Reconstruction of the three-dimensional beat pattern underlying swimming behaviors of sperm.

 The eukaryotic flagellum propels sperm cells and simultaneously detects physical and chemical cues that modulate the waveform of the flagellar beat. Most previous studies have characterized the flagellar beat and swimming trajectories in two space dimensions (2D) at a water/glass interface. Here, using refined holographic imaging methods, we report high-quality recordings of three-dimensional (3D) flagellar bending waves. As predicted by theory, we observed that an asymmetric and planar flagellar beat results in a circular swimming path, whereas a symmetric and non-planar flagellar beat results in a twisted-ribbon swimming path. During swimming in 3D, human sperm flagella exhibit torsion waves characterized by maxima at the low curvature regions of the flagellar wave. We suggest that these torsion waves are common in nature and that they are an intrinsic property of beating axonemes. We discuss how 3D beat patterns result in twisted-ribbon swimming paths. This study provides new insight into the axoneme dynamics, the 3D flagellar beat, and the resulting swimming behavior.

Intravenous thrombolysis for acute ischaemic stroke in the elderly: data from the Baden-Wuerttemberg stroke registry.

BACKGROUND AND PURPOSE: In Europe intravenous thrombolysis (IVT) for ischaemic stroke is still not approved for patients aged >80 years. However, elderly patients are frequently treated based on individual decision making. In a retrospective observational study a consecutive and prospective stroke registry in southwest Germany was analysed. METHODS: The data registry collected 101,349 patients with ischaemic stroke hospitalized from January 2008 to December 2012. Of these, 38,575 (38%) were aged 80 years and older and 10 286 (10.1%) underwent IVT. Favourable outcome at discharge was defined as modified Rankin Scale (mRS) ≤1 or not worse than prior to stroke. Multiple logistic regression models stratified by 10-year age groups were used to assess the relationship between IVT and mRS at discharge, adjusted for patient characteristics, admitting facility and length of hospital stay. RESULTS: The highest IVT rate was 15% in patients aged <50 years, with a continuous decline down to 8% in patients aged ≥90 years. Adjusted odds ratios and 95% confidence intervals for patients 80-89 years of age were 2.20 (1.95-2.47) (P < 0.0001) and 1.25 (0.88-1.78) (P = 0.21) for patients >90 years of age, compared to patients of the same age decade not treated with IVT. CONCLUSIONS: The evidence from routine hospital care in southwest Germany indicates that IVT is an effective treatment also for aged patients with ischaemic stroke in an age range between 80 and 89 years. Although no clear evidence for the effectiveness of IVT beyond 90 years was found, treatment should also be carefully considered in these patients. High age should not discourage from treatment.

Requirements and Application Guide for the Use of Quality Indicators in Medical Care: Results of a Systematic Review.

Background: Quality indicators are employed in the assessment of quality of medical care. Valid measurement and reporting of quality are essential for maintenance and enhancement of high-quality medical care. The aim of this study was to identify the requirements for quality indicators and their successful implementation in routine care. Method: A systematic literature search conducted in Medline using MESH keywords resulted in 573 hits. A complementary hand search additionally identified 153 papers, so that in all 726 abstracts were screened. In conformity with the PRISMA Statement, 83 papers were finally included in this review. Results: Quality criteria are described in 48 publications and requirements for the application of quality indicators in medical care are given in 41 publications. Validity (n=19), feasibility (n=16), reliability (n=15), and interpretability of the quality indicator (n=14) are the most frequently named quality criteria, followed by relevance (n=10), sensitivity (n=8) and risk adjustment (n=6). The most common requirements for the application of quality indicators are integration of quality indicators in the given healthcare setting (n=15) and ability to derive potential improvement (n=11), data validity (n=8), data availability (n=7) as well as acceptance of the measurement in the given setting (n=6). Conclusion: Plausible quality measurements help improve healthcare structures and processes and provide patients and professionals with valid statements on the quality of care. The original articles examined focus primarily on the validity of quality indicators. A consensus on methodological criteria for the development, implementation and application of quality indicators is required. Furthermore, the practical applicability of quality criteria should be tested empirically.

A consecutive and prospective stroke database covers the state of Baden-Wuerttemberg with 10.8 million inhabitants in Germany.

