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PubMedDate not supplied

Energy dependence of correction factors for two models of Keithley diagnostic ion chambers.

The energy dependence for each of two models of ionization chambers compatible with the Keithley model 35020 Digital Dosimeter, is determined by measurement of the exposure correction factors determined over the diagnostic x-ray range (0.4--4.9 mm AL HVL) for several for several samples of each model. The results of an analysis of variance performed by model on the correction factors are reported as mean correction factors for the x-ray beams evaluated, with a relative standard error of less than 1% for both cases. Energy-dependence curves for the two chamber models are given, and their use is described.

Evaluation Studies as Topic↗

PubMed1999

Combination of a clinical risk assessment score and rapid whole blood D-dimer testing in the diagnosis of deep vein thrombosis in symptomatic patients.

PURPOSE: The clinical diagnosis of deep vein thrombosis (DVT) is unreliable in more than 50% of cases, and, in recent years, plasma D-dimer assays have been used to predict the presence of DVT with high sensitivity and negative predictive values. This study investigated the use of a rapid whole blood test that could be performed and interpreted by the bedside in addition to a clinically derived risk assessment score (RAS) to determine whether a practical and cost-effective clinical model could be developed for the diagnosis and exclusion of DVT in symptomatic patients. METHODS: Two hundred consecutive patients who were referred to the vascular laboratory with clinically suspected DVT underwent the following procedures: (1) clinical assessment and stratification into low, moderate, or high risk for DVT on the basis of an RAS related to history, symptoms, and physical examination findings; (2) rapid (5-minute) whole blood D-dimer testing with a semi-qualitative agglutination technique on a fingerprick blood sample; and (3) color flow duplex ultrasound scanning with standard criteria for the diagnosis of proximal and calf DVT. RESULTS: Forty-six patients (23%) had acute DVT on duplex ultrasound scanning. Of these cases, 28 (61%) had proximal DVT and 18 (39%) were confined to the calf. A total of 88 patients were classified as low risk, 67 were classified as moderate, and 45 were classified as high risk on the basis of the RAS method. Of the patients who were classified at low risk, 4.5% (4/88) had DVT, as compared with 17.9% (12/67) in the moderate clinical risk group and 66.7% (30/45) in the high risk group. Isolated calf DVT was found in 30% (9/30), 50% (6/12), and 75% (3/4) of the high, moderate, and low risk groups, respectively. The sensitivity (8.7%, 26.1%, 65.2%), specificity (45.5%, 64.3%, 90.3%), positive predictive value (4.5%, 17.9%, 66.7%), and overall accuracy rate (37%, 55.5%, 84.5%) of the low, moderate, and high risk groups, respectively, in the diagnosis of DVT increased significantly with increasing risk score stratification. The sensitivity, specificity, positive and negative predictive value, and overall accuracy of the rapid D-dimer test for all DVT were 91.3%, 81.9%, 60%, 96.9%, and 84%, respectively, with a 100% sensitivity and negative predictive value for proximal DVT. A combination of the RAS and D-dimer identified a low risk group with a negative D-dimer as having less than a 1% likelihood of DVT and a high risk group with positive D-dimer as having a likelihood of more than 90%. CONCLUSION: A combination of clinical assessment and rapid D-dimer testing provides an effective means of excluding proximal DVT in symptomatic patients. The application of a clinical diagnostic model on the basis of these parameters has the potential for saving a large proportion of unnecessary duplex scans with the associated time and costs.

Female↗

PubMed2026

Mechanism of Action of Hedyotis diffusa Extract in a Rat Model of Acute Lung Injury Based on Transcriptomic Analysis.

