[The "Wunsch- und Wahlrecht" from §9 SGB IX in case of the application for the medical rehabilitation: findings of a regional survey among insurees of a federal pension fund and a compulsory health insurance fund].
The Social Code Book Nine (SGB IX), which was implemented in 2001, contains the "Wunsch- und Wahlrecht" for medical rehabilitation services in para. 9. This describes a right to participate and choose in the process of rehabilitation. The aim of the study was to collect representative data about the implementation of the para. 9 SGB IX during application for medical rehabilitation services from the applicants' point of view. A total of 2 000 applicants for rehabilitation services (all somatic and psychosomatic indications) of a federal pension fund and a compulsory health insurance fund were invited to take part in a postal survey about the "Wunsch- und Wahlrecht". The response rate was 66%. Most respondents reported that their application for rehabilitation services was approved immediately. People who supported respondents during application and gave information about the "Wunsch- und Wahlrecht" differed according to the kind of rehabilitation services the respondent applied for. Half of the respondents reported to have known about their "Wunsch- und Wahlrecht". The percentage was considerably higher for patients applying for post-hospital rehabilitation. Approximately 2/3 of the respondents had wishes concerning the choice of rehabilitation clinic. Half of those respondents reported their wishes to the insurer. Most wishes concerned the choice of a specific clinic, a place/region or the clinic's distance from the applicant's home. Wishes reported to the insurer were often considered (89%). Most important selection criteria for rehabilitation clinics were aspects of accommodation, clinic facilities and location, followed by aspects of treatment and the respectful treatment of rehabilitation patients. Concerning the mode of information about rehabilitation clinics, applicants preferred brochures (vs. internet), comparative and impartial information about the clinic and subjective accounts of individual rehabilitation patients. This study is an evaluation of how the "Wunsch- und Wahlrecht" has been translated to reality of rehabilitation services provided by a federal pension fund and a compulsory health insurance fund. The findings show that many respondents know about their "Wunsch- und Wahlrecht" and make use of it to a certain degree. At the moment wishes still relate mainly to the place or region of rehabilitation. This shows the necessity of informing applicants about their "Wunsch- und Wahlrecht" on a regular basis. At the same time they must be enlightened about potentially important criteria for choosing a rehabilitation clinic.


Synthesis of MnOOH and its application in a supporting hexagonal Pd/C catalyst for the oxygen reduction reaction.
With the expansion of global energy problems and the deepening of research on oxygen reduction reaction (ORR) in alkaline media, the development of low cost and high electrocatalytic performance catalysts has become a research hotspot. In this study, a hexagonal Pd-C-MnOOH composite catalyst was prepared by using the triblock copolymer P123 as the reducing agent and protective agent, sucrose as the carbon source and self-made MnOOH as the carrier under hydrothermal conditions. When the Pd load is 20% and the C/MnOOH ratio is 1 : 1, the 20% Pd-C-MnOOH-1 : 1 catalyst obtained by the one-step method has the highest ORR activity and stability in the alkaline system. At 1600 rpm, the limiting diffusion current density and half-wave potential of the 20% Pd-C-MnOOH-1 : 1 electrocatalyst are -4.78 mA cm-2 and 0.84 V, respectively, which are better than those of the commercial 20%Pd/C catalyst. According to the Koutecky-Levich (K-L) equation and the linear fitting results, the electron transfer number of the 20%Pd-C-MnOOH-1 : 1 electrocatalyst for the oxygen reduction reaction is 3.8, which is similar to that of a 4-electron process. After 1000 cycles, the limiting diffusion current density of the 20%Pd-C-MnOOH-1 : 1 catalyst is -4.61 mA cm-2, which only decreases by 3.7%, indicating that the 20%Pd-C-MnOOH-1 : 1 catalyst has good stability. The reason for the improvement of the ORR performance of the Pd-C-MnOOH composite catalyst is the improvement of the conductivity of the carbon layer formed by original carbonization, the regular hexagonal highly active Pd particles and the synergistic catalytic effect between Pd and MnOOH. The method of introducing triblock copolymers in the synthesis of oxides and metal-oxide composite catalysts is expected to be extended to other electrocatalysis fields.


The Role of Vaccination Centers in a National Mass Immunization Campaign-Policymaker Insights from the German COVID-19 Pandemic Vaccine Roll-Out.
During the COVID-19 vaccination campaign, Germany, like other high-income countries, introduced mass vaccination centers for administering vaccinations. This qualitative study aimed to examine the role that these novel, temporary government healthcare structures played in a mass immunization roll-out and how they can be optimally deployed. In addition, learnings for general emergency preparedness were explored. A total of 27 high-level policymakers responsible for planning and implementing the COVID vaccination campaign at the national and state level in Germany were interviewed in May and June 2022. The semi-structured interviews were analyzed using thematic analysis. Interviewees indicated that mass vaccination structures played an essential role with respect to controllability, throughput, accessibility and openness in line with the key success criteria vaccination coverage, speed and accessibility. In contrast to the regular vaccination structures (private medical practices and occupational health services), public administration has direct authority over mass vaccination centers, allowing for reliable vaccine access prioritization and documentation. The deployment of vaccination centers should be guided by vaccine availability and demand, and vaccine requirements related to logistics, as well as local capacities, i.e., public-health-service strength and the physician density, to ensure effective, timely and equitable access. Improvements to the capacity use, scalability and flexibility of governmental vaccination structures are warranted for future pandemics.


Deformable phantoms of the prostatic urinary tract for urodynamic investigations.
Assessment of urethral dynamics is clinically regarded to be important in analyzing the functional impact of pathological features like urethral obstruction, albeit it is difficult to perform directly in vivo. To facilitate such an assessment, urethra phantoms may serve well as investigative tools by reconstructing urethral dynamics based on anthropomorphic factors. Here, our aim is to design a new class of anatomically realistic, deformable urethra phantoms that can simulate the geometric, mechanical, and hydrodynamic characteristics of the male prostatic urethra. A new lost-core tube casting protocol was devised. It first involved the drafting of urethra geometry in computer-aided design software. Next, 3D printing was used to fabricate the urethra geometry and an outer mold. These parts were then used to cast a urinary tract using a polyvinyl alcohol (PVA)-based material (with 26.6 ± 4.0 kPa Young's elastic modulus). After forming a surrounding tissue-mimicking slab using an agar-gelatin mixture (with 17.4 ± 3.4 kPa Young's modulus), the completed urethra phantom was connected to a flow circuit that simulates voiding. To assess the fabricated phantoms' morphology, ultrasound imaging was performed over different planes. Also, color Doppler imaging was performed to visualize the flow profile within the urinary tract. Deformable phantoms were devised for the normal urethra and a diseased urethra with obstruction due to benign prostatic hyperplasia (BPH). During voiding, the short-axis lumen diameter at the verumontanum of the BPH-featured phantom (0.91 ± 0.08 mm) was significantly smaller than that for the normal phantom (2.49 ± 0.20 mm). Also, the maximum flow velocity of the BPH-featured phantom (59.3 ± 5.8 cm/s; without Doppler angle correction) was found to be higher than that of the normal phantom (22.7 ± 9.0 cm/s). The fabricated phantoms were effective in simulating urethra deformation resulting from urine passage during voiding. They can be used for mechanistic studies of urethral dynamics and for the testing of urodynamic diagnostic techniques in urology.


Neutrophilic figurate erythema.
We herein report a 39-year-old woman presented with annular plaque with central clearing on the back, extremities, and breasts. The lesions had raised, firm erythematous borders included a trailing scale. On histologic examination, a perivascular inflammatory cell infiltrate composed of neutrophils and mononuclear inflammatory cells in the upper dermis was shown. We consider our case to represent idiopathic figurate erythema with a dominant infiltration of neutrophils.


Adverse effects.
In medicine, an adverse effect (AE) is a harmful and undesired effect resulting from a medication or intervention and procedures. Some AEs only occur when starting, increasing or discontinuing a treatment; in this case they are a function of dosage or drug levels at the target organs, or they may also be caused by drug interactions. The distinction between adverse and non-adverse effects is a major undertaking when a new drug is developed and tested. Studies are used to define the dosage to be used in human testing (Phase 1) as well as to calculate the maximum admissible daily intake. Imperfections in clinical trials sometimes lead to public health disasters and the withdrawal of the drug from commerce. Surgery may have a number of undesirable or harmful after-effects. Diagnostic procedures may also have AEs, depending much on whether they are invasive, non-invasive or minimally invasive. In clinical trials, a distinction is made between AEs and Serious Adverse Events (SAEs). Generally, any event which causes death, permanent damage, birth defects, or requires hospitalization is considered an SAE.


Tumor-to-Tumor Metastasis - a Unique Case of Clear Cell Renal Cell Carcinoma Harboring Metastasis of Adenocarcinoma of Unknown Origin.
The tumor-to-tumor metastasis is exclusively rare finding, in which one malignant neoplasia metastasizes to another tumor of different origin. The author describes an 68-year-old woman, who was found to have a solitary tumor in the right kidney, as well as multiple tumor nodules in the liver. She underwent a radical nephrectomy. A histology of lesion in the kidney revealed a conventional clear cell renal cell carcinoma (RCC) harboring multiple metastatic foci of another adenocarcinoma. At that time, there was not possible to reliably specify a primary source. Subsequently, a probatory excision of tumor lesion in the liver was also done. A microscopy confirmed an adenocarcinoma with a similar appearance as found in RCC. Due to unfavourable health condition, a paliative chemotherapy could not be realized and the patient died shortly thereafter. A primary origin of adenocarcinoma remained unclear. A unique case of metastatic adenocarcinoma is described, that was initially diagnosed as an incidental finding within a clear cell RCC of the kidney. Such unexpected feature may represent a great diagnostic challenge for both, pathologist and clinician. From a prognostic point of view, an evidence of intratumoral cancer metastasis within a primary RCC is usually an indicator of disseminated oncologic disease with a poor outcome. Key words: tumor-to-tumor metastasis - donor - recipient - renal cell carcinoma.


