Complete genome sequence of the extreme-pH-resistant Salmonella bacteriophage αα of the family Microviridae.
A novel Salmonella bacteriophage (phage), named αα, was the first reported member of the family Microviridae to exhibit tolerance to both extreme acidic and alkaline conditions (pH 2-12 for 1 h). Phage αα has a circular single-stranded DNA genome of 5,387 nt with a G+C content of 44.66%. A total of 11 putative gene products and no tRNA genes are encoded in the phage αα genome. Whole-genome sequence comparisons revealed that phage αα shares 95% identity with coliphage phiX174 and had a close evolutionary relationship to the phages NC1 and NC7. Phylogenetic analysis of the structural proteins of phage αα and 18 other phiX174-like phages showed that a phylogenetic tree based on protein B sequences had a topology similar to that obtained using whole genome sequences. In addition, variable sites in proteins F and G distributed on the surface of the mature capsid and the conserved protein J were probably involved in maintaining the structural integrity of the phage under extreme pH conditions. Our findings could open up new perspectives for identifying more extreme-pH-resistant phages and their structural proteins and understanding the mechanism of phage adaptation and evolution under extreme environmental stress.


[Growth of a turbidostatic culture of yeast under conditions of thermal stress at various pH's of the media].
A turbidostat Saccharomyces cerevisiae 14 culture was grown at pH 6.0 to 2.25 and subjected to a heat pulse (the optimal temperature of 30 degrees C was elevated to 37.5 degrees C) in order to study its response. The growth rate was determined in the first cell generation after the pulse. The culture grown at pH 6-4 was shown to be thermotolerant whereas the yeast was thermosensitive at pH 2.4-2.25. The cells became thermotolerant at 37.5 degrees C after the transitions: pH 2.25----4 and pH 2.35----4. The yeast thermoresistance was shown to depend on H+ concentration. Apparently, the yeast thermotolerance was determined by the effective functioning of the chemo-osmotic system.


Amyloid peptide attenuates the proteasome activity in neuronal cells.
Previous studies have suggested a possible relationship between the ubiquitin-proteasome pathway and some pathological manifestations of Alzheimer's disease (AD). This study investigated the possibility that the Abeta peptides interact with the ubiquitin-proteasome pathway inside neuronal cells. The ubiquitin-proteasome activity decreased with age in the brains of Tg2576 mice while the Abeta(1-42) levels increased. In cultured neuronal cells, an extracellular treatment of Abeta markedly decreased the proteasome activity and extracellular treated Abeta peptides were found in the cytoplasmic compartment. These results suggest that the extracellular Abeta peptides enter the cell and inhibit the proteasome activity, which might play a role in the pathogenesis of AD.


A helix-loop-helix protein related to the immunoglobulin E box-binding proteins.
A human cDNA encoding a novel protein in the helix-loop-helix family has been isolated by screening a bacteriophage expression library with a probe containing the binding site for major late transcription factor. The protein encoded by this cDNA, TFEB, probably recognizes E-box sequences in the heavy-chain immunoglobulin enhancer.


A new method for off-line removal of ocular artifact.
A new off-line procedure for dealing with ocular artifacts in ERP recording is described. The procedure (EMCP) uses EOG and EEG records for individual trials in an experimental session to estimate a propagation factor which describes the relationship between the EOG and EEG traces. The propagation factor is computed after stimulus-linked variability in both traces has been removed. Different propagation factors are computed for blinks and eye movements. Tests are presented which demonstrate the validity and reliability of the procedure. ERPs derived from trials corrected by EMCP are more similar to a 'true' ERP than are ERPs derived from either uncorrected or randomly corrected trials. The procedure also reduces the difference between ERPs which are based on trials with different degrees of EOG variance. Furthermore, variability at each time point, across trials, is reduced following correction. The propagation factor decreases from frontal to parietal electrodes, and is larger for saccades than blinks. It is more consistent within experimental sessions than between sessions. The major advantage of the procedure is that it permits retention of all trials in an ERP experiment, irrespective of ocular artifact. Thus, studies of populations characterized by a high degree of artifact, and those requiring eye movements as part of the experimental task, are made possible. Furthermore, there is no need to require subjects to restrict eye movement activity. In comparison to procedures suggested by others, EMCP also has the advantage that separate correction factors are computed for blinks and movements and that these factors are based on data from the experimental session itself rather than from a separate calibration session.


Successful thoracoscopic resection of a large mediastinal liposarcoma.
We report a case of a rare, large mediastinal liposarcoma diagnosed in a 74-year-old woman after a syncopal episode. Chest roentgenogram and computed tomographic scan showed a large mass occupying most of the right chest and abutting the great vessels and pericardium. A thoracoscopic approach was used for exploration and surgical excision of this large mediastinal mass. Despite the large size of the mass, the thoracoscopic approach offered excellent visualization of all the mass attachments and required only a small extension of the access incision for tumor removal. The mass was a well-differentiated liposarcoma, which was completely resected with clear margins. The patient remains disease-free almost 3 years after the resection.


Is the Robinson classification of clavicle fractures accurate enough within the setting of the Swedish Fracture Register?
In the Swedish Fracture Register (SFR) clavicle fractures are classified according to the Robinson classification. This study aimed to evaluate the accuracy of the classification of clavicle fractures in the SFR. A secondary aim was to assess inter- and intraobserver agreement. Clavicle fractures (n = 132) were randomly selected from the SFR and radiographs were requested for each patient from their treating departments. Not all radiographs could be acquired, and after exclusion, 115 fractures were independently classified by three expert raters blinded to patient information. The 115 fractures were classified on two occasions, 3 months apart. The raters' consensus classification was used as a gold standard that was compared to the classification registered in the SFR. The accuracy, defined as the degree of agreement between the gold standard and SFR classifications, was reported, as was the inter- and intraobserver agreement for the expert raters. Agreement between the classification in the SFR and the gold standard classification was fair (kappa = 0.35). Fractures with only partial displacement were often incorrectly classified as fully displaced in the SFR (n = 31 of 78 displaced fractures in the SFR). The inter- and intraobserver agreement among the expert raters was almost perfect (interobserver kappa = 0.81-0.87, intraobserver kappa = 0.84-0.94). The accuracy of the classification of clavicle fractures in the SFR was only fair, whereas the inter- and intraobserver agreement among the expert raters was almost perfect. Accuracy in the SFR may be improved if the classification instructions in the SFR are updated by incorporating the original classification displacement criteria, both in text and in illustrated form.


Intellectual outcome, motor skills and BMI of children with congenital hypothyroidism: a population-based study.
To evaluate intellectual outcome, motor skills and anthropometric data of children with congenital hypothyroidism (CH). Children with permanent CH who were born in 1999 in Bavaria were eligible for this prospective, population-based study. Cognitive performance was evaluated by the Kaufman Assessment Battery for Children and motor skills were assessed by the motor test, Motoriktest für vier-bis sechsjahrige Kinder (MOT) 4-6. Eighteen of 21 eligible children participated (86%). Median age of the children was 5.5 years (range 4.9-5.8). Treatment with levothyroxine was started after a median of 7.2 days (range 4-15) with a median dose of 12.0 microg/kg (range 7.2-17.0). Mean intelligence quotient (IQ) of the children was 100.4 (standard deviation [SD] 10.1): no children had IQ values below the normal range. Reactivity and speed of movement were significantly reduced in children with CH. Children with an initial thyroid-stimulating hormone (TSH) value of >200 mU/L performed significantly worse than children with TSH value of <or=200 mU/L (p=0.003). Children with CH had a significant increased risk for overweight (risk ratio [RR] 3.91, 95% confidence interval [CI] 1.22-11.75, p=0.005) compared to the Bavarian reference children. In this study, children with CH had an increased prevalence of overweight compared to reference data. Partially impaired motor skills could be shown, whereas the intellectual development was normal.


The 13-year observation of hip fracture in Poland-worrying trend and prognosis for the future.
Hip fractures are often considered to be one of the most common osteoporotic fractures. In our previous study, we noted the increasing trend in the total number of hip fractures as well as crude and standardized rates, for both women and men. This observation enabled us to delve deeper into the study of osteoporotic fractures. Hospital records between 1.01.2002 and 31.12.2014 with ICD-10 codes S72.0. S72.1 and S72.2 (femoral neck. intertrochanteric, subtrochanteric, and inter and subtrochanteric fracture) were analysed. All fractures occurred in citizens who lived in the district Tarnowskie Góry and the city of Piekary Śląskie aged 50 years and more. 1507 fragility hip fractures (400 in men, and 1107 in women) were registered. The rates increase in both sexes was still observed. The tendency to sustain fractures was lower in female (29.3%) than in the male population (63.6%). We observed a lower increase in urban (35.8%) population when compared to rural (40.8%) population. Incidence rate ratios for female gender were 1.89 (95% CI 1.65-2.18). The rates in 2014 were as follows: crude rate of 216.2 (men 140.9; women 276.5) and standardized 183.9 (131.6 and 219.4, respectively). This observation allowed as to project a total crude rate of 467.2 (men 329.6; women 584.7) for the year 2050. The number of osteoporotic hip fractures in Polish men and women is still relatively low, but the epidemiological situation is getting worse. The over 13 years of follow-up demonstrated that the trend to increase in total number of hip fractures for men and women is still observed. This prognosis is of a major concern.


Language at rest: A longitudinal study of intrinsic functional connectivity in preterm children.
Preterm (PT) children show early cognitive and language deficits and display altered cortical connectivity for language compared to term (T) children. Developmentally, functional connectivity networks become more segregated and integrated, through the weakening of short-range and strengthening of long-range connections. Longitudinal intrinsic connectivity distribution (ICD) values were assessed in PT (n = 13) compared to T children (n = 12) at ages 8 vs. 16 using a Linear Mixed Effects model. Connectivity values in regions generated by the group × age interaction analysis were then correlated to scores on full IQ (FSIQ), verbal IQ (VIQ), verbal comprehension IQ (VCIQ), performance IQ (PIQ), Peabody picture vocabulary test-revised (PPVT-R), and Rapid Naming Composite (RDRL_Cmp). Nine regions were generated by the group × age interaction analysis. PT connectivity significantly increased over time in all but two regions, and they ultimately displayed greater relative connectivity at age 16 than Ts in all areas except the left occipito-temporal cortex (OTC). PTs underwent significant connectivity reductions in the left OTC, which corresponded with worse performance on FSIQ, VIQ, and PIQ. These findings differed from Ts, who did not undergo any significant changes in connectivity over time. These findings suggest that the developmental alterations in connectivity in PT children at adolescence are both pervasive and widespread. The persistent and worsening cognitive and language deficits noted in the PT subjects may be attributed to the loss of connections in the left OTC.