OBJECTIVE: This study established a rat model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) to evaluate pathological damage, collagen deposition, inflammatory cytokine levels, and key gene/protein expression following Hedyotis diffusa water extract (HDWE) intervention. Combined with ultra-high-performance liquid chromatography-quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), transcriptomic analysis, and molecular simulation, this study identified the bioactive components of HDWE, evaluated their potential interactions with ALI-related targets, and explored the multi-omics-based protective mechanisms of HDWE. METHODS: Thirty-six Sprague-Dawley (SD) rats were randomly divided into six groups: Control group, ALI group, DXMS group, HDWE-L group (100 mg/kg), HDWE-M group (200 mg/kg), and HDWE-H group (300 mg/kg). Hematoxylin and eosin (H&E) and Masson's trichrome staining were used to evaluate lung pathological changes and collagen deposition. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum tumor necrosis factor-α TNF-α interleukin-1β IL-1β, erleukin-6 (IL-6), and interleukin-10 (IL-10) levels. Transcriptomic analysis identified differentially expressed genes (DEGs), followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), receiver operating characteristic (ROC), and immune infiltration analyses. Quantitative real-time polymerase chain reaction (qRT-PCR) detected the mRNA expression levels of SPHK1, RELA, and NFKBIA. Immunohistochemistry evaluated the expression of eight hub targets, including endothelin-1 (EDN1), sphingosine kinase 1 (SPHK1), intercellular adhesion molecule 1 (ICAM1), interleukin-17 (IL-17), prostaglandin-endoperoxide synthase 2 (PTGS2/COX-2), NF-κB p65 (encoded by RELA), WT1-associated protein (WTAP), and myeloperoxidase (MPO). UHPLC-Q-Orbitrap HRMS characterized HDWE constituents. Molecular docking analysis was performed between 22 compounds and eight hub targets, followed by 100 ns molecular dynamics simulations and molecular mechanics-Poisson-Boltzmann surface area (MM/PBSA) binding free energy calculations for five core targets. Compared with the control group, the ALI group showed increased levels of TNF-α (86%), IL-1β (107%), and IL-6 (66%), accompanied by a 43% reduction in IL-10 and a 300% increase in lung collagen deposition. All HDWE doses alleviated inflammatory responses, with medium-dose HDWE showing the most pronounced effects. Specifically, medium-dose HDWE increased IL-10 levels by 52% and reduced IL-6, TNF-α, and IL-1β levels by 18%, 22%, and 11%, respectively. Transcriptomic analysis identified 2512 DEGs between the control group and ALI groups, 832 exclusive DEGs between the ALI group and HDWE-M groups, and 876 overlapping DEGs enriched in TNF, IL-17, and NF-κB signaling pathways. The eight-hub-gene diagnostic model achieved an area under the curve (AUC) of 0.969. RELA, SPHK1, and four other hub genes showed positive correlations with Th1, Th17, and neutrophil infiltration. In the ALI group, SPHK1, RELA, and NFKBIA mRNA expression levels were 1.30-, 0.96-, and 0.71-fold of those in the control group, respectively. Compared with the ALI group, high-dose HDWE treatment and low-dose HDWE treatment reduced SPHK1 expression to 0.62- and 0.57-fold, respectively, and increased NFKBIA expression to 1.68- and 1.58-fold, respectively. High-dose HDWE treatment reduced RELA expression to 0.43-fold. The expression levels of inflammation-related proteins were increased in the ALI group and were reduced after HDWE treatment. Twenty-two HDWE components were identified, 16 of which met the docking criteria. Asperulosidic acid exhibited favorable predicted binding affinities with all eight targets, with calculated binding free energies of -14.74, -14.92, -17.58, -23.04, and -16.10 kcal/mol for MPO, IL-17, NF-κB p65, PTGS2/COX-2, and SPHK1, respectively. CONCLUSIONS: This study provides systematic in vivo pharmacodynamic and in silico component-target evidence regarding the protective effects of HDWE against LPS-induced ALI. HDWE treatment increased NFKBIA expression and reduced SPHK1, RELA, and multiple inflammatory protein levels, suggesting that HDWE may regulate the IL-17/NF-κB-associated inflammatory network, although direct causal relationships require further validation. Asperulosidic acid may represent a key bioactive component with broad target-binding potential. This study was limited by the use of an LPS-induced rat ALI model without gene knockout or target inhibitor validation; therefore, further functional experiments are required to confirm the proposed regulatory mechanisms.

Hedyotis diffusa↗

PubMed1997

Comparison of selected methods used to analyze bipolar disorder.

