associated with amyotrophic lateral-sclerosis (ALS). We investigated the associations between estimated chronic kidney disease (CKD), based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C equation, and the risk at onset and prognostic value of CKD for ALS. Between October 2010 and June 2014, 362 ALS cases (59.4% men, mean age 65.7 years) and 681 controls (59.5% men, means age 66.3 years) were included in a population-based case-control study based on the ALS registry Swabia in Southern Germany. All ALS cases were followed-up (median 89.7 months), 317 died. Serum samples were measured for cystatin C to estimate the glomerular filtration rate (eGFR) according to the CKD-EPI equation. Information on covariates were assessed by an interview-based standardized questionnaire. Conditional logistic regression models were applied to calculate odds ratios (OR) for risk of ALS associated with eGFR/CKD stages. Time-to-death associated with renal parameters at baseline was assessed in ALS cases only. ALS cases were characterized by lower body mass index, slightly lower smoking prevalence, more intense occupational work and lower education than controls. Median serum cystatin-C based eGFR concentrations were lower in ALS cases than in controls (54.0 vs. 59.5 mL/min pro 1.73 m2). The prevalence of CKD stage ≥ 3 was slightly higher in ALS cases than in controls (14.1 vs. 11.0%). In the adjusted models, CKD stage 2 (OR 1.82, 95% CI 1.32, 2.52) and stage 3 (OR 2.34, 95% CI 1.38, 3.96) were associated with increased ALS risk. In this cohort of ALS cases, eGFR and CKD stage ≥ 3 (HR 0.94; 95% CI 0.64, 1.38) were not associated with prognosis. In this case-control study, higher CKD stages were associated with increased ALS risk, while in the prospective cohort of ALS cases, no indication of an association of CysC-based CKD on mortality was seen. In addition, our work strengthens the importance to evaluate renal function using a marker independent of muscle mass in ALS patients.

G Protein-Coupled Receptor Kinase 2 Selectively Enhances ß-Arrestin Recruitment to the D2 Dopamine Receptor through Mechanisms That Are Independent of Receptor Phosphorylation.

The D2 dopamine receptor (D2R) signals through both G proteins and ß-arrestins to regulate important physiological processes, such as movement, reward circuitry, emotion, and cognition. ß-arrestins are believed to interact with G protein-coupled receptors (GPCRs) at the phosphorylated C-terminal tail or intracellular loops. GPCR kinases (GRKs) are the primary drivers of GPCR phosphorylation, and for many receptors, receptor phosphorylation is indispensable for ß-arrestin recruitment. However, GRK-mediated receptor phosphorylation is not required for ß-arrestin recruitment to the D2R, and the role of GRKs in D2R-ß-arrestin interactions remains largely unexplored. In this study, we used GRK knockout cells engineered using CRISPR-Cas9 technology to determine the extent to which ß-arrestin recruitment to the D2R is GRK-dependent. Genetic elimination of all GRK expression decreased, but did not eliminate, agonist-stimulated ß-arrestin recruitment to the D2R or its subsequent internalization. However, these processes were rescued upon the re-introduction of various GRK isoforms in the cells with GRK2/3 also enhancing dopamine potency. Further, treatment with compound 101, a pharmacological inhibitor of GRK2/3 isoforms, decreased ß-arrestin recruitment and receptor internalization, highlighting the importance of this GRK subfamily for D2R-ß-arrestin interactions. These results were recapitulated using a phosphorylation-deficient D2R mutant, emphasizing that GRKs can enhance ß-arrestin recruitment and activation independently of receptor phosphorylation.

Five Decades of Data Yield No Support for Adaptive Biasing of Offspring Sex Ratio in Wild Baboons (Papio cynocephalus).