Radiologic contrast-induced renal failure.
RCIRF is a complex syndrome resulting in acute renal dysfunction following exposure to radiologic contrast media. It accounts for 10 per cent of all cases of acute renal failure. The pathogenesis appears multifactorial but most probably involves contrast-mediated renal ischemia and direct tubular toxicity. Significant risk factors include preexisting renal insufficiency, diabetes mellitus, advanced age, volume depletion, and presence of multiple myeloma. The diagnosis should be suspected with acute renal dysfunction temporally related to radiologic contrast administration. The prognosis for recovery is good in most cases. Key preventive measures include identification of high-risk patients, ensuring adequate hydration prior to contrast agent administration, avoiding excessive and repeated contrast exposure, and instituting prophylactic therapy in selected cases.


Small cell carcinoma of prostate: effectiveness of hormonal versus chemotherapy.
Small cell carcinoma of the prostate is rare and associated with a rapidly fatal course. Since 1977, 47 cases have been reported in the world literature with data from 3 additional cases presented herein. The purpose of our review was to determine the effectiveness of hormonal versus chemotherapy. Thirty-four of the 50 cases have known clinical histories. Four patients were not treated, and all were dead of their disease within an average of 2.75 months. Six patients were eliminated from our review because small cell carcinoma was discovered at autopsy. Another 5 cases were omitted because hormonal +/- chemotherapy had already been given for a previous diagnosis of adenocarcinoma, but no specific therapy was given once the small cell carcinoma developed. Of the remaining 19 cases, only 2 have survived. One is still alive forty-three months after hormonal treatment, and another is alive with disease six months after the initiation of hormonal therapy and chemotherapy. Five patients were given hormonal therapy only, and none of them responded. In 4 patients chemotherapy was given after hormonal therapy had failed, and they too died of their disease within a short period of time. However, an additional 8 patients were treated with immediate chemotherapy +/- hormonal therapy and had substantially longer clinical remissions. Therefore, although small cell carcinoma is a uniformly fatal disease, immediate chemotherapy should be considered to promote better clinical remissions.


Assembly and recognition mechanisms of glycosylated PEGylated polyallylamine phosphate nanoparticles: A fluorescence correlation spectroscopy and small angle X-ray scattering study.
Modification of polyallylamine hydrochloride (PAH) with heterobifunctional low molecular weight polyethylene glycol (PEG) (600 and 1395 Da), and subsequent attachment of mannose, glucose, or lactose sugars to PEG, can lead to formation of polyamine phosphate nanoparticles (PANs) with lectin binding affinity and narrow size distribution. Size, polydispersity, and internal structure of glycosylated PEGylated PANs were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and small angle X-ray scattering (SAXS). Fluorescence correlation spectroscopy (FCS) was used to study the association of labelled glycol-PEGylated PANs. The number of polymer chains forming the nanoparticles was determined from the changes in amplitude of the cross-correlation function of the polymers after formation of the nanoparticles. SAXS and fluorescence cross-correlation spectroscopy were used to investigate the interaction of PANs with lectins: concanavalin A with mannose modified PANs, and jacalin with lactose modified ones. Glyco-PEGylated PANs are highly monodispersed, with diameters of a few tens of nanometers and low charge, and a structure corresponding to spheres with Gaussian chains. FCS shows that the PANs are single chain nanoparticles or formed by two polymer chains. Concanavalin A and jacalin show specific interactions for the glyco-PEGylated PANs with higher affinity than bovine serum albumin.


Publisher Correction: Dynamics for El Niño-La Niña asymmetry constrain equatorial-Pacific warming pattern.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Significance of antibody to the host cellular gene derived epitope GOR in chronic hepatitis C virus infection.
The humoral response to the host cellular gene-derived epitope GOR (anti-GOR) was reported to be associated with chronic hepatitis C virus (HCV) infection. To determine the prevalence and clinical significance of anti-GOR, sera from 31 patients (M/F, 19/12, age 30-72) with chronic HCV infection (anti-HCV+ in 30, HCV-RNA+ by PCR in 31) were tested for anti-GOR by enzyme immunoassay. Results were correlated with clinical, biochemical and histological features, and the subsequent response to interferon-alpha therapy (a complete response was defined as normalization of serum ALT at the completion of therapy; a sustained response was defined as having normal serum liver biochemistry during the entire follow-up period). Anti-GOR was detected in 21 patients [67.7%, median optical density (OD) reading 2.634, range 0.865-3.000, cut-off value 0.300]. There was no correlation between the presence or the OD reading of anti-GOR and the clinical features (sex, age, mode of acquisition), biochemical tests (serum ALT, AST, alkaline phosphatase and albumin levels), autoimmune markers [serum globulin levels, anti-nuclear antibody (+ at < 1:80 in 6/31 patients)], and their subsequent response to interferon-alpha therapy (complete response in anti-GOR+ patients: 13/21, anti-GOR-: 5/10, p = NS; sustained response in anti-GOR+ patients: 5/21, anti-GOR-: 2/10, p = NS). There was also no correlation between anti-GOR and the histological features including Knodell score and its components including periportal inflammation, portal inflammation and fibrosis, the presence of lymphoid aggregates, macrovesicular and microvesicular fat, multinucleated hepatocytes, dysplasia, sinusoidal activity or bile duct lesions.(ABSTRACT TRUNCATED AT 250 WORDS)


Physicochemical characterization and toxicological evaluation of plant-based anionic polymers and their nanoparticulated system for ocular delivery.
The water-soluble fractions of mucilages and gum from the seeds of fenugreek, isphagula and mango bark exudate were isolated, purified and characterized using X-ray diffraction (XRD) spectrometry, Fourier transform infrared spectroscopy (FT-IR), maldi/GC-MS, elemental analysis, 1D ((1)H and (13)C) and 2D (HMQC, COSY) nuclear magnetic resonance spectroscopy (NMR). The fenugreek mucilage was identified to be a galactomannan chain consisting of 4 units of galactose attached to the backbone of 6 mannose units in 1:1.5 ratio. The isphagula mucilage was identified to be an arabinoxylan polysaccharide chain consisting of 4 units of arabinofuranose attached to the backbone of 9 xylopyrannose units in 1:3 ratio. The mango gum showed the presence of amylose, α-arabinofuranosyl and β-galactopyranosyl, respectively. The characterized mucilages and gum were individually formulated into nanoparticulate system using their complementarily charged polymer chitosan. The particles were observed to be spherical in shape in the range of 61.5-90 nm having zetapotential between 31 and 34 mV and PDI of 0.097-0.241. The prepared nanoparticles were observed to be nonirritant and nontoxic in vitro and in vivo upto 2000 μg/ml. Therefore, these mucilages and gum can be the alternatives of anionic polymers for the ocular drug delivery system.


[Duplex US evaluation of mesenteric vessels in acute abdomen. Prospective study on 325 patients].
Acute Mesenteric Insufficiency (AMI) is a surgical emergency with a difficult methodological approach. Its high mortality is mainly due to delay in the correct diagnosis. In turn this is due to the lack of specificity of the clinical presentation and of the laboratory data and abdominal radiographic findings, especially in the early-middle phase. To evaluate the positive predictive value (PPV) and negative predictive value (NPV) of Duplex Ultrasound (DU) of mesenteric vessels in the diagnosis of acute mesenteric ischaemia. 325 patients were prospective analyzed with Duplex US (Aloka ssd 1700); 120 with acute abdomen (group A); 120 healthy subjects without abdomen preparation (group B); 85 healthy subjects with abdomen preparation (group C). We considered the B mode visualization, the vessel extension and diameter, the colour signal capture (enhancement), the velocitograms with systolic peak velocity and medium diastolic velocity. In 32 patients with high suspect of AMI we founded 21 really negative results, 3 wrong positive results, 5 really positive results, 3 false negative results. The PPV and NPV were respectively 0.62 and 0.87. The Duplex Us is more useful rather exclude than confirm AMI.


Somatostatin receptor SPECT.
Somatostatin is a peptide with a broad distribution in the nervous system and acts as a neurotransmitter in several organs, having a wide range of mainly inhibiting effects, such as the suppression of growth hormone release, as well as the inhibition of pancreatic and gastrointestinal hormone release. Five somatostatin receptor subtypes have been cloned and demonstrated to have an emphasized expression in all human tumours. In particular, type 2 receptors were identified as the most frequently represented on the surface of neuroendocrine tumour cells, providing the molecular basis for many clinical applications of somatostatin analogues. Towards the end of the 1980s, the in vivo demonstration of somatostatin receptors on the surface of some tumours raised interest in receptor imaging, and indeed the peptide receptor overexpression on tumour cells, as compared to normal tissues, constitutes the basis for molecular imaging of these tumours. This review intends to illustrate the development of single photon emission radiopharmaceuticals for the study of somatostatin receptors and their application in diagnostic imaging.


[The role of vestibular and proprioceptive afferent pathways in the reaction to pushing (author's transl)].
The reaction to pushing was studied in 6 normal subjects and 3 patients with bilateral peripheral vestibular lesions. The reaction to pushing was tested on the anterior tibial and soleus, by modifying the proprioceptive afferent impulses. The respective parts of the vestibular, proprioceptive, visual components, and of a sudden, start are analyzed; the afferent impulses obtain information from the initial posture and modulate the relative importance of these different factors at a supra-segmentary level.


First trimester diagnosis and early in utero treatment of obstructive uropathy.
The earliest diagnosis and treatment of obstructed fetal bladder is reported. Placement of vesico-amniotic shunt at 14.5 weeks of gestation enabled preservation of bilateral renal function and maintenance of normal amniotic fluid volume with normal pulmonary development. The shunt functioned adequately for more than 12 weeks. At birth, a mild 'prune' belly was the only deformity noted.


Cyclic swelling enabled, electrically conductive 3D porous structures for microfluidic urinalysis devices.
Urinalysis is a simple and non-invasive approach for the diagnosis and monitoring of organ health and also is often used as a facile technique in assessment of substance abuse. However, quantitative urinalysis is predominantly limited to clinical laboratories. Here, we present an electrical sensing based, reusable, cellular microfluidic device that offers a fast urinalysis through quantitative reading of the electrical signals. The spatial soft porous scaffolds decorated with electrically conductive multiwalled carbon nanotubes that are capable of physically interacting with biomarkers in urine are developed through a cyclic swelling/absorption process of soft materials and are utilized to manufacture the cellular microfluidic device. The sensing capability, sensitivity and reusability (via sunlight exposure) of the device to monitor red blood cells, Escherichia coli, and albumin are systemically demonstrated by programming mechanical deformation of porous scaffolds. Ex vivo experiments in disease mouse models confirm the diagnosis robustness of the device in comparable results with existing biochemical tests. The full integration of electrically conductive nanomaterials into soft scaffolds provides a foundation for devising bioelectronic devices with mechanically programmable microfluidic features in a low-cost manner, with broad applications for rapid disease diagnoses through body fluid.