Susceptibility genes on chromosome 18, and a parent-of-origin effect, have been suggested for bipolar disorder. We analyzed BP data sets provided by the National Institutes of Mental Health and Johns Hopkins University to the Genetic Analysis Workshop 10. Numerous statistical methods were applied to detect association, linkage, and parent-of-origin effects, under alternative diagnostic models. The methods were subsequently compared. Our results suggest that the evidence of linkage of BP to chromosome 18 markers tends to increase, often substantially, as the classification of "affected" individuals broadens. Additionally, a parent-of-origin effect was detected in some of the families.

Bipolar Disorder↗

PubMed2004

Algorithms based on prostate-specific antigen (PSA), free PSA, digital rectal examination and prostate volume reduce false-positive PSA results in prostate cancer screening.

Our objective was to determine whether multivariate algorithms based on serum total PSA, the free proportion of PSA, age, digital rectal examination and prostate volume can reduce the rate of false-positive PSA results in prostate cancer screening more effectively than the proportion of free PSA alone at 95% sensitivity. A total of 1,775 consecutive 55- to 67-year-old men with a serum PSA of 4-10 microg/l in the European Randomized Study of Screening for Prostate Cancer were included. To predict the presence of cancer, multivariate algorithms were constructed using logistic regression (LR) and a multilayer perceptron neural network with Bayesian regularization (BR-MLP). A prospective setting was simulated by dividing the data set chronologically into one set for training and validation (67%, n = 1,183) and one test set (33%, n = 592). The diagnostic models were calibrated using the training set to obtain 95% sensitivity. When applied to the test set, the LR model, the BR-MLP model and the proportion of free PSA reached 92%, 87% and 94% sensitivity and reduced 29%, 36% and 22% of the false-positive PSA results, respectively. At a fixed sensitivity of 95% in the test set, the LR model eliminated more false-positive PSA results (22%) than the proportion of free PSA alone (17%) (p < 0.001), whereas the BR-MLP model did not (19%) (p = 0.178). The area under the ROC curve was larger for the LR model (0.764, p = 0.030) and the BR-MLP model (0.760, p = 0.049) than for the proportion of free PSA (0.718). A multivariate algorithm can be used to reduce unnecessary prostate biopsies in screening more effectively than the proportion of free PSA alone, but the algorithms will require updating when clinical practice develops with time.

Aged↗

PubMed2000

Putting prions into focus: application of single molecule detection to the diagnosis of prion diseases.

Prion diseases are characterized by the cerebral deposition of an aggregated pathological isoform of the prion protein (PrP(Sc)) which constitutes the principal component of the transmissible agent termed prion. In order to develop a highly sensitive method for the detection of PrP(Sc) aggregates in biological samples such as cerebrospinal fluid (CSF), we used a method based on Fluorescence Correlation Spectroscopy (FCS), a technique which allows detection of single fluorescently labeled molecules in solution. Within the FCS setup, fluorescent photons emitted by molecules passing an open volume element defined by the beam of an excitation laser focussed into a diffraction-limited spot are imaged confocally onto a single photon counting detector. Aggregates of PrP(Sc) could be labeled by co-aggregation of probe molecules such as monomeric recombinant PrP or PrP-specific antibodies tagged with a fluorescent dye. In addition to slow diffusion, labeled aggregates are characterized by high fluorescence intensity, which allows detection and quantification by analysis of fluorescence intensity distribution. To improve detection of rare target particles, the accessible volume element was increased by scanning for intensely fluorescent targets (SIFT). To further improve sensitivity and specificity, two different probes were used simultaneously in a two-color setup. In a diagnostic model system of CSF spiked with purified prion rods, dual-color SIFT was more sensitive than Western blot analysis. In addition, a PrP(Sc)-specific signal was also detected in a number of CSF samples derived from CJD patients but not in controls.

Animals↗

PubMed2002

Age-specific values and cutoff levels for the diagnosis of osteoporosis in quantitative ultrasound measurements at the calcaneus with SAHARA in healthy Japanese women: Japanese population-based osteoporosis (JPOS) study.

