Stabilization of the pelvis with the Hoffmann frame. An aid in diagnosing pelvic instability.
Pelvic instability is a controversial concept. The symptoms and signs are believed to be due to pelvic joint hypermobility. Differentiation from low back pain can often be difficult. As an aid in diagnosis, temporary external fixation of the pelvis with a trapezoid compression frame was used in 12 patients. The effect on clinical signs and limping, tested on an electronic walkway, and symphyseal mobility has been analysed: in 11 of the 12 patients the frame had a positive clinical effect. In five of six patients limping diminished significantly. Stabilizing of symphyseal mobility could not be demonstrated.


Post-transplantation Cyclophosphamide: From HLA-Haploidentical to Matched-Related and Matched-Unrelated Donor Blood and Marrow Transplantation.
Following allogeneic blood and marrow transplantation (BMT), graft-versus-host disease (GvHD) continues to represent a significant cause of treatment failure, despite the routine use of conventional, mainly calcineurin inhibitor-based prophylaxis. Recently, post-transplant cyclophosphamide (PTCy) has emerged as a safe and efficacious alternative. First, omitting the need for ex vivo T-cell depletion in the setting of haploidentical transplantation, growing evidence supports PTCy role in GvHD prevention in matched-related and matched-unrelated transplants. Through improved understanding of GvHD pathophysiology and advancements in drug development, PTCy emerges as a unique opportunity to design calcineurin inhibitor-free strategies by integrating agents that target different stages of GvHD development.


Heteroaryl-fused 2-phenylisothiazolone inhibitors of cartilage breakdown.
The synthesis, biological evaluation, and structure-activity relationships of a series of N-phenyl heteroaryl-fused isothiazolones are described. These isothiazolones have been shown to exhibit potent, dose-dependent inhibition of IL-1 beta-induced breakdown of proteoglycan in a cartilage organ culture assay. This effect is likely due to inhibition of MMP activation and a consequent reduction in MMP activity following IL-1 beta stimulation. Thus these compounds potentially represent simple, non-peptidic disease-modifying agents for the treatment of arthritic diseases. To examine the effects of structure on in vitro activity, three general features of the molecules were varied, substituents on the pendant N-phenyl group, the position of ring fusion to the isothiazolone, and substituents on the fused ring peri to the isothiazolone sulfur.


Standardized low-load repetitive work: evidence of different motor control strategies between experienced workers and a reference group.
The purpose of this laboratory study was to evaluate the possible differences in motor strategies to a new standardized low-load repetitive work task in between healthy experienced workers and a reference group. Work task event duration, i.e. working rhythm, cutting forces, surface electromyographic (EMG) activity from four shoulder muscles, postural activity, and arm and trunk movements in 3D were recorded during low-load repetitive work simulation. The experienced group showed lower EMG activity and frequency contents (P<0.05), more abducted position of the upper arm and forward flexion of the trunk prior to work simulation (P<0.05), and increased arm and trunk range of motion (P<0.05) compared with the reference group. The results highlight that experienced butchers have a different motor strategy compared with a reference group, i.e. more variable form of coordination pattern. Furthermore, the initial implementation of a possible protective motor strategy by experienced workers might be a very important prognostic factor.


Current Perspectives of Telomerase Structure and Function in Eukaryotes with Emerging Views on Telomerase in Human Parasites.
Replicative capacity of a cell is strongly correlated with telomere length regulation. Aberrant lengthening or reduction in the length of telomeres can lead to health anomalies, such as cancer or premature aging. Telomerase is a master regulator for maintaining replicative potential in most eukaryotic cells. It does so by controlling telomere length at chromosome ends. Akin to cancer cells, most single-cell eukaryotic pathogens are highly proliferative and require persistent telomerase activity to maintain constant length of telomere and propagation within their host. Although telomerase is key to unlimited cellular proliferation in both cases, not much was known about the role of telomerase in human parasites (malaria, Trypanosoma, etc.) until recently. Since telomerase regulation is mediated via its own structural components, interactions with catalytic reverse transcriptase and several factors that can recruit and assemble telomerase to telomeres in a cell cycle-dependent manner, we compare and discuss here recent findings in telomerase biology in cancer, aging and parasitic diseases to give a broader perspective of telomerase function in human diseases.


Assessment of risk in radiology using malpractice RVU.
Analysis on the causes and remedies needed to reduce the incidence of malpractice has been under continual studies, although limited data is available regarding quantitative evaluation of the risk. To determine radiological risk in a preventive and quantitative manner and verify if the malpractice relative value units (MP-RVU) are a good indicator of associated risk factors. Radiological examinations executed by our Radiology Department in 2000-2004 have been codified according to nomenclature HCPCS (Healthcare Common Procedure Coding System) used by United States of America Centers for Medicare and Medicaid Services (CMS). For every examination was calculated the annual weight of malpractice. The data has been groupped in macroaggregates by methodology. The ratio MP-RVU/no. examinations has been considered as an index of insurance risk (MP index) A total of 133,005 examinations were performed, which produced 25,252 MP-RVU points, the total mp index was 0.193. Traditional radiology represents 38% of the examinations, accounting for 8% of MP-RVU with a MP index=0.039. Ultrasound represents 35% of the examinations, accounting for 23% of MP-RVU with a MP index=0.125. CT represents 13% of the examinations, accounting for 28% of MP-RVU with a MP index=0.434. MR represents 11% of the examinations, accounting for 39% of MP-RVU with a MP index=0.667. Malpractice relative value units (MP-RVU) are indicative of the risk considered globally and when subgrouped. MP index correlates this risk with number of exams carried out divided by methodology. This model providing quantitative data for projects concerning risk management and in allowing the correlation between data obtained in different departments.


Successes and Challenges in School Meal Reform: Qualitative Insights From Food Service Directors.
The Healthy, Hunger-Free Kids Act of 2010 (HHFKA) directed the US Department of Agriculture (USDA) to revise school meal standards to increase healthy food offerings. A critical stakeholder in the implementation of standards is Food Service Directors (FSDs). We sought to examine FSDs' perspectives on revised school meal standards to gain insight into successful implementation strategies. Semistructured interviews were conducted with FSDs (N = 9) from high schools that had achieved HealthierUS Schools Challenge: Smarter Lunchrooms (HUSSC: SL) status. Qualitative interview data were team coded in Atlas.ti v7 and analyzed with principles of constant comparative analysis. FSDs reported overall positive perceptions of the revised school meal standards and its potential impacts, as well as improved fruit and vegetable consumption, despite initial challenges with plate waste, procurement of whole grain-rich products, and fast paced sodium targets. Implementation was described as complex, ongoing processes; with time and in-service trainings, student acceptance to these changes improved. These findings are directly relevant to future reauthorization of the Child Nutrition Act and to revisions to the implementation time line for the federal school meal standards related to sodium, whole grains, and flavored milk. Insights into FSDs' strategies suggest that more time and targeted technical assistance at federal, state, and local levels is warranted.


Multimodal treatment for resectable esophageal cancer.
Surgical resection has been traditionally the mainstay of treatment for localized esophageal cancers. However, survival after surgery alone for advanced esophageal cancer is not satisfactory. In Japan, the development of multimodal therapy for esophageal cancers has centered mainly on systemic chemotherapy plus surgery to control distant metastasis. Based on the results of the recent Japan Clinical Oncology Group (JCOG) 9907 study, preoperative chemotherapy (consisting of 5-FU and cisplatin) followed by surgery has emerged as the standard treatment. In Western countries, where chemoradiotherapy followed by surgery has been mainly explored for patients with resectable esophageal cancers, two large controlled trials that evaluated the effectiveness of preoperative chemotherapy reported conflicting results. However, a recent meta-analysis reported significant survival benefits for preoperative chemotherapy in patients with adenocarcinoma of the esophagus. We need to find new effective preoperative chemotherapeutic regimens, including molecular target agents, with response rates higher than that of the conventional chemotherapy of 5-FU and cisplatin. However, we also must compare the survival benefits of preoperative chemotherapy with preoperative chemoradiotherapy.


Symptom load and general function among patients with erythema migrans: a prospective study with a 1-year follow-up after antibiotic treatment in Norwegian general practice.
Promptly treated erythema migrans (EM) has good prognosis. However, some patients report persistent symptoms. Do patients with EM have more symptoms than the general population? We describe individual symptoms and general function in EM-patients at time of diagnosis and one year after treatment. Prospective study with 1-year follow up after treatment. Questionnaires included a modified version of the Subjective Health Complaints Inventory, comprising three additional Lyme borreliosis (LB) related symptoms. General function was assessed using a five-point scale modified from the COOP/WONCA charts. Norwegian general practice. A total of 188 patients were included in a randomized controlled trial comparing three antibiotic regimens for EM, of whom 139 had complete data for this study. Individual symptoms, symptom load and general function. Mild symptoms were common, reported by 84.9% at baseline and by 85.6% at follow-up. At baseline, patients reported a mean of 5.4 symptoms, compared with 6.2 after one year. Severely bothersome symptoms and severely impaired general function were rare. Tiredness was the most reported symptom both at baseline and at follow-up. Palsy (other than facial) was the least reported symptom, but the only one with a significant increase. However, this was not associated to the EM. The symptom load was comparable to that reported in the general population. We found an increase in symptom load at follow-up that did not significantly affect general function. Monitoring patients' symptom loads prior to treatment reduce the probability of attributing follow-up symptoms to LB. Key points Erythema migrans has a good prognosis.Patients treated for erythema migrans have a slight increase in symptom load one year after treatment. This increase does not affect general function. The levels of subjective health complaints in patients treated for erythema migrans are comparable to the background population.


Clinical and Experimental Sepsis Impairs CD8 T-Cell-Mediated Immunity.
Septic patients experience chronic immunosuppression resulting in enhanced susceptibility to infections normally controlled by T cells. Clinical research on septic patients has shown increased apoptosis and reduced total numbers of CD4 and CD8 T cells, suggesting contributing mechanism driving immunosuppression. Experimental models of sepsis, including cecal ligation and puncture, reverse translated this clinical observation to facilitate hypothesis-driven research and allow the use of an array of experimental tools to probe the impact of sepsis on T-cell immunity. In addition to numerical loss, sepsis functionally impairs the antigen-driven proliferative capacity and effector functions of CD4 and CD8 T cells. Sepsis-induced impairments in both the quantity and quality of T cells results in reduced protective capacity and increased susceptibility of mice to new or previously encountered infections. Therefore, the combined efforts of clinical and experimental sepsis research have begun to elucidate the impact of sepsis on T-cell-mediated immunity and potential T-cell-intrinsic and -extrinsic mechanisms driving chronic immunosuppression. Future work will explore the impact of sepsis on the recently appreciated tissue-resident memory (TRM) T cells, which provide robust protection against localized infections, and dendritic cells, which are needed to activate T cells and promote effective T-cell responses.


