Radiographic diagnosis of proximal caries-influence of experience and gender of the dental staff.

OBJECTIVES: The aim of this study was to examine the influence of experience and gender on the radiographic detection of proximal caries lesions and on therapeutic decisions. MATERIALS AND METHODS: A survey of 220 examiners (students and employees at three universities and dentists in the field) was taken using a standardized written questionnaire concerning radiographic diagnosis and therapy planning. An expert opinion of four dentists was determined as radiographic reference. A mixed effect logistic regression model was used for statistical evaluation and the odds ratio and p values were calculated (α = 0.05). RESULTS: Examiners with experience had an almost four times greater chance of a correct assessment, if proximal caries lesion was present or not, than examiners with low experience (OR 3.7 (95% CI 2.4-5.8)). No gender-specific differences were discovered (OR women vs. men 0.9 (95% CI 0.6-1.4)). There was a relationship between the severity of the burnout effect on the x-ray and false positive caries diagnosis. Overall, 43% of respondents would plan invasive treatment in the enamel on a patient at low risk of caries and 78% on a high-risk patient. The results showed that the more experienced practitioners would be more likely to postpone restorative therapy on proximal caries until the lesion reached a later stage. CONCLUSIONS: The results of this study suggest that examiner's experience influences the radiographic diagnosis of proximal lesions. No gender-specific differences could be found. CLINICAL RELEVANCE: Examiner's professional experience is an important factor when radiography is included for detection and treatment planning of proximal lesions.

Shot Noise of 1,4-Benzenedithiol Single-Molecule Junctions.

We report measurements of the shot noise on single-molecule Au-1,4-benzenedithiol-Au junctions, fabricated with the mechanically controllable break junction (MCBJ) technique at 4.2 K in a wide range of conductance values from 10(-2) to 0.24 conductance quanta. We introduce a simple measurement scheme using a current amplifier and a spectrum analyzer and that does not imply special requirements regarding the electrical leads. The experimental findings provide evidence that the current is carried by a single conduction channel throughout the whole conductance range. This observation suggests that the number of channels is limited by the Au-thiol bonds and that contributions due to direct tunneling from the Au to the π-system of the aromatic ring are negligible also for high conductance. The results are supported by quantum transport calculations using density functional theory.

Aleglitazar, a dual peroxisome proliferator-activated receptor-α/γ agonist, improves insulin sensitivity, glucose control and lipid levels in people with type 2 diabetes: findings from a randomized, double-blind trial.

The present single-centre, randomized, double-blind, placebo-controlled phase II study investigated the effect of the balanced dual peroxisome proliferator-activated receptor-α/γ agonist aleglitazar on whole-body and liver insulin sensitivity, ß-cell function and other components of cardiometabolic syndrome after 16 weeks of treatment in patients with type 2 diabetes inadequately controlled with metformin monotherapy who received once-daily 150 µg aleglitazar or matching placebo as add-on therapy to metformin. Baseline and 16-week assessments included a two-step hyperinsulinaemic-euglycaemic clamp, followed by a hyperglycaemic clamp, as well as evaluation of glycated haemoglobin (HbA1c), lipids and safety variables. The primary endpoint was change in whole-body insulin sensitivity (M-value) from baseline compared with placebo, derived from the second clamp step. M-value improved significantly from baseline with aleglitazar (n = 16) compared with placebo (n = 24; p = 0.05 for difference between arms). We found statistically significant treatment differences with aleglitazar versus placebo in fasting hepatic insulin resistance index (p = 0.01), and in total glucose disposal (p = 0.03) at the second insulin infusion step. Aleglitazar treatment resulted in significant improvements in HbA1c and lipids and was well tolerated.

Cardiovascular safety of the glucagon-like peptide-1 receptor agonist taspoglutide in people with type 2 diabetes: an individual participant data meta-analysis of randomized controlled trials.