Nucleic acid and protein clocks.
The use of pairwise comparisons of correctly aligned DNA and protein sequences for the measurement of time in historical biology remains a contentious matter. However, the limited success of some molecular evolutionary clocks provides a stimulus to attempt to improve their resolution by the judicious selection of sequences for ease of alignment, commonality of function, taxonomic breadth and appropriate rates of evolution. Existing algorithms for correcting observed distances for superimposed nucleotide substitutions or amino acid replacements appear adequate for the task, given the noise that results from the inherent variability of the process. Some possible approaches are illustrated through the use of gene and protein sequences of the large subunit of ribulose 1,5-bisphosphate carboxylase/oxygenase: an enzyme that is demonstrably homologous from purple bacteria to flowering plants.


An analysis of the 'legal high' mephedrone.
'Legal highs' are compounds, plant or fungal material which can be readily bought from the internet without legal restriction and the single chemicals may be structurally related to illegal drugs of abuse such as the amphetamines. Several recent deaths in the UK have been attributed to these legal highs and unfortunately there is little chemical or biological literature on these materials or certified standards. Here, we detail the analysis of the widely consumed synthetic N-methyl-cathinone analogue known as mephedrone ((1) 2-aminomethyl-1-tolyl-propan-1-one (4'-methylmethcathinone)) and report its spectral data and molecular properties. Material was purchased from an internet site and examined by extensive one- and two-dimensional NMR studies, high-resolution mass spectrometry, elemental analysis and optical rotation, which demonstrated the sample to be of high purity and racemic in nature. Additionally, we report the molecular modelling properties of methyl-cathinones and compare them to their corresponding methyl-amphetamine series. This indicated that the methyl-cathinones are considerably more hydrophilic than the methyl-amphetamines which may account for the higher doses that are needed to demonstrate similar effects. The presence of a ketone in the side chain introduces a far more planar quality to the methyl-cathinones which is absent in the methyl-amphetamine series, and this planarity may contribute to toxicity.


Effects of an Informational Video About Anesthesia on Pre- and Post-Elective Cesarean Section Anxiety and Recovery: A Randomized Controlled Trial.
BACKGROUND Showing an informational anesthesia video can reduce the preoperative anxiety of parturients undergoing elective cesarean section (CS). However, the best method for presenting such videos remains unclear, and whether such videos can reduce the anxiety level of women during the entire perioperative period for CS (including preoperative and postoperative) has not been studied yet. MATERIAL AND METHODS This study was a single-center prospective randomized trial. We randomly divided 121 pregnant women who were scheduled to undergo elective cesarean section (CS) into 2 groups: one group was shown an informational video (video group) and another group was not (control group). Spielberger's state-trait anxiety inventory was used to evaluate the perioperative anxiety level of parturient women at 3 time points: 1 day before CS, after video education, and 2 days after CS. Salivary cortisol level was evaluated to assess the patients' anxiety level at these 3 time points. Finally, the maternal satisfaction scale for CS and an obstetric quality-of-recovery score (OBsQoR-11) were used to evaluate the satisfaction and recovery of the parturient women 2 days after CS. RESULTS Watching a video about anesthesia significantly reduced the anxiety level of the parturient women during the perioperative period (1 day before CS: p=1.00, p=0.96; after video education: p<0.01, p=0.004; 2 days after CS: p=0.01, p=0.01). The postoperative satisfaction scores were significantly improved in the video group (p=0.007). OBsQoR-11 scores in the video group and control group were not significantly different (p=0.48). Maternal anxiety level was moderately positively correlated with cortisol hormone level. CONCLUSIONS Showing an informational video about anesthesia (video+education) can significantly reduce perioperative anxiety and improve satisfaction after CS. Although it did not improve the postoperative recovery, it was still significant for anesthesia.


Influence of maternal environmental tobacco smoke exposure assessed by hair nicotine levels on birth weight.
While the perinatal outcomes of active maternal smoking are well documented, results of the effects of environmental tobacco smoke (ETS) exposure during pregnancy are inconsistent. We aimed to examine the effect of ETS exposure, assessed by maternal hair nicotine levels at 35th week of gestation, on birth weight and the risk of small for gestational age (SGA) and low birth weight (LBW). A total of 871 non-smoking healthy pregnant women were recruited by one Korean hospital between 1 October 2006 and 31 July 2007. Hair samples were collected and anthropometric questionnaires administered at 35th week of gestation. The primary outcome was birth weight and secondary outcomes were the risk of babies being SGA and LBW. Log-transformed hair nicotine concentrations were inversely related with birth weight after adjusting for confounding variables (β=-0.077, p=0.037). After stratifying hair nicotine levels by tertiles (T1, low [0.0-0.28 ng/mg]; T2, medium [0.29-0.62 ng/mg]; and T3, high [0.63-5.99 ng/mg]), the mean birth weight in each groups were 3,342 g (T1) 3,296 g (T2) and 3,290 g (T3), respectively. However the difference between groups was not statistically significant by analysis of co-variance (ANCOVA) adjusting for covariates (p=0.062). In logistic regression analysis, the risk of SGA was higher in the T3 (OR=1.59, 95%CI 1.05-2.42) than in the reference group (T1), after controlling for confounding variables. The risk of low birth weight (<2,500 g, LBW) was not significantly higher (OR=1.44, 95%CI 0.95-2.19), but the risk of babies being below 3,000g birth weight was increased in the T3 group (OR=1.53, 95%CI 1.00-2.36) compared with that in the T1 group. Maternal ETS exposure during pregnancy was inversely related with birth weight. The risk of SGA increased in the highest ETS exposure group compared with in the low exposure group. To prevent ETS exposure during pregnancy, more comprehensive tobacco control policies are needed.


Environmental Light Exposure Is Associated with Increased Body Mass in Children.
The timing, intensity, and duration of exposure to both artificial and natural light have acute metabolic and physiological effects in mammals. Recent research in human adults suggests exposure to moderate intensity light later in the day is concurrently associated with increased body mass; however, no studies have investigated the effect of light exposure on body mass in young children. We examined objectively measured light exposure and body mass of 48 preschool-aged children at baseline, and measured their body mass again 12 months later. At baseline, moderate intensity light exposure earlier in the day was associated with increased body mass index (BMI). Increased duration of light exposure at baseline predicted increased BMI 12-months later, even after controlling for baseline sleep duration, sleep timing, BMI, and activity. The findings identify that light exposure may be a contributor to the obesogenic environment during early childhood.


[Massive gastrointestinal bleeding due to aneurysmal rupture of ileo-colic artery in a patient with Behcet's disease].
Behcet's disease has been recognized as a systemic vasculitis characterized by the involvement of multiple organs such as orogenital ulcers, eye lesions including uveitis and optic neuritis, and skin lesions including folliculitis and erythema nodosum. Vascular involvement occurs occasionally and is classified into thrombosis and aneurysm. However, massive gastrointestinal bleeding from arterial aneurysm is a rare manifestation of intestinal Behcet's disease. Recently, we experienced a case of intestinal Behcet's disease presenting with massive gastrointestinal bleeding due to aneurysmal rupture of ileo-colic artery. A 30-year-old male with Behcet's disease was admitted because of massive gastrointestinal bleeding. A large ileo-cecal ulcer was revealed as a bleeding focus on colonoscopic examination. Celiac angiography showed aneurysm and stenosis of ileo-colic artery. After the failure of hemostasis with arterial embolization, ileocecectomy was performed. After the resection hematochezia was completely stopped.


Continuous electromyography monitoring of motor cranial nerves during cerebellopontine angle surgery.
Electromyography (EMG) monitoring is expected to reduce the incidence of motor cranial nerve deficits in cerebellopontine angle surgery. The aim of this study was to provide a detailed analysis of intraoperative EMG phenomena with respect to their surgical significance. Using a system that continuously records facial and lower cranial nerve EMG signals during the entire operative procedure, the authors examined 30 patients undergoing surgery on acoustic neuroma (24 patients) or meningioma (six patients). Free-running EMG signals were recorded from muscles targeted by the facial, trigeminal, and lower cranial nerves, and were analyzed off-line with respect to waveform characteristics, frequencies, and amplitudes. Intraoperative measurements were correlated with typical surgical maneuvers and postoperative outcomes. Characteristic EMG discharges were obtained: spikes and bursts were recorded immediately following the direct manipulation of a dissecting instrument near the cranial nerve, but also during periods when the nerve had not yet been exposed. Bursts could be precisely attributed to contact activity. Three distinct types of trains were identified: A, B, and C trains. Whereas B and C trains are irrelevant with respect to postoperative outcome, the A train--a sinusoidal, symmetrical sequence of high-frequency and low-amplitude signals--was observed in 19 patients and could be well correlated with additional postoperative facial nerve paresis (in 18 patients). It could be demonstrated that the occurrence of A trains is a highly reliable predictor for postoperative facial palsy. Although some degree of functional worsening is to be expected postoperatively, there is a good chance of avoiding major deficits by warning the surgeon early. Continuous EMG monitoring is superior to electrical nerve stimulation or acoustic loudspeaker monitoring alone. The detailed analysis of EMG-waveform characteristics is able to provide more accurate warning criteria during surgery.


Further studies on the use of protein A in immune electron microscopy for detecting virus particles.
The immune electron microscopic technique which involves pre-coating electron microscope grids with protein A before coating them with the specific antiserum, has been found suitable for detecting isometric insect and plant viruses. With the three virus-antibody combinations tested, the optimum antiserum dilution for protein A plus antiserum treatment was found to be 1:100 or less, whereas in the case of grids treated with antiserum alone it ranged from 1:1000 to 1:2000 although the titre of the antisera ranged from 1:512 to 1:4096. The increase in the number of particles on grids treated with protein A plus antiserum over those treated with antiserum alone, at each optimal antiserum dilution, was 25.7-fold (sugarcane mosaic virus), 2.1-fold (tobacco mosaic virus) and 1.6- and 2.4-fold (Erysimum latent virus--two different sap dilutions). Protein A plus antiserum-coated grids can be stored for up to 6 months at 4 degrees C, but not at room temperature or in a desiccator, and still retain about 25% of their activity, sufficient to detect any virus using the electron microscope. Antisera preserved in glycerol can be used successfully for detecting viruses by immune electron microscopy.


