Characterization of soluble HLA molecules in sweat and quantitative HLA differences in serum of healthy individuals.
Soluble class I molecules were immunoprecipitated from human sweat and serum using the BB7.7 monoclonal antibody (mAb) coupled to immunomagnetic beads. Molecules were analysed biochemically on SDS-PAGE gels and finally by ID-isoelectric-focusing (IEF). Serum- and sweat-HLA IEF-band patterns of the same individual were fully identical, showing that HLA excreted in sweat possess polymorphic structures like those in serum. Quantitatively, we used a highly sensitive competitive enzyme-linked immunosorbent (ELISA) assay to determine soluble class I concentrations. The first group was that of non-HLA-A9 and -Bw62 sera, which were found to contain HLA levels with a mean concentration of 0.82 +/- 0.63 microgram/ml (n = 44). However, sera that were HLA-A23 or -24 (splits of HLA-A9) contained higher levels, with a mean of 3.2 +/- 0.94 microgram/ml (n = 20). Similarly, HLA-Bw62 individuals had a higher mean of 2.05 +/- 0.65 micrograms/ml (n = 10). The difference of the HLA-A9 group to the first group was statistically highly significant, P less than 0.0001, and that of the HLA-Bw62 to the first was also significant, P less than 0.004. Individuals who were both HLA-A9 and -Bw62 (n = 5) did not express significantly higher levels than those who only had one of these specificities. Sweat HLA levels had a mean of 0.42 +/- 0.4 microgram/ml (n = 10). These results show for the first time that soluble class I peptides are excreted in relatively high concentrations in sweat and possess polymorphic structures identical to those of serum HLA and that serum HLA levels are allotype dependent.


[Speech audiometric outcome parameters in clinical trials on hearing improvement].
When comparing clinical studies nationally and internationally, there is great heterogeneity in the applied audiometric outcome parameters. Beside different frequencies included in pure-tone audiometry and the resulting averages, the word recognition scores are measured at varying sound pressure levels, i.e., either with a fixed sound pressure level or with a fixed sensation level. However, a comparison of studies, e. g., in meta-analysis, requires comparable outcome parameters. In this study, the influence of speech-audiometric outcome parameters on the outcome reporting of hearing therapies is studied. Before and after a conservative or a surgical treatment aimed at hearing improvement, 25 patients with hearing impairment were tested with the German Freiburg speech intelligibility test with monosyllables and numbers at various levels, and with the German Oldenburg sentence test in quiet. Additionally, 49 subjects with normal hearing were tested. In a comparison of measurement methods (outcome parameters), the hearing improvement measured using constant sound pressure levels for speech audiometry was significantly greater and therefore more sensitive than using constant sensation levels. To test changes in hearing in clinical studies, fixed sound pressure levels should be preferred to fixed sensation levels. For the development of standardized outcome parameters for measuring speech intelligibility in quiet, fixed sound pressure levels or measurement of speech reception thresholds should be selected.


What do I need to know about immunoglobulin light chain (AL) amyloidosis?
Immunoglobulin light chain (AL) amyloidosis is the most common acquired systemic amyloidoses. Its presentation is often insidious and progressive, which may delay diagnosis. The interval between first symptoms and actual diagnosis along the intrinsic heterogeneity of tissue tropism create a wide spectrum of presentations, both in terms of scope and depth of symptoms and signs and functional status of patients. In this review, the authors review the pathogenesis, diagnosis and differential diagnosis of AL amyloidosis along with the prognosis and state-of-the-art management for patients with this affliction.


Use of eye tracking improves the detection of evoked responses to complex visual stimuli during EEG in infants.
To improve the reliability of detecting EEG responses evoked by complex visual stimuli to the level required for clinical use by integrating an eye tracker to the EEG setup and optimizing the analysis protocol. Infants were presented with continuous orientation reversal (OR), global form (GF), and global motion (GM) stimuli. Eye tracking was used to control stimulus presentation and exclude epochs with disoriented gaze. The spectral responses were estimated from 13 postcentral EEG channels using a circular variant of Hotelling's T2 test statistic. Among 39 healthy infants, statistically significant (p < 0.01) responses to OR/GF/GM stimuli were found from 92%/100%/95% recordings, respectively. The specificity test of the detection algorithm, using non-stimulated baseline EEG, did not yield any false-positive findings. Taken together, this yields 15% improvement on average in the detection performance compared to that in the current literature. Changes to the test protocol and incorporation of the eye tracking information improves the detection of responses to complex visual stimuli in infants. This work presents a test protocol suitable for use in a clinical environment at a level of reliability that allows individual diagnostics.