To establish the reference values of the quantitative ultrasound (QUS) indices in healthy Japanese women and to propose a diagnostic criterion for osteoporosis by means of the QUS indices, 659 healthy women aged 20-79 years recruited from a larger cohort study (JPOS study), were examined for bone mass measurements by QUS at the calcaneus (SAHARA, Hologic Inc., USA) and by dual-energy X-ray absorptiometry at the spine, hip, and distal forearm. We presented 10-year age-specific mean values and T-scores of the QUS indices. The pattern of decrease in the T-score appeared to be linear in the QUS indices and total hip BMD but not in BMD at the spine. The T-score of the QUS of indices of the subjects in their 70s were significantly higher than that of BMD at the spine. The prevalence rates of osteoporosis in the subjects aged 50 and older diagnosed by QUS (8.7% for SOS, 10.7% for BUA) were similar to that diagnosed by total hip BMD (11.5%) and significantly lower than that by the spine BMD (36.1%) when the WHO criteria were applied. We performed receiver-operating characteristic analysis to set a cutoff level of the QUS indices for the diagnosis of osteoporosis to accurately identify the subjects diagnosed by either the spine or total hip BMD. The highest likelihood ratios for SOS and BUA were obtained at the cutoff levels of 1,517.7 m/sec (T-score: -1.58) with the sensitivity of 0.65 and the specificity of 0.65 and 59.5 dB/MHz (T-score: -1.52) with 0.66 and 0.69, respectively. The diagnostic accuracy of QUS indices for osteoporosis was not superior to that of age. However, the QUS indices showed a significant contribution to forming the diagnosis of osteoporosis independently of age and body size in multivariate diagnostic models developed by the logistic regression analysis. Therefore, the cutoff values presented in this study may be used as a tentative criterion until the cutoff levels for the QUS indices are set according to the fracture risk.

Adult↗

PubMed1998

A diagnostic score to predict the difficulty of a laparoscopic cholecystectomy from preoperative variables.

BACKGROUND: Modified logistic regression analysis of 24 variables in 300 patients undergoing laparoscopic cholecystectomy found the following parameters independently predictive for a difficult operation: right upper quadrant pain (p < 0.01), rigidity in right upper abdomen (p < 0.01), previous upper abdominal surgery (p < 0.01), biliary colic within the last 3 weeks (p < 0.05), white blood cell count > 10 x 10(9)/l (p < 0.05), thickening of the gallbladder wall (p < 0.05), hydroptic gallbladder (p < 0.05), pericholecystic fluid (p < 0.01), shrunken gallbladder (p < 0.01), and no filling of the gallbladder in preoperative intravenous cholangiography (p < 0.05). METHODS: Based on these variables a diagnostic model was developed to predict the difficulty of a laparoscopic cholecystectomy, with scores ranging from 0 (ideal case) to IV (conversion to open cholecystectomy expected) prior to surgery. RESULTS: When the reliability of our model was examined in a second study in 340 consecutive patients undergoing laparoscopic cholecystectomy 80% of the patients were predicted correctly. CONCLUSIONS: Our model should help to select patients for either laparoscopic or open cholecystectomy based on the expected difficulties and the experience of the surgeon.

Acute Disease↗

PubMed1996

Induction of daunorubicin carbonyl reducing enzymes by daunorubicin in sensitive and resistant pancreas carcinoma cells.

Daunorubicin (DRC) and other anthracyclines are valuable cytotoxic agents in the clinical treatment of certain malignancies. However, as is the case with virtually all anticancer drugs, tumor cell resistance to these agents is one of the major obstacles to successful chemotherapy. In addition to an increased energy-dependent efflux of chemotherapeutic agents, enzymatic drug-inactivating mechanisms also contribute to multidrug resistance of tumor cells. In the case of DRC, carbonyl reduction leads to 13-hydroxydaunorubicinol (DRCOL), the major metabolite of DRC with a significantly lower antineoplastic potency compared to the parent drug. In the present study, we compared two pancreas carcinoma cell lines (a DRC-sensitive parental line and its DRC-resistant subline) with respect to their capacity of DRC inactivation via carbonyl reduction. In addition, we cultured the two cell lines in the presence of increasing sublethal concentrations of DRC. Evidence is presented that DRC treatment itself leads to a concentration-dependent induction of DRC carbonyl reduction in subcellular fractions of both the sensitive and resistant pancreas carcinoma cells, resulting, surprisingly, in different susceptibilities to DRC. The principal difference between the two cell lines becomes most apparent at high-dose DRC supplementation (1 microgram/mL), at which DRC resistant cells exhibited higher inducibility of DRC-inactivating enzymes, whereas respective sensitive cells already showed an impairment of cellular viability. The use of the diagnostic model substrates metyrapone and p-nitrobenzaldehyde reveals that this adaptive enhancement of DRC inactivation can be attributed to the induction of DRC carbonyl reductases different from known aldehyde and carbonyl reductases. In conclusion, these findings suggest that inactivation of anthracyclines by carbonyl reduction is inducible by the substrate itself, a fact that might be considered as one of the enzymatic mechanisms that contribute to the acquired resistance to these drugs.

