GPR91 deficiency exacerbates allergic contact dermatitis while reducing arthritic disease in mice.

BACKGROUND: Succinate, in addition to its role as an intermediary of the citric acid cycle, acts as an alarmin, initiating and propagating danger signals resulting from tissue injury or inflammatory stimuli. The contribution of this immune sensing pathway to the development of allergic and inflammatory responses is unknown. METHODS: Ear thickness of wild-type (wt) and Sucnr1-deficient (Sucnr1-/- ) mice, sensitized and challenged with oxazolone, was used as a criterion to assess the relevance of SUCNR1/GPR91 expression mediating allergic contact dermatitis (ACD). Results obtained in this system were contrasted with data generated using passive cutaneous anaphylaxis, ovalbumin-induced asthma and arthritis models. RESULTS: We found augmented ACD reactions in Sucnr1-/- mice. This observation correlated with increased mast cell activation in vitro and in vivo. However, exacerbated mast cell activation in Sucnr1-/- mice did not contribute to the enhancement of asthma or arthritis and seemed to be due to alterations during mast cell development as augmented mast cell responses could be recapitulated in wt mast cells differentiated in the absence of succinate. CONCLUSIONS: A deficiency in succinate sensing during mast cell development confers these cells with a hyperactive phenotype. Such a phenomenon does not translate into exacerbation of asthma or mast cell-dependent arthritis. On the contrary, the fact that Sucnr1-/- mice developed reduced arthritic disease, using two different in vivo models, indicates that GPR91 antagonists may have therapeutic potential for the treatment of allergic and autoimmune diseases.

Use of Protein Cross-Linking and Radiolytic Labeling To Elucidate the Structure of PsbO within Higher-Plant Photosystem II.

We have used protein cross-linking with the zero-length cross-linker 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, and radiolytic footprinting coupled with high-resolution tandem mass spectrometry, to examine the structure of higher-plant PsbO when it is bound to Photosystem II. Twenty intramolecular cross-linked residue pairs were identified. On the basis of this cross-linking data, spinach PsbO was modeled using the Thermosynechococcus vulcanus PsbO structure as a template, with the cross-linking distance constraints incorporated using the MODELLER program. Our model of higher-plant PsbO identifies several differences between the spinach and cyanobacterial proteins. The N-terminal region is particularly interesting, as this region has been suggested to be important for oxygen evolution and for the specific binding of PsbO to Photosystem II. Additionally, using radiolytic mapping, we have identified regions on spinach PsbO that are shielded from the bulk solvent. These domains may represent regions on PsbO that interact with other components, as yet unidentified, of the photosystem.

Use of protein cross-linking and radiolytic footprinting to elucidate PsbP and PsbQ interactions within higher plant Photosystem II.

Protein cross-linking and radiolytic footprinting coupled with high-resolution mass spectrometry were used to examine the structure of PsbP and PsbQ when they are bound to Photosystem II. In its bound state, the N-terminal 15-amino-acid residue domain of PsbP, which is unresolved in current crystal structures, interacts with domains in the C terminus of the protein. These interactions may serve to stabilize the structure of the N terminus and may facilitate PsbP binding and function. These interactions place strong structural constraints on the organization of PsbP when associated with the Photosystem II complex. Additionally, amino acid residues in the structurally unresolved loop 3A domain of PsbP ((90)K-(107)V), (93)Y and (96)K, are in close proximity (≤ 11.4 Å) to the N-terminal (1)E residue of PsbQ. These findings are the first, to our knowledge, to identify a putative region of interaction between these two components. Cross-linked domains within PsbQ were also identified, indicating that two PsbQ molecules can interact in higher plants in a manner similar to that observed by Liu et al. [(2014) Proc Natl Acad Sci 111(12):4638-4643] in cyanobacterial Photosystem II. This interaction is consistent with either intra-Photosystem II dimer or inter-Photosystem II dimer models in higher plants. Finally, OH(•) produced by synchrotron radiolysis of water was used to oxidatively modify surface residues on PsbP and PsbQ. Domains on the surface of both protein subunits were resistant to modification, indicating that they were shielded from water and appear to define buried regions that are in contact with other Photosystem II components.

[Contraception's choice: women's opinion, satisfaction and profile. Results of a French national survey of a representative sample of 5963 women]. / Contraception des femmes françaises de 15 à 45ans: enquête nationale sur un échantillon représentatif de 5963 femmes.