AIMS: To study the short-term cardiovascular effects of the once-weekly glucagon-like peptide-1 receptor agonist taspoglutide. METHODS: We conducted a meta-analysis of individual-participant data from nine randomized controlled trials in the T-Emerge programme, which assessed the efficacy and safety of taspoglutide in type 2 diabetes. Our primary outcome was a composite of death from cardiovascular disease (CVD) and acute myocardial infarction, stroke and hospitalization for unstable angina. RESULTS: Overall, 7056 individuals were included in the analysis, and there were 67 primary endpoint events during 7478 person-years of follow-up (40 vs 27 events in the intervention vs control groups, respectively). The odds ratio for the composite endpoint among people randomized to taspoglutide was 0.94 (95% confidence interval 0.57-1.56), which was robust across multiple subgroups. Longer-term data were not available as the development of taspoglutide was stopped because of gastrointestinal intolerance and serious hypersensitivity reactions. CONCLUSIONS: The available data suggest that short-term, once-weekly administration of taspoglutide was not associated with an excess risk of CVD, and provide insights relevant to the development of other novel once-weekly incretin mimetics.

Efficacy, safety and tolerability of aleglitazar in patients with type 2 diabetes: pooled findings from three randomized phase III trials.

AIMS: To evaluate the potential efficacy, safety and tolerability of aleglitazar as monotherapy or add-on therapy to metformin or to a sulphonylurea (either alone or in combination with metformin). METHODS: We conducted a pooled analysis of data from three randomized phase III clinical trials of aleglitazar in patients with type 2 diabetes (n = 591). The three studies focused on: (i) aleglitazar alone; (ii) aleglitazar and metformin; and (iii) aleglitazar and sulphonylurea with or without metformin. Patients were randomized to 26 weeks' treatment with aleglitazar 150 µg/day or placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) concentration from baseline to week 26. Secondary endpoints included changes in lipids, fasting plasma glucose and homeostatic model assessment of insulin resistance (HOMA-IR) at week 26. RESULTS: Reductions in HbA1c concentration from baseline to week 26 were statistically significantly greater with aleglitazar than with placebo. Aleglitazar treatment was associated with more beneficial changes in lipid profiles and HOMA-IR values than was placebo. Aleglitazar was generally well tolerated, with no reports of congestive heart failure. The incidence of peripheral oedema was similar in both groups. Change in body weight was +1.37 kg with aleglitazar and -0.53 kg with placebo. Hypoglycaemia was more frequently reported with aleglitazar (7.8%) than with placebo (1.7%), a result probably driven by the type of background medication. CONCLUSIONS: Development of aleglitazar was halted because of a lack of cardiovascular efficacy and peroxisome proliferator-activated receptor-related side effects in patients with type 2 diabetes post-acute coronary syndrome; however, in the present studies, aleglitazar was well tolerated and effective in improving HbA1c, insulin resistance and lipid variables.

Resistance to powdery mildew in Spanish barley landraces is controlled by different sets of quantitative trait loci.

Twenty-two landrace-derived inbred lines from the Spanish Barley Core Collection (SBCC) were found to display high levels of resistance to a panel of 27 isolates of the fungus Blumeria graminis that exhibit a wide variety of virulences. Among these lines, SBCC145 showed high overall resistance and a distinctive spectrum of resistance compared with the other lines. Against this background, the main goal of the present work was to investigate the genetic basis underlying such resistance using a doubled haploid population derived from a cross between SBCC145 and the elite spring cultivar Beatrix. The population was genotyped with the 1,536-SNP Illumina GoldenGate Oligonucleotide Pool Assay (Barley OPA-1 or BOPA1 for short), whereas phenotypic analysis was performed using two B. graminis isolates. A major quantitative trait locus (QTL) for resistance to both isolates was identified on the long arm of chromosome 6H (6HL) and accounted for ca. 60% of the phenotypic variance. Depending on the B. graminis isolate tested, three other minor QTLs were detected on chromosomes 2H and 7H, which explained less than 5% of the phenotypic variation each. In all cases, the alleles for resistance derived from the Spanish parent SBCC145. The position, the magnitude of the effect observed and the proportion of phenotypic variation accounted for by the QTL on 6HL suggest this is a newly identified locus for broad-based resistance to powdery mildew.

