Functional characterization of T cells bearing the gamma/delta T-cell receptor in patients with primary Sjögren's syndrome.
High percentages of gamma/delta+ T cells in the peripheral blood of a subgroup of patients with primary Sjögren's syndrome (SS) were found. This allowed us to purify and analyze them without their being previously expanded in vitro, and to investigate, therefore, the role of these cells in the pathological immune response which characterizes such systemic autoimmune disorders. The results showed poor proliferation of patient gamma/delta+ T cells in response to anti-CD3, due not to macrophage-dependent suppression but to defective interleukin 2 (IL-2) synthesis. Despite the defective proliferation patient gamma/delta+ cells, unlike those of the normal controls, provided a helper effect in inducing B cells to secrete immunoglobulins (Ig), particularly when they were preincubated with IL-2. The relative increase in a gamma/delta+ T cell subset which, although it secretes low levels of IL-2, is able to provide help for B-cell Ig synthesis, suggests that this T-cell subpopulation may be functional in vivo and may be involved in the pathological immune response encountered in pSS.


Cetuximab every 2 weeks versus standard weekly dosing administration schedule.
Cetuximab every 2 weeks (Q2W) dosing schedule is approved by the US FDA and by the Japanese Pharmaceuticals and Medical Devices Agency in patients with metastatic colorectal cancer and squamous cell carcinoma of the head and neck. Phase II trials have found comparable efficacy and safety for the weekly (Q1W) and Q2W schedules, and real-world studies have shown noninferiority of the Q2W compared with the Q1W schedule. Several guidelines recommend cetuximab Q2W administration as an alternative to the Q1W dosing schedule. Cetuximab Q2W can be administered with a Q2W dose of chemotherapy, making it a more convenient option to the Q1W schedule, potentially resulting in reduced costs for administration, increased flexibility for clinical staff and improved patient adherence.


Design, synthesis, and evaluation of a potent, cell-permeable, conformationally constrained second mitochondria derived activator of caspase (Smac) mimetic.
A potent, cell-permeable, conformationally constrained second mitochondria derived activator of caspase mimetic (SM-131, 2) has been designed, synthesized, and evaluated. Compound 2 binds to X-linked inhibitors of apoptosis proteins (XIAP) with a Ki of 61 nM in a competitive binding assay and directly antagonizes the XIAP inhibition of caspase-9 activity in a cell-free functional assay. Compound 2 achieves an IC50 of 100 nM in inhibition of cell growth and effectively induces cell death in the MDA-MB-231 human breast cancer cell line.


The Electronically Activated Recorder (EAR): A Method for the Naturalistic Observation of Daily Social Behavior.
This article reviews the Electronically Activated Recorder or EAR as an ambulatory ecological momentary assessment tool for the real-world observation of daily behavior. Technically, the EAR is an audio recorder that intermittently records snippets of ambient sounds while participants go about their lives. Conceptually, it is a naturalistic observation method that yields an acoustic log of a person's day as it unfolds. The power of the EAR lies in unobtrusively collecting authentic real-life observational data. In preserving a high degree of naturalism at the level of the raw recordings, it resembles ethnographic methods; through its sampling and coding, it enables larger empirical studies. The article provides an overview of the EAR method, reviews its validity, utility, and limitations, and discusses it in the context of current developments in ambulatory assessment, specifically the emerging field of mobile sensing.


Spirulina supplementation as an adjuvant therapy in enhancement of antioxidant capacity: A systematic review and meta-analysis of controlled clinical trials.
Spirulina, a type of blue-green algae, is used as an adjuvant treatment of metabolic and inflammatory diseases. Evidence about the effects of spirulina on antioxidant system are conflicting. Thus, this quantitative review aimed to summarise the effects of spirulina administration on antioxidant status biomarkers. Systematic searches were conducted using the PubMed/Medline, Scopus, Web of Science and EMBASE, up to May 2021. Random effect analysis was applied to perform meta-analysis. Subgroup analyses and multivariate meta-regression were performed to find heterogeneity sources. Quality assessment was conducted using Cochrane Collaboration's tool. Trim and fill analysis were also carried out in case of the presence of publication bias. A total of nine articles that enrolled 415 subjects were included in the present meta-analysis. Obtained findings exhibited that spirulina supplementation had marginal significant effect on total antioxidant capacity (TAC) (SMD = 0.49; 95% CI: -0.001, 0.98; P = .05) and superoxide dismutase (SOD) activity (SMD = 0.72; 95% CI: -0.03, 1.46; P = .06), while did not affect glutathione peroxidase (GPx) activity (SMD=0.27; 95% CI: -0.23, 0.77; P = .29). Spirulina consumption may exert beneficial effects on enhancement of antioxidant system. A marginal significant increasing effect on TAC and SOD activity were found by spirulina administration. However, it did not affect GPx activity.


A case of metoclopramide-induced oculogyric crisis in a 16-year-old girl with cystic fibrosis.
Oculogyric crisis is a neurologic reaction characterized by bilateral dystonic elevation of visual gaze as well as hyperextension of the neck. This reaction is most commonly explained as an adverse effect of numerous medications, such as dopamine receptor blocking agents or neuroleptic medications and traditional antipsychotic or antiemetic drugs, such as prochlorperazine or metoclopramide. A case of oculogyric crisis induced by metoclopramide is described in this paper.


A Shift in the Direction of the Production Effect in Children Aged 2-6 Years.
Research has found mixed evidence for the production effect in childhood. Some studies have found a positive effect of production on word recognition and recall, while others have found the reverse. This paper takes a developmental approach to investigate the production effect. Children aged 2-6 years (n = 150) from a predominantly white population in Ottawa, Canada were trained on familiar words which were either seen, heard or produced, followed by a recall task. Results showed a developmental shift: younger participants showed a reverse production effect, recalling more words that were heard during training, while older children showed the typical production effect, recalling more produced words. The effect of production on recall is not unidirectional and varies by age.


The metabolism of di-(3,5-di-tert.-butyl-4-hydroxybenzyl) ether (Ionox 201) in the rat.
1. Up to one-third of a single oral dose of Ionox 201 was absorbed in rats. 2. In rats dosed with [(14)C]Ionox 201 86.8-97.2% of the label is excreted in the faeces in 24 days (much of this is eliminated in the first 4 days after dosage), 5.6% in the urine and not more than 0.8% in the exhaled air; 5.0% of (14)C is present in the carcass and viscera after removal of the gut, and most of this is in the fatty tissues. 3. About 65.0% of (14)C in the faeces is due to unchanged antioxidant, 30.0% to 3,5-di-tert.-butyl-4-hydroxybenzoic acid, 3.5% to unidentified polar constituent(s), 1.4% to 3,5-di-tert.-butyl-4-hydroxybenzaldehyde and 0.1% to 3,3',5,5'-tetra-tert.-butyl-4-,4'-stilbenequinone. A variable proportion of (14)C in the urine is due to 3,5-di-tert.-butyl-4-hydroxybenzoic acid (40-60%) and the remainder (60-40%) to the ester glucuronide, when the animals were treated with different doses of antioxidant. In eight individual animals dosed with 6.78mg. of [(14)C]Ionox 201, one-third of (14)C in the bile is due to the free acid, 45% to the ester glucuronide, 20% to an unidentified constituent and 2% to unchanged antioxidant, and, in two animals dosed with 13.56mg., there is a small proportion of free acid and a larger proportion of ester glucuronide. About 80% of (14)C in the body fat is due to unchanged antioxidant, 19% to the free acid and 1% to 3,5-di-tert.-butyl-4-hydroxybenzaldehyde. 4. At least 36.2% of a single oral dose of Ionox 201 is metabolized: 3,5-di-tert.-butyl-4-hydroxybenzoic acid accounts for 30.2% of a dose, (3,5-di-tert.-butyl-4-hydroxybenzoyl beta-d-glucopyranosid)uronic acid for 1.4%, 3,5-di-tert.-butyl-4-hydroxybenzaldehyde for 1.3%, 3,3',5,5'-tetra-tert.-butyl-4,4'-stilbenequinone for 0.1% and unidentified polar metabolite(s) for 3.2%. 5. The metabolism of Ionox 201 in vivo is closely related to its antioxidant action in vitro.


Expression and characterization of recombinant beta-secretase from Trichoplusia ni BTI Tn5B1-4 cells transformed with cDNAs encoding human beta1,4-galactosyltransferase and Gal beta1,4-GlcNAc alpha 2,6-sialytransferase.
Beta-Secretase (betaSEC) was expressed in Trichoplusia ni BTI Tn5B1-4 (Tn5B1-4) cells transformed with cDNAs encoding beta1,4-galactosyltransferase (GalT) and Gal beta1,4-GlcNAc alpha 2,6-sialyltransferase (ST). The apparent molecular weight of recombinant beta-secretase was increased from 57 to 59 k Da. A lectin blot analysis indicated that recombinant beta-secretase from Tn5B1-4 betaSEC/GalT-ST cells (Tn5B1-4 cells co-transformed with cDNAs encoding beta-secretase, glycosyltransferases, GalT, and ST) contained the glycan residues of beta1,4-linked galactose and alpha2,6-linked sialic acid. Two-dimensional electrophoresis revealed that recombinant beta-secretase from Tn5B1-4 beta SEC/GalT-ST cells had a lower isoelectric point than beta-secretase from control Tn5B1-4 betaSEC cells (Tn5B1-4 cells transformed only with beta-secretase cDNA). The enzyme activity of recombinant beta-secretase from Tn5B1-4 betaSEC/GalT-ST cells was enhanced up to 77% compared to control Tn5B1-4 betaSEC cells. The concentrations at half-maximum inhibition (IC(50)) values estimated from inhibition analyses using purified beta-secretases from Tn5B1-4/betaSEC and Tn5B1-4/betaSEC/GalT-ST cells were 32 and 290 nM, respectively.