18 F-sodium fluoride positron emission tomography of the equine distal limb: Exploratory study in three horses.
Positron emission tomography (PET) is a cross-sectional, functional imaging modality that has recently become available to the horse. The use of 18 F-sodium fluoride (18 F-NaF), a PET bone tracer, has not previously been reported in this species. To assess the feasibility of 18 F-NaF PET in the equine distal limb and explore possible applications in the horse in comparison with other imaging modalities. Exploratory descriptive study involving three research horses. Horses were placed under general anaesthesia prior to intravenous (i.v.) administration of 1.5 MBq/kg of 18 F-NaF. Positron emission tomography imaging of both front feet and fetlocks was performed using a portable scanner. Computed tomography (CT) of the distal limb was performed under a separate anaesthetic episode. Bone scintigraphy and magnetic resonance imaging (MRI) were subsequently performed under standing sedation. Images obtained from PET and other imaging modalities were independently assessed and the results correlated. Positron emission tomography images were obtained without complication. The radiation exposure rate was similar to equine bone scintigraphy. Positron emission tomography detected focal 18 F-NaF uptake in areas where other imaging modalities did not identify any abnormalities. This included sites of ligamentous attachment, subchondral compact bone plate and the flexor cortex of the navicular bone. 18 F-NaF uptake was identified in some, but not all, osseous fragments and areas of osseous formation, suggesting a distinction between active and inactive lesions. A small number of horses were included and histopathology was not available. 18 F-NaF PET imaging of the equine distal limb provides useful additional information when compared with CT, MRI and scintigraphy and has the potential for both research and clinical applications in the horse. The Summary is available in Chinese - see Supporting information.


[New insights into the etiopathogenesis of atherosclerosis and atherothrombosis].
The composition of an atherosclerotic plaque is an important determinant of plaque stability. Unstable rupture-prone plaques are characterized by a thin fibrous cap that contains few muscle cells. Several lines of evidence suggest that macrophage activation in the unstable shoulder of the plaque could contribute to plaque rupture by releasing toxic factors, possibly nitric oxide (NO), to smooth muscle cells. These macrophages are also involved in the uptake of apoptotic cells (AC) and the inefficient removal of the latter might contribute to the formation of the necrotic core through accumulation of necrotic debris. Furthermore, these AC rapidly expose phosphatidylserine on their surface, which is a potent substrate for the generation of thrombin and activation of the coagulation cascade. The following new insights in the etiopathogenesis of atherothrombosis will be discussed: (1) Human atherosclerotic plaques contain amyloid precursor protein (APP) and beta-amyloid peptide, which is cleaved from APP and which has been extensively studied in Alzheimer's disease. Macrophages phagocytose platelets,which contain APP in their alpha-granules and this platelet derived APP is subsequently proteolytically processed in these macrophages into beta-amyloid The latter is involved in the upregulation of the inducible NO-synthase which results in an increased production of toxic amounts of NO. (2) Phagocytosis of the pro-coagulant ACS is severely impaired in advanced human atherosclerotic plaques. Several factors present in the atherosclerotic lesion,such as accumulation of indigestible material in the macrophage cytoplasm,oxidative stress,and the presence of oxidized LDL or oxidized erythrocytes may contribute to the impairment of phagocytosis. (3) In order to study the impact of the impaired phagocytosis by the macrophages on the atherosclerotic lesion development,a double knock-out mouse was created which spontaneously develops atherosclerosis combined with a deficient phagocytotic capacity. Completely unexpected the double-knock out mouse developed an until now not described phenotype resembling the metabolic syndrome including a spectacular increase in body weight,accumulation of abdominal fat and fat in the liver and increased plasma levels of cholesterol. Furthermore the atherosclerotic lesions demonstrated a striking different morphology as compared to the lesions present in mice which spontaneously develop atherosclerosis.


Testing beat perception without sensory cues to the beat: the Beat-Drop Alignment Test (BDAT).
Beat perception can serve as a window into internal time-keeping mechanisms, auditory-motor interactions, and aspects of cognition. One aspect of beat perception is the covert continuation of an internal pulse. Of the several popular tests of beat perception, none provide a satisfying test of this faculty of covert continuation. The current study proposes a new beat-perception test focused on covert pulse continuation: The Beat-Drop Alignment Test (BDAT). In this test, participants must identify the beat in musical excerpts and then judge whether a single probe falls on or off the beat. The probe occurs during a short break in the rhythmic components of the music when no rhythmic events are present, forcing participants to judge beat alignment relative to an internal pulse maintained in the absence of local acoustic timing cues. Here, we present two large (N > 100) tests of the BDAT. In the first, we explore the effect of test item parameters (e.g., probe displacement) on performance. In the second, we correlate scores on an adaptive version of the BDAT with the computerized adaptive Beat Alignment Test (CA-BAT) scores and indices of musical experience. Musical experience indices outperform CA-BAT score as a predictor of BDAT score, suggesting that the BDAT measures a distinct aspect of beat perception that is more experience-dependent and may draw on cognitive resources such as working memory and musical imagery differently than the BAT. The BDAT may prove useful in future behavioral and neural research on beat perception, and all stimuli and code are freely available for download.


Incremental value of contrast echocardiography in the diagnosis of atrial myxoma.
Intracardiac myxomas have traditionally been divided into solid ovoid and soft papillary types based on a morphological appearance. Papillary myxomas given their friable nature are far more likely to cause embolic phenomenon and present with neurological symptoms, making it necessary to discriminate between these tumor subtypes. Papillary myxomas have also been demonstrated to be significantly less vascular than their ovoid counterparts in previous angiographic studies. We describe here for the first time, the application of transesophageal real time myocardial contrast echocardiography in a case of atrial papillary myxoma to assess tumor vascularity. (Echocardiography 2010;27:E46-E49).


Risk assessment of botanicals and botanical preparations intended for use in food and food supplements: emerging issues.
At present there is a growing interest for use of botanicals and botanical ingredients in medicines, for teas or in foods and in food supplements. In addition, a number of plant-derived food items form an integral part of regular human diets. Currently, there is an increasing awareness among safety experts and regulators of risks associated with the use of botanicals and botanical ingredients in food including food supplements. It is becoming clear that "natural" does not equal "safe" and that, in modern society, adverse health effects can occur as a result of (mis)use. With the growing awareness of these issues efforts to ensure safety of botanicals and botanical ingredients are also increasing. Several guidance documents on safety assessment of botanicals and botanical preparations to be used as ingredients in food and food supplements have been published, although, at present, relevant legislative frameworks and guidances for risk assessment are not established yet. Furthermore, when defining possible guidance documents for risk assessment of botanicals, several issues emerge that need to be developed beyond the present state-of-the-art. The present paper describes some of the issues to be considered and developed to a further extent to improve risk assessment of botanicals and botanical preparations, illustrated by examples based on some allylalkoxybenzenes. It is concluded that, for an improved and more accurate future risk assessment of botanicals, it is necessary to further develop and validate: (i) the use of the margin of exposure (MOE) concept for compounds that are both genotoxic and carcinogenic; (ii) new ways to quantify and incorporate matrix effects into risk assessment strategies; (iii) the use of analytical chemistry approaches, enabling complete chemical characterisation of complex mixtures. Defining new approaches in risk assessment would be in line with the inspiring attitude of the late Professor Robert Kroes, who, for example by supporting the threshold of toxicological concern (TTC) concept, was a pioneer for development and implementation of new paradigms in the field of risk assessment and food safety.


The scholarship of application: recognizing and promoting nurses' contribution to knowledge development.
The generation of knowledge is fundamental to the practice of nursing and occurs through various forms of scholarship. Boyer recognized this and described knowledge production through research, integration, teaching, and application. The focus of this article is on the scholarship of application and its role in the development of nursing knowledge. Examples of achievement in the scholarship of application are provided with outcomes of work between community and education partners and innovative clinical practice changes. The scholarship of application is of particular importance to nursing as it bridges research, practice, and education, and documents and disseminates nursing knowledge to enable peer critique. Approaches for developing a climate of scholarship are discussed, including differentiating scholarly practice from clinical scholarship and how the scholarship of application is situated in practice arenas. The role of clinical scholars and clinical leaders and the continuing development of future scholars are proposed.


High performance liquid chromatography purification and structural characterization of the subunits of rabbit muscle phosphorylase kinase.
A rapid reverse-phase high performance liquid chromatography (HPLC) method is presented for isolating the alpha, beta, gamma, and delta subunits of rabbit muscle phosphorylase kinase. The HPLC separation allows micropreparative purification of all the subunits with 66-88% recoveries. Relative molecular weights of the subunits as determined by sodium dodecyl sulfate gel electrophoresis in 4, 5, 7, and 10% acrylamide are alpha 132,000, alpha' 127,000, beta 113,000 and gamma 43,000. Amino acid compositions are reported for the HPLC purified subunits. alpha contains about 2 mol of endogenous phosphate/mol of protein and beta, gamma, and delta each contain about 1 mol of phosphate/mol of protein. Despite the identity of delta and calmodulin, essentially no protein-bound phosphate was found associated with bovine brain calmodulin. Holophosphorylase kinase contains about 20 mol of endogenous phosphate/mol of protein. The first NH2-terminal sequence analyses of the alpha, beta, and gamma subunits were determined by Tarr manual Edman degradation. Within the NH2-terminal 23 residues of gamma ( TRDAALPGSHSTHGFYENYESKE . . . ) there are six identities and one conservative interchange with the catalytic subunit of bovine cAMP-dependent protein kinase. The first 17 residues of the NH2-terminal sequence of alpha ( MRSRSNSGVRLDSYARL . . . ) exhibit six identities and one conservative interchange with the transforming protein from the Rous sarcoma virus (Schmidt- Rupin strain) provided a single gap is inserted in the src gene product. Further structural information is required to evaluate the significance of these sequence similarities. The beta subunit has a blocked NH2 terminus.