Home-based exercise programmes improve physical fitness of healthy older adults: A PRISMA-compliant systematic review and meta-analysis with relevance for COVID-19.

This systematic review and meta-analysis aimed to examine the effects of home-based exercise programmes on measures of physical-fitness in healthy older adults. Seventeen randomized-controlled trials were included with a total of 1,477 participants. Results indicated small effects of home-based training on muscle strength (between-study standardised-mean-difference [SMD] = 0.30), muscle power (SMD = 0.43), muscular endurance (SMD = 0.28), and balance (SMD = 0.28). We found no statistically significant effects for single-mode strength vs. multimodal training (e.g., combined balance, strength, and flexibility exercises) on measures of muscle strength and balance. Single-mode strength training had moderate effects on muscle strength (SMD = 0.51) and balance (SMD = 0.65) while multimodal training had no statistically significant effects on muscle strength and balance. Irrespective of the training type, >3 weekly sessions produced larger effects on muscle strength (SMD = 0.45) and balance (SMD = 0.37) compared with ≤3 weekly sessions (muscle strength: SMD = 0.28; balance: SMD = 0.24). For session-duration, only ≤30 min per-session produced small effects on muscle strength (SMD = 0.35) and balance (SMD = 0.34). No statistically significant differences were observed between all independently-computed single-training factors. Home-based exercise appears effective to improve components of health- (i.e., muscle strength and muscular endurance) and skill-related (i.e., muscle power, balance) physical-fitness. Therefore, in times of restricted physical activity due to pandemics, home-based exercises constitute an alternative to counteract physical inactivity and preserve/improve the health and fitness of healthy older adults aged 65-to-83 years.

Caudate nucleus stimulation retroactively impairs complex maze learning in the rat.

Rats, with permanent electrodes implanted bilaterally in the caudateputamen complex, were stimulated with single pulses after reinforcement of each maze learning trial or were stimulated with multiple pulses after each choice point or after reinforcement. Single pulses retarded the development of learning only when stringent learning criteria were required, whereas multiple pulses interfered with acquisition when the criteria for learning were less difficult.

Pioglitazone has anti-inflammatory effects in patients with Type 2 diabetes.

BACKGROUND: Type 2 diabetes is characterized by increased acute phase serum proteins. They are also risk factors for cardiovascular disease. We wanted to study how improvement of glycemic control with pioglitazone or glibenclamide affects their serum concentrations. MATERIALS AND METHODS: A total of 59 patients with Type 2 diabetes (age 57.3+/-1.2 yr, glycosylated hemoglobin (HbA1c) 8.3+/-0.7%, body mass index (BMI) 31.4+/-0.8 kg/m2) participated in the study. They were previously treated either with diet alone or in combination with one oral antihyperglycemic medicine. After a 1-week lead-in period on diet only, the patients were randomized to pioglitazone or glibenclamide. Blood samples for alpha-1-acid glycoprotein (A1GP), Creactive protein (CR P) and serum amyloid A (SAA) were taken before the treatments and during the therapy after 20 and 52 weeks. RESULTS: Baseline A1GP correlated with CR P (r=0.70, p<0.001) and fasting glucose (r=0.32, p<0.02). Baseline CR P correlated with HbA1c (r=0.26, p<0.05) and insulin (r=0.37, p<0.01). The anti-hyperglycemic effect was comparable with HbA1c levels decreasing both in the pioglitazone (from 8.18+/-0.09% to 7.63+/-0.17%, p<0.01) and glibenclamide (from 8.35+/-0.12% to 7.77+/-0.16%, p<0.01) groups. Pioglitazone treatment was associated with a reduction in A1GP at 20 weeks (p<0.001) and at 52 weeks (p<0.05) as compared to baseline. The significance remained also after comparison to glibenclamide therapy (p<0.001 and p<0.05, 20 and 52 weeks respectively). CR P was also more reduced in the pioglitazone group at 20 weeks of treatment (p<0.05). CONCLUSIONS: Inflammatory factors and markers of hyperglycemia are associated in patients with Type 2 diabetes. Pioglitazone treatment results in reduced A1GP concentration suggesting an anti-inflammatory effect.