The protective role of astroglia in the early period of experimental lead toxicity in the rat.
Although the clinical manifestations of lead (Pb) neurotoxicity are documented, the subcellular mechanisms of its action are still an open question. The purpose of this study was to assess the function of nerve ending particles after acute lead exposure and to investigate whether it exerts a toxic effect on astroglial functions. The studies were performed using the rodent model of acute lead toxicity. Cellular fractions were used in biochemical measurements--synaptosomes and glial plasmalemmal vesicles (GPV). Since a procedure for the isolation of the fraction of astroglial origin has been developed, it becomes possible to investigate lead-astroglia interactions after in vivo exposure. It is of importance because most of the studies concerning lead toxicity were performed using astroglial culture systems. It was found that the uptake of glutamate (Glu) to the synaptosomes was lowered and KCl-dependent release was increased, suggesting the impairment of glutamatergic transmission leading to the elevation of extracellular amino acid concentration. In contrast, glutamate uptake to the GPV fraction was significantly elevated. The activity of the marker enzyme--glutamine synthetase (GS) was also significantly increased in the GPV fraction. The activation of glial functions suggest a regulatory role for these cells in the early period of acute lead toxicity.


FARL-11 (STRIP1/2) is required for sarcomere and sarcoplasmic reticulum organization in C. elegans.
Protein phosphatase 2A (PP2A) functions in a variety of cellular contexts. PP2A can assemble into four different complexes based on the inclusion of different regulatory or targeting subunits. The B''' regulatory subunit "striatin" forms the STRIPAK complex consisting of striatin, a catalytic subunit (PP2AC), striatin-interacting protein 1 (STRIP1), and MOB family member 4 (MOB4). In yeast and Caenorhabditis elegans, STRIP1 is required for formation of the endoplasmic reticulum (ER). Because the sarcoplasmic reticulum (SR) is the highly organized muscle-specific version of ER, we sought to determine the function of the STRIPAK complex in muscle using C. elegans. CASH-1 (striatin) and FARL-11 (STRIP1/2) form a complex in vivo, and each protein is localized to SR. Missense mutations and single amino acid losses in farl-11 and cash-1 each result in similar sarcomere disorganization. A missense mutation in farl-11 shows no detectable FARL-11 protein by immunoblot, disruption of SR organization around M-lines, and altered levels of the SR Ca+2 release channel UNC-68.


Postural responses to a suprapostural visual task among children with and without developmental coordination disorder.
We sought to determine the effects of varying the perceptual demands of a suprapostural visual task on the postural activity of children with developmental coordination disorder (DCD), and typically developing children (TDC). Sixty-four (32 per group) children aged between 9 and 10 years participated. In a within-participants design, each child performed a signal detection task at two levels of difficulty, low (LD) and high difficulty (HD). During performance of the signal detection tasks we recorded positional variability of the head and torso using a magnetic tracking system. We found that task difficulty had a greater effect on task performance among the TDC group than among children with DCD. Overall positional variability was greater the DCD group than in the TDC group. In the TDC group, positional variability was reduced during performance of the HD task, relative to sway during performance of the LD task. In the DCD group, positional variability was greater during performance of the HD task than during performance of the LD task. In children, DCD may reduce the strength of functional integration of postural activity with the demands of suprapostural visual tasks.


A mobile-health system to manage chronic obstructive pulmonary disease patients at home.
Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality in Australia and globally, and leads to a substantial burden on healthcare services. Effective and timely management of patients with COPD has been essential to alleviate COPD exacerbation, improve the quality of life, and consequently reduce the economic burden. To achieve this, a mobile and internet technologies assisted home care model (M-COPD) was developed to assist clinicians to remotely monitor and manage COPD conditions and events. This paper will focus on the technical aspect of M-COPD system by describing its setup and discussing how the M-COPD could address the clinical needs in monitoring and managing COPD conditions of patients at home.


Continuity of care in family practice. Part 3: measurement and evaluation of continuity of care.
Continuity of care is basic to the value system of family practice. Yet it is not often treated as a measurable quality, and the role of "continuity" in improving the "outcome" of health care is infrequently evaluated. "Continuity" can be understood in terms of its elements: continuity of a professional relationship, continuity of information, and the actual delivery of service or care. These elements in turn can be related to outcome by means of a series of assertions or hypotheses which together constitute a "theory" of continuity of care. This paper develops these ideas and reviews existing research which has examined continuity of care.


Arm Abduction Provides a Better Reduction of the Bankart Lesion During Immobilization in External Rotation After an Initial Shoulder Dislocation.
Shoulder dislocation often recurs, especially in the younger population. Immobilization in external rotation, in which a Bankart lesion is displaced in the anterior, medial, and inferior directions, was introduced as a new method of nonoperative treatment, but its clinical efficiency is controversial. In terms of reducing the lesion, it is reasonable to incorporate not only external rotation, which makes the anterior soft tissues tight to push the lesion posteriorly and laterally, but also abduction, which makes the inferior soft tissues tight to push the lesion superiorly. Abducting the arm during immobilization in external rotation will improve the reduction of a Bankart lesion. Controlled laboratory study. There were 37 patients with initial shoulder dislocation enrolled in this study. After reduction, MRI was taken in 4 positions of the shoulder: adduction and internal rotation (Add-IR), adduction and external rotation (Add-ER), 30° of abduction and 30° of external rotation (Abd-30ER), and 30° of abduction and 60° of external rotation (Abd-60ER). On radial slices, the separation, displacement of the labrum, and opening angle of the capsule were measured. Add-ER improved the reduction of the anterior labrum but not the inferior labrum when compared with Add-IR. Both Abd-30ER and Abd-60ER improved the reduction of the inferior labrum as compared with Add-IR. Furthermore, Abd-60ER improved the reduction more than Add-ER. Among the 4 positions tested, Abd-60ER is the best position in terms of reducing the Bankart lesion. Abducting the shoulder during immobilization in external rotation is demonstrated to improve the reduction of the Bankart lesion. Therefore, this position is expected to reduce the recurrence rate after initial dislocation of the shoulder. Future clinical trials are necessary.


The cemented custom femoral stem--a 10 year review.
We report a series of 706 patients (759 hip implants) with an average follow up of 10.5 years (range, 10-11 years) following total hip replacement (THR) using a cemented custom-made femoral stem and a cemented HDP acetabular component. The fate of every implant is known. One hundred and seventy-four patients (23%) were deceased at the time of their 10-year review all died with a functioning THR in situ. Four hundred and sixty-two patients (61%) were subsequently reviewed. One hundred and twenty three patients (16%) were assessed by telephone review, as they were too ill or unwilling to attend. Kaplan-Meier survival analysis (all components) demonstrated a median survival at 10 years of 96.05% or 95% Confidence Intervals (CI) for median survival of (94.41% to 97.22%). Revision surgery occurred in 30 cases (3.9%). Seventeen had full revisions (2.2%) and 13 (1.7%) socket revisions only. Twenty-one out of 30 revisions were for infection or dislocation. There were 2 cases (0.3%) of revision for aseptic loosening of the stem. The 10-year results of the custom femoral titanium stem are encouraging and compare well with other cemented systems.


A synthetic BRET-based optogenetic device for pulsatile transgene expression enabling glucose homeostasis in mice.
Pulsing cellular dynamics in genetic circuits have been shown to provide critical capabilities to cells in stress response, signaling and development. Despite the fascinating discoveries made in the past few years, the mechanisms and functional capabilities of most pulsing systems remain unclear, and one of the critical challenges is the lack of a technology that allows pulsatile regulation of transgene expression both in vitro and in vivo. Here, we describe the development of a synthetic BRET-based transgene expression (LuminON) system based on a luminescent transcription factor, termed luminGAVPO, by fusing NanoLuc luciferase to the light-switchable transcription factor GAVPO. luminGAVPO allows pulsatile and quantitative activation of transgene expression via both chemogenetic and optogenetic approaches in mammalian cells and mice. Both the pulse amplitude and duration of transgene expression are highly tunable via adjustment of the amount of furimazine. We further demonstrated LuminON-mediated blood-glucose homeostasis in type 1 diabetic mice. We believe that the BRET-based LuminON system with the pulsatile dynamics of transgene expression provides a highly sensitive tool for precise manipulation in biological systems that has strong potential for application in diverse basic biological studies and gene- and cell-based precision therapies in the future.


Physician response to parental requests to spread out the recommended vaccine schedule.
To assess among US physicians (1) frequency of requests to spread out recommended vaccination schedule for children <2 years, (2) attitudes regarding such requests, and (3) strategies used and perceived effectiveness in response to such requests. An e-mail and mail survey of a nationally representative sample of pediatricians and family physicians from June 2012 through October 2012. The response rate was 66% (534 of 815). In a typical month, 93% reported some parents of children <2 years requested to spread out vaccines; 21% reported ≥ 10% of parents made this request. Most respondents thought these parents were putting their children at risk for disease (87%) and that it was more painful for children (84%), but if they agreed to requests, it would build trust with families (82%); further, they believed that if they did not agree, families might leave their practice (80%). Forty percent reported this issue had decreased their job satisfaction. Most agreed to spread out vaccines when requested, either often/always (37%) or sometimes (37%); 2% would often/always, 4% would sometimes, and 12% would rarely dismiss families from their practice if they wanted to spread out the primary series. Physicians reported using a variety of strategies in response to requests but did not think they were effective. Virtually all providers encounter requests to spread out vaccines in a typical month and, despite concerns, most are agreeing to do so. Providers are using many strategies in response but think few are effective. Evidence-based interventions to increase timely immunization are needed to guide primary care and public health practice.


The Feedback-related Negativity Reflects the Combination of Instantaneous and Long-term Values of Decision Outcomes.
Hundreds of ERP studies have reported a midfrontal negative-going amplitude shift following negative compared with positive action outcomes. This feedback-related negativity (FRN) effect is typically thought to reflect an early and binary mechanism of action evaluation in the posterior midcingulate cortex. However, in prior research on the FRN effect, the instantaneous value and the long-term value of action outcomes have been perfectly confounded. That is, instantaneously positive outcomes were generally consistent with task goals, whereas instantaneously negative outcomes were inconsistent with task goals. In this study, we disentangled these two outcome aspects in two experiments. Our results reveal an interaction of instantaneous and long-term outcome values. More precisely, our findings strongly suggest that the FRN effect is mainly driven by a reward positivity, which is evoked only by outcomes that possess an instantaneously positive value and also help the organism to reach its long-term goals. These findings add to a recent literature according to which the posterior midcingulate cortex acts as a hierarchical reinforcement learning system and suggest that this system integrates instant and long-term action-outcome values. This, in turn, might be crucial for learning optimal behavioral strategies in a given setting.