Interleukin 2 liberation and absorption capacities of rat T lymphocytes in conditions of severe adenylic nucleotide pool depletion due to adenosine deaminase deficiency.
In rat lymph node lymphocytes stimulated for 24 h by concanavalin A in the presence of 10(-5) M 2'-deoxycoformycin (a potent inhibitor of adenosine deaminase) and 10(-5) M 2'-deoxyadenosine the adenylic nucleotide pool was reduced by 55.5% without modification of either the adenylic energy charge or the ability of the cells to liberate interleukin 2. In the same conditions, the ability of rat spleen cells to bind exogenous interleukin 2 activity was not modified. The proliferative response to concanavalin A stimulation was completely inhibited after a 86-h culture period under adenosine deaminase deficiency conditions. It could not be restored by elimination of 2'-deoxyadenosine after a 20-h pretreatment, when adenylic nucleotide pool depletion was 72.4% whereas the interleukin 2 liberation ability was not suppressed. These results suggest that among the early consequences of adenosine deaminase deficiency conditions, which occur before S phase of the cell cycle, the depletion of adenylic nucleotide pool, rather than the impairment of interleukin 2 liberation and absorption capacities, may account for the inability of the lymphocytes to respond to mitogenic stimulation.


First report of fowl aviadenovirus serotypes FAdV-8b and FAdV-11 associated with inclusion body hepatitis in commercial broiler and broiler-breeder flocks in Turkey.
Inclusion body hepatitis (IBH), hydropericardium syndrome (HS), and gizzard erosion (GE) are all economically important diseases in the poultry industry worldwide and are all caused by fowl aviadenovirus (FAdV). It is important to identify the serotype of the virus to differentiate these diseases. In the present study, a total of six recent FAdV serotypes were isolated and identified in broiler and broiler-breeder flocks in Izmir, Manisa, and Aydın provinces of the Aegean region of Turkey between January and March 2019. The viruses were isolated from livers and pooled organs of chickens using primary chicken embryo kidney cell cultures (CEKC). Virus isolates were identified by PCR amplification of the loop 1 (L1) variable region of the hexon gene followed by Sanger sequencing. Sequence analysis revealed the presence of both FAdV-D (serotype 11) and FAdV-E (serotype 8b). The viruses that were isolated were associated with IBH, which is typically characterized by gross lesions such as enlarged and pale yellow liver with multiple petechial hemorrhages. Histopathological examination also showed necrotizing hepatitis with intranuclear inclusion bodies in hepatocytes. This study is the first report of the isolation and identification of FAdV serotypes associated with IBH in commercial broilers and broiler-breeder flocks in Turkey. The results of sequence analysis showed that FAdV-8b and FAdV-11 were the circulating serotypes that caused recent field outbreaks of IBH in the Aegean region between January and March, 2019.


Patterns of response to repetitive transcranial magnetic stimulation (rTMS) in major depression: replication study in drug-free patients.
Repetitive transcranial magnetic stimulation (rTMS) has been found to exert modest to moderate therapeutic effects in major depression, but mechanism of action and its clinical relevance have not been clarified yet. Previous trials have reported patterns of symptomatology predicting response to rTMS. As most patients also received concomitant antidepressant medication these response patterns may rather refer to combined treatment than rTMS alone. Thus, this study aims to replicate previous findings and explore patterns of response in drug-free patients. In the Munich-Berlin Predictor Study data of 79 patients from two open clinical trials evaluating effects of high-frequency rTMS of the left dorsolateral prefrontal cortex were pooled. Previous models predicting the response to rTMS [Fregni, F., Marcolin, M.A., Myczkowski, M., Amiaz, R., Hasey, G., Rumi, D.O., Rosa, M., Rigonatti, S.P., Camprodon, J., Walpoth, M., Heaslip, J., Grunhaus, L., Hausmann, A., Pascual-Leone, A., 2006. Predictors of antidepressant response in clinical trials of transcranial magnetic stimulation. Int. J. Neuropsychopharmacol. 9, 641-654; Brakemeier, E.L., Luborzewski, A., Danker-Hopfe, H., Kathmann, N., Bajbouj, M., 2007. Positive predictors for antidepressive response to prefrontal repetitive transcranial magnetic stimulation (rTMS). J. Psychiatr. Res. 41, 395-403.] were systematically tested and new explorative regression analyses were conducted. Of the 79 patients, 34.2% showed an antidepressant response. Previous models could not be validated. Explorative regression analysis revealed a significant model with therapy resistance, HAMD items 1 (depressed mood), and 2 (feelings of guilt) as negative and retardation as positive predictors. No controlled study; specific statistical issues; sample size; differences concerning patient population and stimulation parameters between study sites. In sum, this study does not confirm clinical valid and robust patterns being predictive for a response to rTMS in depression. The only exception is a high level of therapy resistance being associated with poor outcome. Future predictor studies should focus on large and homogenous samples of rTMS multicenter trials and include neurobiological variables.


Urinary high performance reverse phase chromatography cortisol and cortisone analyses before and at the end of a race in elite cyclists.
A functional and basic method for the quantitative analysis of urine cortisol (F) and cortisone (E) using a Solid-Phase Extraction column and HPLC with ultraviolet detection is here described and validated to analyse urine samples. Urine specimens were analysed to study F and E relation and ratio in athletes and healthy sedentary subjects. The F and E concentrations in random urine specimens were significantly higher in the post exercise versus pre exercise condition in cyclists (F: 136+/-93 nmol/l versus 67+/-50 nmol/l (p<0.001); E: 797+/-400 nmol/l versus 408+/-252 nmol/l (p<0.001)). The F/E ratio was 0.18+/-0.11 versus 0.16+/-0.07, respectively, and a significant difference was only demonstrated comparing sedentary (0.11+/-0.07) and cyclist individuals at rest (p<0.05).


Discovery of potent and selective cytotoxic activity of new quinazoline-ureas against TMZ-resistant glioblastoma multiforme (GBM).
Herein, we report new quinazoline-urea based compounds with potent cytotoxic activities against TMZ-resistant glioblastoma multiforme (GBM) cells. Low micromolar IC₅₀ values were exhibited over a panel of three primary GBM patient-derived cell cultures belonging to proneural (GBM-1), mesenchymal (GBM-2), and classical (GBM-3) subtypes. Eight compounds showed excellent selectivity indices for GBM cells comparing to a normal astrocyte cell line. In JC-1 assay, analogues 11, 12, 20, 22, and 24 exerted promising rates of mPTP opening induction towards proneural GBM subtype. Compounds 11, 20, and 24 bound to the translocator protein 18 kDa (TSPO) in submicromolar range using [(3)H] PK-11195 binding affinity assay. A homology model was built and docked models of 11, 12, 20, 22 and 24 were generated for describing their plausible binding modes in TSPO. In 3D clonogenic assay, compound 20 manifested potent tumoricidal effects on TMZ-resistant GBM cells even at submicromolar concentrations. In addition, CYP450 and hERG assays presented a safe toxicity profile of 20. Taken as a whole, this report presents compound 20 as a potent, selective and safe GBM cytotoxic agent which constitutes a promising direction against TMZ-resistant GBM.


Heterogeneity of oral tolerance defects in autoimmune mice.
Three strains of mice, BXSB, MRL-lpr/lpr, and NZB, which spontaneously develop autoimmune syndromes, all fail to become tolerant to challenge with bovine gamma-globulin (BGG) in adjuvant by prior intraperitoneal (ip) injection of BGG in tolerogenic form. In the present study, these three strains were examined for the ability of a single enteric dose of BGG or ovalbumin (OVA) to tolerize to subsequent challenge with the corresponding antigen in adjuvant. In contrast to lack of ip tolerance to BGG, BXSB mice were tolerant to gastrointestinal (GI) BGG as well as to GI OVA, suggesting that ip and GI forms of tolerance to BGG operate through distinct mechanisms in these mice. MRL-lpr/lpr mice had normal tolerance to GI OVA but not GI BGG. The presence of enteric tolerance to one antigen but not another suggests that the responsible cellular defects vary from one antigen to another. NZB mice lacked tolerance to both GI BGG and GI OVA. Splenectomy of NZB mice allowed normal tolerance to enteric BGG; spleen cells administered to splenectomized NZB mice interfered with BGG tolerance. Congenic NZB.xid mice were tolerant only to OVA. These results suggest that in NZB mice Lyb 5+ cells interfere with tolerance to enteric OVA and Lyb 5- spleen cells interfere with tolerance to enteric BGG.


Incidental extraction of double pigtail catheter during nephrostomy removal.
An unusual complication of nephrostomy removal is presented. A double pigtail catheter was trapped by the nephrostomy tube and accidentally extracted. Suggestions for preventing this complication are presented.


Actor-Partner Effects of Childhood Disadvantage on Later Life Subjective Well-Being Among Individuals in Coresidential Unions.
Prior research on cumulative disadvantage has primarily focused on individuals' own childhood adversity for their later-life outcomes. Nevertheless, partner's childhood disadvantage may also shape respondent's later-life well-being. Drawing on a household-level dataset, I examine respondent's own childhood adversity as well as their partner's childhood adversity (poor childhood health, parental divorce, or father's long-term unemployment) on respondent's subjective well-being, at aged 50 and older. Findings from the actor-partner interdependence model (APIM) show poor childhood health of the male partner as associated with worse mental health and self-rated health of the female partner in later life. For both outcome measures, the partner effects were attenuated after adjusting for the female partner's report of perceived social support. For self-rated health, adjusting for variation in the presence of a chronic illness and household income also attenuated the association. Partnered individuals are nested within a specific context, whereby stress and implications of early life disadvantage may be conceptualized at the couple-level. Future research that assesses how early life experiences of individuals may have implications for family members' later-life well-being may be valuable.


The induction of urothelial hyperplasia by methyl methanesulphonate and ethyl methanesulphonate.
The early and late morphological changes induced in rat bladder urothelium by intravesicular administration of the alkylating agents methyl methanesulphonate (MMS) and ethyl methanesulphonate (EMS) are described. In the short-term, both compounds produced dose-related toxic damage followed by a regenerative hyperplasia of the urothelium. At any given dose-level, the effects of MMS were more severe than those of EMS. Two years after administration of multiple doses of 2.5 mg MMS or 7.5 mg EMS the majority of animals had dose-related simple urothelial hyperplasias with occasional mild dysplasia. However, in three MMS-treated animals the hyperplasias had progressed to well-differentiated transitional-cell carcinomas. No bladder neoplasms were seen in EMS-treated animals. The urothelial response of the rat to MMS and EMS is discussed with reference to the known chemical reactivity of these compounds. It is concluded that EMS is a mitogen for the urothelium and that the few carcinomas which develop following topical exposure of the bladder to MMS do not necessarily reflect any initiating potential in this compound. Rather it is argued that the results are consistent with MMS acting as a promoter in cells which have either been previously initiated or which carry a latent oncogene.