Alcohol Oxidoreductases↗

PubMed1981

Cluster-oriented discriminant analysis; taxonomic classification of the thyroid function.

A computer assisted procedure for the diagnosis of thyroid diseases, based on seven clinical chemical parameters, is proposed. The population studied consisted of 592 consecutive outpatients with a tentative diagnosis of thyroid disease. Thyroxine, triiodothyronine, T3 uptake test, TSH before and after TRH application, its difference and thyroxine binding globulin have been determined. The patients were clinically examined and in each case a Tc-scintigram was obtained. As a first step, 20 biochemical patterns were defined by cluster analysis (pattern cognition). T check how good in grouping process was, linear discriminant analysis was applied after which the reclassification rates were very satisfactory. The clusters found corresponded well to the pathophysiological situations with some exceptions. As a second step, patients were assigned to these patterns by use of the derived discriminant functions (pattern recognition). The proposed method seems to have some advantages over other diagnostic models published hitherto.

Alpha-Globulins↗

PubMed1982

A psychoanalyst-liaison psychiatrist's overview of DSM III.

There has been a groundswell of reaction, mostly favorable, to the most recent edition of the Diagnostic and Statistical Manual. In this paper the author attempts to evaluate the Manual, which purports to provide an atheoretical and descriptive diagnostic model on its own ground, as well as from a psychodynamic and ego-psychological point of view. More specifically, the Manual is evaluated in terms of its usefulness in the diagnosis and management of the Somatoform Disorders, as well as other typical general hospital problems. This assessment raises many questions about the basic tenets of DSM III in general. Concomitantly, suggestions are made to enhance the reliability, validity, and clinical relevance of the Manual.

Diagnosis, Differential↗

PubMed1986

Predictive biochemical assays for late radiation effects.

Surfactant precursors or other products of Type II pneumocytes have the potential to be the first biochemical marker for late radiation effects. This is particularly clinically important in the combined modality era because of the frequent occurrence of pneumonitis and pulmonary fibrosis secondary to radiation or chemotherapy. Accordingly, correlative studies have been pursued with the Type II pneumocyte as a beginning point to understand the complex pathophysiology of radiation pneumonitis and fibrosis. From our ultrastructural and biochemical studies, it is evident that Type II pneumocytes are an early target of radiation and the release of surfactant into the alveolus shortly after exposure persists for days and weeks. Through the use of lavaging techniques, alveolar surfactant has been elevated after pulmonary irradiation. In three murine strains and in the rabbit, there is a strong correlation with surfactant release at 7 and/or 28 days in vivo with later lethality in months. In vitro studies using cultures of type II pneumocytes also demonstrate dose response and tolerance factors that are comparable to the in vivo small and large animal diagnostic models. New markers are being developed to serve as a predictive index for later lethal pneumonopathies. With the development of these techniques, the search for early biochemical markers in man have been undertaken. Through the use of biochemical, histological, and ultrastructural techniques, a causal relationship between radiation effects on type II pneumocytes, pulmonary cells, endothelial cells of blood vessels, and their roles in the production of pneumonitis and fibrosis will evolve.

Animals↗

PubMed1993

Prognosis of rectal cancer in France.