Lung cancer screening and smoking abstinence: 2 year follow-up data from the Dutch-Belgian randomised controlled lung cancer screening trial.
BACKGROUND Lung cancer screening may provide a new opportunity for attempts to quit among smokers or might delay smoking cessation, but studies to date failed to provide evidence for this. This study investigated the effect of lung cancer screening on smoking abstinence in male smokers participating in the Dutch-Belgian randomised controlled lung cancer screening trial (NELSON trial). In the NELSON trial, 50- to 75-year-old participants at high risk for developing lung cancer were randomised to either lung cancer screening or no screening. Smoking behaviour was evaluated in two random samples of male smokers in the screen (n=641) and control arm (n=643) before (T0) and 2 years after randomisation (T1). In addition, the data were also analysed by intention-to-treat (ITT) analysis, as recommended in smoking cessation intervention trials, although non-response in screening trials can also be due to reasons other than continued smoking. Almost 17% (16.6%) of the trial participants quit smoking, which is higher than the 3-7% found in the general adult population. However, screening was associated with a lower prolonged abstinence rate (14.5%) compared with no screening (19.1%) (OR 1.40, 95% CI 1.01 to 1.92; p<0.05). No stastistically significant difference was found after performing an ITT analysis. This study showed that all trial participants were inclined to stop smoking more than average, which suggests that screening is a teachable moment to improve smoking behaviour. In those who underwent screening the smoking abstinence rate was significantly lower than for the control group, although the difference was modest. After ITT analysis this difference was no longer observed.


Characterization of the human pH- and PKA-activated ClC-2G(2 alpha) Cl- channel.
A ClC-2G(2 alpha) Cl- channel was identified to be present in human lung and stomach, and a partial cDNA for this Cl- channel was cloned from a human fetal lung library. A full-length expressible human ClC-2G(2 alpha) cDNA was constructed by ligation of mutagenized expressible rabbit ClC-2G(2 alpha) cDNA with the human lung ClC-2G(2 alpha) cDNA, expressed in oocytes, and characterized at the single-channel level. Adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) treatment increased the probability of opening of the channel (Po). After PKA activation, the channel exhibited a linear (r = 0.99) current-voltage curve with a slope conductance of 22.1 +/- 0.8 pS in symmetric 800 mM tetraethylammonium chloride (TEACl; pH 7.4). Under fivefold gradient conditions of TEACl, a reversal potential of +21.5 +/- 2.8 mV was measured demonstrating anion-to-cation discrimination. As previously demonstrated for the rabbit ClC-2G(2 alpha) Cl- channel, the human analog, hClC-2G(2 alpha), was active at pH 7.4 as well as when the pH of the extracellular face of the channel (trans side of the bilayer; pHtrans) was asymmetrically reduced to pH 3.0. The extent of PKA activation was dependent on pHtrans. With PKA treatment, Po increased fourfold with a pHtrans of 7.4 and eightfold with a pHtrans of 3.0. Effects of sequential PKA addition followed by pHtrans reduction on the same channel suggested that the PKA- and pH-dependent increases in channel Po were separable and cumulative. Northern analysis showed ClC-2G(2 alpha) mRNA to be present in human adult and fetal lung and adult stomach, and quantitative reverse transcriptase-polymerase chain reaction showed this channel to be present in the adult human lung and stomach at about one-half the level found in fetal lung. The findings of the present study suggest that the ClC-2G(2 alpha) Cl- channel may play an important role in Cl- transport in the fetal and adult human lung.


Association between hypertension and overweight in adults in Belém, state of Pará (Brazil), 2005.
Hypertension is a major public health issue affecting 20 to 25% of the global population of adults, and 12 to 35 % of Brazilians. To evaluate the association between hypertension and overweight. A cross-sectional study was conducted in 2005 with a probabilistic sampling of the population >18 years of age in Belém, capital of the state of Pará, in the Northern region of Brazil, using the telephone surveillance system for chronic diseases (SIMTEL). The dependent variable was hypertension, the explanatory variable was overweight and the confounding variables were age, level of education and lifestyle characteristics. The variables associated with hypertension were run through the regression logistic model and odds ratios were calculated for each variable. Hypertension affected 16.2% of men and 18.3% of women, and overweight affected 49.2% of men and 34.1% of women. The prevalence of hypertension was directly associated with age and overweight in both genders. Among men, hypertension was associated with intake of vegetables and low intake of beans (similar to kidney- and pinto-type beans); as for women, hypertension was associated with marital status (widow or separated), and inversely to education level. The risk of hypertension increased directly with weight for both genders (p<0.001), and it was 6.33 times higher among obese men and 3.33 among obese women as compared to normal-weight subjects. Overweight was associated with hypertension. However, variables such as age, education, and food consumption interfere in this relationship, creating circumstances favorable to reducing or increasing that risk.


Qualitative Review of National Nutrition Surveillance Systems in the Eastern Mediterranean Region.
The World Food Conference in 1974 emphasized the significance of establishing global nutrition surveillance to monitor and address nutritional challenges effectively. However, many countries, especially in the EMRO region, continue to encounter substantial difficulties in regularly generating disaggregated data on nutrition. The current study aimed to review the existing nutrition surveillance systems in the region and to identify their strengths and weaknesses, as well as the challenges they face in functioning optimally. This study focused on the functional nutrition surveillance systems in eight Arab countries; namely Kuwait, Morocco, Oman, Palestine, Saudi Arabia, Sudan, Syria, and Yemen. The study's analysis involved utilizing primary data collected from both published and unpublished reports. Additionally, a structured checklist was employed to gather information from all countries involved in the study. Furthermore, interviews were conducted with the EMRO offices to gain deeper insights into the challenges, if any, that these nutrition surveillance systems face in functioning optimally. All countries use health facilities as a basic source of data for their nutrition surveillance, some countries triangulate their nutrition surveillance reports with data from other sources of information such as community or school surveys. Identified nutrition surveillance approaches are closely split between those who operate in stable settings and use routine health information systems (Morocco, Saudi Arabia, Oman, and Kuwait) and other countries that operate in fragile settings; for example, Yemen, Syria, Palestine, and Sudan struggle to provide early warning reports for rapid nutritional responses. Nutrition surveillance systems that utilize existing health information systems are the most sustained in the EMRO region. However, by integrating data from multiple sources, such as health facilities, surveys, and population censuses, countries can provide a holistic view of the nutritional situation, enhance their response to any emergency, and can leverage the infrastructure and resources already in place for health data collection and reporting. Collaboration between countries in the region through sharing experiences and success stories is important in order to reach a standardized system that can be implemented in different settings.


Feline oncovirus-associated cell membrane antigen and feline leukemia virus group-specific antigen expression in bone marrow and serum.
Feline retrovirus-induced possible preneoplastic lesions were identified by detection of feline oncovirus-associated cell membrane antigen (FOCMA) in bone marrow (BM) and mesenteric lymph nodes of noninbred, domestic short- or long-hair kittens. Cell-bound FOCMA was detected 1-3 weeks after feline leukemia virus (FeLV) infection and at least 6 months before a tumor was evident. BM FOCMA was detected earlier and reached higher levels at early periods in cats that became persistently viremic. Serum FeLV group-specific antigen (gsa) increased more rapidly and reached a higher level in cats that became persistently viremic, but nonviremic cats still had detectable gsa as late as 7-9 months after FeLV infection, even in the presence of high levels of viral antibody. The presence in nonviremic cats of FeLV gsa in sera and FOCMA in BM and sera suggests that these cats may have a persistent, low-level FeLV infection.


Isolation of vesicular stomatitis virus defective interfering genomes with different amounts of 5'-terminal complementarity.
I isolated at least 30 different vesicular stomatitis virus defective interfering (DI) genomes, distinguished by chain length, by five independent undiluted passages of a repeatedly cloned virus plaque. Labeling of the 3' hydroxyl ends of these DI genomes and RNase digestion studies demonstrated that the ends of these DI genomes were terminally complementary to different extents (approximately 46 to 200 nucleotides). Mapping studies showed that the complementary ends of all of the DI genomes were derived from the 5' ends of the nondefective minus-strand genome. Regardless of the extent of terminal complementarity, all of the DI genomes synthesized the same 46-nucleotide minus-strand leader RNA.


1,3-Dipolar cycloadditions of diazomethane to chiral electron-deficient olefins: the origin of the pi-facial diastereoselection
The stereochemical outcome of diazomethane cycloadditions to several chiral electron-deficient olefins has been investigated in order to establish the origin of the pi-facial diastereoselection. Nitro olefins, vinyl sulfones, enoates, and 2-amino enoates have been used for such a purpose. These substrates have been prepared from D-glyceraldehyde acetonide through Wittig-type condensations and present an alkoxy substituent, provided by the bulky dioxolane ring, attached to the stereogenic allylic carbon. Syn-adducts have been obtained in all cases as the major isomers, independently of the Z/E stereochemistry of the double bond and the number and the nature of the substituents, the chirality of the asymmetric allylic carbon being the only thing responsible for the diastereoselection. Theoretical calculations show that steric hindrance due to the bulky dioxolane group is the main factor governing the preference for the syn-attack of diazomethane to the olefinic double bond.


Relaxin regulates vascular wall remodeling and passive mechanical properties in mice.
Administration of recombinant human relaxin (rhRLX) to conscious rats increases global arterial compliance, and small renal arteries (SRA) isolated from these rats demonstrate increased passive compliance. Here we characterize relaxin-induced vascular remodeling and examine its functional relevance. SRA and external iliac arteries (EIA) were examined in rhRLX-treated (1.0 μg/h for 5 days) and relaxin knockout mice. Arterial geometric remodeling and compositional remodeling were quantified using immunohistochemical and biochemical techniques. Vascular mechanical properties were quantified using an ex vivo preparation wherein pressure-diameter data were obtained at various axial lengths. Compared with vehicle-treated mice, SRA from rhRLX-treated mice showed outward geometric remodeling (increased unstressed wall area and wall-to-lumen area ratio), increased smooth muscle cell (SMC) density, reduction in collagen-to-total protein ratio, and unchanged elastin-to-tissue dry weight ratio. Compared with wild-type mice, relaxin knockout mice exhibited the opposite pattern: decreased unstressed wall area and wall-to-lumen area ratio, decreased SMC density, and increased collagen-to-total protein ratio. Although tissue biaxial strain energy of SRA was not different between rhRLX- and vehicle-treated groups at low-to-physiological circumferential and axial strains, it was lower for the rhRLX-treated group at the highest circumferential strain. In contrast to SRA, relaxin administration was not associated with any vascular remodeling or changes in passive mechanics of EIA. Thus relaxin induces both geometric and compositional remodeling in vessel-specific manner. Relaxin-induced geometric remodeling of SRA is responsible for the increase in passive compliance under low-to-physiological levels of circumferential and axial strains, and compositional remodeling becomes functionally relevant only under high circumferential strain.