OBJECTIVES: To describe French women's use of contraceptive methods and study their satisfaction and expectations about contraception. PATIENTS AND METHODS: A survey carried out by mail questionnaire filled in by a representative sample group of French women aged 15 to 45 years (Panel Postal Metascope TNS Sofres) in June 2007. RESULTS: Of 10,000 questionnaires sent out, 6044 questionnaires were returned, of which 5963 were usable. Seventy-three percent of women surveyed used some method of contraception, of which 46% was an oral contraceptive, 15% an IUD and 7% used condoms. A minority used new contraceptive methods (implant, patch, vaginal ring). The average age at first sexual relationship was 17.8 years. It was 18.5 among 40-45-year-olds and gradually reduced to 16.7 in the under 25-year-olds. Twenty-three percent of pregnancies remain unwanted and unplanned. For 96% of patients, the choice of contraception was considered to be important. Thirty-six percent thought that contraception could be harmful to health. Only 63% of women believed themselves to be well informed the first time they used contraception. Satisfaction for contraception method was evaluated from 7.3/10 (condom) to 9.7/10 (sterilization). DISCUSSION AND CONCLUSION: Twenty-seven percent of women do not use any contraception and 23% of pregnancies are unwanted despite a large offering of contraceptives. Our study enables the drawing of 'patient-profiles' for the main methods of contraception in order to better determine women's expectations and to pass the findings on to health professionals.

Radiolytic mapping of solvent-contact surfaces in Photosystem II of higher plants: experimental identification of putative water channels within the photosystem.

Photosystem II uses water as an enzymatic substrate. It has been hypothesized that this water is vectored to the active site for water oxidation via water channels that lead from the surface of the protein complex to the Mn4O5Ca metal cluster. The radiolysis of water by synchrotron radiation produces amino acid residue-modifying OH(•) and is a powerful technique to identify regions of proteins that are in contact with water. In this study, we have used this technique to oxidatively modify buried amino acid residues in higher plant Photosystem II membranes. Fourier transform ion cyclotron resonance mass spectrometry was then used to identify these oxidized amino acid residues that were located in several core Photosystem II subunits (D1, D2, CP43, and CP47). While, as expected, the majority of the identified oxidized residues (≈75%) are located on the solvent-exposed surface of the complex, a number of buried residues on these proteins were also modified. These residues form groups which appear to lead from the surface of the complex to the Mn4O5Ca cluster. These residues may be in contact with putative water channels in the photosystem. These results are discussed within the context of a number of largely computational studies that have identified putative water channels in Photosystem II.

Essure® permanent birth control effectiveness: a seven-year survey.

Essure appears to be a safe reliable contraception. The aim of this study is to report French pregnancies after Essure hysteroscopic sterilization. This study is a retrospective national survey between January 2003 and September 2010. Data were collected in two ways: The surgeons contacted in our study were responsible for 63.4% of all Essure procedures in France. Fifty-eight cases of unintended pregnancies after Essure sterilization in France were reported during the study period. Factors associated to unintended pregnancies were patient' non compliance with follow-up (22 pregnancies, 38% of cases) and misinterpretation at the 3rd-month confirmation test (19 cases, 33%). Other causes were physician's deviation from protocol (10 cases) and undetected pre-procedure pregnancy (3 cases). Three pregnancies happened before the 3-months confirmation test. Based on the number of kits sold during the period, the estimated pregnancy rate was between 1.07 and 1.09/1000 procedure. The pregnancy risk after hysteroscopic sterilization may be reduced by improving patient education and physician knowledge concerning the 3rd month confirmation test.

[Permanent tubal hysteroscopic sterilization]. / Contraception permanente par pose hystéroscopique d'implants tubaires.

Tubal sterilization, of common practice all over the world, has had a quick spread in France since its legalization in 2001 and the income of a new hysteroscopic method. As a matter of fact, France is the second greater country for women having Essure® and the first country where Essure® method forestall surgical tubal ligation. Thus we focus on good practice and update knowledge about Essure® method.

[Diagnosis and treatment of pelvic splenosis during exploration of infertility]. / Diagnostic et traitement de splénose pelvienne au cours d'un bilan d'infertilité.

Splenosis is the heterotopic autotransplantation of splenic tissue that usually follows traumatic splenectomy. Rare pelvic localizations are reported. We report here a case of a 36-year-old woman, followed for secondary infertility. On transvaginal ultrasound pelvic scanning hypervascular paracervical nodules were demonstrated. Pelvic splenosis was suspected regarding the patient's medical past (post-traumatic splenectomy). Surgical exploration and resection were decided considering the nodule localization, the risk during ovarian punction for IVF, and the hypothetical risk of bleeding at delivery. Generally, it is recommended to leave in place the splenic tissue, which may be immunologically functional.