AbstractOver the past 50 years, a wealth of testable, often conflicting hypotheses have been generated about the evolution of offspring sex ratio manipulation by mothers. Several of these hypotheses have received support in studies of invertebrates and some vertebrate taxa. However, their success in explaining sex ratios in mammalian taxa-especially in primates-has been mixed. Here, we assess the predictions of four different hypotheses about the evolution of biased offspring sex ratios in the baboons of the Amboseli basin in Kenya: the Trivers-Willard, female rank enhancement, local resource competition, and local resource enhancement hypotheses. Using the largest sample size ever analyzed in a primate population (n=1,372 offspring), we test the predictions of each hypothesis. Overall, we find no support for adaptive biasing of sex ratios. Offspring sex is not consistently related to maternal dominance rank or biased toward the dispersing sex, nor is it predicted by group size, population growth rates, or their interaction with maternal rank. Because our sample size confers power to detect even subtle biases in sex ratio, including modulation by environmental heterogeneity, these results suggest that adaptive biasing of offspring sex does not occur in this population.

Piranha-etched titanium nanostructure reduces biofilm formation in vitro.

OBJECTIVES: Nano-modified surfaces for dental implants may improve gingival fibroblast adhesion and antibacterial characteristics through cell-surface interactions. The present study investigated how a nanocavity titanium surface impacts the viability and adhesion of human gingival fibroblasts (HGF-1) and compared its response to Porphyromonas gingivalis with those of marketed implant surfaces. MATERIAL AND METHODS: Commercial titanium and zirconia disks, namely, sandblasted and acid-etched titanium (SLA), sandblasted and acid-etched zirconia (ZLA), polished titanium (PT) and polished zirconia (ZrP), and nanostructured disks (NTDs) were tested. Polished titanium disks were etched with a 1:1 combination of 98% H2SO4 and 30% H2O2 (piranha etching) for 5 h at room temperature to produce the NTDs. Atomic force microscopy was used to measure the surface topography, roughness, adhesion force, and work of adhesion. MTT assays and immunofluorescence staining were used to examine cell viability and adhesion after incubation of HGF-1 cells on the disk surfaces. After incubation with P. gingivalis, conventional culture, live/dead staining, and SEM were used to determine the antibacterial properties of NTD, SLA, ZLA, PT, and ZrP. RESULTS: Etching created nanocavities with 10-20-nm edge-to-edge diameters. Chemical etching increased the average surface roughness and decreased the surface adherence, while polishing and flattening of ZrP increased adhesion. However, only the NTDs inhibited biofilm formation and bacterial adherence. The NTDs showed antibacterial effects and P. gingivalis vitality reductions. The HGF-1 cells demonstrated greater viability on the NTDs compared to the controls. CONCLUSION: Nanocavities with 10-20-nm edge-to-edge diameters on titanium disks hindered P. gingivalis adhesion and supported the adhesion of gingival fibroblasts when compared to the surfaces of currently marketed titanium or zirconia dental implants. CLINICAL RELEVANCE: This study prepared an effective antibacterial nanoporous surface, assessed its effects against oral pathogens, and demonstrated that surface characteristics on a nanoscale level influenced oral pathogens and gingival fibroblasts. CLINICAL TRIAL REGISTRATION: not applicable.

Conformational flexibility of ß-arrestins - How these scaffolding proteins guide and transform the functionality of GPCRs.

G protein-coupled receptors (GPCRs) constitute the largest family of transmembrane proteins and play a crucial role in regulating diverse cellular functions. They transmit their signaling via binding to intracellular signal transducers and effectors, such as G proteins, GPCR kinases, and ß-arrestins. To influence specific GPCR signaling behaviors, ß-arrestins recruit effectors to form larger signaling complexes. Intriguingly, they facilitate divergent functions for the binding to different receptors. Recent studies relying on advanced structural approaches, novel biosensors and interactome analyses bring us closer to understanding how this specificity is achieved. In this article, we share our hypothesis of how active GPCRs induce specific conformational rearrangements within ß-arrestins to reveal distinct binding interfaces, enabling the recruitment of a subset of effectors to foster specialized signaling complexes. Furthermore, we discuss methods of how to comprehensively assess ß-arrestin conformational states and present the current state of research regarding the functionality of these multifaceted scaffolding proteins.