Circular dichroism and magnetic circular dichroism studies of the biferrous site of the class Ib ribonucleotide reductase from Bacillus cereus: comparison to the class Ia enzymes.
The rate limiting step in DNA biosynthesis is the reduction of ribonucleotides to form the corresponding deoxyribonucleotides. This reaction is catalyzed by ribonucleotide reductases (RNRs) and is an attractive target against rapidly proliferating pathogens. Class I RNRs are binuclear non-heme iron enzymes and can be further divided into subclasses. Class Ia is found in many organisms, including humans, while class Ib has only been found in bacteria, notably some pathogens. Both Bacillus anthracis and Bacillus cereus encode class Ib RNRs with over 98% sequence identity. The geometric and electronic structure of the B. cereus diiron containing subunit (R2F) has been characterized by a combination of circular dichroism, magnetic circular dichroism (MCD) and variable temperature variable field MCD and is compared to class Ia RNRs. While crystallography has given several possible descriptions for the class Ib RNR biferrous site, the spectroscopically defined active site contains a 4-coordinate and a 5-coordinate Fe(II), weakly antiferromagnetically coupled via mu-1,3-carboxylate bridges. Class Ia biferrous sites are also antiferromagnetically coupled 4-coordinate and 5-coordinate Fe(II), however quantitatively differ from class Ib in bridging carboxylate conformation and tyrosine radical positioning relative to the diiron site. Additionally, the iron binding affinity in B. cereus RNR R2F is greater than class Ia RNR and provides the pathogen with a competitive advantage relative to host in physiological, iron-limited environments. These structural differences have potential for the development of selective drugs.


Evaluation of Fundamental Forensic Knowledge and Perceived Ability in Emergency Nurse Practitioner Education via Forensic Simulation.
The need for trauma care and forensic services is among the top five reasons for seeking healthcare in the United States. Critical aspects of caring for a forensic patient include early recognition of the need for implementing forensic approaches to care: assessment, evidence collection and preservation, and forensic documentation. The intent of this study was to examine fundamental forensic knowledge and perceived ability of graduate-level emergency nurse practitioner students. The study was designed to assess fundamental forensic knowledge of graduate-level emergency nurse practitioners using a pretest-and-posttest prospective design utilizing simulation. Students showed an increase in their knowledge of forensic nursing concepts from pretest to posttest (t(39) = 9.63, p < 0.001). In addition, there was an increase in students' perceived ability (confidence) to recognize the forensic aspects of patient care. Two unexpected findings were revealed during debriefing. Although the students were interested in gaining forensic knowledge, they felt it was more important to know when to refer a patient rather than to gain the requisite knowledge to perform forensic functions on their own. Furthermore, students developed an awareness of how their previous clinical experiences influenced their care. Findings from this study will inform further development of graduate-level nursing education to include forensic and multidisciplinary simulation exercises.


Pyridyl-Isonicotinoyl Hydrazone-Bridged Zn(II) Coordination Framework with Thiophenedicarboxylato Link: Structure, Biological Activity, and Electrical Conductivity.
Multidimensional applicability of functional materials is one of the focal attractions in today's scientific research. Highly stable and crystalline coordination polymers served as one of the active members in the club of multifunctional materials. Toward this concept, a 3-dimensional (3D) coordination framework, {[Zn2(tdc)2(pcih)2]n} (1) (tdc2-, 2,5-thiophene dicarboxylate; pcih, pyridine-4-carboxaldehyde isonicotinoyl hydrazine), is designed and has been structurally well characterized by single crystal X-ray crystallography. One of the carboxylate groups of tdc2- chelates to Zn(II), while the other carboxylato group (-COO) acts as bridging-O to neighboring Zn(II); the pcih serves as pyridyl-N bridging motif to two Zn(II) centers. The optical band gap, 3.83 eV (Tauc's plot), implies probable semiconducting ability of the material. Interestingly, the device fabricated using compound 1 measures the electrical conductivity, 2.21 × 10-5 S cm-1, and series resistance (Rs), 807 Ω, at the dark phase, which are improved significantly to 6.36 × 10-5 S cm-1 and 460 Ω, respectively, under illumination conditions. Isoniazid, used to synthesize pcih and hence the Zn(II) compound 1, is a medicine; so, the medicinal efficiency of 1 is checked by measuring the anticancer activity against MDA-MB-231, HeLa, HCT-116, and HepG2 cells. It is observed that drug efficacy is highest on MDA-MB-231 cells (IC50: 19.43 ± 1.36 μM) than other cancer cells [IC50: 24.43 ± 2.02 μM (HeLa), 26.06 ± 3.48 μM (HCT-116), and 44.28 ± 3.04 μM (HepG2)]. Therefore, the material has significant contribution in the area of energy and health toward the sustainable development goals.


MIBI-TOF: A multiplexed imaging platform relates cellular phenotypes and tissue structure.
Understanding tissue structure and function requires tools that quantify the expression of multiple proteins while preserving spatial information. Here, we describe MIBI-TOF (multiplexed ion beam imaging by time of flight), an instrument that uses bright ion sources and orthogonal time-of-flight mass spectrometry to image metal-tagged antibodies at subcellular resolution in clinical tissue sections. We demonstrate quantitative, full periodic table coverage across a five-log dynamic range, imaging 36 labeled antibodies simultaneously with histochemical stains and endogenous elements. We image fields of view up to 800 μm × 800 μm at resolutions down to 260 nm with sensitivities approaching single-molecule detection. We leverage these properties to interrogate intrapatient heterogeneity in tumor organization in triple-negative breast cancer, revealing regional variability in tumor cell phenotypes in contrast to a structured immune response. Given its versatility and sample back-compatibility, MIBI-TOF is positioned to leverage existing annotated, archival tissue cohorts to explore emerging questions in cancer, immunology, and neurobiology.


The accessibility of protein-bound dinitrophenyl groups to univalent fragments of anti-dinitrophenyl antibody.
A series of N-(N-dinitrophenylaminoalkyl)maleimides were sythesized with alkyl-chain lengths of two, four and six carbon atoms. When these compounds reacted with the thiol group of mercaptalbumin, the tryptophan fluorescence of the protein was quenched. This change in fluorescence was used to determine the rate of reaction of the Dnp (dinitrophenyl)-maleimides with mercaptalbumin. The second-order rate constants were similar to those observed in reactions between low-molecular-weight thiol compounds and maleimides. When N-(N-Dnp-aminoalkyl)succinimidomercaptalbumins were added to univalent fragments of anti-Dnp antibody the antibody fluorescence was quenched. Florescence-quenching titrations showed that the protein-bound Dnp groups were fully available to the antibody even when the alkyl chain was short. The apparent dissociation constants were significantly greater than that of the interaction between anti-Dnp antibody and the free hapten, 6-(N-Dnp)-aminohexanoate. The antibody fluorescence was quenched efficienty by [dnp-Lys41]ribonuclease A, also with an increased dissociation constant. It could be concluded from the increase in dissociation constant that the Dnp group spent no more than 0.1% of its time in the dissociated state, available to antibody. The second-order rate constants for the association between the Dnp-mercaptablumins and the antibody were determined and were similar in magnitude to those observed in other interactions between protein and anti-protein antibody.


Experimental genital infection of male guinea pigs with the agent of guinea pig inclusion conjunctivitis and transmission to females.
Male guinea pigs were inoculated intraurethrally with the agent of guinea pig inclusion conjunctivitis (Gp-ic). Cytoplasmic inclusions were found in superficial epithelial cells of the urethra in smears and stained sections. Gp-ic antigen(s) was detected by immunofluorescent staining of sections. There was no marked urethral exudate, but many animals developed bullous lesions on the glans and the body of the penis and a severe inflammatory lesion of the hind leg. All males demonstrated an antibody response and most of them showed a positive skin test reaction. Venereal transmission to females of Gp-ic infection was shown to occur as determined by detection of inclusions in vaginal smears, antibody response, and positive skin tests.


Use of the lysozyme test in the diagnosis of kerato-conjuctivitis sicca in dogs and cats.
Comparative studies of the lysozyme test (LT) and the Schirmer tear test (STT) revealed that the LT was not reliable in the diagnosis of kerato-conjunctivitis sicca (KCS) in dogs and cats. This is in contrast to its successful use in human patients. No M. lysodeikticus lysating substrates were detectable in the tear fluid of the normal cat.


Association of Abdominal Aortic Calcification with Peripheral Quantitative Computed Tomography Bone Measures in Older Women: The Perth Longitudinal Study of Ageing Women.
We have previously shown that abdominal aortic calcification (AAC), a marker of advanced atherosclerotic disease, is weakly associated with reduced hip areal bone mineral density (aBMD). To better understand the vascular-bone health relationship, we explored this association with other key determinants of whole-bone strength and fracture risk at peripheral skeletal sites. This study examined associations of AAC with peripheral quantitative computed tomography (pQCT)-assessed total, cortical and trabecular volumetric BMD (vBMD), bone structure and strength of the radius and tibia among 648 community-dwelling older women (mean ± SD age 79.7 ± 2.5 years). We assessed associations between cross-sectional (2003) and longitudinal (progression from 1998/1999-2003) AAC assessed on lateral dual-energy X-ray absorptiometry (DXA) images with cross-sectional (2003) and longitudinal (change from 2003 to 2005) pQCT bone measures at the 4% radius and tibia, and 15% radius. Partial Spearman correlations (adjusted for age, BMI, calcium treatment) revealed no cross-sectional associations between AAC and any pQCT bone measures. AAC progression was not associated with any bone measure after adjusting for multiple comparisons, despite trends for inverse correlations with total bone area at the 4% radius (rs = - 0.088, p = 0.044), 4% tibia (rs = - 0.085, p = 0.052) and 15% radius (rs = - 0.101, p = 0.059). Neither AAC in 2003 nor AAC progression were associated with subsequent 2-year pQCT bone changes. ANCOVA showed no differences in bone measures between women with and without AAC or AAC progression, nor across categories of AAC extent. Collectively, these finding suggest that peripheral bone density and structure, or its changes with age, are not associated with central vascular calcification in older women.