Direct access to 4-carboxy-1,8-naphthyridines and related compounds through Pfitzinger-type chemistry.
The 4-carboxy-1,8-naphthyrid-2-yl moiety is a useful ligand component in that it promotes lower energy electronic absorption in its metal complexes and also provides a useful tether for anchoring the ligand to a semiconductor surface. The synthon [2-(pivaloylamino)pyrid-3-yl]oxoacetic acid ethyl ester can be easily obtained in two steps from 2-aminopyridine. The Pfitzinger-type condensation of this molecule with a 2-acetylazaaromatic species in ethanolic KOH, after acidification, directly provides bi- and tridentate ligands containing the 4-carboxy-1,8-naphthyrid-2-yl moiety.


Effects of two resin adhesives on mechanical properties of set amalgam.
Two hundred amalgam (Dispersalloy) cylinders, 3 mm high x 4 mm wide, were tested to determine the compressive and diametral tensile strength of amalgam treated with 1 and 3 mixed drops of Amalgambond resin and 1:1 and 3:3 drops of resin powder paste of Panavia Ex resin. Twenty samples of each group, including a control group, were tested with a 1 cm diameter testing rod in an Instron universal testing machine at 0.5 mm/minute speed. All samples tested for compressive strength were not statistically different from one another (ANOVA). ANOVA and Tukey HSD test indicated no significant difference in diametral tension between the Amalgam and Amalgambond 1X materials, but significant differences were demonstrated with the Amalgambond 3X and Panavia 1X and 3X materials.


Identification of an efflux pump gene, pmrA, associated with fluoroquinolone resistance in Streptococcus pneumoniae.
An open reading frame (ORF) homologous to norA was insertionally inactivated with cat in a fluoroquinolone-resistant pneumococcus with an efflux phenotype; this inactivation caused reversion to drug sensitivity. The ORF product has 24% amino acid sequence identity each to NorA and Bmr, which suggests that it is a major facilitator system pump of the 12-transmembrane-segment class.


Signal transduction and pharmacological characteristics of a metabotropic glutamate receptor, mGluR1, in transfected CHO cells.
The signal transduction and pharmacological properties of a metabotropic glutamate receptor, mGluR1, were studied in CHO cells permanently expressing the cloned receptor. mGluR1 stimulated phosphatidylinositol (PI) hydrolysis in the potency rank order of quisqualate greater than L-glutamate greater than or equal to ibotenate greater than L-homocysteine sulfinate greater than or equal to trans-ACPD. This receptor also evoked the stimulation of cAMP formation and arachidonic acid release with comparable agonist potencies. DL-AP3 and L-AP4, the effective antagonists reported for glutamate-stimulated PI hydrolysis in brain slices, showed no appreciable effects on mGluR1, suggesting the existence of an additional subtype of this receptor family. Pertussis toxin and phorbol ester produced distinct effects on the three transduction cascades, implying that mGluR1 independently links to the multiple transduction pathways probably through different G proteins.


[Assessment of the human immunological status by taking into account the correlations among individual indices].
The problem of correlation of the parameters of the immune system in the normal subjects and in patients with immunological diseases has been considered. The most informative relations have been determined and an attempt has been made to reveal common and specific signs of various immunological diseases.


Comparative biotransformation and disposition studies of nabumetone in humans and minipigs using high-performance liquid chromatography with ultraviolet, fluorescence and mass spectrometric detection.
The disposition of the non-steroidal anti-inflammatory drug (NSAID) nabumetone after a single oral dose administration of nabumetone tablets to humans and minipigs was investigated. Nabumetone is a prodrug, which is metabolized in the organism to the principal pharmacodynamically active metabolite -- 6-methoxy-2-naphthylacetic acid (6-MNA), and some other minor metabolites (carbonyl group reduction products, O-desmethylation products and their conjugates with glucuronic and sulphuric acids). Standards of the above-mentioned metabolites were prepared using simple synthetic procedures and their structures were confirmed by NMR and mass spectrometry. A simple HPLC method for the simultaneous determination of nabumetone, 6-MNA and the other metabolites was developed, validated and used for xenobiochemical and pharmacokinetic studies in humans and minipigs and for distribution studies in minipigs. Naproxen was chosen as the internal standard (I.S.), both UV (for higher concentrations) and fluorescence detection (for very low concentrations) were used. The identity of the nabumetone metabolites in biological samples was confirmed using HPLC-MS experiments. Pharmacokinetics of nabumetone, 6-MNA and 6-HNA (6-hydroxy-2-naphthylacetic acid) in human and minipig plasma was evaluated and compared. The concentration levels of nabumetone metabolites in urine, bile and synovial fluid were also evaluated.


Age-dependent loss of adipose Rubicon promotes metabolic disorders via excess autophagy.
The systemic decline in autophagic activity with age impairs homeostasis in several tissues, leading to age-related diseases. A mechanistic understanding of adipocyte dysfunction with age could help to prevent age-related metabolic disorders, but the role of autophagy in aged adipocytes remains unclear. Here we show that, in contrast to other tissues, aged adipocytes upregulate autophagy due to a decline in the levels of Rubicon, a negative regulator of autophagy. Rubicon knockout in adipocytes causes fat atrophy and hepatic lipid accumulation due to reductions in the expression of adipogenic genes, which can be recovered by activation of PPARγ. SRC-1 and TIF2, coactivators of PPARγ, are degraded by autophagy in a manner that depends on their binding to GABARAP family proteins, and are significantly downregulated in Rubicon-ablated or aged adipocytes. Hence, we propose that age-dependent decline in adipose Rubicon exacerbates metabolic disorders by promoting excess autophagic degradation of SRC-1 and TIF2.


Comparing the effects and compliance between volume-assured and pressure support non-invasive ventilation in patients with chronic respiratory failure.
Standard bi-level non-invasive ventilation with fixed-level pressure support (PS) delivery may not maintain ventilation during the changes in pulmonary mechanics that occur throughout day and night, so average volume-assured pressure support (AVAPS) modes that target a preset volume by adjustment of PS may be effective. Our meta-analysis wants to compare AVAPS and pressure support non-invasive ventilation (PS-NIV) regarding arterial blood gases (ABGs), sleep efficiency and compliance. Relevant publications indexed in PubMed, Cochrane Library, Embase, Web of Science, Wanfang Data, China National Knowledge Infrastructure and VIPI were identified. Appropriate articles identified from the reference lists of the above searches were also reviewed. We included randomized controlled trials involved the use of AVAPS and PS-NIV ventilation for chronic respiratory failure. Each included study weighted mean differences, and 95% confidence intervals (CI) were calculated for continuous outcomes. Statistical heterogeneity was assessed using the I2 value ≤ 50% were considered as no statistical heterogeneity and used fixed effects model. Otherwise, a random effects model was used. Eight trials were eligible. No significant difference was observed between AVAPS and PS-NIV groups to compare PaCO2 (OR -0.97, CI-2.54-0.61, P = 0.23) and PaO2 (OR -1.81, CI-4.29-0.67, P = 0.15) in ABGs. There was no significant difference between the two groups with sleep efficiency (OR -3.31, CI-7.58-0.95, P = 0.13) and visual analog scale (OR 0.32, CI-6.97-7.61, P = 0.93). The evidence shows there is no significant difference in clinical outcomes when comparing AVAPS and PS-NIV used for chronic respiratory failure patients.


DNA and cell cycle analysis of retinoblastoma.
We retrospectively analyzed archival retinoblastomas from 44 eyes. The percentage of cycling cells were increased in younger patients, those with advanced disease, and cases with poor prognosis. These data suggest that all cell cycle studies may yield important insights in retinoblastoma.


Update on Innate and Adaptive Immunity in Cystic Fibrosis.
Cystic fibrosis (CF) pathophysiology is hallmarked by excessive inflammation and the inability to resolve lung infections, contributing to morbidity and eventually mortality. Paradoxically, despite a robust inflammatory response, CF lungs fail to clear bacteria and are susceptible to chronic infections. Impaired mucociliary transport plays a critical role in chronic infection but the immune mechanisms contributing to the adaptation of bacteria to the lung microenvironment is not clear. CFTR modulator therapy has advanced CF life expectancy opening up the need to understand changes in immunity as CF patients age. Here, we have summarized the current understanding of immune dysregulation in CF.


A Cautionary Tale: Unveiling Valentino's Syndrome.
In the emergency room, acute pain in the abdomen is one of the most common symptoms that patients present with, and it is a result of a myriad of causes, leading to an exhaustive differential diagnosis. A perforated peptic ulcer is a rare cause of acute right iliac fossa or lower quadrant abdominal pain. It causes leakage of gastrointestinal contents in the area, resulting in localized inflammation and pain that is clinically similar to acute appendicitis. This condition is known as Valentino's syndrome. This study aims to highlight clinical and radiological features for patients with Valentino's syndrome, improving diagnostic accuracy. The authors conducted a retrospective analysis of all diagnosed cases of Valentino's syndrome from multiple facilities within the same organization for the research study. A total of 14 nonsequential cases were gathered. The term "Valentino's syndrome" was used to search in the PubMed and Google Scholar databases for the review of literature, and only 17 cases were found and reviewed. Of the 31 patients, 83.9% were male, with a mean age of 39 years. Of all patients who presented with abdominal pain, 25.8% had it in the lower right abdomen. Vomiting (38.7%), nausea (35.4%), fever (16.1%), and constipation were all associated symptoms (12.9%). All cases were clinically diagnosed as acute appendicitis. Many patients had elevated levels of white blood cells, neutrophils, and CRP. Computed tomography (CT) scan was used in 70.9% of the cases, followed by ultrasound (58%) and x-ray (45.1%), where pneumoperitoneum and duodenal perforations were common. Graham's patch was used in 48.3% of the cases, appendectomy was used in 16.1% of the cases, and conservative care was used in 19.3% of the cases. Most patients were given proton pump inhibitors and antibiotics for Helicobacter pylori. Timely diagnosis of Valentino's syndrome via CT imaging is critical because it leads to immediate perforation repair. Patients' mortality and morbidity may be reduced if they are aware of the condition and receive an accurate, rapid preoperative diagnosis.


The results of the campaign for evaluating sphygmomanometers accuracy and their physical conditions.
To evaluate the sphygmomanometers calibration accuracy and the physical conditions of the cuff-bladder, bulb, pump, and valve. Sixty hundred and forty five aneroid sphygmomanometers were evaluated, 521 used in private practice and 124 used in hospitals. Aneroid manometers were tested against a properly calibrated mercury manometer and were considered calibrated when the error was < or = 3 mm Hg. The physical conditions of the cuffs-bladder, bulb, pump, and valve were also evaluated. Of the aneroid sphygmomanometers tested, 51% of those used in private practice and 56% of those used in hospitals were found to be not accurately calibrated. Of these, the magnitude of inaccuracy ranged from 4 to 8 mm Hg in 70% and 51% of the devices, respectively. The problems found in the cuffs-bladders, bulbs, pumps, and valves of the private practice and hospital devices were bladder damage (34% vs. 21%, respectively), holes/leaks in the bulbs (22% vs. 4%, respectively), and rubber aging (15% vs. 12%, respectively). Of the devices tested, 72% revealed at least one problem interfering with blood pressure measurement accuracy. Most of the manometers evaluated, whether used in private practice or in hospitals, were found to be inaccurate and unreliable, and their use may jeopardize the diagnosis and treatment of arterial hypertension.