Periodontal disease and gestational diabetes mellitus.
We examined the relationship between periodontal disease and different types of diabetes in pregnant and nonpregnant women. This study was based on the data from the third National Health and Nutrition Examination Survey (NHANES III), including 256 pregnant and 4234 nonpregnant women. Women were classified into those with gestational diabetes mellitus (GDM) in current pregnancy, with GDM in previous pregnancy, and with type 1 or 2 diabetes. In pregnant women, the prevalence of periodontitis was 44.8% in women with GDM and 13.2% in nondiabetic women, with adjusted odds ratio (aOR) of 9.11 (95% confidence interval [CI] 1.11-74.9). In nonpregnant women, the prevalence of periodontitis was 40.3% in women with type 1 or 2 diabetes, 25.0% in women with previous history of GDM, and 13.9% in nondiabetic women, with aOR of 2.76 (1.03-7.35) for women with type 1 or 2 diabetes. We found an association between periodontal disease and GDM.


Effect of surfactants on the thermoresponse of PNIPAM investigated in the brush geometry.
Anionic surfactants have been reported to interact with poly(N-isopropyl acrylamide) (PNIPAM), suppressing its thermoresponse. Scattering and NMR studies of the anionic sodium dodecylsulfate (SDS) system propose that the PNIPAM-surfactant interaction is purely hydrophobic. However, prior phenomenological investigations of a range of surfactant identities (anionic, cationic, nonionic) show that only anionic surfactants affect the thermoresponse and conformation of PNIPAM, implying that the hydrophilic head-group also contributes. Crucially, the phenomenological experiments do not measure the affinity of the tested surfactants to the polymer, only their effect on its behaviour. We study the adsorption of six surfactants within a planar PNIPAM brush system, elucidating the polymer conformation, thermoresponse, and surfactant adsorption kinetics using ellipsometry, neutron reflectometry (NR), optical reflectometry and the quartz crystal microbalance technique. NR is used to measure the distribution of surfactants within the brush. We find that only anionic surfactants modify the structure and thermoresponse of PNIPAM, with the greater affinity of anionic surfactants for PNIPAM (relative to cationic and nonionic surfactants) being the primary reason for this behaviour. These results show that the surfactant head-group has a more critical role in mediating PNIPAM-surfactant interaction than previously reported. Taking inspiration from prior molecular dynamics work on the PEO-surfactant system, we propose an interaction mechanism for PNIPAM and SDS that reconciles evidence for hydrophobic interaction with the observed head-group-dependent affinity.


Effects of pentobarbital tolerance and dependence on convulsant and GABAA receptor antagonist binding.
Experiments were performed which examined the effects of pentobarbital tolerance and dependence on GABAA receptor antagonist binding. In rats implanted with pentobarbital pellets for 7 days, followed by 24 hours of withdrawal, there was a significant decrease in the latency of TBPS-induced seizures and an increase in [35S]TBPS binding in the frontal cortex. The pentobarbital tolerant rats had a significant increase in the low affinity KD of [3H]SR95531 binding. Removal of the pellets for 24 hours caused a reversal of the effect on the low affinity KD and caused a decrease in the number of low affinity binding sites. In vitro addition of pentobarbital to binding assays produced a decrease in the number of high affinity [3H]SR95531 binding sites without changing low affinity binding. In the cerebellum, the binding in none of the treatment groups was significantly different from placebo. These observations suggest that pentobarbital tolerance and withdrawal cause changes in the properties of the GABAA receptor antagonist binding site which are different from those caused by in vitro exposure to the drug.


Concurrent varicella and herpes simplex virus reactivation in the same trigeminal dermatome in a person living with HIV.
We report a case of a concurrent reactivation of varicella zoster virus and herpes simplex virus in an immunocompromised patient unaware of her longstanding human immunodeficiency virus (HIV) infection. Despite being a rare event, concurrent reactivation of the two alphaherpesvirinae has been reported in various conditions, either in immunocompetent or immunocompromised patients. However, a reactivation in the same anatomical location in a person living with HIV seems to be an extremely rare event.