Assessment of axillary lymph node involvement in breast cancer patients with positron emission tomography using radiolabeled 2-(fluorine-18)-fluoro-2-deoxy-D-glucose.

BACKGROUND: The presence of metastatic tumor cells in the axillary lymph nodes is an important factor when deciding whether or not to treat breast cancer patients with adjuvant therapy. Positron emission tomography (PET) imaging with the radiolabeled glucose analogue 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (F-18 FDG) has been used to visualize primary breast tumors as well as bone and soft-tissue metastases. PURPOSE: This study was undertaken to evaluate before surgery the diagnostic accuracy of PET for detection of axillary lymph node metastases in patients suspected of having breast cancer. METHODS: Women who were scheduled to undergo surgery for newly discovered, suspected breast cancers were referred for PET imaging of the axilla region. The women were first clinically examined to determine the status of their axillary lymph nodes (i.e., presence or absence of metastases). Fifty-one women were intravenously administered F-18 FDG and were studied by PET imaging. Attenuation-corrected transaxial and coronal images were visually evaluated by two nuclear medicine physicians (blinded to the patient's medical history) for foci of increased F-18 FDG uptake in the axilla region. All patients underwent surgery for their suspected breast cancers. Axillary lymph node dissection was also performed on all patients with breast cancer, with the exception of four patients who received primary chemotherapy for locally advanced breast cancer. A single pathologist analyzed breast tumor and lymph node tissue specimens. RESULTS: The overall sensitivity (i.e., the ability of the test to detect disease in patients who actually have disease) and specificity (i.e., the ability of the test to rule out disease in patients who do not have disease) of this method for detection of axillary lymph node metastases in these patients were 79% and 96%, respectively. When only patients with primary breast tumors larger than 2 cm in diameter (more advanced than stage pT1; n = 23) were considered, the sensitivity of axillary PET imaging increased to 94%, and the corresponding specificity was 100%. Lymph node metastases could not be identified in four of six patients with small primary breast cancers (stage pT1), resulting in a sensitivity of only 33%. Axillary PET imaging provided additional diagnostic information in 12 (29%) of 41 breast cancer patients with regard to the extension of disease to other sites (i.e., other lymph nodes, skin, bone, and lung). CONCLUSIONS: PET imaging with F-18 FDG allowed accurate and noninvasive detection of axillary lymph node metastases, primarily in patients with breast cancer more advanced than stage pT1. Detection of micrometastases and small tumor-infiltrated lymph nodes is limited by the currently achievable spatial resolution of PET imaging. IMPLICATIONS: In clinical practice, PET imaging cannot substitute for histopathologic analysis in detecting axillary lymph node metastases in breast cancer patients. PET imaging, however, improves the preoperative staging of the disease in breast cancer patients and, therefore, might alter therapeutic regimen options.

Metabolic characterization of breast tumors with positron emission tomography using F-18 fluorodeoxyglucose.