Private GPs contribute to TB control in Myanmar: evaluation of a PPM initiative in Mandalay Division.

SETTING: Mandalay Division, Myanmar. AIM: To assess the effect of an initiative to involve private general practitioners (GPs) in the National Tuberculosis Programme (NTP) and to identify lessons learnt for public-private mix scale-up. METHODS: Source of referral/diagnosis and place of treatment were included in the routine recording and reporting systems to enable disaggregated analysis of the contribution of GPs to case notification and treatment outcomes. Case notification trends were compared between the intervention and control areas over a 4-year period. RESULTS: Private GPs contributed 44% of new smear-positive cases registered during the study period (July 2002-December 2004). The notification of new sputum smear-positive TB in the study area increased by 85% between the year prior to the GP involvement and 2 years after (from 46 to 85/100,000). Case notification increased by 57% in the control townships and by 42% in all of Mandalay Division. The treatment success rate for new smear-positive cases treated by GPs was 90%. CONCLUSIONS: The involvement of private GPs substantially increased TB case notification, while a high treatment success rate was maintained. Success factors include a well-developed local medical association branch, strong managerial support, training and supervision by the public sector and provision of drugs and consumables free of charge by the NTP.

[Myosonographic and electromyographic (EMC) evaluation of donor-site morbidity after microsurgical TRAM flap]. / Evaluation der Hebemorbidität nach Entnahme eines mikrovaskulären TRAM-Lappens durch Elektromyographie und Myosonographie.

Due to improved microsurgical techniques the role of autologous breast reconstruction is expanding. One reason is the decreased donor-site morbidity compared to other techniques. Perforator based flaps (DIEP flaps) seemingly decrease the damage of the abdominal wall due to flap harvesting. However, complication rate in perforator flaps is still considered to be higher than in TRAM flaps. Additionally, operating time is increased due to the meticulous microsurgical dissection of perforators. To evaluate whether donor-site morbidity is caused by harvesting a part of the rectus muscle (as TRAM flaps), 15 patients after unilateral muscle sparing TRAM flap underwent EMG and myosonographic examination of the rectus muscle. EMG is the only technique to assess the muscle functionally, as the electrical activity of the muscle is recorded, and motor unit recruitment can be shown. EMG examination clearly revealed that harvesting of a muscle sparing TRAM flap did not impair the rectus muscle compared to the intact contralateral muscle. However, motor units were enlarged. Myosonography (in contrast to MRI) detected particular damage of isolated muscle fibres indicating nerve-related muscle changes. Taking all findings together, harvesting of a part of the rectus muscle shows a distinct damage to the muscle. The muscle however still acts functionally. This indicates that problems after harvesting a TRAM flap (bulging, hernias etc.) are not due to the partial removal of muscle, but due to the general dissection of the abdominal wall, as seen in other abdominal operations.

[Regional networking of medical and vocational rehabilitation-- the bad Krozingen model]. / Regionale Vernetzung medizinischer und beruflicher Rehabilitation: Das Bad Krozinger Modell.

Regional networking facilitates flexible and individual integration of vocational programmes in medical rehabilitation. We present a pilot project of Theresienklinik II in cooperation with the Education centre for occupation and health (Bildungszentrum Beruf und Gesundheit) in Bad Krozingen. Orthopaedic and cardiac patients who are in danger to lose their capacity to work, participate in an integrated vocational reorientation programme during extended medical rehabilitation. The aim of the pilot project is an early assessment of motivation, work hardening, aptitude and interest, in order to accelerate vocational retraining and reintegration. Within one year 30 patients participated in the programme. Presented are the contents and course of the pilot project. First results show a high patient satisfaction with the programme.

Outcome after mild-to-moderate blunt head injury: effects of focal lesions and diffuse axonal injury.

PRIMARY OBJECTIVE: A comparison of the effects of focal and diffuse axonal injury in mild-to-moderate traumatic brain injury (TBI). RESEARCH DESIGN: In a prospective longitudinal study of 138 consecutive patients suffering from TBI who were admitted to the Magdeburg University Hospital, 60 could be assessed neuropsychologically 8--31 days after trauma and 18--45 weeks later. METHODS AND PROCEDURES: GCS, CT-analysis, comprehensive neuropsychological assessment. MAIN RESULTS: The initial GCS-score was significantly correlated with outcome impairments of semantic fluency and memory in the Wechsler Similarities and in two clinical scales (Neurobehavioural Rating Scale, Frontal Lobe Score). The presence of CT-signs of DAI corresponded with deficits in tasks of response selection and suppression, the presence of focal contusions with results in the clinical scales, reaching significance for behavioural deficits with frontal contusions. Improvements between first and second assessments were pronounced in patients with signs of DAI. CONCLUSIONS: The data indicate that traumatic DAI results in mainly transient neuropsychological deficits. Focal frontal contusions result in more relevant deficits at outcome that affect behaviour and, thus, impair rehabilitation prognosis. It is concluded that even in clinically 'mild' TBI, prognosis and rehabilitation requirements should be established by early imaging and post-acute neuropsychological assessment.