Hypertrophic obstructive cardiomyopathy. Initial results and long-term follow-up after Morrow septal myectomy.
This study was performed to assess the initial results and long-term follow-up of Morrow septal myectomy for patients with hypertrophic obstructive cardiomyopathy (HOCM). We studied 38 consecutive patients with HOCM (age, 13 to 74 years) who underwent a Morrow septal myectomy between 1977 and 1992. There were no perioperative deaths, and the postoperative course was uneventful for all except 2 of the patients. One patient required implantation of a pacemaker due to a complete heart block, and in 1 patient a small ventricular septal defect was caused. Follow-up (mean, 6.8 years) was 100% complete. No patient was reoperated for recurrent HOCM. All except 1 patient experienced a major functional improvement with a decrease of the mean New York Heart Association functional class from 3.0 before operation to 1.5 at follow-up (P < .001). Symptoms persisting during follow-up were angina pectoris in 3 of 22 patients (14%), dyspnea in 6 of 30 patients (20%), dizzy spells in 2 of 12 patients (17%), and syncope in 2 of 10 patients (20%). During follow-up no HOCM related death occurred. All patients were restudied by Doppler echocardiography. The peak gradient in the left ventricular outflow tract decreased from 72 +/- 30 mm Hg (range, 31 to 144 mm Hg) to 6 +/- 4 mm Hg (range, 0 to 20; P < .001). A systolic anterior movement was seen in 8 patients (21%) compared with 32 patients (97%) before the operation (P < .001). The left ventricular outflow tract diameter increased from 17 +/- 3 mm (range, 10 to 23 mm) to 22 +/- 3 mm (range, 15 to 33 mm; P < .001), and the mean subaortic septal thickness decreased from 23 +/- 5 mm (range, 15 to 35 mm) to 15 +/- 6 mm (range, 8 to 30 mm; P < .001). Morrow septal myectomy for patients with HOCM is a safe procedure with an excellent clinical and Doppler echocardiographic long-term follow-up.


Preparation and Mechanical Properties of Low Carbon Cementitious Materials with Superfine Cement Reverse Filling High-Volume Mineral Admixtures.
In order to increase the content of mineral admixtures in cement, this study proposes a method for preparing a high-volume mineral admixture cementitious material (HMAC) using superfine cement as a reverse filling material. Firstly, superfine cement is prepared through mechanical grinding. Then, the activity of mineral admixtures (such as slag and fly ash) is enhanced by mechanical grinding, sulfate activation, and alkali activation methods. Meanwhile, the evolution of HMCM from microstructure to macroscopic mechanical behavior is studied by combining a laser particle size analyzer and a scanning electron microscope. Furthermore, the reverse filling mechanism of superfine cement on mineral admixtures under different activation conditions is proposed. Results show that superfine cement can largely improve the utilization rate of cement clinker and the compressive strength of cementitious materials. In the condition that the compressive strength is not lower than that of the control group (without mineral admixture), the content of mineral admixture can be increased to 50%, 70%, and 90% after mechanical grinding, sulfate activation, and alkali activation, respectively. Analysis indicates that the reverse filling effect of superfine cement is the main reason for improving the density of the HMCM.


[Causes of Angina Pectoris in Survivors of Myocardial Infarction and the Role of Optimization of Antianginal Therapy. Data of the LINKOR Study E..]
to analyze causes of attacks of angina pectoris and assess impact of optimization of antianginal therapy on frequency of attacks provoked by various factors. We analyzed diaries of 1226 survivors of myocardial infarction (MI) which occurred within 12months before inclusion in the LINKOR program. Causes of pain and their changes with correction of antianginal therapy were registered during 16 weeks of follow-up. Participants of the study indicated the following factors as causes of pain: physical exertion (74.9%), psycho-emotional stress (52.6%), meteorological factors (25.9%), elevation of arterial pressure(AP) (18.8%), meals (12.1%), alcohol intake (4.7%), sexual activity (4.4%). Attacks at rest in wakeful state and during sleep were reported by 4.5 and 4.5% of patients, respectively. Prescription of ivabradine and in some cases correction of antihypertensive therapy led to double reduction of the number of patients who indicated physical exertion as a cause of angina. Numbers of patients with attacks caused by meals, AP elevation, psycho-emotional stress, alcohol intake, unfavorable meteorological conditions, and sexual activity decreased by 83.2, 75, 63.3, 63.6, 61.3, and 60.9%, respectively. Numbers of patients with attacks at rest in wakeful state, and at night decreased by 79.8 and 69%, respectively. More than two thirds of patients achieved class I of angina. Optimization of antianginal therapy directed to lowering or myocardial oxygen consumption leads to reduction of frequency of attacks of pain caused by various triggers. This improves quality of life, increases everyday activity, secures independence, and loweres risk of depression and anxiety.


Isolation and characterization of a moderately thermophilic nitrite-oxidizing bacterium from a geothermal spring.
Geothermal environments are a suitable habitat for nitrifying microorganisms. Conventional and molecular techniques indicated that chemolithoautotrophic nitrite-oxidizing bacteria affiliated with the genus Nitrospira are widespread in environments with elevated temperatures up to 55 °C in Asia, Europe, and Australia. However, until now, no thermophilic pure cultures of Nitrospira were available, and the physiology of these bacteria was mostly uncharacterized. Here, we report on the isolation and characterization of a novel thermophilic Nitrospira strain from a microbial mat of the terrestrial geothermal spring Gorjachinsk (pH 8.6; temperature 48 °C) from the Baikal rift zone (Russia). Based on phenotypic properties, chemotaxonomic data, and 16S rRNA gene phylogeny, the isolate was assigned to the genus Nitrospira as a representative of a novel species, for which the name Nitrospira calida is proposed. A highly similar 16S rRNA gene sequence (99.6% similarity) was detected in a Garga spring enrichment grown at 46 °C, whereas three further thermophilic Nitrospira enrichments from the Garga spring and from a Kamchatka Peninsula (Russia) terrestrial hot spring could be clearly distinguished from N. calida (93.6-96.1% 16S rRNA gene sequence similarity). The findings confirmed that Nitrospira drive nitrite oxidation in moderate thermophilic habitats and also indicated an unexpected diversity of heat-adapted Nitrospira in geothermal hot springs.


Molecular Mechanism of Dioxin Formation from Chlorophenol based on Electron Paramagnetic Resonance Spectroscopy.
Few studies have investigated the free radical intermediates involved in the formation of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from chlorophenol. This study clarified the reaction pathways during thermochemical formation of PCDDs from 2,3,6-trichlorophenol (TCP) over a Cu(II)O/silica matrix, which was used to simulate fly ash, at 298-523 K. The reaction was studied using electron paramagnetic resonance (EPR) spectroscopy and theoretical calculations. In situ EPR indicated the TCP radical (TCPR) formed by hydrogen abstraction of TCP. Five elementary processes including dimerization of TCPR, ortho-chloride abstraction, Smiles rearrangement, ring closure, and intra-annular elimination of Cl were proposed to occur during formation of PCDDs. The proposed mechanism was further confirmed by the detection of PCDD products from thermochemical experiments in a tube furnace. Several dominant congeners, including 1,2,6,9-tetrachlorodibenzo-p-dioxin (TeCDD), 1,2,6,7-TeCDD, 1,2,8,9-TeCDD, and 1,4,6,9-TeCDD were detected by gas chromatography/quadrupole time-of-flight mass spectrometry, and further confirmed by gas chromatography/high resolution mass spectrometry. The detected PCDD products agree with the proposed PCDD formation mechanism. Relatively high temperatures were found to lead to dechlorination of TCPR to form phenoxy radicals in addition to PCDD/Fs. These radicals will be attached to particles, which will increase their lifetimes. These reactions were further verified by molecular orbital theory calculations. The discovery of persistent phenoxy radicals is of environmental significance because of their potential toxicity. The details of this mechanism could be used for controlling PCDD/F formation during industrial thermal processes.


Fabrication of three-dimensional porous scaffold based on collagen fiber and bioglass for bone tissue engineering.
An ideal scaffold for bone tissue engineering should have interconnected porous structure, good biocompatibility, and mechanical properties well-matched with natural bones. Collagen is the key component in the extracellular matrix (ECM) of natural bones, and plays an important role in bone regeneration. The biological activity of collagen has promoted it to be an advantageous biomaterial for bone tissue engineering; however, the mechanical properties of these scaffolds are insufficient and the porous structures are not stable in the wet state. An effective strategy to solve this problem is to fabricate a hybrid scaffold of biologically derived and synthetic material, which have the necessary bioactivity and mechanical stability needed for bone synthesis. In this work, a three-dimensional macroporous bone scaffold based on collagen (CO) fiber and bioglass (BG) is fabricated by a slurry-dipping technique, and its relevant mechanical and biological properties are evaluated. The CO/BG scaffold is interconnected with a porosity of 81 ± 4.6% and pore size of 40-200 μm. Compared with CO scaffold, water absorption value of CO/BG scaffold decreases greatly from 889% to 52%, which significantly alleviates the swelling behavior of collagen and improves the stability of scaffold structure. The CO/BG scaffold has a compression strength of 5.8 ± 1.6 MPa and an elastic modulus of 0.35 ± 0.01 Gpa, which are well-matched with the mechanical properties of trabecular bones. In vitro cell assays demonstrate that the CO/BG scaffold has good biocompatibility to facilitate the spreading and proliferation of human bone marrow stromal cells. Hence, the CO/BG scaffold is promising for bone tissue engineering application.


Survival and radiation risk in patients obtaining more than six CT examinations during one year.
During a review of the current practice for computer tomography (CT) in 2005 at the Department of Radiology, Aarhus University Hospital, we observed 300 patients with more than six CT examinations during one year. They comprised 8% of the patients and accounted for 27% of all examinations. These patients needed further analysis. The 300 patients were analyzed concerning age, type of diseases indicating multiple CTs and the CT protocols used. The effective dose and risk of low dose radiation was estimated and survival of the patients after >1.5 year was analyzed. A total of 289 patients had malignancies, the most frequent being lung cancer, bladder cancer and colon cancer. A total of 4.3% of the patients with malignancies were < or =40 year old, 13.3% were 41-50 years old and 62.7% 51-70 years old. The highest average number of CT examinations was observed in patients with sarcomas (11.2 examinations per patient). Eleven patients (aged 15-77 years) had traumatic lesions. Their number of examinations varied from 7 to 20. The total radiation dose for all 300 patients was 21.42 Sv, which may imply induction of a fatal cancer in one of the patients. However, only 102 patients survived their disease. A total of 198 patients had serious disease and were not alive 1.5 years after the examinations. The multiple CT examinations were necessary to monitor their treatment. For the surviving 102 patients the use of CT contributed to an optimal therapy, but the examinations implied a risk for radiation induced malignancies.


Gastrointestinal complications of chronic granulomatous disease: case report and literature review.
Chronic granulomatous disease (CGD), an inherited disorder of phagocytic leukocyte function, is characterized by recurrent infections with catalase-positive organisms. Gastrointestinal (GI) tract involvement, present in the majority of affected individuals, may be present initially and recurrently, mimics other entities such as inflammatory bowel disease, and causes substantive morbidity and mortality. Disorders of motility, ulceration, obstruction, and infection (e.g., abscesses) occur from the mouth to the anus and stereotypically manifest with vomiting, diarrhea, abdominal pain, weight loss, and fever. Careful physical examination, in concert with appropriate diagnostic studies, is necessary to delineate intraabdominal pathologic processes. Abdominal radiographs, ultrasonography, computerized tomography, and endoscopy are useful ancillary diagnostic procedures. Drainage of accessible abscesses, antimicrobial therapy based on organisms cultured from blood and tissue, and interferon gamma may lead to suppression or eradication of infections and resolution of symptoms. Corticosteroids are useful for gastric outlet obstruction and sulfasalazine and cyclosporine for large bowel disease. Gallbladder dysfunction may be ameliorated, as in our patient, with administration of cholestyramine.