[Simultaneous determination of six fluorescent whitening agents in plastic and paper packaging materials by high performance liquid chromatography].
A novel analytical method was developed for the simultaneous determination of six fluorescent whitening agents (FWAs:FWA 135, FWA 184, FWA 185, FWA 199, FWA 378 and FWA 393) in paper and plastic food packaging materials by high performance liquid chromatography with fluorescence detection (HPLC-FLD). The sample was extracted with mixed solution of chloroform and acetonitrile (3:7, v/v), then cleaned up by HLB solid phase extraction column. Qualitative and quantitative analyses were carried out by HPLC. The sample was separated on a Phenomenex C18 column using acetonitrile and 5 mmol/L ammonium acetate aqueous solution as mobile phases. The results indicated that the linear range of FWA393 was 15-1500 μg/L and the linear ranges of the other five FWAs were 5-500 μg/L with correlation coefficients greater than 0.999. The recoveries in spiked samples were between 80.4% and 125.0% with RSDs (n=6) of 1%-13%. Furthermore, this method was applied to analyze 12 samples in the market to verify the practicality of the method. The method showed the advantages of simplicity, high recovery and good precision, and is suitable for the detection of the six fluorescent whitening agents in food packaging materials.


Involvement of the endogenous cannabinoid system in the effects of alcohol in the mesolimbic reward circuit: electrophysiological evidence in vivo.
Several lines of evidence indicate that the endogenous cannabinoid system is involved in the pharmacological and behavioural effects of alcohol. The mesolimbic dopaminergic (DA) system and the nucleus accumbens (NAc) process rewarding properties of drugs of abuse, including alcohol and cannabinoids, whereas endocannabinoids in these regions modulate synaptic function and mediate short- and long-term forms of synaptic plasticity. The present study was designed to investigate the contribution of the endogenous cannabinoid system in alcohol electrophysiological effects in the mesolimbic reward circuit. We utilized extracellular single cell recordings from ventral tegmental area (VTA) DA and NAc neurons in anesthetized rats. DA neurons were antidromically identified as projecting to the shell of NAc, whereas NAc putative medium spiny neurons were identified by their evoked responses to basolateral amygdala (BLA) stimulation. Alcohol stimulated firing rate of VTA DA neurons and inhibited BLA-evoked NAc neuron spiking responses. The cannabinoid type-1 receptor (CB1) antagonist rimonabant (SR141716A) fully antagonized alcohol effect in both regions. In the NAc, either inhibition of the major catabolic enzyme of the endocannabinoid anandamide, the fatty-acid amyd hydrolase, with URB597 or a pretreatment with the CB1 receptor agonist WIN55212-2 significantly depressed alcohol-induced effects in the NAc. These results corroborate the notion of the involvement of endocannabinoids and their receptors in the actions of alcohol and highlight the endocannabinoid system as a valuable target in the therapy for alcoholism.


A Protective Role of Glibenclamide in Inflammation-Associated Injury.
Glibenclamide is the most widely used sulfonylurea drug for the treatment of type 2 diabetes mellitus (DM). Recent studies have suggested that glibenclamide reduced adverse neuroinflammation and improved behavioral outcomes following central nervous system (CNS) injury. We reviewed glibenclamide's anti-inflammatory effects: abundant evidences have shown that glibenclamide exerted an anti-inflammatory effect in respiratory, digestive, urological, cardiological, and CNS diseases, as well as in ischemia-reperfusion injury. Glibenclamide might block KATP channel, Sur1-Trpm4 channel, and NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation, decrease the production of proinflammatory mediators (TNF-α, IL-1β, and reactive oxygen species), and suppress the accumulation of inflammatory cells. Glibenclamide's anti-inflammation warrants further investigation.


PTHrP-mediated hypercalcemia in a calcitonin-producing islet cell tumor.
Calcitonin is a peptide hormone that may decrease serum calcium levels. This case report describes a patient with a calcitonin-producing islet cell tumor who was also hypercalcemic. Parathyroid hormone-related peptide (PTHrP) levels were elevated. No other cause for hypercalcemia was found. The hypercalcemia resolved when the tumor was treated with chemotherapy. PTHrP levels also decreased with the chemotherapeutic treatment. This is the first report of a patient with a calcitonin-producing islet cell tumor and hypercalcemia mediated by PTHrP.


[Safety of the strategy of minimizing intestinal resection during surgery for pelvic radiation- induced terminal small intestinal stenosis].
Objective: To investigate the efficacy of strategies for minimizing small bowel resection during surgery for pelvic radiation-induced terminal small intestinal stenosis in preventing postoperative complications such as anastomotic leakage and short bowel syndrome. Methods: This was a retrospective cohort study. There are two subtypes of chronic radiation enteritis (CRE) with combined intestinal stenosis and intestinal obstruction: (1) Type I: terminal ileal lesions with a normal ileal segment of 2-20 cm between the ileal lesion and ileocecal junction; and (2) Type II: the lesion is located in the small bowel at a distance from the ileocecal region, usually accompanied by extensive damage to the bowel segments outside the lesion. The indications for minimal bowel resection are as follows: (1) diagnosis of Type I small bowel CRE; (2) absence of radiological evidence of rectosigmoid damage; and (3) absence of colonic obstruction. The contraindications are: (1) stenotic, penetrating lesions of the distal cecum; (2) emergency surgery; (3) recurrence of malignant tumor or history of radiotherapy for recurrent malignant tumor; (4) interval between radiotherapy and surgery <6 months; and (5) history of preoperative small bowel resection or abdominal chemotherapy. Case data of 40 patients with Type I CRE who met the above criteria and had undergone minimal bowel resection between April 2017 and December 2019 were retrospectively analyzed (minimal bowel resection group; including 13 patients from Jinling Hospital, 16 from the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and 11 from the Affiliated Hospital of Xuzhou Medical University). Forty patients with Type I CRE who had undergone resection of intestinal stenosis lesions and the ileocecal region between October 2015 and March 2017 were included as historical controls (conventional resection group; all from Jinling Hospital). The specific strategy for minimal bowel resection was one-stage partial ileal resection+ileo anastomosis+protective small bowel stoma. In contrast, conventional resection comprised ileocecal resection+ileocecal-ascending colon anastomosis. Postoperative complications, intraoperative and postoperative recovery, and changes in postoperative quality of life were analyzed in both groups. The severity of postoperative complications was assessed by Clavien-Dindo and the Comprehensive Complication Index (CCI). Karnofsky performance scores (KPS) were used to evaluate the quality of life of patients in the two groups preoperatively and postoperatively. The higher the KPS score, the better the quality of life. Results: Baseline patient characteristics did not differ significantly between the two groups (P>0.05). Compared with the conventional resection group, the length of small bowel resected in the minimal bowel resection group (51 [20-200] cm vs. 91 [60-200] cm, Z=5.653, P<0.001), duration of postoperative total enteral nutrition [9 (3-18) days vs. 12 (4-50) days, Z=2.172, P=0.030], and duration of postoperative hospital stay [17 (9-24) days vs 29 (13-57) days, Z=6.424, P<0.001] were shorter; all of these differences are statistically significant. The overall incidence of postoperative complications was lower in the minimal bowel resection group than in the conventional resection group [20.0% (8/40) vs. 70.0% (28/40), χ2=19.967, P<0.001], These comprised short bowel syndrome [5.0% (2/40) vs. 25.0% (10/40), χ2=6.274, P=0.012], anastomotic leakage or fistula [2.5% (1/40) vs. 22.5% (9/40), χ2=7.314, P=0.014], and pleural effusion [7.5% (3/40) vs. 25.0% (10/40), χ2=4.500, P=0.034], all of which occurred less often in the minimal bowel resection than conventional resection group. The CCI index was also lower in the minimal bowel resection group than in the conventional resection group [CCI>40: 2.5% (1/40) vs. 12.5% (5/40), Z=18.451, P<0.001]. KPS scores were higher in the minimal bowel resection group 1 and 3 months postoperatively than they had been 1 day preoperatively (79.9±4.7 vs. 75.3±4.1, 86.2±4.8 vs. 75.3±4.1, both P<0.05). In the minimal bowel resection group, seven patients were satisfied with their current quality of life and refused to undergo stoma reduction at follow-up and one deferred stoma reduction because of rectal bleeding. The remaining 32 patients underwent stoma reduction 3 to 12 months after surgery, 26 of whom underwent ileo-cecal anastomosis. The remaining six underwent resection of the stoma and anastomosis of the ileum to the ascending colon. Conclusions: The strategy of minimal small bowel resection in patients with radiation-induced bowel injuries reduces the length of resected small bowel, decreases the risk and severity of postoperative complications, and is associated with a better prognosis and quality of life than conventional resection.


Tension Sensor Based on Fluorescence Resonance Energy Transfer Reveals Fiber Diameter-Dependent Mechanical Factors During Myelination.
Oligodendrocytes (OLs) form a myelin sheath around neuronal axons to increase conduction velocity of action potential. Although both large and small diameter axons are intermingled in the central nervous system (CNS), the number of myelin wrapping is related to the axon diameter, such that the ratio of the diameter of the axon to that of the entire myelinated-axon unit is optimal for each axon, which is required for exerting higher brain functions. This indicates there are unknown axon diameter-dependent factors that control myelination. We tried to investigate physical factors to clarify the mechanisms underlying axon diameter-dependent myelination. To visualize OL-generating forces during myelination, a tension sensor based on fluorescence resonance energy transfer (FRET) was used. Polystyrene nanofibers with varying diameters similar to neuronal axons were prepared to investigate biophysical factors regulating the OL-axon interactions. We found that higher tension was generated at OL processes contacting larger diameter fibers compared with smaller diameter fibers. Additionally, OLs formed longer focal adhesions (FAs) on larger diameter axons and shorter FAs on smaller diameter axons. These results suggest that OLs respond to the fiber diameter and activate mechanotransduction initiated at FAs, which controls their cytoskeletal organization and myelin formation. This study leads to the novel and interesting idea that physical factors are involved in myelin formation in response to axon diameter.


Mesoporosity--a new dimension for zeolites.
Frameworks of precisely defined pores with diameters matching the size of small molecules endow crystalline zeolites with valuable size- and shape-selectivity. Being important selective adsorbers and separators, zeolites are also indispensable as solid acids in size-selective catalysis. However, despite being extremely beneficial, micropores impose restrictions on the mass transport of reactants, especially when bulky molecules are involved. The prospect to boost the catalytic power of zeolites and to extend their applications into new areas has prompted numerous efforts to synthesize mesoporous zeolitic materials that combine diffusional pathways on two different size scales. Our tutorial review will introduce the reader to this exciting recent development in zeolite science. We will give a general overview of the diverse strategies on how to implement a secondary pore system in zeolites. We will distinguish top-down from bottom-up and template-assisted from 'template-free' procedures. Advantages and limitations of the different methods will also be addressed.