Seasonality in molecular and cytometric diversity of marine bacterioplankton: the re-shuffling of bacterial taxa by vertical mixing.
The 'cytometric diversity' of phytoplankton communities has been studied based on single-cell properties, but the applicability of this method to characterize bacterioplankton has been unexplored. Here, we analysed seasonal changes in cytometric diversity of marine bacterioplankton along a decadal time-series at three coastal stations in the Southern Bay of Biscay. Shannon-Weaver diversity estimates and Bray-Curtis similarities obtained by cytometric and molecular (16S rRNA tag sequencing) methods were significantly correlated in samples from a 3.5 year monthly time-series. Both methods showed a consistent cyclical pattern in the diversity of surface bacterial communities with maximal values in winter. The analysis of the highly resolved flow cytometry time-series across the vertical profile showed that water column mixing was a key factor explaining the seasonal changes in bacterial composition and the winter increase in bacterial diversity in coastal surface waters. Due to its low cost and short processing time as compared with genetic methods, the cytometric diversity approach represents a useful complementary tool in the macroecology of aquatic microbes.


Hemorrhagic cystitis associated with adenovirus infection in bone marrow transplantation.
A retrospective study of bone marrow transplant recipients shedding adenovirus type 11 in the urine was carried out to determine the association between viral shedding and hemorrhagic cystitis in this population. Weekly urine virology surveillance cultures were obtained during the first 100 days following transplantation. Adenovirus type 11 was cultured from five of 502 bone marrow transplant recipients from 1977 through 1984. In four of these five patients there was associated hemorrhagic cystitis. This contrasts with an overall incidence of hemorrhagic cystitis of 20% in this bone marrow transplant population. A case of hemorrhagic cystitis occurred in a patient following bone marrow transplantation. Recognition of a viral origin of hemorrhagic cystitis may explain the occurrence of late hemorrhagic cystitis in patients despite interventions designed to prevent cyclophosphamide-induced hemorrhagic cystitis. Hemorrhagic cystitis may be the presenting sign of a lethal adenoviral infection.


An uncommon presentation of WAGR syndrome with persistent fetal vasculature.
Aniridia is an autosomal dominant congenital malformation associated with mutations in the PAX6 gene. It can be associated with deletion in the contiguous WT1 gene, leading to WAGR syndrome, characterized by Wilm tumor, aniridia, genitourinary anomalies, and mental retardation. Persistent fetal vasculature is a developmental malformation caused by incomplete regression of hyaloid vasculature. Most cases of persistent fetal vasculature occur sporadically; however, some inherited forms are described. We report a case of genetically confirmed WAGR associated with congenital cataract and persistent fetal vasculature.


Ni2Mn-layered double oxide electrodes in organic electrolyte based supercapacitors.
The development of future mobility (e.g. electric vehicles) requires supercapacitors with high voltage and high energy density. Conventional active carbon-based supercapacitors have almost reached their limit of energy density which is still far below the desired performance. Advanced materials, particularly metal hydroxides/oxides with tailored structure are promising supercapacitor electrodes to push the limit of energy density. To date, research has largely focused on evaluation of these materials in aqueous electrolyte, while this may enable high specific capacitance, it results in low working voltage window and poor cycle stability. Herein, we report the development of Ni2Mn-layered double oxides (Ni2Mn-LDOs) as mixed metal oxide-based supercapacitor electrodes for use in an organic electrolyte. Ni2Mn-LDO obtained by calcination of [Ni0.66Mn0.33(OH)2](CO3)0.175·nH2O at 400 °C produced the best performing Ni2Mn-LDOs with high working voltage of 2.5 V and a specific capacitance of 44 F g-1 (at 1 A g-1). We believe the performance of the Ni2Mn-LDOs is related to its unique porous structure, high surface area and the homogeneous mixed metal oxide network. Ni2Mn-LDO outperforms both the single metal oxides (NiO, MnO2) and the equivalent physical mixture of the two oxides. We propose this performance boost arises from synergy between NiO and MnO x due to a more effective homogeneous network of NiO/MnO x domains in the Ni2Mn-LDO. This work clearly shows the advantage of an LDO over the single component metal oxides as well as the physical mixture of mixed metal oxides and highlights the possibilities of development of further mixed metal oxides-based supercapacitors in organic electrolyte using LDH precursors.


Alterations in plasma lipids, lipoproteins and high density lipoprotein subfractions in peripheral arterial disease.
The concentrations of the major lipoprotein classes and of high density lipoprotein (HDL) subfractions in 63 male patients with arteriosclerosis of the lower limbs (claudication) were determined and compared with values from 63 healthy controls. The patients with peripheral arterial disease (PAD) had reduced levels of total HDL-cholesterol and HDL2b of large particle size, increased levels of small HDL3c particles and a high ratio of total plasma-cholesterol to HDL-cholesterol (coronary risk factor). The PAD patients, however, had lower levels of low density lipoprotein (LDL)-cholesterol but higher concentrations of very low density lipoprotein (VLDL)-cholesterol and plasma triglyceride than healthy subjects. This study therefore suggests that in PAD, the protective effect of HDL may be more important than the atherogenic effect of LDL. It further suggests that while HDL-cholesterol HDL2b and the ratio of total plasma-cholesterol to HDL-cholesterol may provide valid indices for identifying individuals at risk of PAD, other factors, such as LDL and total cholesterol, may not provide such an appropriate risk indicator.


TLR signaling at the intestinal epithelial interface.
The intestinal epithelium provides a critical interface between lumenal bacteria and the mucosal immune system. Whereas normal commensal flora do not trigger acute inflammation, pathogenic bacteria trigger a potent inflammatory response. Our studies emanate from the hypothesis that the intestinal epithelium is normally hyporesponsive to commensal pathogen-associated molecular patterns (PAMPs) such as LPS. Our data demonstrate that normal human colonic epithelial cells and lamina propria cells express low levels of TLR4 and its co-receptor MD-2. This expression pattern is mirrored by intestinal epithelial cell (IEC) lines. Co-expression of TLR4 and MD-2 is necessary and sufficient for LPS responsiveness in IEC. Moreover, LPS sensing occurs along the basolateral membrane of polarized IEC in culture. Expression of MD-2 is regulated by IFN-gamma. Cloning of the MD-2 promoter demonstrates that promoter activity is increased by IFN-gamma and blocked by the STAT inhibitor SOCS3. We conclude from our studies that the intestinal epithelium down-regulates expression of TLR4 and MD-2 and is LPS unresponsive. The Th1 cytokine IFN-gamma up-regulates expression of MD-2 in a STAT-dependent fashion. The results of our studies have important implications for understanding human inflammatory bowel diseases.


Bias in psychiatric case-control studies: literature survey.
Case-control studies are vulnerable to selection and information biases which may generate misleading findings. To assess the quality of methodological reporting of case-control studies published in general psychiatric journals. All the case-control studies published over a 2-year period in the six general psychiatric journals with impact factors of more than 3 were assessed by a group of psychiatrists with training in epidemiology using a structured assessment devised for the purpose. The measured study quality was compared across type of exposure and journal. The reporting of methods in the 408 identified papers was generally poor, with basic information about recruitment of participants often absent. Reduction of selection bias was described best in the "pencil and paper" studies and worst in the genetic studies. Neuroimaging studies reported the most safeguards against information bias. Measurement of exposure was reported least well in studies determining the exposure with a biological test. Poor reporting of recruitment strategies threatens the validity of reported results and reduces the generalisability of studies.


Reference change value and measurement uncertainty in the evaluation of tumor markers.
The use of measurement uncertainty among clinical laboratories becomes widespread. Measurement uncertainty can be reported with the result, as well as be used in certain reference change value (RCV) calculation equations. RCV is especially recommended for use in tests with a low individuality index. In our study, we calculated the measurement uncertainty of AFP, CA 125, CA 15-3, CA 19-9, CEA tumor markers with the ISO TS 20914:2019. We compared results with limits. Two Beckman Coulter DXI-800 (Minnesota, USA) autoanalysers' results were used. We calculated the RCV values using the classical Fraser method, logarithmic Lund Method, and Clinical Laboratory Standards Institute (CLSI) method as Minimal Difference (MD). We found the same permissible measurement uncertainty limit as 15.97% for all five tumor markers. The highest RCV value was found as 90% upstream for AFP test with Lund logarithmic approach, the lowest RCV value was found as 12% for CEA with MD, all other RCV results were between these two values. We do not recommend the use of MD, as values for Biological variation are not used in the MD approach. We also recommend using the logarithmic approach, although it gives higher results. There are also clinical studies on the significance of tumor markers in a follow-up that show different results. These differences may be because the studies are conducted with different systems. Therefore, each laboratory needs to calculate its own RCV values. We also recommend informing the clinicians about the tests with high measurement uncertainty.


[Comparative study of organ cultures of human, rat, mouse and chick embryonic livers].
The organ cultures of the human, rat, mouse and chick embryonic liver were studied comparatively. Three developmental stages were established upon the long-term cultivation of the explants: adaptation of tissue, optimal growth, and terminal stage resulting in the culture death. The species and strain differences in the morphology and survival of the cultures were revealed. Foci of growth of small basophilic epithelial-like cells, differing from usual embryonic hepatocytes by morphology, growth pattern, survival and proliferative activity, were found in the organ cultures. The results obtained are interesting for the understanding of histogenesis of the normal liver and of mechanisms of hepatocarcinogenesis.


Antibiotic-disc tests for rapid identification of non-sporing anaerobes.
The sensitivity patterns to a number of antibiotic-impregnated discs of 126 strains of Gram-negative anaerobes and 36 strains of Gram-positive non-sporing anaerobes from various sources have been examined. The sensitivity patterns shown by Bacteroids fragilis and Bacteroides melaninogenicus were useful for the rapid identification of these organisms. Consistent and useful sensitivity patterns were not shown by the Gram-positive anaerobes.