The neuropsychology of blunt head injury in the early postacute stage: effects of focal lesions and diffuse axonal injury.

This investigation evaluated the neuropsychological symptoms in the early posttraumatic period following blunt head injury and their correlation to routine imaging data in a consecutive series of TBI patients (Magdeburg Neurotrauma Databank). Of 135 consecutive patients, 68 could be assessed neuropsychologically 8-21 days after trauma. In 61 patients, routine clinical CT data were sufficient for neuroradiological analysis focusing on the presence or absence of CT signs of diffuse axonal injury (DAI) or focal traumatic injury. In these patients, the initial GCS score was significantly correlated with the presence of DAI but not with focal pathology. The presence of DAI was correlated with behavioral and cognitive symptoms of frontal lobe dysfunction, especially in interference tasks (Go/NoGO and Stroop reaction times) and semantic fluency. The presence of local frontal or temporal traumatic lesions was associated with deficits in concept formation, fluency tasks and behavioral symptoms, but not with increased interference. Patients with frontal contusions were impaired in a task of visuomotor planning and performance (Block design). Our data indicate that both traumatic DAI and focal lesions result in frontal lobe symptoms. We conclude that, even in clinically "mild" TBI, brain imaging should be used to identify patients with substantial brain damage. These should be assessed neuropsychologically for possible posttraumatic cognitive or behavioral impairment. In consideration of its easy accessibility, the refined use of the CT is considered a promising and valid tool for patient stratification. The application of MRI and biochemical markers may further improve prognostic predictions.

Release of biochemical markers of damage to neuronal and glial brain tissue is associated with short and long term neuropsychological outcome after traumatic brain injury.

OBJECTIVES: The present study aimed at the analysis of release patterns of neurobiochemical markers of brain damage (neuron specific enolase (NSE) and protein S-100B) in patients with traumatic brain injury and their predictive value with respect to the short and long term neuropsychological outcome. METHODS: Serial NSE and S-100B concentrations were analysed in blood samples taken at the first, second, and third day after traumatic brain injury. In 69 patients who fulfilled the inclusion criteria (no history of neurological or psychiatric disorder or alcohol or drug dependency, blood sampling according to the scheduled time scale, aged between 16 and 65 years) standardised neurological examinations and qualitative and quantitative evaluation of CT were performed. Comprehensive neuropsychological assessment was performed in 39 subjects 2 weeks after admission and in 29 subjects at a 6 month follow up examination. RESULTS: Most patients presented with minor head injuries (GCS>/=13) at the time of admission. Six months later most patients were fully independent in activities of daily living. Two thirds of the patients, however, still had neuropsychological dysfunction. Patients with short and long term neuropsychological disorders had significantly higher NSE and S-100B serum concentrations and a significantly longer lasting release of both markers. A comparative analysis of the predictive value of clinical, neuroradiological, and biochemical data showed initial S-100B values above 140 ng/l to have the highest predictive power. CONCLUSIONS: The analysis of post-traumatic release patterns of neurobiochemical markers of brain damage might help to identify patients with traumatic brain injury who run a risk of long term neuropsychological dysfunction.

Temporal profile of release of neurobiochemical markers of brain damage after traumatic brain injury is associated with intracranial pathology as demonstrated in cranial computerized tomography.

This study aimed at the investigation of release patterns of neuron specific enolase (NSE) and protein S-100B after traumatic brain injury (TBI) and their association with intracranial pathologic changes as demonstrated in computerized tomography (CT). We analyzed NSE and S-100B concentrations in serial venous blood samples taken one to three days after TBI in 66 patients by the use of immunoluminometric assays. These markers are considered to be specific neurobiochemical indicators of damage to glial (S-100B) or neuronal (NSE) brain tissue. Standardized neurological examination and plani- and volumetric evaluation of computerized tomography scans were performed in all patients. Patients with medium severe to severe TBI [Glasgow Coma Scale (GCS) score at the site of accident < or =12] exhibited significantly higher NSE and S-100B concentrations and a significantly longer release compared to patients with minor head injury (GCS: 13-15). Both, patients with and without visible intracerebral pathology in CT scans exhibited elevated concentrations of NSE and S-100B after TBI and a significant decrease in the follow-up blood samples. Release patterns of S-100B and NSE differed in patients with primary cortical contusions, diffuse axonal injury (DAI), and signs of cerebral edema (ICP) without focal mass lesions. All serum concentrations of NSE and S-100B were significantly correlated with the volume of contusions. The data of the present study indicate that the early release patterns of NSE and S-100 may mirror different pathophysiological consequences of traumatic brain injury.