Overproduction, purification and preliminary X-ray diffraction analysis of YncE, an iron-regulated Sec-dependent periplasmic protein from Escherichia coli.
The yncE gene of Escherichia coli encodes a predicted periplasmic protein of unknown function. The gene is de-repressed under iron restriction through the action of the global iron regulator Fur. This suggests a role in iron acquisition, which is supported by the presence of the adjacent yncD gene encoding a potential TonB-dependent outer-membrane transporter. Here, the preliminary crystallographic structure of YncE is reported, revealing that it consists of a seven-bladed beta-propeller which resembles the corresponding domain of the ;surface-layer protein' of Methanosarcina mazei. A full structure determination is under way in order to provide insight into the function of this protein.


A toxicity study of the treatment of T3 bladder tumours with a combination of radiotherapy and chemotherapy.
18 patients with category T3 bladder cancer were treated with a combination of radical radiotherapy followed after an interval of 1-3 months by pulsed chemotherapy with adriamycin and 5-fluorouracil. Providing the chemotherapy was limited to 4 cycles, there was no serious toxicity and the regime was well tolerated.


Effect of an early detection programme on duration of untreated psychosis: part of the Scandinavian TIPS study.
It is unclear whether an early detection programme increases or decreases the number of patients with a long duration of untreated psychosis (DUP), and whether these differ from other patients with a long DUP. To investigate whether the number and characteristics of patients with a long DUP in the early detection programme differ from those with a long DUP in the non-early detection programme. We compared the number and characteristics of patients with a DUP > or =2 years in an early detection area and a non-early detection area. The early detection programme recruited slightly fewer patients with a long DUP than the non-early detection programme. The patients in the early detection programme had lower PANSS scores, but more frequently had a deteriorating course of premorbid social functioning. An early detection programme does not seem to drain a pool of previously undetected patients with a long DUP. The patients in the early detection programme seem to have a lower symptom level at baseline and to have had a deteriorating premorbid social course.


Sliding plasty using the triple-orifice technique for tricuspid endocarditis.
A 29-year-old male with tricuspid endocarditis related to a residual ventricular septal defect was studied. A large vegetation was resected along with partial excision of the valve. The tricuspid valve was reconstructed using a single-stitch triple-orifice technique. No regurgitation or stenosis was detected at the valve 6 months after surgery.


Differential effect of stress on in vivo dopamine release in striatum, nucleus accumbens, and medial frontal cortex.
Microdialysis was used to assess extracellular dopamine in striatum, nucleus accumbens, and medial frontal cortex of unanesthetized rats both under resting conditions and in response to intermittent tail-shock stress. The dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid also were measured. The resting extracellular concentration of dopamine was estimated to be approximately 10 nM in striatum, 11 nM in nucleus accumbens, and 3 nM in medial frontal cortex. In contrast, the resting extracellular levels of 3,4-dihydroxyphenylacetic acid and homovanillic acid were in the low micromolar range. Intermittent tail-shock stress increased extracellular dopamine relative to baseline by 25% in striatum, 39% in nucleus accumbens, and 95% in medial frontal cortex. 3,4-Dihydroxyphenylacetic acid and homovanillic acid also were generally increased by stress, although there was a great deal of variability in these responses. These data provide direct in vivo evidence for the global activation of dopaminergic systems by stress and support the concept that there exist regional variations in the regulation of dopamine release.


Patients treated for acute headache with intranasal droperidol spend less time in the emergency department: A retrospective observational study.
Headache is a common presenting complaint to the ED. Using time from the first provider to discharge as a surrogate for effectiveness, we aimed to determine if intranasal (IN) droperidol is as beneficial as usual treatment for acute headache in the ED. There were 1213 consecutive presentations of adults with acute headache over a 42-month period. Electronic records for each event were interrogated, 406 events met pre-determined exclusion criteria. Of the remaining 805 eligible patient events, 139 received IN droperidol, whereas 666 were given usual therapy. There was a 20 min reduction of mean and median ED length of stay (LOS) for the group that got treated with IN droperidol. IN droperidol reduced LOS in the ED. There are potential cost savings of this effective treatment via this novel route. A prospective multi-centre study of the use of IN droperidol for the treatment of acute headache in the ED is recommended.


Mononuclear cell-fibroblast interactions in scleroderma.
We studied cell proliferation and collagen biosynthesis in cocultures of dermal fibroblasts with peripheral blood mononuclear cells (MNC) from scleroderma patients and from age-matched normal controls. Autologous one-way mixed MNC-fibroblast cultures revealed that fibroblasts do not stimulate MNC proliferation. Conversely, MNC stimulate autologous fibroblasts from scleroderma patients as well as from normal controls. This effect is increased in cells from scleroderma patients in which it seems to be mediated both by cell-to-cell interaction and through the production of soluble factors by MNC. In normal control cell systems we found no proliferative effect of supernatants of unstimulated cells or from those stimulated in autologous mixed-lymphocyte reactions. Coculture of fibroblasts with autologous MNC resulted in increased [14C]proline incorporation into both collagenic and noncollagenic proteins. This effect was mediated mostly by soluble factors that are released into the culture medium. Protein synthesis by MNC-fibroblast cocultures from scleroderma patients was significantly greater than protein synthesis by those from normal controls. Culture supernatants from unstimulated MNC or from autologous mixed-lymphocyte cultures caused a slight decrease in collagenic protein synthesis by cultured fibroblasts from scleroderma patients but not by those from normal controls. This effect of culture supernatants could be reproduced, and magnified, with purified IL-1 on cells from either patients or controls. Our findings indicate abnormal MNC-fibroblast interactions in scleroderma that could play an important role in the pathogenesis of fibrosis, the hallmark of this condition.


Antimicrobial potentials of Helicteres isora silver nanoparticles against extensively drug-resistant (XDR) clinical isolates of Pseudomonas aeruginosa.
Pseudomonas aeruginosa is a leading opportunistic pathogen and its expanding drug resistance is a growing menace to public health. Its ubiquitous nature and multiple resistance mechanisms make it a difficult target for antimicrobial chemotherapy and require a fresh approach for developing new antimicrobial agents against it. The broad-spectrum antibacterial effects of silver nanoparticles (SNPs) make them an excellent candidate for use in the medical field. However, attempts made to check their potency against extensively drug-resistant (XDR) microbes are meager. This study describes the biosynthesis and biostabilization of SNPs by Helicteres isora aqueous fruit extract and their characterization by ultraviolet-visible spectroscopy, transmission electron microscopy, dynamic light scattering, X-ray diffraction, and Fourier transform infrared spectroscopy. Majority of SNPs synthesized were of 8--20-nm size. SNPs exhibited dose-dependent antibacterial activities against four XDR P. aeruginosa (XDR-PA) clinical isolates as revealed by growth curves, with a minimum inhibitory concentration of 300 μg/ml. The SNPs exhibited antimicrobial activity against all strains, with maximum zone of inhibition (16.4 mm) in XRD-PA-2 at 1000 μg/ml. Amongst four strains, their susceptibilities to SNPs were in the following order: XDR-PA-2 > XDR-PA-4 > XDR-PA-3 > XDR-PA-1. The exposure of bacterial cells to 300 μg/ml SNPs resulted into a substantial leakage of reducing sugars and proteins, inactivation of respiratory chain dehydrogenases, and eventual cell death. SNPs also induced lipid peroxidation, a possible underlying factor to membrane porosity. The effects were more pronounced in XDR-PA-2 which may be correlated with its higher susceptibility to SNPs. These results are indicative of SNP-induced turbulence of membranous permeability as an important causal factor in XDR-PA growth inhibition and death.


Radiation Therapy for Thoracic Malignancies.
Radiotherapy is the most commonly used nonsurgical modality in treatment of lung cancers, non-small cell lung cancer (NSCLC) in particular. Radiation therapy has been increasingly used as definitive radical treatment, either alone or in combination with concurrent chemoradiation for locally advanced disease. More recently with the advent of novel radiation techniques and modalities such as stereotactic radiotherapy and proton therapy, radiotherapy can now be used as sole radical treatment of small solitary tumors. This article reviews the current indications and future directions of radiotherapy in lung cancer management.


[Evaluation of diabetic vegetative neuropathy using non-invasive cardiovascular explorations].
The alterations in autonomic nervous system due to diabetes mellitus are described. We propose a series of non-invasive methods to assess the autonomic function in this type of patients.


The role of the central metal ion of ethane-bridged bis-porphyrins in histidine sensing.
Ethane-bridged bis-porphyrin derivatives are reported for the selective detection of various analytes in sensing applications. The central metal ion is able to rule specific molecular arrangements upon analyte binding. Three bis-porphyrin compounds: a free base (metal free), Ni complex, and Cu complex, have been tested for histidine detection in aqueous media. Histidine is involved in various biological processes, including such deadly disease as lung cancer. The conformational changes of bis-porphyrins, induced by histidine binding, can be detected by monitoring the Soret band position. The spectroscopic characterization, at the air-water subphase interface, indicates that, in the presence of histidine, the Ni and Cu metallated derivatives undergo conformational changes. This behaviour was confirmed when these two derivatives were deposited onto the solid support by Langmuir-Schaefer (LS) technique. A prototypal Surface Plasmon Resonance (SPR) detection system for histidine based on these two porphyrin LS films was developed. The Cu substituted compound based SPR system allows the histidine sensing down to nanomolar concentration. Furthermore, a SPR response of the Ni bis-porphyrin shows a semilogarithmic dependence on the histidine concentration up to 10-6 M proposing the use of these two porphyrins in a sensor array for the monitoring of histidine levels in plasma.


A simple and improved method for diagnosis of tuberculosis using hypertonic saline and sodium hydroxide to concentrate and decontaminate sputum.
We report the use of hypertonic saline and sodium hydroxide (HS-SH) for concentration-decontamination of sputum samples for the diagnosis of tuberculosis. This method increases detection of mycobacteria in smears compared to examination of direct smears, is comparable and reduces contamination in cultures compared to NALC-NaOH.


Hybridization and introgression of the genomes of Drosophila nasuta and Drosophila albomicans: evolution of new karyotypes.
Drosophila nasuta (2n = 8) and Drosophila albomicans (2n = 6) are cross-fertile allopatric sibling chromosomal races of the nasuta subgroup of Drosophila. Hybrids of these races can be maintained for any number of generations. Some of the introgressed hybrid lineages of D. nasuta and D. albomicans, after passing through a transient phase of karyotypic polymorphism, ended up with a stable karyotype whose composition is different from those of the parental races. Such hybrid populations were called cytoraces, in which the chromosomes of D. nasuta and D. albomicans are represented in different combinations. The karyotypic composition of 16 such cytoraces have been presented and discussed with reference to evolutionary strategies such as balancing selection, directional selection, and sex-specific effect on different components of the evolving karyotypes.