Volitional Yoga Breathing Influences Attention and Anxiety: An Exploratory Randomized Crossover Study.
Previous studies assessed yoga breathing practices individually. This exploratory, randomized crossover study assessed attention and anxiety following four yoga breathing practices, breath awareness, and quiet seated rest. Thirty-eight male volunteers between 20 and 37 years (group mean age ± SD; 24.08 ± 4.01 years) were assessed in six sessions in random order (www.randomizer.org) on separate days. The sessions were: (i) alternate nostril yoga breathing, (ii) bellows yoga breathing, (iii) bumblebee yoga breathing, (iv) high-frequency yoga breathing, (v) breath awareness, and (vi) quiet seated rest. The sessions were for 18 min each. Six letter cancellation test (SLCT) and Spielberger's State Trait Anxiety Inventory-state (STAI-s) were administered pre and post each session. Data analysis used general linear mixed model analysis, with fixed effect of states (pre and post) and sessions. A significant main effect of states was observed on total attempted (F1,407 = 5.374, p = 0.021) and net attempted scores (F1,407 = 6.178, p = 0.013) of the SLCT, with a significant increase in scores following high-frequency yoga breathing (padj = 0.031 for total attempted scores; padj = 0.029 for net attempted scores). Also, a significant main effect of states on STAI-s scores was observed (F1,407 = 33.979, p < 0.001), with a significant decrease in scores following alternate nostril yoga breathing (padj = 0.001), bellows yoga breathing (padj = 0.008), bumblebee yoga breathing (padj = 0.002), and high-frequency yoga breathing (padj = 0.042) compared to the corresponding pre state. There was a significant main effect of sessions (F5,407 = 3.043, p = 0.010) on STAI-s scores, with scores post alternate nostril yoga breathing significantly lower than post breath awareness (padj = 0.037). Following high-frequency yoga breathing sustained attention was better than before while state anxiety decreased in post-pre comparisons of alternate nostril yoga breathing, bellows yoga breathing, bumblebee yoga breathing, and high-frequency yoga breathing. The differences between breathing practices may be due to differences in degree of volitional regulation of breathing and in the breath patterns modified volitionally. The generalizability of the findings was limited by including an all male, yoga experienced sample. Future research should include participants of both genders and could include different levels of yoga experience, with assessments including objective measures of attention and anxiety.


Lignans from the roots of Urtica dioica and their metabolites bind to human sex hormone binding globulin (SHBG).
Polar extracts of the stinging nettle (Urtica dioica L.) roots contain the ligans (+)-neoolivil, (-)-secoisolariciresinol, dehydrodiconiferyl alcohol, isolariciresinol, pinoresinol, and 3,4-divanillyltetrahydrofuran. These compounds were either isolated from Urtica roots, or obtained semisynthetically. Their affinity to human sex hormone binding globulin (SHBG) was tested in an in vitro assay. In addition, the main intestinal transformation products of plant lignans in humans, enterodiol and enterolactone, together with enterofuran were checked for their activity. All lignans except (-)-pinoresinol developed a binding affinity to SHBG in the in vitro assay. The affinity of (-)-3,4-divanillyltetrahydrofuran was outstandingly high. These findings are discussed with respect to potential beneficial effects of plant lignans on benign prostatic hyperplasia (BPH).


NRF2 activates growth factor genes and downstream AKT signaling to induce mouse and human hepatomegaly.
Hepatomegaly can be triggered by insulin and insulin-unrelated etiologies. Insulin acts via AKT, but how other challenges cause hepatomegaly is unknown. Since many hepatomegaly-inducing toxicants and stressors activate NRF2, we examined the effect of NRF2 activation on liver size and metabolism using a conditional allele encoding a constitutively active NRF2 variant to generate Nrf2Act-hep mice in which NRF2 is selectively activated in hepatocytes. We also used adenoviruses encoding variants of the autophagy adaptor p62/SQSTM1, which activates liver NRF2, as well as liver-specific ATG7-deficient mice (Atg7Δhep) and liver specimens from patients with hepatic sinusoidal obstruction syndrome (HSOS) and autoimmune hepatitis (AIH). RNA sequencing and cell signaling analyses were used to determine cellular consequences of NRF2 activation and diverse histological analyses were used to study effects of the different manipulations on liver and systemic pathophysiology. Hepatocyte-specific NRF2 activation, due to p62 accumulation or inhibition of KEAP1 binding, led to hepatomegaly associated with enhanced glycogenosis, steatosis and G2/M cell cycle arrest, fostering hyperplasia without cell division. Surprisingly, all manipulations that led to NRF2 activation also activated AKT, whose inhibition blocked NRF2-induced hepatomegaly and glycogenosis, but not NRF2-dependent antioxidant gene induction. AKT activation was linked to NRF2-mediated transcriptional induction of PDGF and EGF receptor ligands that signaled through their cognate receptors in an autocrine manner. Insulin and insulin-like growth factors were not involved. The NRF2-AKT signaling axis was also activated in human HSOS- and AIH-related hepatomegaly. NRF2, a transcription factor readily activated by xenobiotics, oxidative stress and autophagy disruptors, may be a common mediator of hepatomegaly; its effects on hepatic metabolism can be reversed by AKT/tyrosine kinase inhibitors. Hepatomegaly can be triggered by numerous etiological factors, including infections, liver cancer, metabolic disturbances, toxicant exposure, as well as alcohol abuse or drug-induced hepatitis. This study identified the oxidative stress response transcription factor NRF2 as a common mediator of hepatomegaly. NRF2 activation results in elevated expression of several growth factors. These growth factors are made by hepatocytes and activate their receptors in an autocrine fashion to stimulate the accumulation of glycogen and lipids that lead to hepatocyte and liver enlargement. The protein kinase AKT plays a key role in this process and its inhibition leads to reversal of hepatomegaly.


Rapid acidification of endocytic vesicles containing asialoglycoprotein in cells of a human hepatoma line.
Acidification of endocytic vesicles has been implicated as a necessary step in various processes including receptor recycling, virus penetration, and the entry of diphtheria toxin into cells. However, there have been few accurate pH measurements in morphologically and biochemically defined endocytic compartments. In this paper, we show that prelysosomal endocytic vesicles in HepG2 human hepatoma cells have an internal pH of approximately 5.4. (We previously reported that similar vesicles in mouse fibroblasts have a pH of 5.0.) The pH values were obtained from the fluorescence excitation profile after internalization of fluorescein labeled asialo-orosomucoid (ASOR). To make fluorescence measurements against the high autofluorescence background, we developed digital image analysis methods for estimating the pH within individual endocytic vesicles or lysosomes. Ultrastructural localization with colloidal gold ASOR demonstrated that the pH measurements were made when ligand was in tubulovesicular structures lacking acid phosphatase activity. Biochemical studies with 125I-ASOR demonstrated that acidification precedes degradation by more than 30 min at 37 degrees C. At 23 degrees C ligand degradation ceases almost entirely, but endocytic vesicle acidification and receptor recycling continue. These results demonstrate that acidification of endocytic vesicles, which causes ligand dissociation, occurs without fusion of endocytic vesicles with lysosomes. Methylamine and monensin raise the pH of endocytic vesicles and cause a ligand-independent loss of receptors. The effects on endocytic vesicle pH are rapidly reversible upon removal of the perturbant, but the effects on cell surface receptors are slowly reversible with methylamine and essentially irreversible with monensin. This suggests that monensin can block receptor recycling at a highly sensitive step beyond the acidification of endocytic vesicles. Taken together with other direct and indirect estimates of endocytic vesicle pH, these studies indicate that endocytic vesicles in many cell types rapidly acidify below pH 5.5, a pH sufficiently acidic to allow receptor-ligand dissociation and the penetration of some toxin chains and enveloped virus nucleocapsids into the cytoplasm.


[Importance of ocular biopsies in the etiologic diagnosis of uveitis].
In many uveitis cases a biopsy of ocular tissues can enable an exact diagnosis to be established, unnecessary additional examinations to be avoided, and an appropriate therapeutic regimen to be selected. In general, follicle biopsy is performed where sarcoidosis is suspected, keratocentesis in viral uveitis and toxoplasmosis, and vitreous biopsy in tentatively diagnosed primary intraocular lymphoma (reticulosarcoma) and bacterial or mycotic endophthalmitis.


Derivation and validation of a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality in 20 countries.
Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings. We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool. A total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84). The PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality.


Hyperkalemia and hyperglycemic increments in plasma potassium in diabetes mellitus.
The frequency of persistent or intermittent hyperkalemia in patients with diabetes is unknown. In 405 predominantly insulin-treated patients, major hyperkalemia was not common (< 5.0 mEq/L in 2.5%). In ten insulin-treated patients sampled hourly from 8 AM through 8 PM, major intermittent hyperkalemia was not detected (< 4.8 mEq/L in all samples). However, mean plasma potassium values paralleled mean glucose values; these variables were significantly correlated in seven of ten patients. In contrast, there were no relationships between plasma potassium and plasma free insulin, glucagon, epinephrine, or norepinephrine values. We conclude that (1) hyperkalemia--fasting or intermittent--does not occur commonly in patients with diabetes, and (2) hyperglycemia, but not insulin or epinephrine lack or glucagon excess, appears to be a direct determinant of plasma potassium but is not a sufficiently potent determinant to commonly produce clinically important hyperkalemia in insulin-treated diabetic patients.