Serum prolidase and oxidative stress levels in patients with recurrent aphthous stomatitis: a prospective, controlled study.
Recurrent aphthous stomatitis is a common disease characterized by single or multiple, self-healing, well-circumscribed, periodic ulcers occurring in the oral cavity. Although the relationship between recurrent aphthous stomatitis and oxidative stress has been extensively reviewed in the past, its relationship with prolidase enzyme levels has not been previously investigated. The aim of this study is to investigate plasma antioxidant status and prolidase enzyme levels in patients with recurrent aphthous stomatitis. The serum total oxidant status, total antioxidant status, oxidative stress index, prolidase and paraoxonase levels of 34 recurrent aphthous stomatitis patients (mean age 35.1) and 34 healthy controls (mean age 37.7) were compared in this study. Total oxidant status was significantly higher in the recurrent aphthous stomatitis group (P < 0.005). The mean total oxidant status value was 5.19 mmol/L in the recurrent aphthous stomatitis group, while it was 2.90 mmol/L in the control group. Oxidative stress index was significantly higher in the recurrent aphthous stomatitis group (P = 0.016*). The mean oxidative stress index level was 0.28 AU in the recurrent aphthous stomatitis group, while it was 0.18 AU in the control group. When control and patient groups were compared, there was no significant difference between groups with regard to the total antioxidant status (P = 0.343). The total antioxidant status levels were 1.09 and 1.14 mmol/L in control and patient groups, respectively. There was no statistically significant difference between PON1 levels of recurrent aphthous stomatitis and control groups (P = 0.218). Mean PON1 levels were 326 U/L in the recurrent aphthous stomatitis group and 381 U/L in the control group. Prolidase levels were not significantly different between recurrent aphthous stomatitis and control groups (P = 0.955). The mean prolidase level was 219.79 U/L in the recurrent aphthous stomatitis group and 219.26 U/L in the control group. The limitation of this study is the small size of both patient and control groups and exclusion of pediatric patients., Similar studies performed in pediatric patient populations with a comparison to adults may be useful in providing meaningful results. We detected that the total oxidant status and oxidative stress index was higher in patients with recurrent aphthous stomatitis as compared to healthy controls. We could not demonstrate a significant difference in total antioxidant status, PON1 and prolidase values.


Primitive neuroectodermal tumor and extraskeletal Ewing sarcoma arising primarily around the spinal column: report of four cases and a review of the literature.
Report of four cases and a review of the literature. To study the clinical features and prognosis of primitive neuroectodermal tumor or extraskeletal Ewing sarcoma arising around the spinal column. Primitive neuroectodermal tumor or extraskeletal Ewing sarcoma that originates around the spinal column is very rare, and its prognosis is very poor. Four patients were diagnosed and underwent treatment. Although all the patients received high-dose chemotherapy with or without radiotherapy after surgery, three patients died of the disease. Only one patient who received en bloc resection of the tumor combined with multiagent chemotherapy followed by high-dose chemotherapy with peripheral blood stem cell transplantation remains alive and continues to be disease free. The prognosis of the patients with primitive neuroectodermal tumor or extraskeletal Ewing sarcoma around the spinal column is very poor. Multiagent chemotherapy combined with en bloc resection and radiation therapy is the preferred treatment for patients with primitive neuroectodermal tumor or extraskeletal Ewing sarcoma around the spinal column.


Effects of botulinum neurotoxin on spatio-temporal gait parameters of patients with chronic stroke: a prospective open-label study.
Nowadays, administration of botulinum neurotoxin type A is considered a safe, well tolerated and effective treatment for muscles tone reduction in focal spasticity care. Lack of evidence regards instead its functional role on gait parameters, as well patterns. To assess the botulinum neurotoxin treatment efficacy on chronic poststroke subjects, in order to investigate its functional effects on spatio-temporal gait parameters, in addition to the evaluation of spasticity grade based on clinical scales. A prospective open-label study along 16-weeks trials. Outpatient neurophysiology rehabilitation structure and laboratory of movement and gait analysis. Twenty chronic poststroke patients, suffering from equinovarus foot deformity, with a stabilized hemiparesis were recruited according to inclusion criteria of the protocol. Single neurotoxin-based local intramuscular injections were given according to a specific protocol concerning both the considered muscles and the relative toxin doses, with a maximum total dose ranged between 200 U and 400 U. Patients were observed both at baseline (t0) and for 4 following monthly visits (t1, t2, t3, t4) after injections at baseline. Gait analysis sessions were performed at each visit, by means of a video-cameras based system and body reflective markers attached to the body, based on a protocol. Authors focus on both global and local gait temporospatial parameters, such as walking speed, stride-length, cadence, stride-time, step-width, single limb support, double support and limp index to point out the functional changes due to the treatment. For comparison prior to and after the treatment, clinical scales like Modified Ashworth Scale, Berg Balance Scale and Rivermead Mobility Index have been also considered. Subsequent to the neurotoxin intramuscular injections, patients reported statistical significant gait improvements after 90 days (t3) regarding temporospatial parameters: (P<0.05) for walking speed, single limb support and double support and (P<0.10) for stride-length, stride-time, cadence and step-width. The botulinum neurotoxin treatment has demonstrated its efficacy for a functional recovery of gait, as pointed out by a statistically significant improvement of some spatio-temporal parameters. Thus, the analyzed changes reveal an improved balance and self-confidence in gait. Studies involving a wider population data are nevertheless needed to better confirm this efficacy. The poststroke botulinum neurotoxin-based treatment is a safe and potentially useful neurorehabilitative approach for the analyzed data.


The challenge of antibiotic selection in prosthetic joint infections due to Corynebacterium striatum: a case report.
Corynebacterium striatum is a gram-positive facultative anaerobe found in the environment and human flora that has historically been considered a contaminant. More recently, Corynebacterium striatum has been implicated in human infections, including respiratory infections, endocarditis, and bone and joint infections, particularly those involving hardware or implanted devices. A 65-year-old man presented for washout of his left total knee arthroplasty following a revision 20 days prior. The patient underwent debridement of his left total knee and revision of the left total femur arthroplasty. Daptomycin was initiated empirically due to a previous rash from vancomycin. Operative tissue cultures grew Staphylococcus haemolyticus, Staphylococcus epidermidis and Corynebacterium striatum. Given concern for daptomycin resistance and the reliability of vancomycin susceptibility, daptomycin was discontinued and vancomycin initiated following a graded challenge. Within a few days, the patient developed a diffuse, blanching, erythematous, maculopapular rash and daptomycin was restarted. Over the next 72 h, his rash progressed and he met criteria for drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. Daptomycin was stopped and oral linezolid initiated; rash improved. C. striatum returned with susceptibility to gentamicin, linezolid, vancomycin and daptomycin. Due to concern for adverse effects on long-term linezolid, daptomycin was restarted and was tolerated for 20 days, at which point purulent drainage from incision increased. The patient underwent another arthroplasty revision and washout. Operative cultures from this surgery were again positive for C. striatum. Repeat C. striatum susceptibilities revealed resistance to daptomycin but retained susceptibility to linezolid. Daptomycin was again changed to linezolid. He completed six weeks of linezolid followed by linezolid 600 mg daily for suppression and ultimately opted for disarticulation. C. striatum has historically been regarded as a contaminant, particularly when grown in tissue culture in the setting of prosthetic joint infection. Based on the available literature and susceptibility patterns, the most appropriate first-line therapy is vancomycin or linezolid. Treatment with daptomycin should be avoided, even when isolates appear susceptible, due to the risk of development of high-level resistance (MIC > 256 µg/mL) and clinical failure.


Chronic stress-induced effects of corticosterone on brain: direct and indirect.
Acutely, glucocorticoids act to inhibit stress-induced corticotrophin-releasing factor (CRF) and adrenocorticotrophic hormone (ACTH) secretion through their actions in brain and anterior pituitary (canonical feedback). With chronic stress, glucocorticoid feedback inhibition of ACTH secretion changes markedly. Chronically stressed rats characteristically exhibit facilitated ACTH responses to acute, novel stressors. Moreover, in adrenalectomized rats in which corticosterone was replaced, steroid concentrations in the higher range are required for facilitation of ACTH responses to occur after chronic stress or diabetes. Infusion of corticosterone intracerebroventricularly into adrenalectomized rats increases basal ACTH, tends to increase CRF, and allows facilitation of ACTH responses to repeated restraint. Therefore, with chronic stressors, corticosterone seems to act in brain in an excitatory rather than an inhibitory fashion. We believe, under conditions of chronic stress, that there is an indirect glucocorticoid feedback that is mediated through the effects of the steroid +/- insulin on metabolism. Increased energy stores feedback on brain to inhibit hypothalamic CRF and decrease the expression of dopamine-beta-hydroxylase in the locus coeruleus. These changes would be expected to decrease the level of discomfort and anxiety induced by chronic stress. Moreover, central neural actions of glucocorticoids abet the peripheral effects of the steroids by increasing the salience and ingestion of pleasurable foods.


Catalytic core of alphavirus nonstructural protein nsP4 possesses terminal adenylyltransferase activity.
The RNA-dependent RNA polymerase nsP4 is an integral part of the alphavirus replication complex. To define the role of nsP4 in viral RNA replication and for a structure-function analysis, we expressed Sindbis virus nsP4 in Escherichia coli. The core catalytic domain of nsP4 (Delta97nsP4, a deletion of the N-terminal 97 amino acids), which consists of the predicted polymerase domain containing the GDD amino acid motif required for viral RNA synthesis, was stable against proteolytic degradation during expression. Therefore, the recombinant core domain and selected mutants were expressed and purified to homogeneity. We determined that Delta97nsP4 possesses terminal adenylyltransferase (TATase) activity, as it specifically catalyzed the addition of adenine to the 3' end of an acceptor RNA in the presence of divalent cations. Furthermore, Delta97nsP4 is unable to transfer other nucleotides (UTP, CTP, GTP, and dATP) to the acceptor RNA in the absence or presence of other nucleotides. Delta97nsP4 possessing a GDD-to-GAA mutation completely inactivates the enzymatic activity. However, a GDD-to-SNN mutation did not inactivate the enzyme but reduced its activity to approximately 45% of that of the wild type in the presence of Mg(2+). Investigation of the TATase of the GDD-to-SNN mutant revealed that it had TATase equivalent to that of the wild type in the presence of Mn(2+). Identification of Delta97nsP4 TATase activity suggests a novel function of the alphavirus RNA-dependent RNA polymerase in the maintenance and repair of the poly(A) tail, an element required for replication of the viral genome.