Degradation of refractory organic matter in MBR effluent from treating landfill leachate by UV/PMS and UV/H2O2: a comparative study.
This study applied ultraviolet/peroxymonosulfate (UV/PMS) and UV/hydrogen peroxide (UV/H2O2) processes to the advanced treatment of membrane bioreactor (MBR) effluent. The degradation efficiency of refractory organic matter and the reaction mechanisms of the two processes were systematically investigated. The results showed that the degradation efficiency of the UV/PMS processes was significantly lower than that of the UV/H2O2 process when the PMS concentration was significantly lower than the H2O2 concentration, e.g. the UV254 removals under optimal conditions were 72.92% and 82.21%, respectively. Additionally, the UV/PMS process could operate over a broader pH range. The degradation efficiency of the UV/PMS process was slightly increased by HCO3- and Cl- due to the activation of PMS, while in the UV/H2O2 process, HCO3- and Cl- depressed the degradation efficiency by competing with organic matter to react with reactive oxygen species (ROS). After the two processes, the aromaticity, humification, condensation degree, and molecular weight of refractory organic matter in the MBR effluent were considerably decreased. Fulvic- (HA) and humic-like substances (FA) were greatly degraded by the two processes. The UV/PMS had a superior degradation efficiency for macromolecular HA in the early stage of the reaction, and the UV/H2O2 could degrade HA to protein-like substances in the latter stage of the reaction. These differences between the two processes could be attributed to the dominance of different ROS, with SO4•- and HO• dominating in the UV/PMS, and HO• dominating in the UV/H2O2. The results of this study provide theoretical support for the application of MBR effluent treatment.


[Motivational and Volitional Processes in the Context of Applying for Medical Rehabilitation Services].
We analyzed if intention and planning of an application for medical rehabilitation can be described using the health action process approach. Data were used from the "Third German Sociomedical Panel of Employees". A questionnaire comprising 8 scales was developed. The scales assess outcome expectancies (3 scales), support by family and physicians (2 scales), self-efficacy, intention and action planning (1 scale each). A confirmatory factor analysis was performed to examine the factorial validity of the questionnaire. Structural equation modeling was used to explain intention and planning of an application for medical rehabilitation. 3 294 persons participated in the survey. The average age was 47.9 years (range 40-54 years, SD=4.1). 53% of the participants were women. Further analyses included data of 2 911 (listwise deletion) and 3 288 participants (estimated missing values), respectively. The anticipated 8-factor structure of the questionnaire was confirmed. The model fit of the structural equation model was good. Intention was explained by family-related negative outcome expectancies, self-efficacy, and support by family and physicians. Intention and support by physicians directly affected planning. Additionally, family-related negative outcome expectancies, family and physician support, and self-efficacy were indirectly associated with planning. This indirect effect was mediated by intention. 51% of the variance of intention and 65% of the variance of planning were explained. The findings of the structural equation model indicate that the health action process approach is useful to describe the process of applying for medical rehabilitation. A validation of the model needs longitudinal data on actual applications. The health action process approach supports our understanding of motivational and volitional determinants of an application for medical rehabilitation. Our results underline the important role that family doctors and occupational physicians have if an application for medical rehabilitation is needed.


TRIP13 promotes the cell proliferation, migration and invasion of glioblastoma through the FBXW7/c-MYC axis.
Thyroid hormone receptor interactor 13 (TRIP13) is an AAA + ATPase that plays an important role in the mitotic checkpoint. TRIP13 is highly expressed in various human tumours and promotes tumorigenesis. However, the biological effect of TRIP13 in GBM cells remains unclear. We generated GBM cell models with overexpressed or silenced TRIP13 via lentivirus-mediated overexpression and RNAi methods. The biological role of TRIP13 in the proliferation, migration and invasion of GBM cells has been further explored. Our research indicated that TRIP13 was highly expressed in GBM tissues and cells. We found that the proliferation, migration and invasion abilities were inhibited in TRIP13-knockdown GBM cells. These results indicated that TRIP13 plays an important role in the tumorigenesis of GBM. Moreover, we found that TRIP13 first stabilised c-MYC by inhibiting the transcription of FBXW7, which is an E3 ubiquitin ligase of c-MYC, by directly binding to the promoter region of FBXW7. Therefore, our study indicated that the TRIP13/FBXW7/c-MYC pathway might provide a prospective therapeutic target in the treatment of GBM. These results indicated that TRIP13 plays an oncogenic role in GBM. The TRIP13/FBXW7/c-MYC pathway might act as a prospective therapeutic target for GBM patients.