We studied changes in the prognosis of cancer of the rectum (excluding the rectosigmoid junction) from 1978 to 1986 in the French department of Calvados on the basis of the 616 cases in the cancer registry. Taken as whole, survival has improved slightly with time (P < 0.01), but the improvement is only significant for men (P < 0.02), patients under 70 years (P < 0.01) and patients living in urban areas (P < 0.05). With regard to tumour characteristics, the improvement was significant only for patients with Dukes' stage C tumours at surgery (P < 0.02). To determine the reasons for the improvement in survival, the year of diagnosis and all other prognostic factors were studied in a multivariate model. Diagnostic conditions such as age and tumour stage did not vary from 1978 to 1986; in contrast, the rates of tumour resection and adjuvant radiation therapy increased, possibly explaining at least part of the improvement, particularly for patients with Dukes' stage C tumours.

Aged↗

PubMed2006

A strategy for identifying phenotypic subtypes: concordance of symptom dimensions between sibling pairs who met screening criteria for a genetic linkage study of childhood-onset bipolar disorder using the Child Bipolar Questionnaire.

BACKGROUND: Specific symptom dimensions have been used to establish phenotypic subgroups in recent genetic studies of bipolar disorder. In preparation for a genetic linkage study of childhood-onset bipolar disorder (COBPD), we conducted an exploratory analysis of the concordance of prominent symptom dimensions between sibling pairs (N=260) who screened positive for COBPD. This report presents data on the potential usefulness of these dimensions in genotyping. METHOD: A principal components factor analysis was conducted on the symptoms of 2795 children who screened positive for COBPD on the Child Bipolar Questionnaire (CBQ). The resulting factors were used in a concordance analysis between 260 proband/sibling pairs and 260 proband/matched comparison pairs. RESULTS: Ten factors were extracted. The strongest concordance coefficients (rho) between probands and siblings, and the widest contrasts between proband/sibling vs. proband/comparison pairs, were for Factor 9 (Fear of harm), Factor 5 (Aggression), Factor 10 (Anxiety), Factor 4 (Sensory sensitivity), Factor 6 (Sleep-wake cycle disturbances), and Factor 2 (Attention/Executive function deficits). Based on factor loadings and multivariate analyses, CBQ items were selected for a "Core Index" subscale that had a robust concordance estimate in the sibpair group (rho=0.514, 95% CI 0.450-0.577) as compared to the proband-matched comparison group (rho=0.093, 95% CI 0.008 to 0.178). LIMITATIONS: Research diagnostic interviews (K-SADS P/L) were conducted to confirm bipolar diagnosis in only a subsample (N=100) of the children whose data were used for the concordance analysis. CONCLUSIONS: Our data suggest a profile of heritable clinical dimensions in addition to classic mood symptomatology in COBPD. These features may represent a more homogeneous phenotypic subtype of COBPD that may prove more useful for delineating the neurobiology and genetics of the disorder than standard diagnostic models.

Adolescent↗

PubMed2004

Synthesis and characterization of branched poly(L-glutamic acid) as a biodegradable drug carrier.

Polymeric drug delivery systems are used not only to improve aqueous solubility of drug molecules but also to achieve desirable pharmacokinetics and an enhanced therapeutic index. New biodegradable polymers are needed to improve the biodistribution and targeting-ability of polymeric carriers. In this study, the synthesis and characterization of branched poly(L-glutamic acid) (PG) containing multiple PG chains centered on a poly(amidoamine) (PAMAM) dendrimer or polyethyleneimine (PEI) cores were described. The branched PG polymers were obtained by ring-opening polymerization of benzyl ester of L-glutamic acid N-carboxyanhydride using PAMAM or PEI as the initiator. These polymers were degradable in the presence of the lysosomal enzyme cathepsin B, albeit more slowly than linear PG. Unlike conventional linear PG, each branched PG possessed multiple terminal amino groups. This made it possible to attach multiple targeting moieties selectively to the termini of branched PG. Conjugation of monofunctional or heterodifunctional polyethylene glycol to the chain ends of branched PG was demonstrated in the presence of side chain carboxyl groups. Furthermore, folic acid, a model targeting moiety, and the near-infrared dye indocyanine green, a model diagnostic agent, were successfully conjugated to the terminal amino groups and the side chain carboxyl groups of branched PG, respectively. The resulting conjugate had reduced nonspecific interaction and bound selectively to tumor cells expressing folate receptors. Thus, branched PG may be useful as a polymeric carrier for targeted drug delivery.