Virus-specific T cells as correlate of (cross-)protective immunity against influenza.
Since inactivated influenza vaccines mainly confer protective immunity by inducing strain-specific antibodies to the viral hemagglutinin, these vaccines only afford protection against infection with antigenically matching influenza virus strains. Due to the continuous emergence of antigenic drift variants of seasonal influenza viruses and the inevitable future emergence of pandemic influenza viruses, there is considerable interest in the development of influenza vaccines that induce broader protective immunity. It has long been recognized that influenza virus-specific CD8(+) T cells directed to epitopes located in the relatively conserved internal proteins can cross-react with various subtypes of influenza A virus. This implies that these CD8(+) T cells, induced by prior influenza virus infections or vaccinations, could afford heterosubtypic immunity. Furthermore, influenza virus-specific CD4(+) T cells have been shown to be important in protection from infection, either via direct cytotoxic effects or indirectly by providing help to B cells and CD8(+) T cells. In the present paper, we review the induction of virus-specific T cell responses by influenza virus infection and the role of virus-specific CD4(+) and CD8(+) T cells in viral clearance and conferring protection from subsequent infections with homologous or heterologous influenza virus strains. Furthermore, we discuss vector-based vaccination strategies that aim at the induction of a cross-reactive virus-specific T cell response.


[Traumatic splenic injury].
While the management of penetrating as well as blunt splenic injury with hemodynamic instability is straightforward with immediate operative intervention, the management of blunt splenic injury with stable hemodynamic underwent a paradigm shift over the last 3 decades. Nowadays 80 per cent of hemodynamically stable patients with blunt splenic injury can successfully be treated with a non-operative management. Angiographic embolization in selected cases is generally reported to increase the success rates of non-operative management currently approaching 95 per cent.


FtsZ ring stability: of bundles, tubules, crosslinks, and curves.
The first step in bacterial cytokinesis is the assembly of a stable but dynamic cytokinetic ring made up of the essential tubulin homolog FtsZ at the future site of division. Although FtsZ and its role in cytokinesis have been studied extensively, the precise architecture of the in vivo medial FtsZ ring (Z ring) is not well understood. Recent advances in superresolution imaging suggest that the Z ring comprises short, discontinuous, and loosely bundled FtsZ polymers, some of which are tethered to the membrane. A diverse array of regulatory proteins modulate the assembly, stability, and disassembly of the Z ring via direct interactions with FtsZ. Negative regulators of FtsZ play a critical role in ensuring the accurate positioning of FtsZ at the future site of division and in maintaining Z ring dynamics by controlling FtsZ polymer assembly/disassembly processes. Positive regulators of FtsZ are essential for tethering FtsZ polymers to the membrane and promoting the formation of stabilizing lateral interactions, permitting assembly of a mature Z ring. The past decade has seen the identification of several factors that promote FtsZ assembly, presumably through a variety of distinct molecular mechanisms. While a few of these proteins are broadly conserved, many positive regulators of FtsZ assembly are limited to small groups of closely related organisms, suggesting that FtsZ assembly is differentially modulated across bacterial species. In this review, we focus on the roles of positive regulators in Z ring assembly and in maintaining the integrity of the cytokinetic ring during the early stages of division.


Identification of novel selective P2Y6 receptor antagonists by high-throughput screening assay.
The P2Y6 nucleotide receptor is widely involved in inflammatory responses, and is a promising molecular target for the treatment of inflammatory diseases. Although several P2Y6 receptor antagonists have been developed and evaluated thus far, none has successfully been developed into a therapeutic drug. In this study, we explored new promising compounds that inhibit the human P2Y6 receptor. High-throughput screening (HTS) was used to study the effects of various compounds on human P2Y6 receptors expressed in 1321N1 human astrocytoma cells by monitoring intracellular Ca2+ concentration ([Ca2+]i) levels using an FDSS7000 real-time fluorescence detector. IL-8 concentration was measured by enzyme-linked immunosorbent assay. Among structurally diverse chemical libraries totalling 141,700 compounds, 43 compounds with an inhibitory activity against the P2Y6 receptor were identified. Further studies using a dose-response assay, receptor selectivity assay, and chemokine measurement assay revealed the selective P2Y6 receptor inhibitor TIM-38, which inhibited UDP-induced [Ca2+]i elevation in a dose-dependent manner. TIM-38 had an IC50 value of 4.3μM and inhibited P2Y6 without affecting the response induced by four other human P2Y or muscarinic receptors. In addition, TIM-38 inhibited UDP-induced interleukin-8 release in a dose-dependent manner without affecting releases caused by other stimulus such as interleukin-1β or tumour necrosis factor-α. Analyses of TIM-38 derivatives revealed that the nitro moiety is vital to P2Y6 receptor inhibition. TIM-38 acts as a novel structural antagonist of P2Y6 receptor and may be a good lead compound for developing a P2Y6 receptor-targeted anti-inflammatory drug.


Additional evidence for the close linkage of amy-1 and amy-2 in the mouse.
The enzyme amylase is produced in large quantities in two mammalian tissues, the pancreas and the parotid salivary gland. A substantial body of biochemical and genetic evidence is consistent with the existence of distinct genes encoding salivary and pancreatic amylases, but testcrosses in mice have indicated that the two putative loci must be very closely linked. We have studied crosses between two pairs of inbred mice that differ with respect to electrophoretic mobility of salivary and pancreatic amylases. Among 343 potentially recombinant chromosomes examined, no recombinants were found. Our data sets an upper limit of 0.87 cM (P = 0.95) for the distance between the salivary and pancreatic loci.


Electromagnetic interference may cause false asystole alarms in certain Philips IntelliVue monitoring products.
Electromagnetic interference (EMI) may cause some Philips Healthcare IntelliVue MMS, MP2, MP5, and X2 patient monitoring products to incorrectly display a flat electrocardiogram (ECG) waveform and generate a false asystole alarm. This occurs while the devices' pace pulse rejection feature is enabled. Facilities that suspect such behavior in their inventories should contact Philips to discuss whether installation of firmware version D.02.05 will help address the problem.


[New bridges for gaps in psychotherapeutic service provision by the internet: hopes, challenges and a solution].
Modern communication technologies such as internet, e-mail or SMS open up new possibilities for the optimization of the psychotherapeutic service provision. However, their use places new challenges. Ethical and legal requirements must be considered, technical and communicative aspects must be integrated into supplying concepts. This paper presents central requirements for the use of the Internet and a possible solution by the example of the project "Internet-Brücke" (internet bridge). In this project internet chat groups are tested as an aftercare program following inpatient treatment in a specialized hospital for psychotherapy and psychosomatic medicine. It is discussed, in what respect the solutions fit the specific requirements of this project and what can be learned for further applications.


Nucleotide specificity of the human terminal nucleotidyltransferase Gld2 (TUT2).
The nontemplated addition of single or multiple nucleotides to RNA transcripts is an efficient means to control RNA stability and processing. Cytoplasmic RNA adenylation and the less well-known uridylation are post-transcriptional mechanisms regulating RNA maturation, activity, and degradation. Gld2 is a member of the noncanonical poly(A) polymerases, which include enzymes with varying nucleotide specificity, ranging from strictly ATP to ambiguous to exclusive UTP adding enzymes. Human Gld2 has been associated with transcript stabilizing miRNA monoadenylation and cytoplasmic mRNA polyadenylation. Most recent data have uncovered an unexpected miRNA uridylation activity, which promotes miRNA maturation. These conflicting data raise the question of Gld2 nucleotide specificity. Here, we biochemically characterized human Gld2 and demonstrated that it is a bona fide adenylyltransferase with only weak activity toward other nucleotides. Despite its sequence similarity with uridylyltransferases (TUT4, TUT7), Gld2 displays an 83-fold preference of ATP over UTP. Gld2 is a promiscuous enzyme, with activity toward miRNA, pre-miRNA, and polyadenylated RNA substrates. Apo-Gld2 activity is restricted to adding single nucleotides and processivity likely relies on additional RNA-binding proteins. A phylogeny of the PAP/TUTase superfamily suggests that uridylyltransferases, which are derived from distinct adenylyltransferase ancestors, arose multiple times during evolution via insertion of an active site histidine. A corresponding histidine insertion into the Gld2 active site alters substrate specificity from ATP to UTP.


Deactivation of phosphatidylinositol 3,4,5-trisphosphate/Akt signaling mediates neutrophil spontaneous death.
Neutrophil spontaneous death plays essential roles in neutrophil homeostasis and resolution of inflammation, whereas the underlying molecular mechanisms are still ill-defined. Neutrophils die because of programmed cell death or apoptosis. However, treatment with inhibitor of caspases, which are responsible for the majority of apoptotic cell deaths, does not prevent the spontaneous death of neutrophils. PKB/Akt possesses prosurvival and antiapoptotic activities in a variety of cells. In this study, we show that Akt activity decreases dramatically during the course of neutrophil death. Both phosphatidylinositol 3-kinase and Akt inhibitors enhance neutrophil death. Conditions delaying neutrophil death, such as treatment with granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, or IFN-gamma, restore Akt activity. Finally, we demonstrate that neutrophils depleted of PTEN, a phosphatidylinositol 3'-phosphatase that negatively regulates Akt activity, live much longer than WT neutrophils. Thus, we establish Akt deactivation as a causal mediator of neutrophil spontaneous death.


Cerebrovascular reactivity after functional activation of the Brain using Photic Stimulation in Migraine and Tension Type Headache: a transcranial doppler Ultrasonography Study.
Previous studies in headache patients measured the cerebrovascular reactivity (CVR) in response to photic stimulation but they have yielded contradictory results. The purpose of study was to measure CVR of both migraine and chronic tension headache (TTH) patients in response to photic stimulation. The study included 37 migraineurs and 24 chronic TTH patients compared with 50 age- and sex-matched healthy volunteers. Peak systolic, end diastolic, mean flow velocities and CVR (PSV, EDV, MFV, and CVR) were measured using TCD ultrasonography of the middle, anterior, posterior cerebral and vertebral arteries (MCA, ACA, PCA, and VA) before and after 100 s of 14 Hz photic stimulation. A three-way repeated measures ANOVA interaction with main factors of Vessels (MCA, ACA, PCA, VA), Time (pre-post photic) and Groups (migraine, TTH, and control group) revealed significant 3-way interactions for measures of PSV (P = 0.012) and MFV (P = 0.043). In the migraine patients there was significantly higher PSV, EDV, and MFV in the MCA, ACA, and PCA after photic stimulation compared with baseline. The CVR of the MCA was also significantly higher in migraineurs than controls. In the TTH group, there was significantly higher PSV, EDV, and MFV (P = 0.003, 0.012, 0.002 respectively) in the VA after photic stimulation than at baseline. The CVR was significantly higher in the VA of TTH patients than controls. Compared with controls after photic stimulation, the higher CVR of the MCA in migraineurs and of the VA in TTH patients could be used as diagnostic tool to differentiate between the two types of headaches.