High cost sharing and specialty drug initiation under Medicare Part D: a case study in patients with newly diagnosed chronic myeloid leukemia.
Specialty drugs often offer medical advances but are frequently subject to high cost sharing. This is particularly true with Medicare Part D, where after meeting a deductible, patients without low-income subsidies (non-LIS) typically face 25% to 33% coinsurance (initial coverage phase with "specialty tier" cost sharing), followed by ~50% coinsurance (coverage gap phase), and then 5% coinsurance (catastrophic phase). Yet, no studies have examined the impact of such high cost sharing on specialty drug initiation under Part D. Oral tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML), making it an apt case study. A retrospective claims-based analysis utilizing 2011 to 2013 100% Medicare claims. TKI initiation rates and time to initiation were compared between fee-for-service non-LIS Part D patients newly diagnosed with CML and their LIS counterparts who faced nominal cost sharing of ≤ $5. The first 30-day TKI fill "straddled" benefit phases, for a mean out-of-pocket cost of $2600 or more for non-LIS patients. Non-LIS patients were less likely than LIS patients to have a TKI claim within 6 months of diagnosis (45.3% vs 66.9%; P < .001) and those initiating a TKI took twice as long to fill it (mean = 50.9 vs 23.7 days; P < .001). Cox regressions controlling for sociodemographic, clinical, and plan characteristics confirmed descriptive findings (hazard ratio, 0.59; 95% CI, 0.45-0.76). Extensive sensitivity analyses confirmed the robustness of our findings. High cost sharing was associated with reduced and/or delayed initiation of TKIs. We discuss policy strategies to reduce current financial barriers that adversely impact access to critical therapies under Medicare Part D.


v-myb does not prevent the expression of c-myb in avian erythroblasts.
The v-myb oncogene of avian myeloblastosis virus transforms myeloid cells exclusively, both in vivo and in vitro. The c-myb proto-oncogene from which v-myb arose is expressed at relatively high levels in immature hematopoietic cells of the lymphoid, erythroid, and myeloid lineages but not in myeloblasts transformed by v-myb. This finding suggested that the nuclear v-myb gene product p48v-myb might act directly to inhibit the normal expression of the c-myb gene. I have therefore used a selectable avian retroviral vector to express p48v-myb in avian erythroblasts which normally express high levels of the c-myb gene product p75c-myb. The results demonstrate that p48v-myb and p75c-myb can be coexpressed in the nuclei of cloned cells. Therefore, p48v-myb does not invariably prevent the expression of p75c-myb.


Both PD-1 ligands protect the kidney from ischemia reperfusion injury.
Acute kidney injury (AKI) is a common problem in hospitalized patients that enhances morbidity and mortality and promotes the development of chronic and end-stage renal disease. Ischemia reperfusion injury (IRI) is one of the major causes of AKI and is characterized by uncontrolled renal inflammation and tubular epithelial cell death. Our recent studies demonstrated that regulatory T cells (Tregs) protect the kidney from ischemia reperfusion-induced inflammation and injury. Blockade of programmed death-1 (PD-1) on the surface of Tregs, prior to adoptive transfer, negates their ability to protect against ischemic kidney injury. The present study was designed to investigate the role of the known PD-1 ligands, PD-L1 and PD-L2, in kidney IRI. Administration of PD-L1 or PD-L2 blocking Abs prior to mild or moderate kidney IRI significantly exacerbated the loss of renal function, renal inflammation, and acute tubular necrosis compared with mice receiving isotype control Abs. Interestingly, blockade of both PD-1 ligands resulted in worse injury, dysfunction, and inflammation than did blocking either ligand alone. Genetic deficiency of either PD-1 ligand also exacerbated kidney dysfunction and acute tubular necrosis after subthreshold ischemia. Bone marrow chimeric studies revealed that PD-L1 expressed on non-bone marrow-derived cells is critical for this resistance to IRI. Finally, blockade of either PD-1 ligand negated the protective ability of adoptively transferred Tregs in IRI. These findings suggest that PD-L1 and PD-L2 are nonredundant aspects of the natural protective response to ischemic injury and may be novel therapeutic targets for AKI.


Prognostic value of serum lactate kinetics in critically ill patients with cirrhosis and acute-on-chronic liver failure: a multicenter study.
Lactate clearance (Δ24Lac) was reported to be inversely associated with mortality in critically ill patients. The aim of our study was to assess the value of Δ24Lac for the prognosis of critically ill patients with cirrhosis and acute-on-chronic liver failure (ACLF). We analysed 954 cirrhotic patients with hyperlactatemia admitted to intensive care units (ICUs) in the United States and eastern China. The patients were followed up for at least 1 year. In the unadjusted model, we observed a 15% decrease in hospital mortality with each 10% increase in Δ24Lac. In the fully adjusted model, the relationship between the risk of death and Δ24Lac remained statistically significant (hospital mortality: odds ratio [OR] 0.84, 95% confidence interval [CI]: 0.78- 0.90, p < 0.001; 90-day mortality: hazard ratio [HR] 0.94, 95%CI 0.92- 0.97, p < 0.001; for Δ24Lac per 10% increase). Similar results were found in patients with ACLF. We developed a Δ24Lac-adjusted score (LiFe-Δ24Lac), which performed significantly better in the area under the receiver operating characteristic curves (AUROCs) than the original LiFe score for predicting mortality. Lactate clearance is an independent predictor of death, and the LiFe-Δ24Lac score is a practical tool for stratifying the risk of death.


Dry mixing technique for the large scale production of iodine fortified salt in India.
Dry mixing technique was used successfully in three factories in India for the manufacture of iodine fortified salt. Permitted food additives, calcium carbonate and magnesium carbonate, were used with potassium iodate. The technology was smooth and free from any problem. Since the formerly conventional, but now superceded on analytical performance criteria, spray-mixing system was not used in the study, plants of the economics either batch mixing or continuous processes were more in evidence, and could be compared with avoidable spray mixing production performance data. The iodine fortified salt was free-flowing and retained the colour of the common salt. The iodine distribution was uniform (about 30 ppm). Long distance road transportation did not affect the iodine stability and its consistency. Storage studies showed satisfactory stability and the fortified salt had prolonged shelf-life beyond one year.


Medical abortion in lactating women--low levels of mifepristone in breast milk.
Medical abortion using mifepristone followed by misoprostol is increasingly used for termination of an unwanted pregnancy. Consequently, an increasing number of women undergo medical abortion while still breastfeeding from a previous pregnancy. But there are no data on mifepristone use during lactation. We studied the levels of mifepristone in breast milk collected from women undergoing medical abortion. DESIGN AND SAMPLES: Samples of milk were collected from 12 women during the first 7 days after intake of either 200 mg (n = 2) or 600 mg (n = 10) of mifepristone. In addition, serum samples were collected on day 3 (n = 4). Main outcome measures. The levels of mifepristone, quantified using radioimmunoassay. The milk concentrations of mifepristone were highest in the first samples collected during the first 12 hours following drug intake, and ranged from undetectable (< 0.013 micromol/l) to 0.913 micromol/l. Thereafter, declining concentrations of mifepristone were detected up to 7 days. The lowest levels of mifepristone in milk were measured following ingestion of the 200 mg dose. The milk:serum ratio of mifepristone ranged from < 0.013:1 to 0.042:1 on day 3 (n = 4). The calculated relative infant dose (RID) was 1.5% at its highest. The levels of mifepristone in milk are low, especially when using the 200 mg dose. Breastfeeding can be safely continued in an uninterrupted manner during medical abortion of this kind.


Revising Dietary Phosphorus Advice in Chronic Kidney Disease G3-5D.
We summarize how practicing dietitians combined available evidence with clinical experience, to define revised dietary recommendations for phosphorus in chronic kidney disease G3-5D. As well as a review of the evidence base, 4 priority topics were reviewed. These were translated into 3 nutrient level recommendations: the introduction of some plant protein where phosphorus is largely bound by phytate; consideration of protein intake in terms of phosphorus load and the phosphorus to protein ratio; and an increased focus on avoiding phosphate additives. This review summarizes and interprets the available evidence in order to support the development of practical food-based advice for patients with chronic kidney disease.


A Chimeric NiFe Hydrogenase Heterodimer to Assess the Role of the Electron Transfer Chain in Tuning the Enzyme's Catalytic Bias and Oxygen Tolerance.
The observation that some homologous enzymes have the same active site but very different catalytic properties demonstrates the importance of long-range effects in enzyme catalysis, but these effects are often difficult to rationalize. The NiFe hydrogenases 1 and 2 (Hyd 1 and Hyd 2) from E. coli both consist of a large catalytic subunit that embeds the same dinuclear active site and a small electron-transfer subunit with a chain of three FeS clusters. Hyd 1 is mostly active in H2 oxidation and resistant to inhibitors, whereas Hyd 2 also catalyzes H2 production and is strongly inhibited by O2 and CO. Based on structural and site-directed mutagenesis data, it is currently believed that the catalytic bias and tolerance to O2 of Hyd 1 are defined by the distal and proximal FeS clusters, respectively. To test these hypotheses, we produced and characterized a hybrid enzyme made of the catalytic subunit of Hyd 1 and the electron transfer subunit of Hyd 2. We conclude that catalytic bias and sensitivity to CO are set by the catalytic subunit rather than by the electron transfer chain. We confirm the importance of the proximal cluster in making the enzyme Hyd 1 resist long-term exposure to O2, but we show that other structural determinants, in both subunits, contribute to O2 tolerance. A similar strategy based on the design of chimeric heterodimers could be used in the future to elucidate various structure-function relationships in hydrogenases and other multimeric metalloenzymes and to engineer useful hydrogenases that combine the desirable properties of distinct, homologous enzymes.


E1B-deleted adenovirus replicates in p53-deficient lung cancer cells due to the absence of apoptosis.
E1B55K adenovirus codes the protein that inactivates the p53 protein of host cells and facilitates its own cell proliferation. We prepared E1B55K-deleted adenovirus and investigated its cytopathic effects in primary lung cancer cells to evaluate the possibility of its application in gene therapy. A p53 wild-type small cell lung cancer cell line (SBC3) and three p53 mutant cell lines (SBC5, small cell lung cancer; PC3, adenocarcinoma; and EBC1, squamous cell carcinoma) were infected with AxE1AdB, in which the E1B55K gene was deleted, to assess the cytotoxicity and induction of apoptosis. Moreover, the mRNA expression in virus-infected cells was studied with cDNA array analysis to investigate the response of cancer cells to the virus infection. As a result, AxE1AdB had no detectable cytopathic effect on SBC3 cells, and SBC3 cells continued to replicate. In contrast, AxE1AdB killed SBC5, PC3, and EBC1 cells with great efficiency. In SBC3, apoptosis of the host cells was observed in the early infection stage; in the p53-mutant cell lines, apoptosis of the cells was restricted. An analysis of gene expression in the host cells indicated a significant increase of Bax mRNA in SBC3 and its deficiency in SBC5. Overall, our results suggest that AxE1AdB replicated selectively in the p53-mutant lung cancer cells and showed strong cytotoxicity against them. In the p53-intact cells, p53 induced apoptosis through Bax expression and prevented virus replication and escalation of the infection.