PURPOSE: To evaluate the diagnostic value of position emission tomographic (PET) imaging with F-18 fluorodeoxyglucose (FDG) in differentiating between benign and malignant breast tumors. PATIENTS AND METHODS: Fifty-one patients, with suspicious breast lesions newly discovered either by physical examination or by mammography, underwent PET imaging before exploratory surgery. FDG-PET images of the breast were analyzed visually and quantitatively for objective assessment of regional tracer uptake. RESULTS: Primary breast cancer was identified visually with a sensitivity of 68% to 94% and a specificity of 84% to 97% depending on criteria used for image interpretation. Quantitative analysis of FDG uptake in tumors using standardized uptake values (SUV) showed a significant difference between benign (1.4 +/- 0.5) and malignant (3.3 +/- 1.8) breast tumors (P < .01). Receiver operating characteristic (ROC) curve analysis exhibited a sensitivity of 75% and a specificity of 100% at a threshold SUV value of 2.5. Sensitivity increased to 92% with a corresponding specificity of 97% when partial volume correction of FDG uptake was performed based on independent anatomic information. CONCLUSION: PET imaging allowed accurate differentiation between benign and malignant breast tumors providing a high specificity. Sensitivity for detection of small breast cancer ( < 1 cm) was limited due to partial volume effects. Quantitative image analysis combined with partial volume correction may be necessary to exploit fully the diagnostic accuracy. PET imaging may be helpful as a complimentary method in a subgroup of patients with indeterminate results of conventional breast imaging.

Brief hospitalization: two-year follow-up.

This article presents the long-term follow-up effects of brief vs standard hospitalization on families. One hundred seventy-five newly admitted inpatients who lived with their families were randomly assigned to standard inpatient care, brief hospitalization followed by the availability of transitional day care, and brief hospitalization. All patients were offered follow-up outpatient treatment. Initial length of stay was 11 days for both brief hospitalization groups and 60 days for the standard group. The long-term results generally indicate little differential effect between treatments. When differences occurred, they generally favored the brief groups. For example, at one year the standard group families were judged to have a higher overall level of burden than the brief-day families. The findings suggest that patients are more likely to be rehospitalized because of their psychopathology than because of family burden.

Brief vs standard hospitalization: for whom?

An effort was made to determine patient characteristics that have differential prognostic significance, depending on treatment assignment to one of three treatment approaches: standard inpatient care (n = 63), brief hospitalization followed by day care (n = 61), and brief hospitalization without day care (n = 51). All were followed by outpatient care. Both demographically and clinically assessed behavioral variables were related to a number of outcome measures, including days in the community, clinical ratings, and family assessment. Generally, the standard treatment was inferior to the two brief treatments. Multiple previous admissions were particularly contraindicative for standard treatment. High overt anger score was especially contraindicative for brief hospitalization without day care and particularly indicative for brief hospitalization with day care.

Intermittent vs maintenance medication in schizophrenia. Two-year results.

This is a 2-year, double-blind, placebo-controlled study of 101 patients, evaluating the relative efficacy of intermittent medication (given only when the patient shows early signs of relapse) compared with moderate doses of maintenance medication for stable schizophrenic outpatients. Patients were dropped from the study if they had three prodromal episodes in 1 year or if an episode lasted more than 9 weeks. Fourteen percent of patients given maintenance treatment were dropped from the study compared with 46% of intermittently treated patients. Relapse rates were 16% for patients given maintenance treatment and 30% for intermittently treated patients, a nonsignificant difference. Intermittently treated patients were receiving significantly less medication, but there were no differences found in drug side effects. There appears to be no advantage in using the intermittent approach, but we found that the use of an early intervention strategy reduced the relapse and rehospitalization rates for these patients.

A program for relapse prevention in schizophrenia: a controlled study.