Improved resolution of the initial fast phase of heavy sarcoplasmic reticulum Ca2+ uptake by Ca2+:antipyrylazo III dual-wavelength spectroscopy.
The effect of ATP upon difference absorbance due to Ca2+ and Mg2+ complexation with the metallochromic dye, Antipyrylazo III (AP III), was investigated. At divalent cation concentrations appropriate for Sarcoplasmic Reticulum Ca2+ transport, wavelengths (greater than 670 nm) were found whereupon the addition of up to 1mM nucleotide did not alter divalent cation:AP III difference absorbance. At these sample wavelengths an initial rapid uptake of Ca2+ by Heavy SR (HSR) was clearly resolved by dual wavelength spectroscopy of Ca2+:dye difference absorbance. Elimination of ATP interference of Ca2+:AP III absorbance by Mg2+ elevation (3-10mM) was shown to be an inappropriate general strategy for AP III spectroscopic studies of HSR Ca2+ transport due to Mg2+ inhibition of ryanodine receptor mediated Ca2+ release.


Functional analysis of whether the glycine residue of the GMN motif of the Arabidopsis MRS2/MGT/CorA-type Mg2+ channel protein AtMRS2-11 is critical for Mg2+ transport activity.
Magnesium (Mg2+) plays a critical role in many physiological processes. The AtMRS2/MGT family, which contains nine Arabidopsis genes (and two pseudogenes), belongs to a eukaryotic subset of the CorA superfamily of divalent cation transporters. AtMRS2-11/MGT10 possesses the signature GlyMetAsn sequence (the GMN motif) conserved in the CorA superfamily; however, little is known about the role of the GMN motif in AtMRS2. Direct measurement using the fluorescent dye mag-fura-2 revealed that reconstituted AtMRS2-11 mediated rapid Mg2+ uptake into proteoliposomes at extraliposomal Mg2+ concentrations of 10 and 20 mM. Mutations in the GMN motif, G417 to A, S or V, did not show a significant change in Mg2+ uptake relative to the wild-type protein. The G417W mutant exhibited a significant increase in Mg2+ uptake. The functional complementation assay in Escherichia coli strain TM2 showed that E. coli cells expressing AtMRS2-11 with mutations in G of the GMN motif did not grow in LB medium without Mg2+ supplementation, while growth was observed in LB medium supplemented with 0.5 mM Mg2+; no difference was observed between the growth of TM2 cells expressing the AtMRS2-11 G417W mutant and that of cells expressing wild-type AtMRS2-11. These results suggested that the Mg2+ transport activity of the AtMRS2-11 GMN-motif mutants was low at low physiological Mg2+ concentrations; thus, the Gly residue is critical for Mg2+ transport, and the Mg2+ transport activity of the GMN-motif mutants was increased at high Mg2+ concentrations.


Effectiveness of focused meditation for patients with chronic low back pain-A randomized controlled clinical trial.
We aimed to evaluate the effectiveness of an 8-week meditation program (focused meditation) in patients with chronic low-back pain. A randomized clinical trial was conducted on 68 patients (55 years;75% female) with chronic low-back pain who scored >40mm on a 100mm Visual-Analogue-Scale. Subjects were allocated to an 8-week meditation program (focused meditation) with weekly 75min classes or to a self-care exercise program with a wait-list offer for meditation. Both groups were instructed to practice at home. Outcomes were assessed baseline and after 4 and 8 weeks. The primary outcome measure was the change in mean back pain at rest after 8 weeks. Secondary outcomes included function, pain-related bothersomeness, perceived stress, quality-of-life (QOL), and psychological outcomes. Twelve (meditation) and 4 (exercise) patients were lost to follow-up. The primary outcome, pain at rest after 8 weeks, was reduced from 59.3±13.9mm to 40.8±21.8mm with meditation vs. 52.9±11.8mm to 37.3±18.2mm with exercise (adjusted group difference: -1.4 (95%CI:11.6;8.8;p=n.s.) Perceived stress was significantly more reduced with meditation (p=0.011). No significant treatment effects were found for other secondary outcomes as pain-related bothersomeness, function, quality-of-life and psychological scores, although the meditation group consistently showed non-significant better improvements compared to the exercise group. Focused meditation and self-care exercise lead to comparable, symptomatic improvements in patients with chronic low back pain. Future studies should include longer-term follow-ups and develop guided meditation programs to support compliance.


Description of trauma among French service members in the Department of Defense Trauma Registry: understanding the nature of trauma and the care provided.
Since 2001, the French Armed Forces have sustained many casualties during the Global War on Terror; however, even today, there is no French Military trauma registry. Some French service members (SMs) were treated in US Military Medical Treatment Facilities (MTFs) and were recorded in the US Department of Defense Trauma Registry (DoDTR). Our objective was to conduct a descriptive analysis of the injuries sustained by French SMs reported in the DoDTR and subsequent care provided to them to assist in understanding the importance of building a French Military trauma registry. Using DoDTR data collected from 2001 to 2017, a retrospective descriptive analysis was conducted. We identified 59 French SMs treated in US MTFs. The characteristics of the SMs' demographics, injuries, care provided to them, and discharge outcomes were summarized. Among the 59 French SMs identified, 46 (78%) sustained battle injuries (BIs) and 13 (22%) sustained nonbattle injuries (NBIs). There were 47 (80%) SMs injured in Afghanistan (Opération Pamir), while 12 (20%) were injured in Opération Chammal in Iraq and Syria. Explosives accounted for 52.5% of injuries, while 25.4% were due to gunshot wounds; all were BIs. The majority of reported injuries were penetrating (59.3%), most of which were BIs (71.7%). The mean Injury Severity Score for BIs was 12 (SD = 8.9) compared to 6 (SD = 1.7) for NBIs. Around half of SMs (n = 30; 51%) were injured in Afghanistan between the years 2008-2010. Among a total of 246 injuries sustained by 59 patients, extremities were the body part most prone to BIs followed by the head and face. Four SMs died after admission (6.8%). The DoDTR provides extensive data on trauma injuries that can be used to inform injury prevention and clinical care. The majority of injuries sustained by French SMs were BIs, caused by explosives, and predominantly occurring to the extremities; these findings are similar to those of other studies conducted in combat zones. There is a need to establish a French Military trauma registry to improve the combat casualty care provided to French SMs, and its creation may benefit from the DoDTR model.


Radiographic landmarks for tunnel placement in reconstruction of the medial patellofemoral ligament.
To verify the findings of previous studies in confirming radiographic landmarks for the femoral attachment of the medial patellofemoral ligament (MPFL), but also to define radiographic landmarks for the patellar attachment. Assess the effect of limb rotation upon these radiographic landmarks. The medial patellofemoral ligament was identified in ten fresh-frozen human cadaveric knees. A headed pin was used to mark the centre of the femoral and patellar attachments. True lateral radiographs were performed followed by lateral radiographs in 10° and 20° of internal and external rotation. Posterior-anterior and proximal-distal position of the headed pin was evaluated. The femoral attachment averaged 3.8 ± 5.0 mm anterior to the posterior femoral cortical line and 0.9 ± 2.4 mm distal to the perpendicular line intersecting the posterior aspect of Blumensaat's line. The patellar attachment averaged 7.4 ± 3.5 mm anterior to the posterior patellar cortical line, 5.4 ± 2.6 mm distal to the perpendicular line intersecting the proximal margin of the patellar articular surface. There was a significant relationship between limb rotation and distance of femoral and patellar attachment from the posterior cortical line (P < 0.0001 and P < 0.0002 respectively). Radiographic landmarks for the femoral attachment of the MPFL identified in this study are comparable with other recent work. This study describes new radiographic landmarks for the patellar attachment of the MPFL and highlights that it is essential to acquire true lateral radiographs if these radiographic landmarks are to be interpreted accurately.


Properties of voltage dependent potassium currents in acutely isolated rat oculomotor neurons.
Voltage-dependent potassium currents in oculomotor neurons (OMNs) were studied with whole-cell patch clamp recordings. Fast inactivating outward currents (I(fast)) had half activation voltage (Vh) of -37.1 mV with slope factor (Vc) of 10.9 mV. I(fast) had half inactivation voltage (Vh) of -66.5 mV and Vc of 11.4 mV. I(fast) decayed with a time constant(tau) of 5.1 ms at +10 mV. I(fast) were sensitive to 4-aminopyridine, showing 50% inhibitory concentration (IC(50)) of 0.97 mM. Slowly inactivating outward currents (I(slow)) had two components. The low-concentration-TEA-sensitive currents had Vh of -3.7 mV with Vc of 9.7 mV in activation and had Vh of -54.7 mV with Vc of 23.8 mV in inactivation. The persistent currents had Vh of 7.4 mV and Vc of 11.8 mV in activation and Vh of -54.4 mV and Vc of 21.2 mV in inactivation. Decay of I(slow) (+10 mV) followed a double exponential time course (tau 215, 1165.6 ms). Low-concentration-TEA-sensitive currents were blocked completely by tetraethylammonium (TEA) of 3 mM with an IC(50) of 1.52 mM. Higher concentrations (3-20 mM) of TEA blocked the persistent currents, with an IC(50) of 6.9 mM.


Baseline blood eosinophil count as a predictor of treatment response to the licensed dose of mepolizumab in severe eosinophilic asthma.
Previous analyses examining the relationship between blood eosinophil count and mepolizumab treatment effects in severe eosinophilic asthma have used a range of doses and administration routes. This post hoc meta-analysis included data from the MENSA (MEA115588/NCT01691521) and MUSCA (200862/NCT02281318) trials. Patients (≥12 years) with severe eosinophilic asthma who experienced ≥2 exacerbations in the prior year received either mepolizumab 100 mg subcutaneously (SC) or 75 mg intravenously, or placebo plus standard of care every 4 weeks. This meta-analysis reports data from patients receiving the licensed dose of mepolizumab (100 mg SC) or placebo only. The primary endpoint was the annual rate of clinically significant exacerbations; secondary endpoints included rate of exacerbations requiring hospitalization/emergency room (ER) visit, proportion of patients with no clinically significant exacerbations, and changes from baseline in forced expiratory volume in 1 s, Asthma Control Questionnaire-5 and St George's Respiratory Questionnaire scores. Analyses were stratified by baseline blood eosinophil count (<150, ≥150, ≥300, ≥400, ≥500, ≥750, ≥1000, ≥150-<300, or ≥300-<500 cells/μL). Mepolizumab reduced annual clinically significant exacerbation rates by 45%-85%, exacerbations requiring hospitalization/ER visit by 60%-70%, and increased the odds of no clinically significant exacerbations across all eosinophil threshold subgroups versus placebo, and improved all other secondary endpoints in subgroups ≥150 cells/μL. Greater treatment effects with increasing blood eosinophil count were observed. Mepolizumab demonstrated consistent clinical benefits in patients with baseline blood eosinophil counts ≥150 cells/μL, confirming the suitability of this cut-off for identifying patients responsive to the licensed mepolizumab dose.