Photophysics of Fluorescent Contact Sensors Based on the Dicyanodihydrofuran Motif.
Fluorescent molecular rotors have been used for measurements of local mobility on molecular length scales, for example to determine viscosity, and for the visualization of contact between two surfaces. In the present work, we deepen our insight into the excited-state deactivation kinetics and mechanics of dicyanodihydrofuran-based molecular rotors. We extend the scope of the use of this class of rotors for contact sensing with a red-shifted member of the family. This allows for contact detection with a range of excitation wavelengths up to ∼600 nm. Steady-state fluorescence shows that the fluorescence quantum yield of these rotors depends not only on the rigidity of their environment, but - under certain conditions - also on its polarity. While excited state decay via rotation about the exocyclic double bond is rapid in nonpolar solvents and twisting of a single bond allows for fast decay in polar solvents, the barriers for both processes are significant in solvents of intermediate polarity. This effect may also occur in other molecular rotors, and it should be considered when applying such molecules as local mobility probes.


Cloning of the SAP6 gene of Metschnikowia reukaufii and its heterologous expression and characterization in Escherichia coli.
The SAP6 gene (without signal sequence) encoding Metschnikowia reukaufii acid protease was amplified by PCR and fused to the expression vector pET-24a(+). The carboxy-terminal 6x His-tagged recombinant acid protease (rSAP6) was expressed from pET-24a(+)SAP6-6His in Escherichia coli BL21 (DE3) and purified with affinity chromatography using a Ni-NTA column. SDS-PAGE analysis and Western blotting revealed that the molecular mass of the purified rSAP6 was 54kDa. The optimal temperature and pH of the purified rSAP6 were 40 degrees C and 3.4, respectively. The enzyme was stable below 45 degrees C and between pH 2.6 and 5.0. The results show that Mn(2+) had an activating effect on the enzyme, while Cu(2+), Mg(2+), Zn(2+) and Ag(+) acted as inhibitors of the enzyme. However, Ca(2+) had no effect on the enzyme activity. The purified rSAP6 was characterized as an aspartic protease as it was inhibited by aspartic protease-specific inhibitors, such as pepstatin. It was also found that the purified rSAP6 had milk-clotting activity.


[C-reactive protein, lactate and LDH isoenzymes in the cerebrospinal fluid in the diagnosis in childhood meningitis].
C reactive protein lactate and LDH isoenzymes were quantified in CSF of 32 children with meningitis (27 bacterial and 5 viral). Results in cases with bacterial meningitis were as follows. C reactive protein sensitivity was 11.1% and specificity was 100%. Lactate sensitivity was 33.3% and its specificity was 80%. LDH1 and LDH5 had a sensitivity of 44.4%, and specificities of 100 and 60% respectively. Considering these results an has believe that none of these tests is definitive in diagnosis of bacterial meningitis in children.


Geometric Features Associated with Middle Cerebral Artery Bifurcation Aneurysm Formation: A Matched Case-Control Study.
The pathogenesis of intracranial aneurysms is multifactorial and includes genetic, environmental, and anatomic influences. We aimed to identify image-based morphological parameters that were associated with middle cerebral artery (MCA) bifurcation aneurysms. We evaluated three-dimensional morphological parameters obtained from CT angiography (CTA) or digital subtraction angiography (DSA) from 317 patients with unilateral MCA bifurcation aneurysms diagnosed at the Brigham and Women's Hospital and Massachusetts General Hospital between 1990 and 2016. We chose the contralateral unaffected MCA bifurcation as the control group, in order to control for genetic and environmental risk factors. Diameters and angles of surrounding parent and daughter vessels of 634 MCAs were examined. Univariable and multivariable statistical analyses were performed to determine statistical significance. Sensitivity analyses with smaller (≤ 3 mm) aneurysms only and with angles excluded, were also performed. In a multivariable conditional logistic regression model we showed that smaller diameter size ratio (OR 0.0004, 95% CI 0.0001-0.15), larger daughter-daughter angles (OR 1.08, 95% CI 1.06-1.11) and larger parent-daughter angle ratios (OR 4.24, 95% CI 1.77-10.16) were significantly associated with MCA aneurysm presence after correcting for other variables. In order to account for possible changes to the vasculature by the aneurysm, a subgroup analysis of small aneurysms (≤ 3 mm) was performed and showed that the results were similar. Easily measurable morphological parameters of the surrounding vasculature of the MCA may provide objective metrics to assess MCA aneurysm formation risk in high-risk patients.