Tuberous Sclerosis Complex: A Classic Presentation.
An 11-year-old girl presented with an insidiously evolving, reddish-brown, small, hard, elevated lesion, occupying the midsection of her face, which had been present since early childhood. There were also a few small white spots over the trunk. There was no history of seizures or visual deficit, and no burning on exposure to sunlight. There were no known congenital defect noted at birth, and her parents were nonconsanguineous. There was no significant family history. There were numerous 2- to 4-mm reddish-brown papules located symmetrically on the nose, nasolabial folds, and cheeks (Figure 1A). In addition, there was an uneven 3-cm plaque in the lumbosacral region that resembled orange peel-a shagreen patch (Figure 1B). There were also two well-defined, 5- to 10-mm, hypomelanotic, ivory-white macule(s) with irregular margins (Figure 1C). The buccal mucosa and nails were unremarkable, and indirect ophthalmoscopic and slitlamp examination of the eye was normal. Laboratory studies were unremarkable. Ultrasonography of the abdomen was normal, as were abdominal and chest x-rays.


MAIT cells accumulate in placental intervillous space and display a highly cytotoxic phenotype upon bacterial stimulation.
During pregnancy, the maternal immune system must tolerate the developing foetus, and yet retain a potent antimicrobial response to prevent infections. Mucosal associated invariant T (MAIT) cells recognize microbial-derived vitamin B metabolites presented on the MR1 molecule, but their presence and function at the foetal-maternal interface is not known. We here isolated mononuclear cells from paired samples of peripheral blood (PB), intervillous blood (IVB), and decidua parietalis (DP) following uncomplicated term pregnancies. Interestingly, MAIT cells were highly enriched in IVB compared to PB and DP. The activation status of IVB MAIT cells was similar to that of PB MAIT cells, except for a lower expression of PD-1. Both IVB MAIT cells and conventional T cells were more dominated by an effector memory phenotype compared to PB MAIT cells and T cells. IVB MAIT cells also responded more vigorously with expression of IFN-γ, granzyme B, and perforin in response to Escherichia coli stimulation compared to PB. MR1 was not expressed in syncytiotrophoblasts, but in placental villous and decidual macrophages. These data indicate that maternal MAIT cells accumulate in the intervillous space of the placenta and that they are highly armed to quickly respond if bacteria are encountered at the foetal-maternal interface.


[Effect of lindane on protein nutritive utilization in trout (Salmo gairdneri) (author's transl)].
Rainbow trout weighing 100 + 10 g were fed three diets of different proteic content (67.6%, 53.2% and 36.1%) and exposed to 0.01 and 0.001 ppm of Lindane in water during 21 days. The parameters calculated were: Protein Productive Value (PPV), Conversion Index (CI) and Protein Efficiency Ratio (PER). The PPV parameter increased with a diet proteic level decrease, at control and at Lindane treated groups. Minimum protein utilization corresponds to 67.6% proteic content diet and 0.01 ppm Lindane, while maximum, to 36.1% proteic content and Lindane 0.001 ppm. The CI and PER parameters were markedly different in groups on extreme diets (67.6% and 36.1%) with higher contamination level (0.01 ppm) from all the others. The experimental parameters were not practically affected by the presence or absence of Lindane in groups on diets of medium proteic content.


Persistent fever in the ICU.
Disorders of elevated body temperature may be classified as either fever or hyperthermia. Fever is caused by a pyrogen-mediated upward adjustment of the hypothalamic thermostat; hyperthermia results from a loss of physiologic control of temperature regulation. Fever in the ICU can be due to infectious or noninfectious causes. The initial approach to a febrile, critically ill patient should involve a thoughtful review of the clinical data to elicit the likely source of fever prior to the ordering of cultures, imaging studies, and broad-spectrum antibiotics. Both high fever and prolonged fever have been associated with increased mortality; however, a causal role for fever as a mediator of adverse outcomes during non-neurologic critical illness has not been established. Outside the realm of acute brain injury, the practice of treating fever remains controversial. To generate high-quality, evidence-based guidelines for the management of fever, large, prospective, multicenter trials are needed.


Molecular hydrogen stimulates the gene expression of transcriptional coactivator PGC-1α to enhance fatty acid metabolism.
We previously reported that molecular hydrogen (H2) acts as a novel antioxidant to exhibit multiple functions. Moreover, long-term drinking of H2-water (water infused with H2) enhanced energy expenditure to improve obesity and diabetes in db/db mice accompanied by the increased expression of fibroblast growth factor 21 (FGF21) by an unknown mechanism. H2 was ingested by drinking of H2-water or by oral administration of an H2-producing material, MgH2. The comprehensive gene expression profile in the liver of db/db mice was analyzed by DNA microarray. The molecular mechanisms underlying the gene expression profile was investigated using cultured HepG2 cells. Moreover, the effects on lifespan of drinking H2-water were examined using wild-type mice that were fed a fatty diet. Pathway analyses based on comprehensive gene expression revealed the increased expression of various genes involved in fatty acid and steroid metabolism. As a transcription pathway, the PPARα signaling pathway was identified to upregulate their genes by ingesting H2. As an early event, the gene expression of PGC-1α was transiently increased, followed by increased expression of FGF21. The expression of PGC-1α might be regulated indirectly through sequential regulation by H2, 4-hydroxy-2-nonenal, and Akt/FoxO1 signaling, as suggested in cultured cell experiments. In wild-type mice fed the fatty diet, H2-water improved the level of plasma triglycerides and extended their average of lifespan. H2 induces expression of the PGC-1α gene, followed by stimulation of the PPARα pathway that regulates FGF21, and the fatty acid and steroid metabolism.


Online palliative care and oncology patient education resources through Google: Do they meet national health literacy recommendations?
The Google search engine is a resource commonly used by patients to access health-related patient education information. The American Medical Association and National Institutes of Health recommend that patient education resources be written at a level between the third and seventh grade reading levels. We assessed the readability levels of online palliative care patient education resources using 10 readability algorithms widely accepted in the medical literature. In October 2016, searches were conducted for 10 individual terms pertaining to palliative care and oncology using the Google search engine; the first 10 articles written for the public for each term were downloaded for a total of 100 articles. The terms included palliative care, hospice, advance directive, cancer pain management, treatment of metastatic disease, treatment of brain metastasis, treatment of bone metastasis, palliative radiation therapy, palliative chemotherapy, and end-of-life care. We determined the average reading level of the articles by readability scale and Web site domain. Nine readability assessments with scores equivalent to academic grade level found that the 100 palliative care education articles were collectively written at a 12.1 reading level (standard deviation, 2.1; range, 7.6-17.3). Zero articles were written below a seventh grade level. Forty-nine (49%) articles were written above a high school graduate reading level. The Flesch Reading Ease scale classified the articles as "difficult" to read with a score of 45.6 of 100. The articles were collected from 62 Web site domains. Seven domains were accessed 3 or more times; among these, www.mskcc.org had the highest average reading level at a 14.5 grade level (standard deviation, 1.4; range, 13.4-16.1). Most palliative care education articles readily available on Google are written above national health literacy recommendations. There is need to revise these resources to allow patients and their families to derive the most benefit from these materials.


A highly specific probe for sensing hydrogen sulfide in live cells based on copper-initiated fluorogen with aggregation-induced emission characteristics.
Here we reported the first fluorescent probe with aggregation-induced emission characteristics, namely AIE-S, for the detection of hydrogen sulfide (H2S) in live cells. The detection system is selective for complicated biological application and the response is fast enough to complete within seconds. Moreover, the probe exhibits the unique advantage of being immune to aggregation-caused quenching which is a detrimental phenomenon limiting the application of most current available H2S fluorescent probes. The detection mechanism was investigated and postulated to be S(2-) initiated de-coordination and thereafter aggregation of the AIE-S complex.


Eukaryotic diversity at pH extremes.
Extremely acidic (pH < 3) and extremely alkaline (pH > 9) environments support a diversity of single-cell and to a lesser extent, multicellular eukaryotic life. This study compared alpha and beta diversity in eukaryotic communities from seven diverse aquatic environments with pH values ranging from 2 to 11 using massively-parallel pyrotag sequencing targeting the V9 hypervariable region of the 18S ribosomal RNA (rRNA) gene. A total of 946 operational taxonomic units (OTUs) were recovered at a 6% cut-off level (94% similarity) across the sampled environments. Hierarchical clustering of the samples segregated the communities into acidic and alkaline groups. Similarity percentage (SIMPER) analysis followed by indicator OTU analysis (IOA) and non-metric multidimensional scaling (NMDS) were used to determine which characteristic groups of eukaryotic taxa typify acidic or alkaline extremes and the extent to which pH explains eukaryotic community structure in these environments. Spain's Rio Tinto yielded the fewest observed OTUs while Nebraska Sandhills alkaline lakes yielded the most. Distinct OTUs, including metazoan OTUs, numerically dominated pH extreme sites. Indicator OTUs included the diatom Pinnularia and unidentified opisthokonts (Fungi and Filasterea) in the extremely acidic environments, and the ciliate Frontonia across the extremely alkaline sites. Inferred from NMDS, pH explained only a modest fraction of the variation across the datasets, indicating that other factors influence the underlying community structure in these environments. The findings from this study suggest that the ability for eukaryotes to adapt to pH extremes over a broad range of values may be rare, but further study of taxa that can broadly adapt across diverse acidic and alkaline environments, respectively present good models for understanding adaptation and should be targeted for future investigations.