Cloning and expression of a third calcium channel beta subunit.
The skeletal muscle dihydropyridine receptor/Ca2+ channel consists of five distinct subunits (alpha 1, alpha 2 delta, beta 1, and gamma). Homologous alpha 1, alpha 2 delta, and beta 2 subunits are expressed in heart and brain. The present study reports the cloning and expression of a third beta subunit, beta 3, which is expressed predominantly in brain. Its open reading frame encodes a protein with 484 amino acids with a predicted molecular mass of 54,571 Da. Coexpression of beta 3 with a cardiac alpha 1 in Xenopus oocytes induces similar changes in Ca2+ channel activity as beta 1 and beta 2, that is, it increases peak currents, modulates the voltage dependence of activation, and accelerates activation. In addition, beta 3 accelerates the rate of inactivation at positive test potentials.


Pharmacokinetics of ornidazole in neonates and infants after a single intravenous infusion.
The single dose pharmacokinetics of ornidazole has been evaluated in 12 neonates or infants (aged 1 to 42 weeks) after the infusion of 20 mg/kg over 20 min. Plasma disposition was described by a two-compartment open model. The distribution phase was short (T1/2 (1) = 0.31 h) and was followed by an elimination phase (t1/2 (2) = 14.67 h). The mean apparent volume of distribution was 0.961/kg-1. These results did not differ from data previous by reported in adults. Total plasma clearance was between 0.4 and 1.4 ml X min-1 X kg-1. The plasma concentration 24 h after the infusion was 7.32 mg X l-1, which was above the minimum inhibitory concentration for clinically significant anaerobic bacteria. Based on the pharmacokinetic results and residual concentrations at 24 h, a single daily infusion of ornidazole 20 mg X kg-1 appears adequate for therapy in neonates and infants.


Regulated Cell Death of Retinal Ganglion Cells in Glaucoma: Molecular Insights and Therapeutic Potentials.
Glaucoma is a group of diseases characterized by the degeneration of retinal ganglion cells (RGCs) and progressive, irreversible vision loss. High intraocular pressure (IOP) heightens the likelihood of glaucoma and correlates with RGC loss. While the current glaucoma therapy prioritizes lower the IOP; however, RGC, and visual loss may persist even when the IOP is well-controlled. As such, discovering and creating IOP-independent neuroprotective strategies for safeguard RGCs is crucial for glaucoma management. Investigating and clarifying the mechanism behind RGC death to counteract its effects is a promising direction for glaucoma control. Empirical studies of glaucoma reveal the role of multiple regulated cell death (RCD) pathways in RGC death. This review delineates the RCD of RGCs following IOP elevation and optic nerve damage and discusses the substantial benefits of mitigating RCD in RGCs in preserving visual function.


Trinucleotide repeat expansions in neurological disease.
During the past year, new examples of human neurological disease have been discovered that have an unprecedented type of mutation as their cause: the remarkable expansion of trinucleotide repeats. These triplet repeats are normally polymorphic and exonic, though not always coding. In disease states they become markedly unstable and may expand moderately or by thousands of repeats in a single generation, influencing gene expression, message stability or protein structure.


Pain and discomfort experienced after placement of a conventional or a superelastic NiTi aligning archwire. A randomized clinical trial.
Two nickel-titanium arch-wire types commonly used for initial tooth alignment were compared with regard to the pain/discomfort patients experience during the initial phase of tooth movement. The two arch wires used were a superelastic nickel-titanium alloy, 0.014 inch Sentalloy, Light (GAC International Inc. Central Islip, NY, USA) and a 0.014 inch Nitinol (Unitek, Monrovia, CA, USA), a conventional nickel-titanium aligning archwire. One hundred and twenty-eight consecutive patients attending an orthodontic university clinic and 2 private practices for routine placement of a fixed appliance were randomly assigned one of these 2 initial arch wires. Assessments of pain/discomfort were made daily by means of a 100 mm visual analog scale (VAS) over the first 7-day period after bonding. On the first day, recordings were made every hour for the first 11 hours. The results showed that the level of discomfort increased continuously every hour after the insertion of either a Sentalloy or a Nitinol as first arch wires, with a peak in the first night, remaining high on the second day and decreasing thereafter to baseline level after 7 days. During the first 10 hours it was apparent that the pain/discomfort experienced after placement of a Sentalloy was less than that found with the Nitinol archwire, although a significant difference could be found at 4 hours only. No significant gender-specific differences were found in either archwire group. A significant difference between the upper and lower dental arches was observed during the first 11 hours after placement of either a Sentalloy or a Nitinol arch wire, with the lower arch having the higher pain experience.


Outcomes in Enteral Access Based on Specialty and Approach: A Single-Center Three-Year Experience.
Interventional radiologic, endoscopic, and surgical approaches are commonly utilized to establish durable enteral access in adult patients. The purpose of this study is to examine differences in nutritional outcomes in a large cohort of patients undergoing enteral access creation. Adult patients who underwent enteral access procedures by interventional radiologists, gastroenterologists, and surgeons between 2018 and 2020 at a single institution were reviewed. Included access types were percutaneous endoscopic gastrostomy (PEG), open or laparoscopic gastrostomy, laparoscopic jejunostomy, and percutaneous gastrostomy (perc-G), percutaneous jejunostomy , or primary gastrojejunostomy. 912 patients undergoing enteral access cases met the criteria for inclusion. PEGs and perc-Gs were the most common procedures. PEGs had higher Charlson scores (4.5 [3.0-6.0] versus 2.0 [1.0-2.0], P = 0.007) and lower starting albumin (3.0 [2.6-3.4] versus 3.6 [3.5-3.8] g/dL, P < 0.0001). Time to goal feeds (4 [2-6] vs 4 [3-5] d, P = 0.970), delta prealbumin (3.6 [0-6.5] versus 6.2 [2.3-10] mg/L, P = 0.145), time to access removal (160 [60-220] versus 180 [90-300] d, P = 0.998), and enteral access-related complications (19% versus 16%, P = 0.21) between PEG and perc-G were similar and differences were not statistically significant. A greater percent change in prealbumin was noted for perc-G (10 [-3-20] versus 41.7% [11-65], P = 0.002). Despite having higher Charlson scores and worse preoperative nutrition, there is a similar incidence of enteral access-related complications, time to goal feeds, delta prealbumin, or time to access removal between PEG and perc-G patients. Our data suggest that access approach should be made on an individual basis, accounting for anatomy and technical feasibility.


Recovery and survival in vivo of platelet concentrates prepared with prostaglandin E1.
In follow-up to previous studies showing that stimulators of adenylate cyclase inhibit the activation of platelets in platelet concentrates (PC), the posttransfusion recovery and survival of autologous platelets prepared and stored after the addition of prostaglandin E1 (PGE1) to platelet-rich plasma at a concentration of 1.3 X 10(-8) M were investigated. Six normal subjects were studied on the two occasions, using PC stored with and without PGE1 and radiolabeling with 51Cr. The mean recovery of platelets prepared with PGE1 (35.2 +/- 8.1%) was significantly lower (p less than 0.013) than that of routinely prepared platelet concentrates (46.3 +/- 9.4%). The mean life-spans of platelets prepared with and without PGE1 were 7.1 +/- 0.4 and 6.2 +/- 1.0 days, respectively (p = NS). Despite its ability to inhibit the activation of platelets during concentration and storage, prostaglandin E1 appears to reduce posttransfusion recovery of platelets significantly in this experimental model and cannot be recommended at this time as an adjunct for PC preparation.


Charity raises a glass to brewery windfall.
Sales of more than 45,000 pints of beer named after heroic first world war nurse Edith Cavell have raised more than £2,000 for a nurses' charity.


Cloning, sequencing, and overexpression of a [2Fe-2S] ferredoxin gene from Escherichia coli.
Escherichia coli contains a soluble, [2Fe-2S] ferredoxin of unknown function (Knoell, H.-E., and Knappe, J. (1974) Eur. J. Biochem. 50, 245-252). Using antiserum to the purified protein to screen E. coli genomic expression libraries, we have cloned a gene (designated fdx) encoding this protein. The DNA sequence of the gene predicts a polypeptide of 110 residues after removal of the initiator methionine (polypeptide M(r) = 12,186, holoprotein M(r) = 12,358). The deduced amino acid sequence is strikingly similar to those of the ferredoxins found in animal mitochondria which function with cytochrome P450 enzymes and to the ferredoxin from Pseudomonas putida which functions with P450cam. The overall sequence identity is approximately 36% when compared with human mitochondrial and P. putida ferredoxins, and the identities include 4 cysteine residues proposed to coordinate the iron cluster. The protein was overproduced approximately 500-fold using an expression plasmid, and the holoprotein was assembled and accumulated in amounts exceeding 30% of the total cell protein. The overexpressed ferredoxin exhibits absorption, circular dichroism, and electron paramagnetic resonance spectra closely resembling those of the animal ferredoxins and P. putida ferredoxin.


The transoropalatal approach to the atlantoaxial-clival region: considerations for the head and neck surgeon.
The transoropalatal approach to the atlantoaxial-clival area provides excellent exposure for neurosurgical decompression and fusion procedures. The technique has been effectively applied in the treatment of bony and soft tissue abnormalities of the anterior spinal region. Although this approach is safe and reliable, it is not part of the otolaryngologist's usual surgical armamentarium. In the present study, we describe the case histories of five patients who underwent resection of the odontoid process for cervicomedullary compression. Neurological compromise was manifested by progressive upper and/or lower extremity paresis in all patients. In each patient, a transoropalatal approach was used. The surgical technique is discussed, and the prevention of possible sequelae, including velopharyngeal incompetence and palatal or pharyngeal wound dehiscence, is addressed.


Exploring Smart Glasses for Augmented Reality: A Valuable and Integrative Tool in Precision Livestock Farming.
The growing interest in Augmented Reality (AR) systems is becoming increasingly evident in all production sectors. However, to the authors' knowledge, a literature gap has been found with regard to the application of smart glasses for AR in the agriculture and livestock sector. In fact, this technology allows farmers to manage animal husbandry in line with precision agriculture principles. The aim of this study was to evaluate the performances of an AR head-wearable device as a valuable and integrative tool in precision livestock farming. In this study, the GlassUp F4 Smart Glasses (F4SG) for AR were explored. Laboratory and farm tests were performed to evaluate the implementation of this new technology in livestock farms. The results highlighted several advantages of F4SG applications in farm activities. The clear and fast readability of the information related to a single issue, combined with the large number of readings that SG performed, allowed F4SG adoption even in large farms. In addition, the 7 h of battery life and the good quality of audio-video features highlighted their valuable attitude in remote assistance, supporting farmers on the field. Nevertheless, other studies are required to provide more findings for future development of software applications specifically designed for agricultural purposes.