BACKGROUND: In 1998 Baden-Wuerttemberg (BW), a federal state in southwest Germany with 10.8 million inhabitants, implemented a structured medical concept for the treatment of acute stroke. METHODS: Since 2004 participation in the BW stroke database is mandatory for all hospitals in BW involved in acute stroke care. The stroke database includes all inpatients ≥18 years of age who have suffered an ischemic or hemorrhagic stroke within 7 days before hospitalization. This article presents methodological aspects and first results of the BW stroke database in the time period from 2007 to 2011. RESULTS: Annual inclusion numbers increased continuously (29,422 vs. 35,724, p < 0.001). Median age of stroke onset was stable over time. The proportion of stroke patients ≥80 years increased from 36.9 to 38.8% (p < 0.001). Rates of patients treated in neurology departments rose from 50.7 to 60.9% (p < 0.001) and numbers of patients treated in stroke units rose from 59.1 to 68.4% (p < 0.001). Admission via emergency medical systems increased from 42.8 to 49.7% (p < 0.001) and arrival within 3 h increased from 29.8 to 34.4% (p < 0.001). CONCLUSION: We present results from a large, prospective and consecutive stroke patient database. This first analysis demonstrates a continuous increase of absolute and relative numbers of stroke patients who arrive within 3 h after onset, are hospitalized in neurology departments and treated in stroke units, and are aged ≥80 years.

[Syphilis. Part 2: Laboratory diagnostics, therapy and prevention]. / Syphilis. Teil 2: Labordiagnostik, Therapie und Prävention.

Sexually transmitted infections and sexually transmitted diseases such as syphilis are a great problem for public health systems worldwide. Syphilis can be curatively treated with penicillin after early diagnosis, competent therapy and consistent monitoring. The fundamentals of syphilis diagnostics are direct and serological methods for pathogen detection. Prevention of syphilis includes exposition prophylaxis and in particular the routine use of condoms and the consistent education of affected persons and their sexual contacts.

[Syphilis. Part 1: Introduction, pathology and clinical aspects]. / Syphilis. Teil 1: Pathologie und Klinik.

In Germany more than 3,500 people become infected with syphilis annually. As elsewhere in Western Europe there is a low level endemicity with a concentration among population subgroups with high rates of partner exchange, such as men who have sex with other men. In Germany after initially reduced numbers of cases, the incidence rate has increased after the turn of the millennium. In 2011 the incidence reached 4.5 cases per 100,000 inhabitants, which is the highest incidence since the introduction of the Infection Protection Act of 2001. Syphilis, like other sexually transmitted infections and diseases with its manifold clinical manifestations and complex diagnostics, is a large global problem for public health systems. The recent resurgence of syphilis presents a challenge for all physicians but particularly for dermatologists and venereologists because the skin and adjacent mucous membranes are initially affected. Rapid diagnosis, differential diagnosis, consequent treatment and monitoring can cure the disease. Prevention of misdiagnosis is essential otherwise severe, sometimes fatal cardiovascular complications, neurosyphilis and transfer to unborn and newborn children can occur. The synergy of syphilis and sexually transmitted human immunodeficiency virus (HIV) is of special importance. Syphilis together with genital herpes and other sexually transmitted genital and oral ulcers is an important pacemaker for HIV.

Temperature rise during adhesive and composite polymerization with different light-curing sources.

AIM: This study evaluated the temperature rise of the adhesive system Single Bond (SB) and the composite resins Filtek Z350 flow (Z) and Filtek Supreme (S), when polymerized by light-emitting diode (LED XL 3000) and quartz-tungsten halogen (QTH Biolux). METHODS: Class V cavities (3 yen2 mm) were prepared in 80 bovine incisors under standardized conditions. The patients were divided as follows: G1: Control; G2: SB; G3: SB + Z; G4: SB + S. The groups were subdivided into two groups for polymerization (A: QTH, B: LED). Light curing was performed for 40 s and measurement of temperature changes during polymerization was performed with a thermocouple positioned inside the pulp chamber. Data were statistically analyzed using ANOVA and Tukey tests. RESULTS: The factors material (P<0.00001) and curing unit (P<0.00001) had significant influence on temperature rise. The lowest temperature increase (0.15 degrees C) was recorded in G2 B and the highest was induced in G1 A (0.75 degrees C, P<0.05). In all groups, lower pulp chamber temperature measurements were obtained when using LED compared to QTH (P<0.05). CONCLUSION: QTH caused greater increases in tooth temperature than LED. However, both sources did not increase pulpal temperature above the critical value that may cause pulpal damage.

The steering gaits of sperm.