The Impact of Sevoflurane on Coupling of the Left Ventricular-to-Systemic Vasculature in Rats With Chronic Pulmonary Hypertension.
The relationship between left ventricular function and afterload has not been investigated as much as the right ventricular function under chronic pulmonary hypertension (PH) during anesthesia. This study was designed to investigate effects of sevoflurane on the intrinsic coupling relationship between the left ventricle and systemic vasculature in the presence of PH. A randomized, controlled study. University hospital. Sprague-Dawley rats. Monocrotaline (MCT) was injected intraperitoneally to induce a PH model. Four weeks later, rats with MCT injection demonstrated significantly increased pulmonary arterial pressure and right/left ventricular systolic ratio of ventricular pressure (p < 0.001). Rats were treated with 1.5% sevoflurane inhalation. The PV catheters were inserted and left ventricular pressure-volume loops were measured at baseline, 30, 60, and 90 minutes during sevoflurane treatment. Preload recruitable stroke work and end-systolic elastance were decreased markedly in rats with MCT injection (p < 0.05). However, arterial elastance decreased similarly in both groups. Sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) level was decreased and the expression of phospholamban (PLB) was increased in the PH group and after sevoflurane treatment. PH rats suffered further SERCA2/PLB ratio decrease from their already low baseline. The left ventricular contractility and ventricular-vascular coupling were decreased in rats with PH after sevoflurane inhalation. Sevoflurane reduced SERCA2a expression and increased PLB expression in PH rats. This partially could explain why the LV contractility and ventricular-to-vasculature coupling of PH rats were attenuated after sevoflurane treatment.


Investing in the health of future populations through a youth-focused programme.
This paper describes different approaches and results of the holistic integrated model of Rahnuma Family Planning Association of Pakistan (R-FPAP). The model seeks to provide sexual and reproductive health (SRH) services to adolescents and young people based on their rights as opposed to simply on their needs. Combined methodical efforts were performed by the organization for the provision of SRH services to adolescents and young people including youth-friendly services at clinics, outreach interventions, youth empowerment, and advocating for youth sexual and reproductive health rights (SRHR). Service delivery statistics available in the organization from 2007-2011 were utilized for estimating the results of these efforts. An increase of 157.5% in the total number of SRH services received by adolescent and young clients aged 10-24 years was observed during a span of five years. About 310.8% more human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and reproductive tract infection (RTI)/sexually transmitted infection (STI)-related services were received by the clients of the same age group. The integration of different methodical efforts helped in reaching one of every 100 adolescents and young people in Pakistan aged 10-24 years during 2011, which was an increase from four of every 1,000 adolescents and young people of the same age bracket served in year 2007. The unmet need of the SRH rights of adolescents and youth, especially underserved young clients, can be addressed comprehensively through rights-based integrated approaches by providing clinical services, involving them through outreach initiatives, advocating for their SRHR, and facilitating them by establishing conducive environments for the promulgation of supportive laws and policies.


Geometric Shape Regulation and Noncovalent Synthesis of One-Dimensional Organic Luminescent Nano-/Micro-Materials.
Noncovalent synthesis of one-dimensional (1D) organic nano-/micro-materials with controllable geometric shapes or morphologies and special luminescent and electronic properties is one of the greatest challenges in modern chemistry and material science. Control of noncovalent interactions is fundamental for realizing desired 1D structures and crucial for understanding the functions of these interactions. Here, a series of thiophene-fused phenazines composed of a halogen-substituted π-conjugated plate and a pair of flexible side chains is presented, which displays halogen-dependent 1D self-assemblies. Luminescent 1D twisted wires, straight rods, and zigzag wires, respectively, can be generated in sequence when the halogen atoms are varied from the lightest F to the heaviest I. It was demonstrated that halogen-dependent anisotropic noncovalent interactions and mirror-symmetrical crystallization dominated the 1D-assembly behaviors of this class of molecules. The methodology developed in this study provides a potential strategy for constructing 1D organic materials with unique optoelectronic functions.


Entering the duodenal diverticulum: a method for cannulation of the intradiverticular papilla.
Successful cannulation of the common bile duct may be difficult in patients in whom the papilla is located entirely within a diverticulum. In this study, we report successful biliary cannulation in three patients following intubation of the distal tip of the duodenoscope into the duodenal diverticulum and locating the major papilla. No complications occurred during the operation or during the postoperative period. This method didn't need second incubation an endoscope and might lower the burden of patients. So this skill is useful to deal with the papilla hidden inside the large diverticulum because of its safety and convenience.


Cholesterol metabolism in patients with hemodialysis in the presence or absence of coronary artery disease.
Little is known about the interrelationship between the lipid profile, cholesterol metabolism, and coronary risk factors in patients with hemodialysis (HD) in the presence or absence of coronary artery disease (CAD). Ninety-five patients with HD were selected (HD group). Fifty-eight age-, gender-, and body mass index (BMI)-matched patients who had at least 1 cardiovascular risk factor were selected as a non-HD group. Total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), non-HDL-C, and the ratio of LDL-C to HDL-C (L/H) in the HD group were significantly lower than those in the non-HD group. All markers of cholesterol absorption (campesterol/TC, sitosterol/TC, and cholestanol/TC) and the ratio of campesterol to lathosterol in the HD group were significantly higher. In addition, in the HD group, L/H was negatively correlated with lathosterol/TC, campesterol/TC, sitosterol/TC, and cholestanol/TC. Finally, CAD was significantly associated with lathosterol/TC (P=0.028), which was positively associated with BMI in the HD group, whereas CAD was significantly associated only with hypertension (P=0.020) in the non-HD group. HD patients showed lower cholesterol concentrations than non-HD patients, and, as compensation, their cholesterol absorption might be accelerated. However, higher cholesterol synthesis, which was correlated with higher BMI, might be an independent predictor for the presence of CAD in HD patients.


Recombinant human granulocyte colony-stimulating factor increases circulating burst forming unit-erythron and red blood cell production in patients with severe human immunodeficiency virus infection.
Erythropoietin (EPO) is a major regulatory factor controlling red blood cell (RBC) production in humans. Although other humoral factors can alter the proliferation of committed early erythroid progenitors in vitro, no factor other than EPO has been clearly shown to induce proliferation of these cells in vivo. In a clinical trail of recombinant granulocyte colony-stimulating factor (G-CSF) and recombinant EPO in patients with advanced human immunodeficiency virus (HIV) infection, we noted reticulocytosis and increases in hemoglobin when G-CSF was administered before the administration of EPO. Subsequent studies demonstrated a significant increase in circulating burst forming unit-erythron (BFU-E) during daily recombinant G-CSF therapy. This increase was both time- and dose-dependent. The magnitude of increase in BFU-E correlated with the magnitude of increase in neutrophils and was associated with a mean increase in reticulocytes of 32,363/microL and a significant increase in mean hemoglobin of 1.04 +/- 0.34 g/dL over an 18-day interval. There was a significant increase in iron binding capacity and decreases in iron saturation and ferritin levels. In patients who were not recently transfused, there was an associated fall in endogenous erythropoietin levels. The increase in RBC production was most marked in patients who were severely anemic, transfusion-dependent, and who had elevated pretreatment EPO levels. There was no correlation between the increase in BFU-E and endogenous EPO levels or the time since last dose of zidovudine. The addition of recombinant EPO therapy three times weekly to patients did not result in further significant increases in BFU-E but did significantly increase hemoglobin. Our data suggest that recombinant G-CSF may be one of the hematopoietic factors that influences production of BFU-E and RBCs in humans.


General Approach to the Immobilization of Glycoenzyme Chains Inside Calcium Alginate Beads for Bioassay.
A general method to obtain the efficient entrapment of mixtures of glycoenzymes in calcium alginate hydrogel is proposed in this paper. As a proof of principle, three glycoenzymes acting in series (trehalase, glucose oxidase, and horseradish peroxidase) have been coimmobilized in calcium alginate beads. The release of the enzymes from the hydrogel mesh (leakage) is avoided by exploiting the enzyme's aggregation induced by the concanavalin A. The aggregation process has been monitored by dynamic light scattering technique, while both enzyme encapsulation efficiency and leakage have been quantified spectrophotometrically. Obtained data show an encapsulation efficiency above 95% and a negligible leakage from the beads when enzyme aggregates are larger than 300 nm. Operational stability of "as prepared" beads has been largely improved by a coating of alternated shells of polycation poly(diallyldimethylammonium chloride) and of alginate. As a test for the effectiveness of the overall procedure, analytical bioassays exploiting the enzyme-containing beads have been developed for the optical determination of glucose and trehalose, and limit of detection values of 0.2 and of 40 μM, respectively, have been obtained.


[Severe neonatal thrombopenia. Analysis of the etiologic data on 64 cases].
In many cases of neonatal thrombocytopenia, etiology does not fit with usually known causes. Analyzing, in an intensive care unit, 64 cases of severe neonatal thrombocytopenia (platelets less than 50 x 10(9)/l before hour 72), the authors attempted to determine other possible causes of the disorder. In this study, classical etiologies were present in 33% of cases. In the other 67%, hypotrophy and/or hypoxia were significantly more frequent (p less than 0.01) than in the first group. With reference to clinical and experimental data in the literature, the possible role of acute or chronic hypoxia as a cause of thrombocytopenia is discussed.


Efficacy of a couple-based randomized controlled trial to help Latino fathers quit smoking during pregnancy and postpartum: the Parejas trial.
Although many Latinos in the United States smoke, they receive assistance to quit less often than non-Latinos. To address this disparity, we recruited Latino couples into a randomized controlled trial and provided a smoking cessation program during a teachable moment, when men's partners were pregnant. We compared two interventions: (i) written materials plus nicotine replacement therapy (NRT) to (ii) materials, NRT, and couple-based counseling that addressed smoking cessation and couples communication. We recruited 348 expectant fathers who smoked via their pregnant partners from county health departments. Our primary outcome was 7-day point prevalence smoking abstinence and was collected from November 2010 through April 2013 and analyzed in February 2014. We found high rates of cessation but no arm differences in smoking rates at the end of pregnancy (0.31 vs. 0.30, materials only vs. counseling, respectively) and 12 months after randomization (postpartum: 0.39 vs. 0.38). We found high quit rates among nondaily smokers but no arm differences (0.43 vs. 0.46 in pregnancy and 0.52 vs. 0.48 postpartum). Among daily smokers, we found lower quit rates with no arm differences but effects favoring the intervention arm (0.13 vs. 0.16 in pregnancy and 0.17 vs. 0.24 postpartum). A less intensive intervention promoted cessation equal to more intensive counseling. Postpartum might be a more powerful time to promote cessation among Latino men. Less intensive interventions when delivered during teachable moments for Latino men could result in a high smoking cessation rate and could reduce disparities.