Penetrating keratoplasty: indications, outcomes, and complications.
Corneal transplantation is the most common form of transplantation with approximately 2500 grafts undertaken annually in the United Kingdom. The modern day success of transplantation is attributed to eye bank storage techniques, ocular pharmacology, and improved surgical techniques. This retrospective case note review identified 203 penetrating keratoplasties (PKs) performed during a period from 1 January 2000 to 31 December 2003 at Manchester Royal Eye Hospital. Preoperative risk factors, surgical technique, postoperative complications, and Snellen acuity were analysed. The mean age of the recipient group was 56.7 years, with 107 right eyes and 96 left eyes. The mean follow-up was 61 months. The overall 5-year survival was 82%, with keratoconus and corneal dystrophies at 93 and 89%, respectively. Visual acuity had improved to 6/12 or better in 48% of patients postoperatively, compared with 8% preoperatively. Forty-three donor grafts (21%) underwent at least a single episode of endothelial rejection. Glaucoma was a finding in 37 (18%) of patients following PK. In all, 16 grafts of 15 patients were noted to have suffered microbial keratitis (MK), an incidence of 8%. PK is currently an effective long-term treatment option for improving visual function. An overall survival rate of 82% over 5 years is comparable with other published studies and is largely dependent on recipient factors. This report emphasises the significant complications of immunological rejection, glaucoma, and microbial keratitis, which continue to limit success.


Biodegradation and ecotoxicity of HFCs and HCFCs.
Hydrofluorocarbons (HFCs) and hydrochlorofluorocarbons (HCFCs) are used or developed as substitutes for fully halogenated chlorofluorocarbons. Based on the results of closed-bottle tests, the biodegradation of HFC-32, HCFC-123, HCFC-124, HFC-125, HFC-134a, HCFC-141b, HCFC-225ca, and HCFC-225cb was less than 60% after 28 days and therefore these compounds are considered not readily biodegradable. Standard acute toxicity tests with HCFC-123, HCFC-141b, and HCFC-225ca using algae, water fleas, and fish revealed EC50 values in the range of 17-126 mg/L. EC50 values of HFC-134a ranged between 450-980 mg/L. Fish studies with HCFC-141b and HCFC-225ca revealed bioaccumulation factors of <3 and 15-64, respectively. A study with plants revealed no effect of HCFC-141b on seed germination and growth of wheat (Triticum aestivum), radish (Raphanus sativus), and cress (Lepidium sativum). In conclusion, HFCs and HCFCs are not very toxic to aquatic organisms and terrestrial plants. No evidence for any aerobic biodegradation for most of the HFCs and HCFCs was found.


Study on the interaction mechanism of 2-aminoanthraquinone with calf thymus DNA.
By utilizing multispectrosopic techniques, the toxic interaction of 2-aminoanthraquinone (2-AAQ) with calf thymus deoxyribonucleic acid (ctDNA) was investigated in vitro under simulated physiological conditions. The experimental results proved that 2-AAQ has a toxic interaction with ctDNA. The binding capacity of DNA with 2-AAQ is diminishing as the pH value of system increasing in the optimization of experimental condition. Moreover we selected pH 7.4, which is nearly physiological condition to enhance the practical significance. According to the Stern-Volmer equation, the quenching was the static quenching process. And the quenching constant Kq can be derived from the fluorescence quenching spectrogram. Ultraviolet absorption spectra and the change in the fluorescence intensity at different ionic strengths further indicated that there was electrostatic binding between 2-AAQ and ctDNA. The circular dichroism experiment showed that the DNA conformation varied from B to A conformation. The basic group enhanced after 2-AAQ embedding. The double helix is more compact, and the DNA conformation changes.


Efficacy and safety of lomitapide in homozygous familial hypercholesterolaemia: the pan-European retrospective observational study.
Lomitapide is a lipid-lowering agent indicated as an adjunct therapy for adult homozygous familial hypercholesterolaemia (HoFH). This study evaluated the medium-term effectiveness and safety of lomitapide in a large cohort of HoFH patients in Europe. In a multicentre retrospective, observational study including 75 HoFH patients treated with lomitapide in a real-world clinical setting from 9 European countries, low-density lipoprotein cholesterol (LDL-C) changes, adverse events (AEs), and major adverse cardiovascular events (MACE) were assessed. After a median 19 months (interquartile range 11-41 months) of treatment with a mean dosage of 20 mg of lomitapide. Low-density lipoprotein cholesterol decreased by 60%, from baseline 280.5 mg/dL (191.8-405.0 mg/dL) to 121.6 mg/dL (61.0-190.5 mg/dL). At the last visit, 32.0% of patients achieved LDL-C <100 mg/dL and 18.7% <70 mg/dL. At baseline, 38 HoFH patients were receiving LDL apheresis (LA), but after initiation of lomitapide 36.8% of patients discontinued LA. During follow-up, lomitapide was permanently interrupted in 13% of patients. Gastrointestinal AEs occurred in 40% and liver transaminases increased (3-5 × upper limits of normal) in 13% of patients. Among patients with liver ultrasound evaluation (n = 45), a modest increase in hepatic steatosis was noted during treatment; however, liver stiffness measured by elastography in 30 of them remained within the normal range. Among HoFH patients exposed to lomitapide for at least 2 years, MACE incident rate was 7.4 per 1000 person-years in the 2 years after as compared to 21.2 per 1000 person-years before treatment with lomitapide. In this medium-term real-world experience, lomitapide proved to be very effective in reducing LDL-C in HoFH. Gastrointestinal AEs were common, but liver safety was reassuring with no sign of increased risk of liver fibrosis. A signal of cardiovascular protection was also observed.


Health-related quality of life in patients with lung cancer: validation of the Mexican-Spanish version and association with prognosis of the EORTC QLQ-LC13 questionnaire.
Lung cancer (LC) is the first cause of cancer-related mortality worldwide and health-related quality of life (HRQL) is a fundamental outcome for evaluating treatment results. Our objective was to validate the Mexican-Spanish versions of the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life QLQ-LC13 disease-specific questionnaire module in Mexican patients with LC; and to explore the possible prognostic role of HRQL data. Translation procedures followed EORTC guidelines. Both instruments were completed by patients with LC. Tests for reliability and validity were performed. A subset of patients was administered HRQL evaluations before and after chemotherapy. HRQL was associated with prognosis in chemotherapy-naïve patients. The protocol was approved by the Institute's Ethics Committee. One hundred fifty three patients (mean age, 60.3 years; 84 females and 69 males) completed both questionnaires. Compliance rates were high, and the questionnaires were well accepted. Nine of 10 multi-item scales of both questionnaires presented Cronbach's alpha coefficients > 0.7. Multi-trait scaling analysis demonstrated good convergent and discriminant validity. Patients with better Karnofsky or Eastern Cooperative Oncology Group (ECOG) performance status reported better functional HRQL scores. Different scales in the EORTC QLQ-C30 and EORTC QLQ-LC13 questionnaires were accurately related with clinical characteristics. Functional as well as disease-symptom scales improved after chemotherapy, but treatment side-effects scales worsened in test-retest analysis. Better role functioning and absence of thoracic pain scales were associated with longer overall survival (OS) (p = 0.009 and p = 0.035, respectively). The Mexican-Spanish versions of the EORTC QLQ-C30 and EORTC QLQ-LC13 questionnaires are reliable and valid for HRQL measurement in Mexican patients with LC and can be used in clinical trials.


Counting the costs of treatment: the reproductive and gynaecological consequences of adjuvant therapy in young women with breast cancer.
As the mortality rate from breast cancer decreases, the issues facing breast cancer survivors are becoming increasingly important. Survivors of all ages may face physical and psychosocial consequences of their diagnosis and treatments. However, the long-term fertility and menopause-related side-effects of adjuvant therapy uniquely affect younger premenopausal breast cancer survivors. This article provides an evidence-based overview of the reproductive and gynaecological impact of breast cancer therapy for premenopausal women diagnosed with breast cancer. The physical and psychosocial implications of premature menopause are presented. Strategies for preserving fertility in selected patients are also discussed. Recent clinical trials strongly indicate that premenopausal women with oestrogen receptor positive tumours should receive endocrine therapy. The increased use of endocrine therapies in younger women raises important questions regarding patient information needs and treatment decision-making.


The mycobacteriology of non-tuberculous mycobacteria.
The genus Mycobacterium consists of >50 species that have been associated with human disease. Mycobacterium are categorised into M. tuberculosis and NTM that are also subdivided into rapid growers and non-rapid growers. Five major clinical syndromes have been described that are attributable to mycobacterium. These include: pulmonary disease; lymphadenitis; skin, soft tissue, and skeletal infections; catheter-related blood-stream infections in immunocompromised hosts; and disseminated disease in persons with AIDS. There is very limited documentation of person-to-person transmission of NTM. Nosocomial infections and outbreaks caused by inadequate disinfection/sterilisation of medical devices or environmental contamination of medications or medical devices are well described. Staining for AFB, culture, histopathologic, or genetic amplification technologies are used to detect and identify mycobacterium. Pulsed- field gel electrophoresis is the method of choice to determine strain relatedness. At present, susceptibility testing for non-tuberculous mycobacteria is not fully standardised and has not been correlated with clinical outcomes.


The role of surface tension on the growth of bubbles by rectified diffusion.
Rectified diffusion has wide and important applications in sonochemistry, ultrasonic cleaning and medical ultrasound. Recent experimental results have demonstrated that the addition of surfactant substantially enhances bubble growth rate. As a hypothesis, this was widely attributed to the acoustic microstreaming and mass transfer resistance caused by surfactants. In this research, the effects of the surfactant of sodium dodecyl sulphate on the rectification have been simulated by considering only the variation of the surface tension coefficient due to the surfactant. The computations are carried out using a newly developed tractable model based on the multi-scale method and the method of matched asymptotic expansions, which allows the prediction of bubble growth taking place over millions of oscillation cycles. The rate of bubble growth observed in the experiments is accurately predicted by our computations, for a range for bulk surfactant SDS concentrations less than or equal to 2.4 mM. Contrary to the widely held hypothesis in the published literature, this has demonstrated that the dominant physical mechanisms remain the shell and area effects in this range of bulk surfactant concentrations. The further enhancement of bubble growth rate provided by either acoustic microstreaming or the resistance to mass transfer is only evident at higher bulk surfactant concentrations. Therefore, the role of surface tension in rectified diffusion for aqueous surfactant solutions is more significant than previously understood. The new results also show that the bubble growth rate is sensitive to small changes in the bubble radius which may account for its unpredictability in applications of sonochemistry.