Sperm are highly specialized cells, which have been subject to substantial evolutionary pressure. Whereas some sperm features are highly conserved, others have undergone major modifications. Some of these variations are driven by adaptation to mating behaviours or fitness at the organismic level. Others represent alternative solutions to the same task. Sperm must find the egg for fertilization. During this task, sperm rely on long slender appendages termed flagella that serve as sensory antennas, propellers and steering rudders. The beat of the flagellum is periodic. The resulting travelling wave generates the necessary thrust for propulsion in the fluid. Recent studies reveal that, for steering, different species rely on different fundamental features of the beat wave. Here, we discuss some examples of unity and diversity across sperm from different species with a particular emphasis on the steering mechanisms. This article is part of the Theo Murphy meeting issue 'Unity and diversity of cilia in locomotion and transport'.

Cytotoxicity and genotoxicity of pulp capping materials in two cell lines.

AIM: The aim of this study was to evaluate the cytotoxicity and genotoxicity of the new castor oil bean cement (COB) material in comparison to commonly used pulp capping materials. METHODOLOGY: Specimens of COB, calcium hydroxide (Hydro C), and mineral trioxide aggregate (white and gray MTA) were extracted in culture medium (91.6 mm(2) sample surface mL(-1)). Transfected human pulp cells (tHPCs) were exposed to dilutions of the extracts for 1 h, and the generation of reactive oxygen species (ROS) was determined by flow cytometry (FACS) using H(2)DCF-DA as a dye. Survival of tHPCs was measured photometrically using a crystal violet assay after a 24-h exposure period. Genotoxicity as indicated by the formation of micronuclei in V79 cells, and the modification of the normal cell cycle by extracts of the materials was analysed by FACS. RESULTS: Clear cytotoxic effects were detected only with extracts of Hydro C under the current experimental conditions. The two MTA preparations induced an insignificant reduction in the number of cells. In contrast, the extracts of COB slightly induced cell proliferation. Extracts of Hydro C caused a twofold increase in ROS production, whilst the other tested materials were ineffective. An increase in the number of micronuclei was not detected with any material tested; Hydro C slightly increased the number of cells in G1 and G2. CONCLUSIONS: The COB and the two MTA preparations did not negatively influence cell survival or ROS production and may thus be further considered for pulp capping studies.

Six-month follow-up of naltrexone and psychotherapy for alcohol dependence.

BACKGROUND: The goal of this study was to examine the persistence of naltrexone's effects on drinking outcomes among alcoholics following discontinuation of treatment and to determine whether coping skills therapy improves long-term outcomes compared with supportive therapy. METHODS: Eighty of 97 alcohol-dependent subjects randomized to receive naltrexone or placebo and either coping skills therapy or supportive therapy for 12 weeks were assessed at a 6-month off-treatment follow-up. RESULTS: Subjects who received naltrexone were less likely to drink heavily or to meet criteria for alcohol abuse or dependence than subjects who received placebo. The effect of naltrexone therapy on abstinence rates persisted only through the first month of follow-up. Coping skills therapy was associated with decreased levels of drinking among subjects who received placebo. Psychotherapy condition, however, did not predict alcohol diagnosis at follow-up. CONCLUSIONS: Some but not all of the benefits resulting from short-term naltrexone treatment persist after discontinuation of treatment. The findings suggest that continued treatment with naltrexone may be beneficial for some patients.

Experience of a "slip" among alcoholics treated with naltrexone or placebo.

OBJECTIVE: This study tested the hypothesis that naltrexone reduces relapse rates among alcoholics by modifying the reinforcing effects of initial alcohol consumption and alcohol-induced craving. METHOD: Sixteen alcoholic patients treated with naltrexone and 27 treated with placebo who participated in a 12-week clinical trial reported retrospectively on their subjective responses to their first episode of a lapse into alcohol consumption and on their reasons for terminating the drinking episode. RESULTS: Compared to the subjects who received placebo, the subjects who received naltrexone reported lower levels of craving for alcohol and were more likely to give reasons for terminating drinking that were consistent with decreased incentive to drink. CONCLUSIONS: These findings support the hypothesis that a central effect of naltrexone is the modification of alcohol-induced craving.

Massive weight loss does not restore normal insulin secretory pulses in obese patients with type 2 (non-insulin-dependent) diabetes mellitus.