Alisol A is potentially therapeutic in human breast cancer cells.
Recent developments in breast cancer therapy have significantly improved patient survival rate; however, recurrence remains a major problem. Systemic treatment of breast cancer with available therapies is not curative. Natural products can be potentially used for treating cancer. Recently, a wide range of pharmacological activities has been reported for Alismatis Rhizoma, a popular traditional Chinese medicine. However, the mechanisms via which its compounds act on breast cancer remain unclear. The present study aimed to investigate the potential of natural therapeutic agents from Alismatis Rhizoma for treating breast cancer. Human breast cancer MDA‑MB‑231 cells were treated with four main protostane triterpenes from Alismatis Rhizoma, including alisol A, alisol A 24‑acetate, alisol B and alisol B 23‑acetate. Among these, alisol A significantly inhibited cell viability. Alisol A induced cell apoptosis, G1 phase cell cycle arrest, autophagy, and intracellular reactive oxygen species (ROS) generation in MDA‑MB‑231 cells. The number of APE1‑/γH2AX‑/LC3‑II positive cells was also significantly higher compared with that of negative control cells. All these results were dose‑dependent. Cleaved caspase‑3, cleaved caspase 9, Bcl‑2, and p‑p38 expression indicated cell apoptosis after alisol A treatment. The changes in cyclin A and cyclin D1 expression was associated with cell cycle arrest upon alisol A treatment. Furthermore, LC3‑II expression upon alisol A treatment was indicative of autophagy. Alisol A treatment can induce autophagy‑dependent apoptosis in human breast cancer cells via induction of ROS and DNA damage. Thus, Alisol A might serve as a new therapeutic agent against breast cancer.


Genetic analysis of sperm and implications of severe male infertility--a review.
The use of fluorescence in situ hybridization (FISH) on decondensed sperm heads has allowed to analyse the chromosome constitution of spermatozoa in different populations. In controls, the mean incidence of disomy (including all chromosomes) is about 6.7 per cent; diploidy increases with age, and some individuals may show a special tendency to nondisjunction. Carriers of numerical sex chromosome anomalies show a low incidence of sex chromosome disomies (2.54-7.69 per cent), and the need to screen ICSI candidates for these conditions has to be reconsidered. Carriers of inversions produce from 0 to 54.3 per cent abnormal sperm. Carriers of Robertsonian translocations produce from 3.4 to 36.0 per cent abnormal sperm, and carriers of reciprocal translocations produce from 47.5 to 81.0 per cent abnormal spermatozoa. However, carriers of translocations usually produce more abnormal embryos than expected from these figures. This may be partly related to interchromosomal effects induced by some structural reorganizations. Males with oligoasthenozoospermia, low motility and/or high FSH concentrations show frequent synaptic anomalies, resulting in the production of aneuploid and diploid sperm. Testicular sperm show extremely high rates of chromosomal abnormalities. The risk of recurrent abortion is increased by the presence of chromosome abnormalities in sperm.


Utility of point-of-care ultrasound in patients with suspected diverticulitis in the emergency department.
In emergency department (ED) cases with clinically suspected diverticulitis, diagnostic imaging is often needed for diagnostic confirmation, to exclude complications, and to direct patient management. Patients typically undergo a CT scan in the ED; however, in a subset of cases with suspected diverticulitis, point-of-care ultrasound (POCUS) may provide sufficient data to confirm the diagnosis and ascertain a safe plan for outpatient management.We review the main sonographic features of diverticulitis and discuss the diagnostic accuracy and potential benefits of a POCUS First model.


Effect of Vitamin D Supplementation on Lipid Profile in Vitamin D-Deficient Children with Type 1 Diabetes and Dyslipidemia.
Vitamin D (VD) was suggested to have both direct and indirect effects on modifying lipid profile in patients with diabetes through its regulatory action that increases the activity of lipoprotein lipase in adiposity. To detect the relationship between serum 25-hydroxyvitamin D (25OHD) and lipid profiles in dyslipidemic T1D patients and study the effect of VD supplementation on lipid profiles of VD-deficient T1D patients. Fifty patients with T1D (for >2 years) and dyslipidemia were included. 25OHD was assessed and patients were divided accordingly into 2 groups: VD sufficiency (>30 ng/mL) and VD deficiency (VDD) or insufficiency (<29 ng/mL) who were allocated to VD3 supplementation for 4 months, then lipid profile was reevaluated in both groups. Thirty patients had VDD, while 20 patients had VD sufficiency. There was no significant correlation between 25OHD and different study parameters (p > 0.05). A significant difference was found among both groups in the family history of coronary heart disease (p = 0.036) and free tetraiodothyronine 4 (p = 0.035). After 4 months of VD supplementation in VDD group, the mean difference (at 0 and 4 months) in low-density lipoproteins (LDL) and hemoglobin A1c (HbA1c) was statistically significant (p = 0.02 and 0.04 respectively) between both groups. The mean basal LDL was 126.91 mg/dL in VDD group that improved to 117.13 mg/dL after 4 months of VD therapy with a mean difference of -9.7 mg/dL compared to a mean difference of -2 mg/dL in VD sufficiency group. VDD was highly prevalent in patients with T1D. There was no significant correlation between 25OHD levels and lipid profile in patients with T1D. VD supplementation for 4 months had a significant lowering effect on LDL and HbA1c.


Modelling extracellular electrical stimulation: part 4. Effect of the cellular composition of neural tissue on its spatio-temporal filtering properties.
The objective of this paper is to present a concrete application of the cellular composite model for calculating the membrane potential, described in an accompanying paper. A composite model that is used to determine the membrane potential for both longitudinal and transverse modes of stimulation is demonstrated. Two extreme limits of the model, near-field and far-field for an electrode close to or distant from a neuron, respectively, are derived in this paper. Results for typical neural tissue are compared using the composite, near-field and far-field models as well as the standard isotropic volume conductor model. The self-consistency of the composite model, its spatial profile response and the extracellular potential time behaviour are presented. The magnitudes of the longitudinal and transverse components for different values of electrode-neurite separations are compared. The unique features of the composite model and its simplified versions can be used to accurately estimate the spatio-temporal response of neural tissue to extracellular electrical stimulation.


In vivo measured joint friction in hip implants during walking after a short rest.
It has been suspected that friction in hip implants is higher when walking is initiated after a resting period than during continuous movement. It cannot be excluded that such increased initial moments endanger the cup fixation in the acetabulum, overstress the taper connections in the implant or increase wear. To assess these risks, the contact forces, friction moments and friction coefficients in the joint were measured in vivo in ten subjects. Instrumented hip joint implants with telemetric data transmission were used to access the contact loads between the cup and head during the first steps of walking after a short rest. The analysis demonstrated that the contact force is not increased during the first step. The friction moment in the joint, however, is much higher during the first step than during continuous walking. The moment increases throughout the gait cycle were 32% to 143% on average and up to 621% individually. The high initial moments will probably not increase wear by much in the joint. However, comparisons with literature data on the fixation resistance of the cup against moments made clear that the stability can be endangered. This risk is highest during the first postoperative months for cementless cups with insufficient under-reaming. The high moments after a break can also put taper connections between the head and neck and neck and shaft at a higher risk. During continuous walking, the friction moments individually were extremely varied by factors of 4 to 10. Much of this difference is presumably caused by the varying lubrication properties of the synovia. These large moment variations can possibly lead to friction-induced temperature increases during walking, which are higher than the 43.1°C which have previously been observed in a group of only five subjects.


[Thermographic examination of cutaneous melanocytic nevi].
Comparative examination with dermoscopy, thermography, and histopathology of cutaneous melanocytic nevi. The study was done in 245 patients with 735 melanocytic nevi and in 12 patients with malignant melanoma. All melanocytic lesions were studied with Heine delta 10 dermatoscope and the total dermatoscopy score (TDS) was calculated. ThermaCAM S.C.500 thermographic camera was used to measure the maximal (Tmax), minimal (Tmin), and average temperatures and to calculate the difference between maximal and minimal temperatures deltaT (degrees C) = Tmax - Tmin for all lesions. Histopathology was performed in the case of 127 melanocytic nevi and 12 malignant melanomas. Statistical analysis was done using Statistica 6.0 software. Mean values in the groups were compared with Student's t-test and Pearson's linear correlation coefficient (r) was calculated to disclose relationships between variables. TDS was 4.03 +/- 0.68 for all 735 melanocytic nevi, 3.89 +/- 0.30 for 554 ordinary melanocytic nevi, 5.19 +/- 0.21 for 181 atypical melanocytic nevi, and 5.96 +/- 0.25 for 12 malignant melanomas. Mean maximal temperature for all 735 melanocytic nevi was 33.5 +/- 0.3 degrees C and did not differ significantly from the control group (33.2 +/- 0.6 degrees C; p > 0.05). Mean maximal temperature was 33.1 +/- 0.7 degrees C (p > 0.05) for 554 benign melanocytic nevi, 33.7 +/- 0.4 degrees C (p < 0.05) for 181 atypical melanocytic nevi, and 34.1 degrees 0.8 degrees C (p < 0.01) for 12 malignant melanomas. Mean average temperature for all 735 melanocytic nevi was 31.9 +/- 1.0 degrees C and did not differ significantly from the control group (31.8 +/- 0.9 dgrees C; p > 0.05). Mean average temperature was 31.8 +/- 1.0 degrees C (p > 0.05) for 554 benign melanocytic nevi, 32.0 +/- 1.1 degrees C (p > 0.05) for 181 atypical melanocytic nevi, and 33.0 +/- 0.9 degrees C (p < 0.01) for 12 malignant melanomas. Mean deltaT (degrees C) for all melanocytic nevi was 1.2 +/- 0.2 and did not differ significantly from the control group (1.1 +/- 0.2; p > 0.05). Mean deltaT (degrees C) was 1.1 +/- 0.3 (p > 0.05) for 554 benign melanocytic nevi, 1.39 +/- 0.28 (p < 0.001) for 181 atypical melanocytic nevi, and 1.6 +/- 0.4 (p < 0.001) for 12 malignant melanomas. Positive correlations were found between the results of dermoscopic, thermographic, and histopathologic examination of melanocytic nevi. (1) Thermography may supplement dermoscopy during examination of atypical melanocytic nevi and other skin lesions suspected of neoplastic metaplasia. (2) Dermoscopic findings (including TDS) correlate with thermographic findings--including deltaT (degrees C), as well as with histopathologic findings. (3) Melanocytic nevi demonstrating delta (degrees C) > 1.4 and TDS > 4.75 require surgical intervention or follow-up for neoplastic metaplasia. (4) Average temperatures of benign and atypical melanocytic nevi do not differ significantly from the average temperature of the skin without pigmented lesions.