Olfactory specific chymotrypsin-like serine protease from the aesthetasc tegumental gland of the lobster, Homarus americanus.
Numerous proteases and protease inhibitors are expressed in the lobster olfactory organ. One of these proteases, olfactory enriched transcript 03 (OET-03), is particularly interesting because its mRNA is expressed only in one cell type of the olfactory organ of the American lobster, Homarus americanus. We have obtained a full-length cDNA clone of OET-03. The predicted amino acid sequence is equally divided between a novel N-terminal domain and a conserved serine protease catalytic domain at the C-terminus. Heterologous expression in HEK293 cells allowed protease assays demonstrating that OET-03 cleaved a specific serine protease substrate, N-alpha benzoyl-L-arginine p-nitroanilide, but did not cleave a substrate of metalloproteases and cysteine proteases. OET-03 protease activity was significantly inhibited by the chymotrypsin-like protease inhibitor, tosyl-L-phenylalanine chloromethyl ketone, but not by the general protease inhibitor, phenylmethylsulfonyl fluoride. Immunoreactivity for OET-03 was detected only in the cells previously shown to contain OET-03 mRNA. The cytoplasm of these cells was filled with enlarged smooth endoplasmic reticulum (a characteristic of secretory cells) that appeared to expand into large electron-translucent areas at the ventral end of the cell. The ventral ends of these secretory cells were apposed to phalloidin-labeled triangular structures reminiscent of the beginnings of the ducts of crustacean tegumental glands. This putative gland was found only in association with the aesthetasc sensory units of the olfactory organ, hence the name, aesthetasc tegumental gland.


Mice deficient in the chemokine receptor CXCR4 exhibit impaired limb innervation and myogenesis.
The chemokine CXCL12/SDF-1 and its receptor CXCR4 regulate the development and the function of the hematopoietic system and control morphogenesis of distinct brain areas. Here, we demonstrate that inactivation of CXCR4 results in a massive loss of spinal cord motoneurons and dorsal root ganglion neurons and, subsequently, in a reduced innervation of the developing mouse fore- and hindlimbs. However, only the death of sensory neurons seems to be a direct consequence of receptor inactivation as suggested by the observations that DRG neurons, but not motoneurons, of wild-type animals express CXCR4 and respond to CXCL12 with an increase in cell survival. In contrast, the increased death of motoneurons in CXCR4-deficient animals seems to result from impaired limb myogenesis and a subsequent loss of muscle-derived neurotrophic support. In summary, our findings unravel a previously unrecognized complex role of CXCL12/CXCR4 in the control of limb neuromuscular development.


Ethyl Pyruvate Alleviating Inflammatory Response after Diabetic Cerebral Hemorrhage.
This study's purpose is to investigate the neuroprotective role of ethyl pyruvate (EP) in the pathogenesis of diabetic intracerebral hemorrhage. The present study used a mouse model of collagenase-induced intracerebral hemorrhage (ICH) and streptozotocin-induced diabetes. The C57BL/6 mice were randomly divided into 3 groups: sham operation, diabetic cerebral hemorrhage, and diabetic cerebral hemorrhage with EP. The EP (80 mg/kg) and EP (50 mg/kg) were injected intraperitoneally one day and one hour before modeling. The protein expression levels of high mobility group box 1 (HMGB1) and NOD-like receptors 3 (NLRP3) were detected with western blot. The mRNA levels of HMGB1 and toll-like receptor 4 (TLR4) were measured by quantitative real-time polymerase chain reaction (PCR). Immunofluorescence and ELISA were performed to confirm some inflammatory factors. Compared to the normal diabetic intracerebral hemorrhage group, the mRNA and protein expression levels of HMGB1 and TLR4 were downregulated in the EP-affected group with diabetic cerebral hemorrhage, together with the downregulation of the expression of inflammasomes, including NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), and caspase 1. EP can reduce the inflammatory response after diabetic intracerebral hemorrhage and may inhibit the activation of inflammasomes by the HMGB1/TLR4 pathway.