[Long-term study of patients with coeliac disease in childhood and adolescence: latent and transient coeliac disease].
Coeliac disease (CD) is known as a lifelong condition of gluten intolerance. In case of some patients, the time after which gluten exposition leads to damage of the small intestinal mucosa may be very long. In addition to the florid form of CD, there are also silent (atypical mono- and oligosymptomatic with typical damage of the small intestinal mucosa) and latent forms (often asymptomatic without clear mucosal changes, antibody titres often normal). Occasionally the development of gluten tolerance is postulated (transient CD). We investigated 47 subjects diagnosed in childhood definitely as CD patients. In the age of 16.3 +/- 4.8 years, the patients started a gluten containing diet. After 6 to 9 months of gluten containing diet a small intestinal biopsy was performed in all patients. Surprisingly we found 11 patients with normal small intestinal mucosa (group 1). The other 36 patients showed a flattened mucosa as expected (group 2). The further development of group 1 was followed. In 9 patients a further biopsy was performed after more than 2 (at maximum after 8.1) years of gluten containing diet. In all patients the morphology of the mucosa was normal. In 7 of 11 cases normal numbers of intraepithelial lymphocytes were counted. Only in two patients raised titres of gliadin and endomysium antibodies were found after 4.5 and 15 years of gluten containing diet. In the other 9 patients no increase in antibody titers was found up to 10.3 years. However, in group 1, mucosal lactase activity was decreased as was also the case for group 2. A high number of adolescent coeliac patients does not respond or responds only minimally to reintroduction of gluten into the diet over a period longer than two years. These patients should regularly be further controlled serologically.


Enhanced Bacterial Wilt Resistance in Potato Through Expression of Arabidopsis EFR and Introgression of Quantitative Resistance from Solanum commersonii.
Bacterial wilt (BW) caused by Ralstonia solanacearum is responsible for substantial losses in cultivated potato (Solanum tuberosum) crops worldwide. Resistance genes have been identified in wild species; however, introduction of these through classical breeding has achieved only partial resistance, which has been linked to poor agronomic performance. The Arabidopsis thaliana (At) pattern recognition receptor elongation factor-Tu (EF-Tu) receptor (EFR) recognizes the bacterial pathogen-associated molecular pattern EF-Tu (and its derived peptide elf18) to confer anti-bacterial immunity. Previous work has shown that transfer of AtEFR into tomato confers increased resistance to R. solanacearum. Here, we evaluated whether the transgenic expression of AtEFR would similarly increase BW resistance in a commercial potato line (INIA Iporá), as well as in a breeding potato line (09509.6) in which quantitative resistance has been introgressed from the wild potato relative Solanum commersonii. Resistance to R. solanacearum was evaluated by damaged root inoculation under controlled conditions. Both INIA Iporá and 09509.6 potato lines expressing AtEFR showed greater resistance to R. solanacearum, with no detectable bacteria in tubers evaluated by multiplex-PCR and plate counting. Notably, AtEFR expression and the introgression of quantitative resistance from S. commersonii had a significant additive effect in 09509.6-AtEFR lines. These results show that the combination of heterologous expression of AtEFR with quantitative resistance introgressed from wild relatives is a promising strategy to develop BW resistance in potato.


Effects of exercise training on insulin sensitivity in adolescents with type I diabetes.
We investigated the influence of a program of exercise training consisting of three weekly sessions, each 45 min long, for 12 wk, on indices of physical fitness, glycemic control, and insulin sensitivity in nine adolescents with type I diabetes; six age-matched adolescents with diabetes of equivalent duration served as nonexercised controls. All subjects were instructed not to change dialy insulin dose or caloric intake. In the exercised group, maximal oxygen uptake during graded cycle ergometry to volitional exhaustion increased by 9 +/- 2.7% (P less than 0.01) and lean body mass increased by 4 +/- 1.8% (P less than 0.05). Insulin sensitivity, assessed via the euglycemic clamp technique at insulin infusion rates of 100 mU/M2/min, showed an increase of insulin-mediated glucose disposal from 274 +/- 33 to 338 +/- 28 mg/M2/min, representing an increase in insulin sensitivity of 23 +/- 5% (P less than 0.01). None of these indices changed in the control group. Despite increased insulin sensitivity, glycohemoglobin levels remained at 12 +/- 1% before and after the 12 wk of exercise training, indicating no improvement in overall glycemic control. No increase in hypoglycemic reactions was reported in either group. We conclude that exercise training may be a valuable adjunct in managing type I diabetes providing there is concomitant attention to diet and insulin. Exercise training alone, however, does not improve glycemic control, although it improves physical fitness and insulin sensitivity.


A nurse practitioner-led urgent care center: meeting the needs of the patient with cancer.
Providing comprehensive care for patients with cancer is complex with regard to severe treatment-related side effects. Hundreds of thousands of patients with cancer visit the emergency department (ED) each year, and more than half report multiple visits. In the United States, few of the National Cancer Institute-designated cancer centers have an ED specifically for patients with cancer. EDs often are an overcrowded and expensive way in which to care for the urgent needs of patients with cancer. In addition, a looming shortage exists for both primary care providers and oncologists who can address symptom issues. As the Affordable Care Act is implemented, more patients will enter the healthcare system, placing a demand on providers that the current supply cannot meet. A report from the Institute of Medicine advocates that nurse practitioners (NPs) are more than competent to provide for the unique urgent care needs of patients with cancer. The aim of this article is to describe an NP-led urgent care center for patients with cancer and how that care center provides access to vital, expeditious, and cost-effective care.


Serum-based protein biomarkers in blast-induced traumatic brain injury spectrum disorder.
The biological consequences of exposure to explosive blast are extremely complex. Serum protein biomarkers in blast-induced traumatic brain injury (bTBI) can aid in determining injury severity, monitoring progress, and predicting outcome. Exposure to blast results in varying degrees of physical injury. Explosive blast can also induce psychological stress that can contribute to or amplify the extent of physical damage. Given the complexity, scale of injury, and variety of symptoms, bTBI may be best described as a spectrum disorder. In this focused review, we summarize the status of serum protein biomarkers in bTBI in the context of the classification and pathological changes of other forms of TBI. Finally, we recommend specific and easily implementable measures to accelerate serum protein biomarker discovery and validation in bTBI.


The taming of an impossible child: a standardized all-in approach to the phylogeny of Hymenoptera using public database sequences.
Enormous molecular sequence data have been accumulated over the past several years and are still exponentially growing with the use of faster and cheaper sequencing techniques. There is high and widespread interest in using these data for phylogenetic analyses. However, the amount of data that one can retrieve from public sequence repositories is virtually impossible to tame without dedicated software that automates processes. Here we present a novel bioinformatics pipeline for downloading, formatting, filtering and analyzing public sequence data deposited in GenBank. It combines some well-established programs with numerous newly developed software tools (available at http://software.zfmk.de/). We used the bioinformatics pipeline to investigate the phylogeny of the megadiverse insect order Hymenoptera (sawflies, bees, wasps and ants) by retrieving and processing more than 120,000 sequences and by selecting subsets under the criteria of compositional homogeneity and defined levels of density and overlap. Tree reconstruction was done with a partitioned maximum likelihood analysis from a supermatrix with more than 80,000 sites and more than 1,100 species. In the inferred tree, consistent with previous studies, "Symphyta" is paraphyletic. Within Apocrita, our analysis suggests a topology of Stephanoidea + (Ichneumonoidea + (Proctotrupomorpha + (Evanioidea + Aculeata))). Despite the huge amount of data, we identified several persistent problems in the Hymenoptera tree. Data coverage is still extremely low, and additional data have to be collected to reliably infer the phylogeny of Hymenoptera. While we applied our bioinformatics pipeline to Hymenoptera, we designed the approach to be as general as possible. With this pipeline, it is possible to produce phylogenetic trees for any taxonomic group and to monitor new data and tree robustness in a taxon of interest. It therefore has great potential to meet the challenges of the phylogenomic era and to deepen our understanding of the tree of life.


Preimplantation genetic diagnosis: a national multicenter obstetric and neonatal follow-up study.
To study whether women conceiving after preimplantation genetic diagnosis (PGD) and their children have greater risks of adverse pregnancy and birth outcomes compared with children conceived spontaneously or after IVF with or without intracytoplasmic sperm injection (ICSI). Historical cohort study. Not applicable. All deliveries following PGD treatment for single gene and sex-linked disorders or structural chromosomal aberrations (n = 126 deliveries/149 children), IVF/ICSI treatment (n = 30,418 deliveries/36,115 children), and spontaneous conception (n = 896,448 deliveries/909,624 children). None. Adverse obstetric and neonatal outcomes, such as pre-eclampsia, preterm primary rupture of membranes, placenta previa, abruption of placenta, preterm birth, low birth weight, malformations, and neonatal admission. Compared with spontaneously conceived pregnancies, PGD pregnancies were at significantly increased risk of placenta previa (adjusted odds ratio [ORa] 9.1; 95% confidence interval [95% CI] 3.4, 24.9), cesarean section (ORa 2.0; 95% CI 1.3, 2.9), preterm birth (ORa 1.6; 95% CI 1.0, 2.7), shorter gestation (mean difference -3.4 days; 95% CI -5.7, -1.1 days), and longer neonatal admission (mean difference 21 days; 95% CI 15, 28 days). The risks were comparable to that of pregnancies following IVF/ICSI. In subanalyses, adverse outcomes were only present in children conceived by PGD owing to parental monogenetic disorder and comparable to those of children born to parents with monogenic disorders conceiving without PGD, except for a higher risk of placenta previa. In this cohort study, the risk of adverse obstetric and neonatal outcomes was mainly related to the underlying parental condition rather than the PGD procedure.


Work related risk factors for musculoskeletal complaints in the spinning industry in Lithuania.
To describe the prevalence of self reported musculoskeletal complaints in the back, arms or neck, and legs among workers in the spinning industry, and to investigate the relations between these complaints and work related variables. An interview based questionnaire survey was carried out in two spinning industry factories in Lithuania. The study group consisted of all workers in production (n = 363). Symptoms of the legs were the musculoskeletal symptom reported most often (61%). Many subjects had arms or neck (55%) or back problems (28%). 20% had experienced pain from all three sites. Almost 25% had had musculoskeletal pain every day and 16% had experienced constant pain during previous year. Packers had the highest risk of arms or neck problems whereas spinners had the highest risk of back or leg problems. Working in a strained posture (bending, work with arms raised up above shoulder level, and repetitive movements of the fingers) was associated with all three complaints. Only arms or neck complaints were associated with age. Musculoskeletal disorders are a common problem among workers producing gobelin or synthetic thread in Lithuania and working in a strained posture is a risk factor for developing musculoskeletal disorders in three body sites: legs, arms or neck, and back. To better understand the different aspects of physical load as risk factors, a more detailed study of the frequency of postural changes as well as an observation of individually adopted postures would be necessary. This applies to intervention studies in factories of the spinning industry to prevent complaints of the legs and shoulders.