To study the effects of massive weight loss on insulin secretion, we analysed the oscillations of fasting peripheral insulin levels in obese patients who underwent vertical banded gastroplasty as treatment for morbid obesity. Patients were studied before and 6 months after surgery. Serial measurements of plasma free insulin levels were obtained in duplicates from 0 to 60 min at one-minute intervals. Insulin levels were then analysed by autocorrelation and Fourier transformation. In normal controls and obese patients, the first oscillatory insulin component was detected between 10 and 14 min. Compared to obese controls (n = 4), overt Type 2 diabetic patients (n = 4) had reduced amplitudes of insulin pulses and no oscillatory component. These defects were not as pronounced in patients with impaired glucose tolerance (IGT) after an oral glucose tolerance test (OGTT) (n = 5). When detected, the periodicity of the oscillations occurred at different periods. In 3/5 IGT patients, the first positive peak of correlation was found at 13.3 +/- 2.3 min. Weight loss (mean +/- SD) after 6 months was 24.3 +/- 3.7 for subjects with normal glucose tolerance (NGT), 37.9 +/- 9 for those with IGT and 29.8 +/- 5 kgs for Type 2 diabetic subjects. After weight loss, insulin oscillatory activity was detected in 4/5 IGT patients, with a period of 13 +/- 3 min. Weight loss did not reverse the defects observed in obese diabetic patients despite a significant reduction in peripheral insulin levels from 28.6 +/- 6 to 15.6 +/- 6 mU/l (p < 0.05). Insulin values remained higher than in obese controls (7.82 +/- 2, p < 0.05), and Type 2 patients remained mildly hyperglycaemic. These findings indicate that beta-cell activity is abnormal in Type 2 diabetic patients. The absence of modification after weight loss suggests that inherent beta-cell defects may contribute to hyperglycaemia.

Interpersonal loss and self-mutilation.

Self-mutilation was hypothesized to increase in frequency during periods of interpersonal loss in a treatment program for seriously disturbed adolescents. The study examined changes in the frequency of acts of self-mutilation, aggression, and running away for 32 teenagers who experienced interpersonal loss when staff members left employment. Data were collected for a 4-year period. Statistical findings indicated that the frequency of self-mutilation increased significantly during the time period of anticipated loss, 2 weeks prior to staff terminations. There was no significant increase in the frequency of self-mutilation immediately following the staff terminations. Also, there was no significant change in the rates of aggression or running away either before or after the loss events. It was concluded that the time of anticipated loss was the period of highest risk for these adolescents in terms of self-mutilative behavior.

[Ethical recommendations for the genetic screening of hereditary endocrine diseases]. / Recommandations éthiques dans le cadre du dépistage génétique des affections endocrines à caractère héréditaire.

Predisposition to inherited diseases has been extensively studied over the last few years. Genetic studies have created a major concern about the psychological and ethical impact of risk evaluation in predisposed families. A significant number of inherited endocrine diseases are late-onset diseases and genetic risk assessment using molecular genetics leads to more accurate clinical and therapeutic follow-up of gene carriers. We describe minimal recommendations which could be associated to the official French laws published in July 1994 and analyze their concrete applications in clinical and genetic follow-up of patients and kindreds defined as gene carriers in predisposed families.

[Circulating antigliadin antibodies. Prevalence in a diabetic (type 1 or 2) and non diabetic adult population]. / Anticorps anti-gliadine circulants. Prévalence dans une population adulte diabétique (de type 1 ou 2) et non diabétique.

OBJECTIVES: The level of circulating antigliadin antibodies is an essential element in diabetic patients with signs of coeliac disease. Intolerance to gluten can disrupt glucose regulation leading to greater risk of hypoglycaemia. Search for antigliadin antibodies could be a routine test in diabetics. METHODS: Plasma gliadin antibodies were measured by immunoenzymatic assay in adult subjects: 80 type 1 diabetics, 80 type 2 diabetics, 80 non diabetics without auto-immune disease. RESULTS: IgA antibodies were present in 6 type 1 diabetics (7.5%), 8 type 2 diabetics (10%) and 6 non-diabetics (7.5%). Anti-reticulin and anti-endomysium antibodies were measured in type 1 diabetics with antigliadine antibodies. They were present only in one patient (Tunisian) who suffered from a coeliac disease. CONCLUSION: In France, the prevalence of coeliac disease is very low. Antigliadin antibodies measurement is justified only in patients with clinical and/or biological symptoms of coeliac disease.

Antiviral activity in vitro of two preparations of the herbal medicinal product Sinupret® against viruses causing respiratory infections.