Vascular endothelial growth factor plays a major role in development of experimental obliterative bronchiolitis.
Obliterative bronchiolitis (OB) is the major limitation for long-term survival of lung allograft recipients. The exact molecular and cellular mechanisms contributing to obliterative lesion formation are unknown. Pathological characteristics of OB are epithelial damage, peribronchial inflammation, and increasing obliteration of bronchioli. Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that exerts proinflammatory effects by increasing endothelial permeability and inducing expression of endothelial adhesion molecules. We investigated the role of VEGF in the development of OB in rat tracheal allografts and the role of VEGF receptors (VEGFR)-1 and -2 in the development of OB in mouse tracheal allografts. In nontreated allografts, with increasing loss of epithelium and airway occlusion, VEGF messenger RNA (mRNA) and protein expression vanished in the epithelium and increased in smooth muscle cells and mononuclear inflammatory cells compared with syngeneic grafts. Intragraft VEGF overexpression by adenoviral transfer of a mouse VEGF164 gene led to a decrease in epithelial necrosis but increased luminal occlusion by >50% compared with AdLacZ-treated rat tracheal allografts. When compared with the control immunoglobulin (Ig)G group, simultaneous treatment with antibodies against VEGFR-1 and -2 significantly lowered the degree of luminal occlusion of mouse tracheal allografts.


Stereoselective pharmacokinetics of bisoprolol after intravenous and oral administration in beagle dogs.
The stereoselective pharmacokinetics of bisoprolol, a highly beta 1-selective adrenoceptor blocking agent, was studied in dogs. After intravenous and oral administration of the racemate, there was a difference in the plasma concentration between S(-)- and R(+)-bisoprolol. The area under the curve (AUC) of concentration versus time of S(-)-bisoprolol was approximately 1.5 times higher than that of R(+)-bisoprolol and the elimination half-life of S(-)-bisoprolol was approximately 1.4 times longer than that of R(+)-bisoprolol. However, no differences were observed in the volume of distribution, absolute bioavailability, and renal clearance between the two enantiomers. The plasma protein binding of S(-)-bisoprolol was also the same as that of the R(-)-isomer. No chiral inversion or enantiomer-enantiomer interaction was observed, when enantiomers were solely administered via the intravenous route. The comparison of the oxidative metabolic rate of two enantiomers using dog liver microsomes demonstrated that the metabolite was more slowly formed from S(-)- than from R(+)-bisoprolol. Consequently, we concluded that the stereoselective difference in the metabolic clearance between S(-)- and R(+)-bisoprolol caused the difference in the disposition of bisoprolol enantiomers.


Can and should nurses be aware of patients' expectations for their nursing care?
Patients' expectations for their care have long been identified as a critical factor in patient satisfaction that has become a decisive element in hospital reimbursement. But the standard definition of expectations as the level of care patients imagine they would receive in the ideal hospital setting may be off the mark. Most patients do not enter the ideal hospital, so we need to focus on patients' expectations of their real nurses in the actual hospital they are entering. Nurses who are aware of patients' expectations of them may have a distinct advantage in influencing patients' expectations and thus positively affect patients' level of satisfaction with their nursing care. The author discusses what changes may need to occur to shift our focus toward the advantages of nurses becoming aware of patients expectations and reports on her initial efforts to study nurses' awareness of patients' expectations of them.


Assessment of pesticides removal using two-stage Integrated Aerobic Treatment Plant (IATP) by Bacillus sp. isolated from agricultural field.
The biodegradation of synthetic wastewater containing Atrazine, Malathion and Parathion was studied in two stage Integrated Aerobic Treatment Plant using Bacillus sp. (consortia) isolated from agricultural field. The influent stream containing these pesticides with initial COD of 1232mg/L were fed to first reactor and treated effluent of first reactor was fed to second reactor. The maximum removal of pesticides in IATP was found to be greater than 90%. The various process parameters such as pH, DO, Redox potential and BOD5/COD were monitored during the treatment. The degradation of pesticides and its metabolites in the treated effluent were confirmed by GC-MS. Kinetic parameters such as first order rate constant (Kobs), cell yield (YX/C) and decay coefficients (Kdp) were evaluated and found to be 0.00425 per hr, 0.696mg of COD/mg MLSS and 0.0010 per hr respectively. This integrated process was found more effective than physico-chemical treatment of pesticides.


Sustaining an Aboriginal wellbeing program: Informing health promotion practice and policy.
Aboriginal and Torres Strait Islander Peoples' holistic concepts of wellbeing are inadequately represented in the health promotion discourse. The aim of this article was to explore what sustains an Aboriginal wellbeing program, to inform critical reflection and reorientation to empower Aboriginal wellbeing approaches in health promotion practice and policy. Aboriginal and non-Indigenous researchers collaboratively designed a critically framed, strengths-based research approach with Aboriginal Community Controlled Health Service staff and wellbeing program participants. Data from Individual Yarning (n = 15) with program participants and staff inspired co-researchers to co-develop interpretations over two half-day Collaborative Yarning sessions (n = 9). Co-researchers depicted five lifeworld qualities that sustain an Aboriginal wellbeing program: love, connection, respect, culture and belonging. The lifeworld qualities are relational, communicative and involve the dynamics of identity, power and self-determination. The five qualities support a lifeworld approach to an Aboriginal wellbeing program, opening communicative and relational opportunities to mediate culturally responsive interactions. The qualities mediated interactions between people in the lifeworld including program participants and coordinators, and systems representatives including health service providers. A lifeworld approach provides a way to empower Aboriginal self-determination and leadership through embedment of cultural determinants of health in wellbeing programs. SO WHAT?: Health service providers and policy makers can use lifeworld approaches to guide critical reflection and reorient practice and policy related to Aboriginal health. The lifeworld qualities that encompass this approach in wellbeing programs are communicative and relational, centred on local community voices and co-produced with community for Aboriginal identity, empowerment and self-determination.


Alcohol use and partner expectations among newly married couples.
The objective of this work was to determine if a spouse's expectations about a married person's drinking patterns affected his/her partner's alcohol use and alcohol use-related problems. Alcohol use and problems were assessed in a U.S. urban sample of 634 couples at the time they applied for their marriage license (1996-1999) and at their first and second anniversaries. Husbands' expectations about married women's alcohol use, as well as wives' expectations about married men's alcohol use, were assessed at each wave using a three-item scale. Linear regression models were used to identify the longitudinal association between a person's expectations of married individuals' drinking patterns and his/her spouse's alcohol use the following year. Evidence was found to support the relation between one spouse's expectations and his/her partner's alcohol use. However, wives' expectations appeared more influential compared to husbands and this influence is not present at the start of marriage, but rather develops slightly later. The study's limitations are noted.


Bilateral erector spinae plane blocks using a small volume of local anesthetic for acute pain control after single-port laparoscopic surgery.
In the era of enhanced recovery after surgery, clinicians are encouraged to develop optimized programs for patients who require surgery. Minimal intervention with laparoscopic surgery and multimodal pain management mostly with peripheral nerve block are key components. We are developing a departmental program for enhanced recovery after surgery for single-port laparoscopic surgery. We applied an erector spinae plane block, a novel, newly recognized block, bilaterally at the T10 transverse process with a small dose (10 mL) of local anesthetic. This method was effective and safe and resulted in successful analgesia in a patient who received single-port surgery. This surgery requires a 3-5 cm horizontal or longitudinal periumbilical incision, which was performed in this case, and our results were promising and encouraging.


Severe preeclampsia complicating mitral valve stenosis.
We present a report of a parturient with severe mitral valve stenosis diagnosed during a previous pregnancy who developed severe preeclampsia. Labor and subsequent abdominal delivery were managed with epidural analgesia and anesthesia. The clinical management was guided by invasive hemodynamic monitoring, including a flow-directed pulmonary artery catheter. Peripartum maternal and neonatal outcomes were satisfactory. Postpartum complications included pulmonary edema as well as peripartum heart failure and pulmonary thromboembolism 4 weeks postpartum.


Molecular interplay of murein synthases and murein hydrolases in Escherichia coli.
Affinity chromatography using different lytic transglycosylases as a specific ligand revealed an interaction of both murein hydrolases and murein synthases. This interaction is taken as evidence for the assemblage into a multienzyme complex that could function as a murein replicase precisely copying the given three-dimensional structure of the murein sacculus. The sacculus of the mother cell would function as a template, which is identically replicated by copying the lengths of the existing glycan strands and the pattern of crosslinkages. A hypothetical enzyme complex specifically involved in cell division and a complex specifically involved in cell elongation are presented. It is postulated that PBPs 1a and/or 1b are present in both complexes, whereas the presence of PBP2 or PBP3 defines the specificity of the murein-synthesizing machinery as being involved in either cell elongation or septation. Moreover, the proposed "holoenzyme" suprastructure could explain why the specific inhibition of PBPs 1a/1b results in bacteriolysis and why inhibition of PBP2 and PBP3 causes the well-known morphological alterations, spherical growth, and filamentation, respectively.


Direct Image-Based Attenuation Correction using Conditional Generative Adversarial Network for SPECT Myocardial Perfusion Imaging.
Attenuation correction (AC) is important for an accurate interpretation and quantitative analysis of SPECT myocardial perfusion imaging. Dedicated cardiac SPECT systems have invaluable efficacy in the evaluation and risk stratification of patients with known or suspected cardiovascular disease. However, most dedicated cardiac SPECT systems are standalone, not combined with a transmission imaging capability such as computed tomography (CT) for generating attenuation maps for AC. To address this problem, we propose to apply a conditional generative adversarial network (cGAN) for generating attenuation-corrected SPECT images (SPECTGAN ) directly from non-corrected SPECT images (SPECTNC ) in image domain as a one-step process without requiring additional intermediate step. The proposed network was trained and tested for 100 cardiac SPECT/CT data from a GE Discovery NM 570c SPECT/CT, collected retrospectively at Yale New Haven Hospital.The generated images were evaluated quantitatively through the normalized root mean square error (NRMSE), peak signal to noise ratio (PSNR), and structural similarity index (SSIM) and statistically through joint histogram and error maps. In comparison to the reference CT-based correction (SPECTCTAC ), NRMSEs were 0.2258±0.0777 and 0.1410±0.0768 (37.5% reduction of errors); PSNRs 31.7712±2.9965 and 36.3823±3.7424 (14.5% improvement in signal to noise ratio); SSIMs 0.9877±0.0075 and 0.9949±0.0043 (0.7% improvement in structural similarity) for SPECTNC and SPECTGAN , respectively. This work demonstrates that the conditional adversarial training can achieve accurate CT-less attenuation correction for SPECT MPI, that is quantitatively comparable to CTAC. Standalone dedicated cardiac SPECT scanners can benefit from the proposed GAN to reduce attenuation artifacts efficiently.