FK506 promotes functional recovery in crushed rat sciatic nerve.

In this study we examine whether the systemic administration of FK506 or Cyclosporin A (CsA) expedited functional recovery following an axonotmetic nerve injury, and compared their effects in a rat model. Seventy-five adult Buffalo rats received a crush injury to the right posterior tibial nerve and subsequently underwent either no treatment (group I), daily injections of FK506 (group II), or daily injections of CsA (group III). Walking track analysis demonstrated return of hindlimb function by 20 days postoperatively in group I, 14 days in group II, and 18 days in group III. The blood-nerve barrier (BNB) was reconstituted by postoperative day (POD) 7 in both FK506- and CsA-treated animals and by POD 13 in control animals. These results suggest that recovery of function is more rapid with daily administration of FK506 than with CsA or no treatment, perhaps because of earlier restoration of the blood-nerve barrier. Agents that facilitate nerve regeneration have the potential to limit the extent of motor endplate loss and muscle atrophy seen with prolonged denervation, thereby limiting permanent functional loss.

An assessment and intervention strategy for managing staff needs during change.

Currently, change is rampant in healthcare. Amid the economic pressures of managed care, nursing leaders find themselves pouring over financial spread-sheets and crunching numbers at the expense of staff interaction. While staff members feel overwhelmed by the whirlwind of change around them, nursing leaders struggle to balance staff needs with countless other responsibilities. The assessment and intervention strategy presented provides nursing leaders with a straightforward and efficient means of identifying and addressing issues that affect staff productivity, retention, and satisfaction.

Conditions predisposing to maternal mortality in twins and singletons, US birth cohort 1989.

Twin pregnancy is one of the most important conditions associated with increased perinatal mortality and morbidity. The consequences of twin pregnancy on the mother have not been explored in great detail. The aim of this study was to analyze the population-based data from the United States and delineate the various conditions of twin pregnancies which predispose to maternal mortality. Results of this study show that multiple pregnancy is strongly associated with maternal mortality and requires further analysis in order to prepare appropriate therapeutic and prophylactic protocols.

Early neurobehavioral outcome after stroke is related to release of neurobiochemical markers of brain damage.

BACKGROUND AND PURPOSE: The study aimed to investigate the predictive value of neurobiochemical markers of brain damage (protein S-100B and neuron-specific enolase [NSE]) with respect to early neurobehavioral outcome after stroke. METHODS: We investigated 58 patients with completed stroke who were admitted to the stroke unit of the Department of Neurology at Magdeburg University. Serial venous blood samples were taken after admission and during the first 4 days, and protein S-100B and NSE were analyzed by the use of immunoluminometric assays. In all patients, lesion topography and vascular supply were analyzed and volume of infarcted brain areas was calculated. The neurological status was evaluated by a standardized neurological examination and the National Institutes of Health Stroke Scale (NIHSS) on admission, at days 1 and 4 on the stroke unit, at day 10, and at discharge from the hospital. Comprehensive neuropsychological examinations were performed in all patients with first-ever stroke event and supratentorial brain infarctions. Functional outcome was measured with the Barthel score at discharge from the hospital. RESULTS: NSE and protein S-100B concentrations were significantly correlated with both volume of infarcted brain areas and NIHSS scores. Patients with an adverse neurological outcome had a significantly higher and significantly longer release of both markers. Neuropsychological impairment was associated with higher protein S-100B release, but this did not reach statistical significance. CONCLUSIONS: Serum concentrations and kinetics of protein S-100B and NSE have a high predictive value for early neurobehavioral outcome after acute stroke. Protein S-100B concentrations at days 2 to 4 after acute stroke may provide valuable information for both neurological status and functional impairment at discharge from the acute care hospital.

Protection from digoxin-induced coronary vasoconstriction in patients with coronary artery disease by calcium antagonists.

Intravenous digoxin induces constriction of normal and stenotic coronary arteries in patients with coronary artery disease, which may lead to ischemic complications. We found that pretreatment with oral nisoldipine and intracoronary nitroglycerin neutralizes this digoxin-induced effect.