Effects of salmon calcitonin in postmenopausal osteoporosis: a controlled double-blind clinical study.
In this paper we present the results of a 12-month double-blind clinical multicenter study assessing the effects of synthetic salmon calcitonin (CT) administration in a group of white postmenopausal osteoporotic women. Treated patients were given 100 MRC units of synthetic salmon CT injected i.m. in the morning every other day. Control patients received a placebo injection. All patients received 500 mg of elementary calcium p.o., b.i.d. Bone mineral content (BMC) was measured at the extreme distal radius of the nondominant arm by a dual photon bone densitometer which utilizes two radionuclides, 241Am and 125I, with energies of about 60 keV and 30 keV respectively. Biochemical parameters of calcium-phosphorus metabolism were also measured. After 12 months of treatment a significant mean increment of BMC and nondialyzable OHPr/creatinine values and a significant decrease of total OHPr/creatinine values were observed in the treated group, while controls showed a significant decrease in BMC values. These results, together with the observation that in some patients the decrease in total OHPr/creatinine values was not accompanied by an increment of BMC, show that long-term salmon CT treatment may be of benefit in postmenopausal osteoporosis and that the effects of CT on bone mass may be due not only to the inhibition of bone resorption but also to the stimulation of bone formation.


Targeted tissue perfusion versus macrocirculation-guided standard care in patients with septic shock (TARTARE-2S): study protocol and statistical analysis plan for a randomized controlled trial.
Septic shock has a 90-day mortality risk of up to 50 %. The hemodynamic targets, including mean arterial pressure (MAP) are not based on robust clinical data. Both severe hypotension and high doses of vasopressors may be harmful. Hence, re-evaluation of hemodynamic targets in septic shock is relevant. The targeted tissue perfusion versus macrocirculation-guided standard care in patients with septic shock (TARTARE-2S) trial is a prospective, two-parallel-group, randomized, open-label, multicenter trial with assessor-blinded outcome evaluation. We will randomize at least 200 patients with septic shock in four European intensive care units (ICUs) to test whether a tissue perfusion-guided treatment strategy based on capillary refill time, peripheral temperature, arterial lactate concentrations, and accepting lower MAP levels, leads to a faster resolution of shock than macrocirculation target-guided standard care. The primary outcome measure is days alive in 30 days with normal arterial blood lactate (first value of <2 mmol/L) and without any inotropic or vasopressor agent. Secondary outcomes include individual components of the primary outcome, days alive without renal replacement, days alive without mechanical ventilation in 30 days, and new acute kidney injury. The sample size enables detection of a 13.5-h difference in the primary outcome with a type 1 error of 5 % and power of 80 %, assuming 25 % mortality and a mean of 650 h (SD 30) among the 30-day survivors. After 150 included patients the statistician masked for allocation group will recalculate the sample size potentially increasing the sample up to 300. The Data Safety and Monitoring Board (DSMB) will review the safety data after 100 patients. The TARTARE-2S trial will provide important clinical data on treatment targets in septic shock, evaluating the impact of clinical tissue perfusion-guided hemodynamic treatment on a surrogate outcome combining resolution of shock (hyperlactatemia and vasopressors/inotropes), and 30-day mortality. ClinicalTrials.gov: NCT02579525 . Registered on 19 October 2015.


Enhancing the role of radiotherapy in non-small cell lung cancer.
Radiation therapy plays an important role in the treatment of patients with unresectable non-small cell lung cancer. Local control rates with past radiation therapy techniques have been poor, in the range of 10% to 15%. Recent advances in dose planning and delivery, as well as radiation biology, offer the promise of improved control and better protection of dose limiting normal tissues.


[Feeding practices in infants: a 6-month prospective cohort study].
The aims of this work were to assess timing of complementary feeding in infants and to precise the underlying factors that may cause inappropriate complementary feeding. A cohort of 167 newborns, born in the same maternity ward during a 6 week-period, was prospectively analyzed. Only healthy neonates were included in the study. A phone questionnaire was filled at 4 and 6 months of age to evaluate modality of complementary feeding. Multivariate analysis (segmentation tree, analyse by multiple correspondence) was used to study factors associated with inappropriate diversification. Out of the 167 neonates included in the study, 132 mothers could be contacted at 4 months and 116 at 6 months of age. Sixty-seven per cent of mothers started breast feeding at birth. Among these, 33% still breastfed -at least partially- at 4 months and 17% at 6 months. Fifty-two percent of mothers started complementary feeding before 4 months, and 24% of infants received gluten at 4 months of age. Multi-gravida mothers, mothers aged more than 35 years old and mothers who gave infant or follow-up formulae before 4 months, started complementary feeding significantly earlier (P<0.05). Infants who were formula fed received more frequently complementary feeding before the age of 4 months than breast fed infants (57% vs 33%, P<0.05). Our study showed that half of infants were introduced solid food too early and allowed to identify a population at risk that could benefit from nutritional intervention programs.


Angina bullosa hemorrhagica: report of 4 cases.
Angina bullosa hemorrhagica is characterized by the sudden appearance of solitary or multiple hemorrhagic blisters on oral mucosa, with diameters ranging from 2 mm to 3 cm. The soft palate is most commonly affected, but angina bullosa hemorrhagica may also appear on the buccal mucosa, lips and tongue border. Clinically, the blisters have a dark red to purple appearance, and may or may not be painful. The blisters usually break, releasing bloody content and leaving an ulcer surface that heals within 7 to 10 days. In this article the authors describe four cases of angina bullosa hemorrhagica attended in Stomatology Department of Dental School, Sao Paulo State University. In case 1, a 29-year-old male presented with a sudden hemorrhagic blister on the soft palate. A drainage was performed and after seven days of follow-up the patient reported no symptoms. In case 2, a 63-year-old male presented complaining of a blister on the palate six days earlier that had spontaneously broken. General exam showed hypertension under medical control. An incisional biopsy was performed and after seven days follow-up the healing was completed. In case 3, a 61-year-old male arrived complaining of a sudden appearance of an hemorrhagic blister on the soft palate that had spontaneously broken. The patient had systemic hypertension under medical control. The ulcer healed in 10 days follow-up. In case 4, a 49-year-old woman presented complaining of pain and an ulcer on the soft palate. The patient reported the rapid onset of a blood blister during a meal that broke in few minutes. The resolution occurred after 14 days. Angina bullosa hemorrhagica seems to be more common than reported in the literature and knowledge of the condition is important to right diagnosis and approach when necessary.


Perceptual organization, visual attention, and objecthood.
We have previously demonstrated that the mere organization of some elements in the visual field into an object attracts attention automatically. Here, we explored three different aspects of this automatic attentional capture: (a) Does the attentional capture by an object involve a spatial component? (b) Which Gestalt organization factors suffice for an object to capture attention? (c) Does the strength of organization affect the object's ability to capture attention? Participants viewed multi-elements displays and either identified the color of one element or responded to a Vernier target. On some trials, a subset of the elements grouped by Gestalt factors into an object that was irrelevant to the task and not predictive of the target. An object effect - faster performance for targets within the object than for targets outside the object - was found even when the target appeared after the object offset, and was sensitive to target-object distance, suggesting that the capture of attention by an object is accompanied by a deployment of attention to the object location. Object effects of similar magnitude were found for objects grouped by a combination of factors (collinearity, closure, and symmetry, or closure and symmetry) or by a single factor when it was collinearity, but not symmetry, suggesting that collinearity, or closure combined with symmetry, suffices for automatic capture of attention by an object, but symmetry does not. Finally, the strength of grouping in modal completion, manipulated by varying contrast polarity between and within elements, affected the effectiveness of the attentional capture by the induced object.


Bracing versus casting in ankle fractures.
Casting and splinting techniques for treating patients with fractures have been used for centuries. Functional bracing after ankle fracture has recently been utilized in an effort to avoid the atrophy and stiffness sometimes associated with casting; functional bracing allows for early mobilization of the ankle joint during recovery. Our review investigated the published literature comparing bracing with casting after ankle fracture. Studies examining both operatively and nonoperatively treated ankle fractures were included. There is minimal evidence supporting the use of functional bracing over cast immobilization to improve functional outcome, range of motion, swelling, or post-traumatic arthrosis after ankle fracture in the long term. The primary benefits of functional bracing are the potential to return to work earlier and bracing may facilitate activities of daily living, such as bathing and dressing. In addition, there may be a decreased patient risk of developing deep vein thrombosis due to immobilization. However, there is an increased risk of wound infection when using a brace after open reduction and internal fixation of an unstable ankle fracture. Functional bracing can be used for treating stable and postoperative ankle fractures in compliant patients to potentially expedite and facilitate the recovery process.


Evaluating culture practices used to identify infection in patients with brain injury.
The neurosurgical intensive care unit staff at Harborview Medical Center, Seattle, Washington, had a strong desire to implement strategies to lower temperatures in their patients with brain injury because the patients with elevated temperatures often have lower Glasgow Coma Scores. In addition, neurologic improvement was demonstrated when high temperatures were lowered. Hospital policy dictated that temperatures be allowed to climb to more than 38.5°C before treatment because this temperature was used as the trigger for culture collection every 24 hours. The expressed rationale was that temperature management would obscure the trigger and infections would be missed. Thus, the investigators wanted to determine whether temperature elevation was a reliable indicator of infection. A quality improvement tool was developed, and the patient populations to be evaluated were those admitted with the diagnosis of subarachnoid hemorrhage, arteriovenous malformation, or traumatic brain injury. The number of times each patient was cultured and whether he or she was cultured because of temperature, a white blood cell count elevation, or clinical indicators were tracked. Findings showed that the use of temperature as a screening indicator for infection produced few positive cultures and that the practice of daily cultures yielded few positive results generally. Conclusions made from the data were that temperature is not an accurate indicator of infection in these patients with brain injury and fever management would not adversely impact infection identification. Policy within the Neuroscience intensive care unit was changed to reflect these findings.


Quality of life and smoking among industrial workers in Greece.
Smoking is a predictor of quality of life, while socio-economic factors influence the prevalence of smoking habits. Occupational medical research has been fairly late in coming to study quality of life aspects in working populations. The aim of the study is the assessment of smoking prevalence among blue- and white-collar workers industrial workers in Greece and its impact on health-related quality of life. In a cross-sectional study the Euro-Qol 5D questionnaire was been used in a random sample of 472 blue and white-collar heavy industry workers. 57% of the study population were current smokers. The difference in prevalence of smoking across all the examined socio-demographic variables (sex, age, education and occupation) was not statistically significant. Smoking had a significant impact on the health-related quality of life. Smokers recorded significant lower scores (74.9) in the overall Visual Analogue Scale in comparison with non-smokers (79.1), (p = 0.007). Further analysis revealed that age, smoking and education were significant predictors of VAS score. A non-significant contribution was found for occupation and sex. Smokers reported significantly higher rates of problems regarding mobility, self-care and anxiety/depression than non-smokers. Logistic regression analysis showed an independent impact of smoking on mobility, self-care and anxiety/depression level. Smoking is a significant hazard and a strong predictor of poor quality of life among the blue- and white-collar workers under study. Anti-smoking policies integrated into a broader context of occupational health and safety at work could reduce smoking rates and thus improve worker's quality of life.