Bcl11b and combinatorial resolution of cell fate in the T-cell gene regulatory network.
T-cell development from hematopoietic progenitors depends on multiple transcription factors, mobilized and modulated by intrathymic Notch signaling. Key aspects of T-cell specification network architecture have been illuminated through recent reports defining roles of transcription factors PU.1, GATA-3, and E2A, their interactions with Notch signaling, and roles of Runx1, TCF-1, and Hes1, providing bases for a comprehensively updated model of the T-cell specification gene regulatory network presented herein. However, the role of lineage commitment factor Bcl11b has been unclear. We use self-organizing maps on 63 RNA-seq datasets from normal and perturbed T-cell development to identify functional targets of Bcl11b during commitment and relate them to other regulomes. We show that both activation and repression target genes can be bound by Bcl11b in vivo, and that Bcl11b effects overlap with E2A-dependent effects. The newly clarified role of Bcl11b distinguishes discrete components of commitment, resolving how innate lymphoid, myeloid, and dendritic, and B-cell fate alternatives are excluded by different mechanisms.


Comparison of two brief neuropsychological batteries in people with multiple sclerosis.
We compared two brief neuropsychological batteries devised to assess people with multiple sclerosis (MS) and used them to assess the relationship between cognitive impairment and dinical characteristics. We administered either the Brief Repeatable Battery of Neuropsychological Tests (BRBNT) or the Screening Examination for Cognitive Impairment (SEFCI) to 213 consecutive MS outpatients and 213 individually matched controls. Administration times were longer for BRBNT than SEFCI, for MS and controls (p=0.001). People with MS had lower scores in all individual tests than controls (p<0.001, BRBNT and SEFCI). By the criterion of poor performance on one or more tests, the sensitivity of BRBNT was 41.9% and that of SEFCI 31.5%. The corresponding figures by poor performance on two or more tests were 16.2% for BRBNT and 18.5% for SEFCI. The Buschke Selective Reminding and Paced Auditory Serial Addition were the tests best discriminating between people with MS and controls for BRBNT, and the Symbol Digit Modalities test for SEFCI. The only clinical variable independently associated with impaired performance on these batteries was EDSS. Both cognitive batteries were well accepted and easy to administer. Administration time for SEFCI was significantly shorter than for BRBNT; however, alternative forms for serial evaluation are available only for BRBNT. The BRBNT was slightly more sensitive in detecting impairment by the criterion of poor perfomance on one or more tests. EDSS score was the only clinical variable independently associated with cognitive impairment


Aminoguanidine and aortic wall mechanics, structure, and composition in aged rats.
With aging, the aortic wall becomes stiffer. This could be because of changes in wall stress or composition. We investigated whether a specific change in wall composition, ie, accumulation of advanced glycation end products (AGEs) on the extracellular matrix, is a major factor. We measured aortic mechanics, geometry, and composition in 3-, 10-, 15-, 20-, and 30-month-old inbred normotensive Wistar-Glaxo/Rijswick rats and in a group of 30-month-old rats treated from 20 months onward with aminoguanidine (AG, 42 mg/kg per day), an inhibitor of AGE formation. Thoracoabdominal aortic (pressure) pulse-wave velocity (PWV) increased progressively with age (44% from 3 to 30 months). This age-related increase in aortic PWV was not related to changes in wall stress. For all ages, central (and peripheral) aortic mean blood pressures were not statistically different. Dilatation occurred (18% increase in internal diameter from 3 to 30 months), but this was accompanied by outward hypertrophic remodeling, with an increase in the medial cross-sectional area of 95% and in the ratio of medial thickness to internal diameter of 29%. Wall stress decreased with age (-34%). There was an increase in the ratio of elastic modulus (calculated from the Moens-Korteweg equation) to wall stress (calculated from the Lamé equation, 117% from 3 to 30 months), suggesting that a change in the composition of the wall is responsible for the age-linked increase in wall stiffness. Dry weight decreased slightly but significantly (-14%) with age. Total protein, elastin, collagen, and nonscleroprotein protein [total-(elastin+collagen)] contents did not change with age, but calculated densities of all 4 were halved (as the medial cross-sectional area doubled). The elastin/collagen ratio was statistically similar at all ages. The only significant effect of AG treatment was a fall in PWV (-20%), leading to a fall in the elastic modulus/wall stress ratio (-27% at 10 months of AG treatment versus 30 months of no treatment). In conclusion, the age-related increase in aortic wall stiffness is prevented by 10 months of treatment with AG, which has no effect on wall stress or composition, suggesting that AG may improve aortic wall stiffness by lowering the degree of AGE-induced cross-linking of the extracellular matrix scleroproteins, such as collagen.


Basal and luminal breast cancers: basic or luminous? (review).
Three major, fast developing lines of research are elucidating the biology of the mammary gland and its malignant transformation: phenotypical analyses of epithelial cells and mammary proliferative lesions, the identification, purification and characterization of mammary stem cells and breast cancer-initiating cells, and gene expression profiling studies using high-throughput microarray technologies. These three approaches are providing a flux of new, increasingly coherent information and are improving cellular and molecular models of breast epithelium and its malignancies. A new conceptual framework is emerging, altering viewpoints on the differentiation and transformation of the mammary epithelial cells. The combined effects of these progresses on our understanding of breast cancer biology should have major consequences on the way this disease is managed.


Spectral analysis of heart rate variability in the assessment of autonomic diabetic neuropathy.
We studied heart rate variability in 49 uncomplicated diabetics (27 with insulin therapy; 22 with oral hypoglycemic agents) and in 40 age-matched controls. An automatic autoregressive algorithm was used to compute the power spectral density (PSD) of beat by beat RR variability derived from the surface ECG. The PSD contains two major components (a low frequency approximately 0.1 Hz (LF) and a high frequency, respiratory linked, approximately 0.25 Hz (HF] that provide, respectively, quantitative markers of sympathetic and vagal modulatory activities and of their balance. As compared to controls, in diabetics, besides a reduced RR variance at rest (2722 +/- 300 and 1436 +/- 241 ms2, respectively), we observed during passive tilt an altered response of spectral indices of sympathetic activation and vagal withdrawal, suggestive of a complex modification in the neural control activities. In addition, we compared this approach to the commonly used clinical tests score, and observed that the latter provides overall results similar to those obtained with spectral changes induced by tilt (r = 0.42; P less than 0.01). Of potential clinical importance is that the data obtained with spectral analysis appear more thoroughly quantifiable and do not require the active collaboration of the patients.


Imaging inward and outward trafficking of gold nanoparticles in whole animals.
Gold nanoparticles have emerged as novel safe and biocompatible tools for manifold applications, including biological imaging, clinical diagnostics, and therapeutics. The understanding of the mechanisms governing their interaction with living systems may help the design and development of new platforms for nanomedicine. Here we characterized the dynamics and kinetics of the events underlying the interaction of gold nanoparticles with a living organism, from the first interaction nanoparticle/cell membrane, to the intracellular trafficking and final extracellular clearance. By treating a simple water invertebrate (the cnidarian Hydra polyp) with functionalized gold nanoparticles, multiple inward and outward routes were imaged by ultrastructural analyses, including exosomes as novel undescribed carriers to shuttle the nanoparticles in and out the cells. From the time course imaging a highly dynamic picture emerged in which nanoparticles are rapidly internalized (from 30 min onward), recruited into vacuoles/endosome (24 h onward), which then fuse, compact and sort out the internalized material either to storage vacuoles or to late-endosome/lysosomes, determining almost complete clearance within 48 h from challenging. Beside classical routes, new portals of entry/exit were captured, including exosome-like structures as novel undescribed nanoparticle shuttles. The conservation of the endocytic/secretory machinery through evolution extends the value of our finding to mammalian systems providing dynamics and kinetics clues to take into account when designing nanomaterials to interface with biological entities.


Reduced cardiotoxicity and nephrotoxicity with preservation of antitumor activity of doxorubicin entrapped in stable liposomes in the LOU/M Wsl rat.
LOU M/Wsl rats inoculated s.c. with 10(4) immunoglobulin immunocytoma cells have a palpable tumor at Day 17. Doxorubicin (DXR) has been entrapped in negatively charged liposomes (lip- DXR) composed of egg phosphatidylcholine, cholesterol, and phosphatidylserine and in positively charged liposomes (lip+ DXR) composed of phosphatidylcholine, cholesterol, and stearylamine. DXR, lip- DXR, and lip+ DXR were administered i.v. (0, 0.25, 0.5, 1.0, and 2.0 mg/kg) at Day 17 for 5 consecutive days and then weekly. Control animals showed progressive tumor growth leading to death 27 days after inoculation. Antitumor activity for all three preparations was dose dependent. DXR and lip- DXR showed the same antitumor activity; lip+ DXR had less antitumor activity. The overall survival of tumor-bearing animals treated with 2.0-mg/kg lip- DXR was significantly prolonged (p less than 0.05) in comparison to the animals treated with 2.0-mg/kg free DXR. Grade III cardiomyopathy was observed 47 days after treatment with free DXR; treatment with lip- DXR resulted in Grade I cardiomyopathy. In animals treated with 1.0-mg/kg and 2.0-mg/kg free DXR urinary albumin concentrations of 10 g/liter were observed. Treatment with 1.0-mg/kg lip- DXR and 1.0-mg/kg lip+ DXR resulted in urinary albumin concentration of less than 3.0 and less than 1.0 g/liter, respectively. Free DXR, 1.0 mg/kg, resulted in a decline of serum albumin concentration from 27.8 +/- 3.2 g/liter to 9.6 +/- 4.2 g/liter. No such decline was observed after treatment with lip- DXR and lip+ DXR. Treatment with a 1.0-mg/kg dose of free DXR resulted in severe glomerular and tubular lesions which were not found after treatment with 1.0-mg/kg lip- DXR and 1.0 mg/kg lip+ DXR. Administration of lip- DXR resulted in lower DXR levels in cardiac and renal tissue compared to administration of free DXR. After administration of lip+ DXR, very low tissue and tumor DXR levels were found. In conclusion, treatment with lip- DXR or lip+ DXR resulted in a prolonged survival, less albuminuria, and higher serum albumin levels. Also, fewer lesions in heart and kidney were found, correlating with lower DXR levels in these organs. Only lip- DXR had the same antitumor effect as free DXR.