BACKGROUND: This study examined whether a program for relapse prevention (PRP) is more effective than treatment as usual (TAU) in reducing relapse and rehospitalization rates among outpatients with schizophrenia. METHODS: Eighty-two outpatients with DSM-III-R schizophrenia or schizoaffective disorder were randomly assigned to receive either PRP (experimental group, n = 41) or TAU (control group, n = 41) and were followed up for an 18-month prospective controlled study. Patients in both groups were prescribed standard doses of maintenance antipsychotic medication. Treatment with PRP consisted of a combination of psychoeducation, active monitoring for prodromal symptoms with clinical intervention when such symptoms occurred, weekly group therapy for patients, and multifamily groups. The TAU consisted of biweekly individual supportive therapy and medication management. RESULTS: Outcome rates over 18 months were 17% for relapse (7 patients) and 22% for rehospitalization (9 patients) in the PRP group, compared with 34% for relapse (14 patients) and 39% for rehospitalization (16 patients) in the TAU group (P = .01 and P = .03, respectively). Addition of age, sex, baseline Global Assessment Scale score, Positive and Negative Syndrome Scale scores (3 measures), and substance abuse to the proportional hazards regression models all yielded nonsignificant effects. The PRP teams were much more likely than the TAU psychiatrists to identify prodromal episodes before patients met objective relapse criteria or needed hospitalization. CONCLUSIONS: The PRP was effective in detecting prodromal symptoms of relapse early in an episode. Crisis intervention including increased antipsychotic medication use during the prodromal phase reduced relapse and rehospitalization rates.

Detection of trisomy 8 on blood smears using fluorescence in situ hybridization.

In this study, fluorescence in situ hybridization (ISH) with an alphoid probe was used for the detection of trisomy 8 on archival blood smears (BS). The results were compared with hybridization experiments performed on methanol/acetic acid fixed cells of cytogenetic preparations (CP) which are widely used for ISH. Five controls and 20 patients with myeloid leukemias were examined. In the controls, CP and BS had the same percentages of cells with two or three fluorescence signals. In 5/20 patients, trisomy 8 was detected both on CP and BS. Two of the patients had 7 to 10% interphase cells with three hybridization signals, indicating the presence of small subclones with trisomy 8; one of the subclones was not detected by G-banding analysis. The remaining 15 patients were disomic for chromosome 8; hybridization results were within the range of the controls both on CP and BS. We conclude that using a chromosome 8 specific alphoid probe, fluorescence ISH to interphase cells can be performed on BS with the same efficiency that is reached on methanol/acetic acid fixed cells of CP.

Relapse in schizophrenia.

Although schizophrenia is a chronic illness with exacerbations and remissions, there has been surprisingly little systematic study of early signs of relapse. The authors gave 145 chronic schizophrenic patients and 80 family members a structured interview regarding early signs of relapse and other information related to the relapse period. Most patients and family informants were aware of a prodromal period during which patients experienced such symptoms as having trouble sleeping, having trouble concentrating, loss of appetite, and feeling depressed. The authors discuss the implications of these findings for the treatment of chronic schizophrenic patients.

Limitations of Brief Hospital Treatment.

A total of 175 newly admitted inpatients who lived with their families were randomly assigned to three treatment groups: standard inpatient care and brief hospitalization with and without transitional day care. Case reports of 6 of the 9 patients considered "study failures" illustrate that effective postdischarge adaptation is limited by the patients' degree of impairment as well as the family and community capacity to accept them. Although rapid return to the community is beneficial to many patients, rigid adherence to this policy is neither wise nor clinically effective.

Brief versus standard hospitalization: the differential costs.

The authors compared the use of inpatient and day care services, number of readmissions, use of special services, use of drugs, costs to family and community, and differential dollar costs of three treatment approaches--brief hospitalization followed by day care, brief hospitalization followed by outpatient care, and standard hospitalization. They found that, among patients who had families willing to care for them, brief hospitalization followed by either day or outpatient care was less expensive in terms of hospital costs and costs to the family than standard hospitalization.

Brief hospitalization of patients with families: initial results.

A total of 175 newly admitted inpatients who lived with families were randomly assigned to three treatment groups: standard inpatient care (discharge at the therapist's discretion), brief hospitalization (one week or less) with transitional day care available, and brief hospitalization without day care. Outpatient aftercare was offered to all patients. The three groups showed no significant differences as to amount of improvement in levels of psychopathology at 3 and 12 weeks, but the briefly hospitalized patients were able to resume their vocational roles sooner. There were no significant differences among the groups in readmission rates.