Sinupret(®), a herbal medicinal product made from Gentian root, Primula flower, Elder flower, Sorrel herb, and Verbena herb is frequently used in the treatment of acute and chronic rhinosinusitis and respiratory viral infections such as common cold. To date little is known about its potential antiviral activity. Therefore experiments have been performed to measure the antiviral activity of Sinupret(®) oral drops (hereinafter referred to as "oral drops") and Sinupret(®) dry extract (hereinafter referred to as "dry extract"), in vitro against a broad panel of both enveloped and non-enveloped human pathogenic RNA and DNA viruses known to cause infections of the upper respiratory tract: influenza A, Chile 1/83 (H1N1) virus (FluA), Porcine Influenza A/California/07/2009 (H1N1) virus (pFluA), parainfluenza type 3 virus (Para 3), respiratory syncytial virus, strain Long (RSV), human rhinovirus B subtype 14 (HRV 14), coxsackievirus subtype A9 (CA9), and adenovirus C subtype 5 (Adeno 5). Concentration-dependent antiviral activity (EC(50) between 13.8 and 124.8 µg/ml) of Sinupret(®) was observed against RNA as well as DNA viruses independent of a viral envelope. Remarkable antiviral activity was shown against Adeno 5, HRV 14 and RSV in which dry extract was significantly superior to oral drops. This could be ascertained with different assays as plaque-reduction assays in plaque forming units (PFU), the analyses of a cytopathogenic effect (CPE) and with enzyme immunoassays (ELISA) to determine the amount of newly synthesised virus. Our results demonstrate that Sinupret(®) shows a broad spectrum of antiviral activity in vitro against viruses commonly known to cause respiratory infections.

Modification of a commercial atomic force microscopy for low-noise, high-resolution frequency-modulation imaging in liquid environment.

A key issue for high-resolution frequency-modulation atomic force microscopy imaging in liquids is minimizing the frequency noise, which requires a detailed analysis of the corresponding noise contributions. In this paper, we present a detailed description for modifying a commercial atomic force microscope (Bruker MultiMode V with Nanoscope V controller), aiming at atomic-resolution frequency-modulation imaging in ambient and in liquid environment. Care was taken to maintain the AFMs original stability and ease of operation. The new system builds upon an optimized light source, a new photodiode and an entirely new amplifier. Moreover, we introduce a home-built liquid cell and sample holder as well as a temperature-stabilized isolation chamber dedicated to low-noise imaging in liquids. The success of these modifications is measured by the reduction in the deflection sensor noise density from initially 100 fm/√Hz to around 10 fm/√Hz after modification. The performance of our instrument is demonstrated by atomically resolved images of calcite taken under liquid conditions.

Integrity in scientific publication

The available Razi Institute antivenom is still, empirically, used by intramuscular (IM) administration for the treatment of scorpion stings in humans by six medically dangerous species including Hemiscorpius lepturus (H. lepturus). The aim of this study was to assess the neutralizing ability and effectiveness of the antivenom in inhibiting hemoglobinuria, biochemical changes, increased microalbuminuria and urinary lactate dehydrogenase (LDH) following H. lepturus sting. Simultaneous intramuscular administration of 10 µL and 100 µL of antivenom, after 24 hours, had no significant preventive effect on the extent and degree of hemoglobinuria or proteinuria produced in venom-treated rats. After IM administration of antivenom, no significant changes in decreased red blood cell (RBC) count and hemoglobin were observed. Immediate intramuscular administration of 10 µL of antivenom had no significant effects on both LDH and microalbuminuria. The present findings did not present correlation with clinical signs. Therefore, to fully assess the efficacy of the available antivenom and make appropriate recommendations, more in vivo or in vitro investigations including antigen-antibody interaction, enzymatic analysis and route-dependent administration are required.(AU)

Cytotoxicity of substances leached or dissolved from pulp capping materials.

AIM: To evaluate the cytotoxic effects of substances leached or dissolved from pulp capping materials on human pulp fibroblasts. METHODOLOGY: The substances were applied to cell cultures in conditioned media. The experimental groups were: GI (control; n = 24)--cultures treated with fresh medium; GII (n = 24)--cultures treated with calcium hydroxide cement; GIII (n = 24)--cultures treated with adhesive resin and GIV (n = 24)--cultures treated with 37% orthophosphoric acid. The media were conditioned by placing the crude materials in contact with fresh culture medium for 1 h. The cytotoxicity analysis was performed using the Trypan blue dye exclusion assay at times of 0, 6, 12 and 24 h for cell viability assay, and at 1, 3, 5 and 7 days for survival assay. Data were treated by anova (P < 0.05) and Tukey's test (P < 0.05). RESULTS: GI and II presented similar cell viability and cell growth. GIII and IV exhibited statistically significant lower percentages of cell viability: GIV only at the 0 h experimental time, whereas in GIII this viability markedly diminished reaching values of 10% by 12 h. Cell growth was impaired only in cultures of GIII. CONCLUSIONS: Substances dissolved from the adhesive system tested were cytotoxic for human dental pulp fibroblasts in culture, whilst substances leached from calcium hydroxide were biocompatible.