Differential expression of cytokines, chemokines and their receptors in follicular lymphoma and reactive follicular hyperplasia: assessment by complementary DNA microarray.
Follicular lymphoma (FL) is pathologically categorised as a low-grade B-cell lymphoma and histopathologically shows follicular proliferation of neoplastic B cells. In the neoplastic follicles of FL, the presence of T cells, macrophages and follicular dendritic cells (FDCs) suggests that these cells may promote a favourable environment for the growth of FL cells. Because FL cells are generally associated with FDCs, FDCs may be considered an important source of cytokines and chemokines. FDCs form the framework for germinal centres and also provide networks for nodules of FL. To evaluate the gene expression in neoplastic follicles of FL and reactive follicles of reactive follicular hyperplasia (RFH), we performed gene expression profiling of FL (n=5) and RFH (n=5) using complementary DNA (cDNA) microarray of cytokines/chemokines and their receptors. FL and RFH exhibited a diffuse down-regulated profile compared with normal peripheral blood cells, which were used as controls, although some genes displayed up-regulated profiles. Hierarchical clustering analysis separated FL and RFH into two distinct groups based on their gene expression profiles. FL cases exhibited significantly higher expression of interleukin 3 receptor alpha (IL-3Ralpha) than RFH. Immunohistochemically, neoplastic follicles of FL frequently expressed IL-3Ralpha, especially in FDCs, but not in FL cells. However, IL-3Ralpha expression was rare or weak in the reactive follicles of RFH. These findings suggest the importance of the micro-environment for FL cell growth. Further studies of cDNA microarray should provide new insight into the molecular pathology of FL and may allow the design of improved therapies.


Hyperechoic and hypoechoic hepatic hemangiomas smaller than 3 cm seldom coexist.
The purpose of this study was to determine whether hyperechoic and hypoechoic hepatic hemangiomas coexist. Archives of 456 patients with multiple smaller (≤3 cm) hepatic hemangiomas were reviewed, including sex, age, imaging study (ultrasound [US], computed tomography [CT], and magnetic resonance imaging [MRI]), follow-up, and laboratory test. Patients with chronic liver disease or other malignancy and diameter of lesion larger than 3 cm were excluded. The mean age of the patients was 41.8 ± 13.9 years (range, 18-78 years). The liver was observed with US; undetermined cases were evaluated by using CT and/or MRI. The follow-up time was from 35 to 39 months (mean, 36.3 months). Echo patterns, patterns of enhancement on CT and MRI, and associated findings of the hepatic hemangiomas were studied. The number of hemangiomas was from 2 to 6, including 154 patients with 2 lesions, 196 patients with 3 lesions, 78 patients with 4 lesions, 18 patients with 5 lesions, and 10 patients with 6 lesions. Among them, hyperechoic accounts for 71.93% (328/456), hypoechoic 27.85% (127/456), and hyperechoic and hypoechoic coexistence 0.22% (1/456). There were significant differences of distribution between the hyperechoic and hypoechoic coexistence and other echo patterns (all P < 0.001). Diameter of the hemangioma was from 8.6 and 30.0 mm (15.5 ± 4.9 mm). Hyperechoic and hypoechoic hemangiomas rarely coexist in the liver. In the event that hypoechoic and hyperechoic lesions are simultaneously found in the liver, CT, MRI, or contrast-enhanced US should be performed for a definitive diagnosis.


A humanistic-educative approach to evaluation in nursing education.
A continuing challenge for nurse educators is to create a learning environment in which students receive fair and timely evaluations. Traditional or behavioural evaluation methods have been criticized as being too limited. A humanistic-educative evaluation method is offered with its emancipation of faculty and students and emphasis on collaboration, caring, creativity, critical thinking and self-assessment. A teacher-student shared home visit for a Family Nursing clinical assignment is provided to illustrate this approach. The potential benefit of the method for developing self-directed and competent professional nurses is proposed.


Neurophysiological and behavioral responses to music therapy in vegetative and minimally conscious States.
Assessment of awareness for those with disorders of consciousness is a challenging undertaking, due to the complex presentation of the population. Debate surrounds whether behavioral assessments provide greatest accuracy in diagnosis compared to neuro-imaging methods, and despite developments in both, misdiagnosis rates remain high. Music therapy may be effective in the assessment and rehabilitation with this population due to effects of musical stimuli on arousal, attention, and emotion, irrespective of verbal or motor deficits. However, an evidence base is lacking as to which procedures are most effective. To address this, a neurophysiological and behavioral study was undertaken comparing electroencephalogram (EEG), heart rate variability, respiration, and behavioral responses of 20 healthy subjects with 21 individuals in vegetative or minimally conscious states (VS or MCS). Subjects were presented with live preferred music and improvised music entrained to respiration (procedures typically used in music therapy), recordings of disliked music, white noise, and silence. ANOVA tests indicated a range of significant responses (p ≤ 0.05) across healthy subjects corresponding to arousal and attention in response to preferred music including concurrent increases in respiration rate with globally enhanced EEG power spectra responses (p = 0.05-0.0001) across frequency bandwidths. Whilst physiological responses were heterogeneous across patient cohorts, significant post hoc EEG amplitude increases for stimuli associated with preferred music were found for frontal midline theta in six VS and four MCS subjects, and frontal alpha in three VS and four MCS subjects (p = 0.05-0.0001). Furthermore, behavioral data showed a significantly increased blink rate for preferred music (p = 0.029) within the VS cohort. Two VS cases are presented with concurrent changes (p ≤ 0.05) across measures indicative of discriminatory responses to both music therapy procedures. A third MCS case study is presented highlighting how more sensitive selective attention may distinguish MCS from VS. The findings suggest that further investigation is warranted to explore the use of music therapy for prognostic indicators, and its potential to support neuroplasticity in rehabilitation programs.


Adenosine 3',5'-phosphate phosphodiesterase and pheromone response in the yeast Saccharomyces cerevisiae.
Theophylline, aminophylline, and isobutylmethylxanthine, compounds reported to be inhibitors of adenosine 3',5'-phosphate (cAMP) phosphodiesterase, prevented the alpha-factor-induced cell cycle arrest of Saccharomyces cerevisiae a cells. To determine whether the in vivo effect of these methylxanthines on yeast pheromone response was related to their known biochemical mode of action, two assays for cAMP phosphodiesterase based on affinity of the product of the reaction (5'-AMP) for boronate groups were developed and were used to monitor the activity of the low Km cAMP phosphodiesterase present in yeast extracts. It was found that the relative efficacy of the methylxanthines as inhibitors of this enzyme in vitro was correlated with the degree to which they antagonized alpha-factor action in vivo. These results were consistent with our previous proposal that pheromone action involves a lowering of cAMP level in the target cell.


Diagnosis, Treatment, and Surgical Repair in a Case of Isolated Conjunctival Lichen Planus Causing Cicatricial Entropion.
A 50-year-old male presented with bilateral cicatricial entropion with subepithelial fibrosis and fornix foreshortening. Conjunctival biopsy showed lymphocytic infiltrate along the interface of the epithelium and lamina propria with linear, shaggy fibrinogen deposition along the epithelial basement membrane zone, supporting a diagnosis of lichen planus. The patient was treated with commercially available topical cyclosporine for 5 months after which bilateral lower eyelid splitting procedure with recession of the anterior lamella and complete excision of the lower eyelid lashes was performed.


[The dynamic study of retinoic acid and its alginate sodium microspheres in rabbit eye].
To obtain a intravitreous delay release system by injection of biodegradable polymers (alginate sodium-retinoic acid microspheres, AGS-RA microspheres) to the rabbit vitreous and study the release character of RA delivery system in vitro. RA was mixed with 1.5% alginate sodium and microspheres was made by a special electrostatic generator after dissolved in organic solvent; The content of AGS-RA in the microspheres and its release from the microspheres were measured by spectrophotometer. The characteristic of the metabolic dynamics of AGS-RA in the microspheres was analyzed by HPLC. The size of microspheres we manufacture is (95.2443 +/- 8.6265) microm; Medicine contain quantity of RA is (1.7644 +/- 0.0453) microg/mg; Vitro test show that RA in the microspheres is release evenly in the 28 days of observation; Inject medicine to vitreous cavity show no poisonous side effect; The medicine dynamics research of microspheres showed that medicine is being even in 6 weeks releasing [the aqueous RA density of 1, 3 d, 1, 2, 3, 4, 5, 6 weeks is (23.79 +/- 0.15), (33.45 +/- 0.48), (19.95 +/- 0.79), (21.12 +/- 0.47), (19.65 +/- 0.35), (20.01 +/- 0.25), (18.24 +/- 0.27), (18.5 +/- 0.68) ng/ml, respectively]. Just in the 3rd day there is a release summit. In vivo and in vitro tests show that AGS-RA microspheres can delay RA release uniformity.


Probing the molecular forces involved in binding of selected volatile flavour compounds to salt-extracted pea proteins.
Molecular interactions between heterologous classes of flavour compounds with salt-extracted pea protein isolates (PPIs) were determined using various bond disrupting agents followed by GC/MS analysis. Flavour bound by proteins decreased in the order: dibutyl disulfide>octanal>hexyl acetate>2-octanone=benzaldehyde. Benzaldehyde, 2-octanone and hexyl acetate interacted non-covalently with PPIs, whereas octanal bound PPIs via covalent and non-covalent forces. Dibutyl disulfide reacted with PPIs covalently, as its retention was not diminished by urea and guanidine hydrochloride. Using propylene glycol, H-bonding and ionic interactions were implicated for hexyl acetate, benzaldehyde, and 2-octanone. A protein-destabilising salt (Cl3CCOONa) reduced bindings for 2-octanone, hexyl acetate, and benzaldehyde; however, retention for octanal and dibutyl disulfide increased. Conversely, a protein-stabilising salt (Na2SO4) enhanced retention for benzaldehyde, 2-octanone, hexyl acetate and octanal. Formation of a volatile flavour by-product, 1-butanethiol, from dibutyl disulfide when PPIs were treated with dithiothreitol indicated occurrence of sulfhydryl-disulfide interchange reactions.