Cell Line, Tumor↗

PubMed2024

Integrated Multi-Omics Analyses Reveal Lipid Metabolic Signature in Osteoarthritis.

Osteoarthritis (OA) is the most common degenerative joint disease and the second leading cause of disability worldwide. Single-omics analyses are far from elucidating the complex mechanisms of lipid metabolic dysfunction in OA. This study identified a shared lipid metabolic signature of OA by integrating metabolomics, single-cell and bulk RNA-seq, as well as metagenomics. Compared to the normal counterparts, cartilagesin OA patients exhibited significant depletion of homeostatic chondrocytes (HomCs) (P = 0.03) and showed lipid metabolic disorders in linoleic acid metabolism and glycerophospholipid metabolism which was consistent with our findings obtained from plasma metabolomics. Through high-dimensional weighted gene co-expression network analysis (hdWGCNA), weidentified PLA2G2A as a hub gene associated with lipid metabolic disorders in HomCs. And an OA-associated subtype of HomCs, namely HomC1 (marked by PLA2G2A, MT-CO1, MT-CO2, and MT-CO3) was identified, which also exhibited abnormal activation of lipid metabolic pathways. This suggests the involvement of HomC1 in OA progression through the shared lipid metabolism aberrancies, which were further validated via bulk RNA-Seq analysis. Metagenomic profiling identified specific gut microbial species significantly associated with the key lipid metabolism disorders, including Bacteroides uniformis (P < 0.001, R = -0.52), Klebsiella pneumonia (P = 0.003, R = 0.42), Intestinibacter_bartlettii (P = 0.009, R = 0.38), and Streptococcus anginosus (P = 0.009, R = 0.38). By integrating the multi-omics features, a random forest diagnostic model with outstanding performance was developed (AUC = 0.97). In summary, this study deciphered the crucial role of a integrated lipid metabolic signature in OA pathogenesis, and established a regulatory axis of gut microbiota-metabolites-cell-gene, providing new insights into the gut-joint axis and precision therapy for OA.

Humans↗

PubMed2005

Techniques to facilitate provisionalization of implant restorations.

PURPOSE: The aim of this article was to review current methods for immediate provisionalization of single unit implant restorations. METHODS: Four methods are discussed and illustrated in detail, including: preoperative preparation of an abutment and provisional crown using diagnostic models; abutment placement and modification at the time of implant placement; the use of 1-piece or non-prepable abutments; and methods of indexing. Material characteristics for indexing are presented to provide the clinician with an understanding of material handling in relation to accuracy of indexing. CONCLUSION: Depending on clinician and patient case specific criteria, immediate provisionalization of implant restorations can be performed in an efficient manner.

Dental Abutments↗

PubMed1997

Management of temporomandibular disorders: concepts and controversies.

STATEMENT OF PROBLEM: Controversy continues in the area of epidemiology, etiology, diagnosis, and management of temporomandibular disorders (TMD). The field is replete with testimonials and clinical opinion, but it has been lacking in scientific foundation. PURPOSE: This article reviews the recent temporomandibular disorder and orofacial pain literature and summarizes the concepts published in the 1993 and 1996 American Academy of Orofacial Pain guidelines. Temporomandibular disorders rarely occur as single entities but rather as multiple problems with overlapping symptoms. CLINICAL SIGNIFICANCE: The multicausal nature of these problems and the number of conditions with similar signs and symptoms demand an effective differential diagnostic process. Diagnostic criteria are used from an operational standpoint to establish specific diagnoses based on a multiaxial diagnostic model. CONCLUSION: Because little is known about the natural course of the various classifications of temporomandibular disorders, and because most treatment approaches are reported to be equally effective, a conservative, noninvasive management program is endorsed. The emphasis is on a medical multidisciplinary model similar to ones used for other musculoskeletal disorders that involve the patient in the physical and behavioral management of his or her own problem. This article concludes that a majority of temporomandibular disorder patients achieve good relief of symptoms with noninvasive reversible therapy.

Adolescent↗