Generation of a human induced pluripotent stem cell line (UEFi003-A) carrying heterozygous A673T variant in amyloid precursor protein associated with a reduced risk of Alzheimer's disease.
A673T mutation in the amyloid precursor protein (APP) is a rare variant associated with a reduced risk of late-onset Alzheimer's disease (AD) and age-related cognitive decline. The A673T mutation decreases beta-amyloid (Aβ) production and aggregation in neuronal cultures in vitro. Here we have identified a Finnish non-diseased male individual carrying a heterozygous A673T mutation, obtained a skin biopsy sample from him, and generated an iPSC line using commercially available integration-free Sendai virus-based kit. The established iPSC line retained the mutation, expressed pluripotency markers, had a normal karyotype, and differentiated into all three germ layers in vitro.


Covid-19 Nasopharyngeal Swab Related CSF Rhinorrhoea: A case report.
With the onset of the COVID-19 pandemic, the number of nasopharyngeal swab samples has increased significantly. In this case report, the treatment of a patient who developed unilateral rhinorrhea after nasopharyngeal swab sample is presented. It is aimed to draw attention to the fact that this complication can be prevented with the appropriate technique during nasopharyngeal swab sampling.


Suicide in the elderly in Kaniyambadi block, Tamil Nadu, South India.
Inefficient civil registration systems, non-report of deaths, variable standards in certifying death and the legal and social consequences of suicide are major obstacles in investigating suicide in the developing world. Very high rates of suicide have been recorded in the region in the general population and among younger people. This paper describes the suicide rate among the elderly in Kaniyambadi block, Tamil Nadu, South India for the years 1994-2002 using verbal autopsies. The setting for the study was a comprehensive community health program in a development block in rural South India. The main outcome measure was death by suicide diagnosed by a detailed verbal autopsy and census, birth and death data to identify the population base. The average annual suicide rate was 189 per 100,000 for people over 55 years of age. The ratio of male to female suicides was 1: 0.66. The age-specific suicide rate for men and women increased with age. Hanging (52%) and poisoning with organo-phosphorus compounds (39%) were the commonest methods employed for committing suicide. Significantly more women chose drowning or burning than men who preferred poisoning or hanging (chi2 19.75; df 1; p < 0.001). The suicide rate documented in this study among the elderly is very high. The reasons for the high suicide rate observed in older people are not known. There is a need to develop innovative strategies to reduce deaths by suicide.


Cryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter.
AA amyloidosis is a systemic disease characterized by deposition of misfolded serum amyloid A protein (SAA) into cross-β amyloid in multiple organs in humans and animals. AA amyloidosis occurs at high SAA serum levels during chronic inflammation. Prion-like transmission was reported as possible cause of extreme AA amyloidosis prevalence in captive animals, e.g. 70% in cheetah and 57-73% in domestic short hair (DSH) cats kept in zoos and shelters, respectively. Herein, we present the 3.3 Å cryo-EM structure of AA amyloid extracted post-mortem from the kidney of a DSH cat with renal failure, deceased in a shelter with extreme disease prevalence. The structure reveals a cross-β architecture assembled from two 76-residue long proto-filaments. Despite >70% sequence homology to mouse and human SAA, the cat SAA variant adopts a distinct amyloid fold. Inclusion of an eight-residue insert unique to feline SAA contributes to increased amyloid stability. The presented feline AA amyloid structure is fully compatible with the 99% identical amino acid sequence of amyloid fragments of captive cheetah.


Impact of sub-setting the data of the main Limousin beef cattle population on the estimates of across-country genetic correlations.
Cattle international genetic evaluations allow the comparison of estimated breeding values (EBV) across different environments, i.e. countries. For international evaluations, across-country genetic correlations (rg) need to be estimated. However, lack of convergence of the estimated parameters and high standard errors of the rg are often experienced for beef cattle populations due to limited across-country genetic connections. Furthermore, using all available genetic connections to estimate rg is prohibitive due to computational constraints, thus sub-setting the data is necessary. Our objective was to investigate and compare the impact of strategies of data sub-setting on estimated across-country rg and their computational requirements. Phenotype and pedigree information for age-adjusted weaning weight was available for ten European countries and 3,128,338 Limousin beef cattle males and females. Using a Monte Carlo based expectation-maximization restricted maximum likelihood (MC EM REML) methodology, we estimated across-country rg by using a multi-trait animal model where countries are modelled as different correlated traits. Values of rg were estimated using the full data and four different sub-setting strategies that aimed at selecting the most connected herds from the largest population. Using all available data, direct and maternal rg (standard errors in parentheses) were on average equal to 0.79 (0.14) and 0.71 (0.19), respectively. Direct-maternal within-country and between-country rg were on average equal to - 0.12 (0.09) and 0.00 (0.14), respectively. Data sub-setting scenarios gave similar results: on average, estimated rg were smaller compared to using all data for direct (0.02) and maternal (0.05) genetic effects. The largest differences were obtained for the direct-maternal within-country and between-country rg, which were, on average 0.13 and 0.12 smaller compared to values obtained by using all data. Standard errors always increased when reducing the data, by 0.02 to 0.06, on average. The proposed sub-setting strategies reduced the required computing time up to 22% compared to using all data. Estimating all 120 across-country rg that are required for beef cattle international evaluations, using a multi-trait MC EM REML approach, is feasible but involves long computing time. We propose four strategies to reduce computational requirements while keeping a multi-trait estimation approach. In all scenarios with data sub-setting, the estimated rg were consistently smaller (mainly for direct-maternal rg) and had larger standard errors.