Extracellular matrix-derived and low-cost proteins to improve polyurethane-based scaffolds for vascular grafts.
Vascular graft surgeries are often conducted in trauma cases, which has increased the demand for scaffolds with good biocompatibility profiles. Biodegradable scaffolds resembling the extracellular matrix (ECM) of blood vessels are promising vascular graft materials. In the present study, polyurethane (PU) was blended with ECM proteins collagen and elastin (Col-El) and gelatin (Gel) to produce fibrous scaffolds by using the rotary jet spinning (RJS) technique, and their effects on in vitro properties were evaluated. Morphological and structural characterization of the scaffolds was performed using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Micrometric fibers with nanometric rugosity were obtained. Col-El and Gel reduced the mechanical strength and increased the hydrophilicity and degradation rates of PU. No platelet adhesion or activation was observed. The addition of proteins to the PU blend increased the viability, adhesion, and proliferation of human umbilical vein endothelial cells (HUVECs). Therefore, PU-Col-El and PU-Gel scaffolds are promising biomaterials for vascular graft applications.


Predictors for Excellent Versus Partial Response to Prolonged Exposure Therapy: Who Needs Additional Sessions?
In practice, the duration of psychotherapy is determined by the patient's response to treatment. Identifying predictors for treatment responses is of great clinical utility to guide clinicians in their treatment planning. Demographic characteristics, trauma history, comorbidity, and early reduction of posttraumatic stress disorder (PTSD) symptoms were examined as predictors of excellent versus partial response to prolonged exposure therapy (PE) for PTSD. Participants were 96 female assault survivors with chronic PTSD who received at least eight PE sessions with or without cognitive restructuring. Participants were classified as excellent responders (n = 27) or partial responders (n = 69) based on whether they achieved at least 70% improvement in self-reported PTSD severity on the PTSD Symptom Scale-Self-Report at the end of Session 8. Excellent responders terminated therapy after Session 9, and partial responders were offered up to three additional sessions. Logistic regression was conducted to investigate predictors of response to PE. Results showed that prior interpersonal violence and comorbid alcohol use disorder were associated with partial response. Comorbid depressive disorder and early PTSD symptom reduction were associated with excellent response. Being treated by a cognitive behavioral therapy expert predicted higher excellent response for patients with a history of prior interpersonal violence. The model accounted for 56.6% of the variance in treatment response and correctly predicted responder status for 83.3% of the sample. These findings contribute to the field's understanding of factors that predict or moderate response to PE and have implications for treatment planning.


[Multifocal Langerhans cell granulomatosis. Report of a clinical case].
Langerhans' cell granulomatosis is a rare disease whose incidence on adults is valued about one case out of 3.000.000. The multifocal form is rarer than the single eosinophilic granuloma of the bone. It mainly affects males during childhood and it is usually localized in the long bones, hands, feet, and in the skull. We present the case of a young woman affected by multifocal Langerhans cell granulomatosis with bones and skin involved. Unusual in the presented clinical case is the age in which the disease come out. There is the highest incidence of multifocal lesions during childhood, while the monofocal kind is more typical of the years of adult age. Bone localization in the sternum is also quite unusual. In fact it is impossible to find reports of it in recent literature. As the patient refused to undergo chemotherapy she was treated with radiant therapy as for as bone localization concerned and with mecloretamin for local administration on skin lesion. Eleven months after the diagnosis we have not noticed the appearance of new lesions.


Parathyroid hormone as a marker for hypoperfusion in trauma: A prospective observational study.
Hyperparathyroidism is common in critical illness. Intact parathyroid hormone has a half-life of 3 minutes to 5 minutes due to rapid clearance by the liver, kidneys, and bone. In hemorrhagic shock, decreased clearance may occur, thus making parathyroid hormone a potential early marker for hypoperfusion. We hypothesized that early hyperparathyroidism predicts mortality and transfusion in trauma patients. A prospective observational study was performed at a Level I trauma center in consecutive adult patients receiving the highest level of trauma team activation. Parathyroid hormone and lactic acid were added to the standard laboratory panel drawn in the trauma bay on arrival, before the administration of any blood products. The primary outcomes assessed were transfusion in 24 hours and mortality. Forty-six patients were included. Median age was 47 years, 82.6% were men, 15.2% suffered penetrating trauma, and 21.7% died. Patients who were transfused in the first 24 hours (n = 17) had higher parathyroid hormone (182.0 pg/mL vs. 73.5 pg/mL, p < 0.001) and lactic acid (4.6 pg/mL vs. 2.3 pg/mL, p = 0.001). Patients who did not survive to discharge (n = 10) also had higher parathyroid hormone (180.3 pg/mL vs. 79.3 pg/mL, p < 0.001) and lactic acid (5.5 mmol/L vs. 2.5 mmol/L, p = 0.001). For predicting transfusion in the first 24 hours, parathyroid hormone has an area under the receiver operating characteristic curve of 0.876 compared with 0.793 for lactic acid and 0.734 for systolic blood pressure. Parathyroid hormone has an area under the receiver operating characteristic curve of 0.875 for predicting mortality compared with 0.835 for lactic acid and 0.732 for systolic blood pressure. Hyperparathyroidism on hospital arrival in trauma patients predicts mortality and transfusion in the first 24 hours. Further research should investigate the value of parathyroid hormone as an endpoint for resuscitation. Prognostic, level II.


Parental perceptions of family adjustment in childhood developmental disabilities.
Based on the adjustment phase of the double ABC-X model of family stress (McCubbin and Patterson, 1983) this study examined the impact of parenting stress, positive appraisal of the impact of child disability on the family, and parental self-esteem on parental perceptions of family adjustment in families of children with disabilities. For mothers, self-esteem and positive appraisal predicted maternal-perceived family adjustment and mediated the relationship between parenting stress and family adjustment. For fathers, while self-esteem and positive appraisal were not significant in directly predicting perceived family adjustment, self-esteem moderated the relationship between parenting stress and family adjustment. These results suggest that interventions that bolster self-esteem in parents may be useful in enhancing perceptions of family adjustment. Similarly, interventions that enhance mothers' experiences of the positive aspects of parenting a child with disabilities hold potential to strengthen family adjustment.


Simvastatin and biphasic calcium phosphate affects bone formation in critical-sized rat calvarial defects.
To investigate the effects of locally applied simvastatin plus biphasic calcium phosphate (BoneCeramic(r)) or collagen sponge on bone formation in critical-sized bone defects. Thirty defects of 5mm in diameter were created bilaterally with a trephine bur in the calvariae of fifteen Wistar rats. The defects were divided into five groups: group 1 - control, no treatment; group 2 (BoneCeramic(r)); group 3 (BoneCeramic(r) + 0.1mg simvastatin); group 4 (collagen sponge); and group 5 (collagen sponge + 0.1mg simvastatin). After eight weeks the animals were euthanized and their calvariae were histologically processed. Hematoxylin and eosin-stained sections were subjected to histological and histomorphometrical analyses. The area of newly formed bone was calculated and compared between groups. The greater amount of a bone-like tissue was formed around the carrier in group 3 (BoneCeramic(r) + 0.1mg simvastatin) followed by group 2 (BoneCeramic(r)), and almost no bone was formed in the other groups. Group 3 was significantly different compared to group 2, and both groups were significantly different compared to the other groups. Simvastatin combined with BoneCeramic(r) induced significantly greater amounts of newly formed bone and has great potential for the healing of bone defects.


[Gender stereotypes in gynecology and obstetrics: obstacles for young male physicians?].
Up to the mid 1990s, a 'feminization' of medicine took place that was especially pronounced in the field of gynecology. The present paper looks into the reasons for this change based on the literature and results from a study conducted by the author. In 2001, two thirds of the new qualifications in gynecology/obstetrics were awarded to women. The feminist movement has led to the emancipation of women and the assertion that women should be treated by female doctors only. Parallel to this development, gender roles also underwent a change: nowadays, the ideal woman or man is 'androgynous'. Young physicians are both highly instrumental and highly expressive. The increasing similarities between the sexes exert an influence on lifestyle and biographical planning. An increasing number of young physicians no longer prioritize their profession. Male physicians with high expressiveness are often family oriented and consciously refrain from choosing to specialize in gynecology/obstetrics because of the long hours and heavy workload. On the other hand, quite a few women physicians are more instrumental and prioritize their professional commitment. If more male physicians are not attracted into gynecology/obstetrics over the next few years, a process of 'horizontal segregation' could occur, with women physicians accomplishing the patient-focused work while their male colleagues take over the surgery and scientific part of the specialty. It is the very differences between the sexes, however, and the exchange between them, which allow a medical discipline to thrive.


"It Is OK Not to Be OK": Nursing Students' Backgrounds and Perceptions of Mental Health Stigma and Implications for Mental Health Nursing Education.
There has been a notable increase in reported mental illnesses in recent years. Although mental illness is being discussed more openly, stigma toward mental illness still exists. Stigma can result in inadequate care for people with mental illnesses. Students come into nursing from a variety of backgrounds and these backgrounds influence their nursing clinical judgments, especially related to caring for people with mental illnesses. A qualitative descriptive analysis was conducted using 60 undergraduate nursing student reflections on their backgrounds and perceptions of mental health stigma. Students wrote about their Previously Held Beliefs and the Influence of Culture, Overcoming Stigma through their Experiences with Friends and Family, Influence of Popular Culture, and Personal Experiences, and their New Understanding of mental illness and what that means for their future nursing practice. These findings have important implications for nursing education including providing more opportunities for nursing students to care for people with mental illnesses, reframing how mental health content is delivered in undergraduate nursing programs, and providing additional support for students with personal mental illnesses.


Prediction of goal orientation and perceived competence on intensity and direction of precompetitive anxiety among adolescent handball players.
This study explored the main and interactive effects of goal orientations and perceived competence on intensity and direction of the symptoms of precompetitive cognitive and somatic anxiety. 109 handball players from 16 high school teams (M = 16.2 yr., SD = 1.5) participated. All were asked to complete the Task and Ego Orientation in Sport Questionnaire, Perceived Competence Questionnaire, and a modified version of the Competitive State Anxiety Inventory-2. Using separated multiple hierarchical regression analyses, direction of the symptoms of precompetitive somatic anxiety was predicted by perceived competence and interaction of ego orientation x perceived competence. Perceived competence and the interaction of ego orientation x task orientation x perceived competence were significant predictors of direction of the symptoms of precompetitive cognitive anxiety. The results suggest that perceptions of competence and task orientation moderate the relationship between ego orientation and direction of the symptoms of precompetitive anxiety.