Underdiagnosis of asthma in the elderly.
One hundred and ninety-nine elderly men and women were assessed for their pulmonary function and their mental ability. One hundred and twenty-one patients had a PEFR less than 70% of the predicted for their age and height. Reversibility tests showed that 82 patients had 15% or more improvement in their PEFR following 200 micrograms salbutamol. However, only 6% of the patients were receiving respiratory-related medication. Further analysis showed that there was no correlation between the patients' age, sex, amounts of sputum production, wheeze, breathlessness, smoking habits, chest expansion, hospitalization, mental function and airway reversibility. 'Reversible' patients did, however, have a high incidence of cough and a low pre-test PEFR value. The predominant symptom of 'reversible' and 'non-reversible' patients was cough. The study emphasizes the importance of routinely performing lung function tests in elderly patients and the use of reversibility tests to identify reversible airways obstruction. These results suggest that in old age potentially reversible airways obstruction is often overlooked or misdiagnosed.


Have changing pneumococcal vaccination programmes impacted disease in Ontario?
Publicly funded infant 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in Ontario, Canada in 2005 and was replaced by 10- and 13-valent vaccines (PCV10, PCV13) in October 2009 and November 2010, respectively. Among adults ≥ 65 years, a 23-valent polysaccharide vaccine (PPV23) has been universally available since 1996. In January 2012, PCV13 was approved for adults ≥ 50 years. This study examines the impact of publicly funded vaccination programmes on invasive pneumococcal disease (IPD). Laboratory data from population-based surveillance for IPD conducted at the Toronto Invasive Bacterial Disease Network and from Public Health Ontario Laboratories between January 1, 2008 and December 31, 2010 were analyzed. Between 2008 and 2010 there were 3259 cases of IPD; overall incidence was 7.4/9.3/8.3 per 100,000 in 2008/9/10, respectively. Incidence increased significantly among adults 65+ years during the period; this group had the highest incidence (21.5-25.6/100,000). The second highest incidence in 2008 and 2009 was in infants <1 year, whereas in 2010 it was in children 1-4 years. Among children <5 years, 68% and 19% of serotypes were covered by PCV13 and PCV10, respectively, between 2008 and 2010. In 2009, 6 cases with the 3 additional PCV10 serotypes were reported in infants compared with 2 in 2010. Among persons eligible for PCV7 (born≥2004), there was a 77% decrease in the rate of IPD due to PCV7 serotypes between 2008 and 2010 and a 60% decrease in PCV7 serotypes among persons not vaccine-eligible (born<2004). There was a 15% difference in serotype coverage between PCV13 and the 23-valent polysaccharide vaccine in adults≥50 years. During Ontario's PCV7 programme, serotype-specific decreases in IPD were observed, suggesting vaccine programme success, including herd immunity. Our results also suggest some early impact among infants from PCV10 introduction. A substantial burden of disease was also observed among older adults.


Assessing the efficacy of treatments for ADHD : overview of methodological issues.
Attention-deficit hyperactivity disorder (ADHD) is a common and impairing psychiatric condition that affects significant numbers of children, adolescents and adults. Clinicians in a variety of practice settings (hospital, outpatient, residential, research) strive to diagnose, treat and monitor ADHD in an efficient and evidence-based manner. Tools that facilitate the gathering and interpretation of information from a variety of sources can effectively augment a diagnostic assessment, and can also be useful for longitudinal monitoring. Multiple assessment tools are available, with varying degrees of psychometric validity, clinical utility and overall feasibility (time and cost). This review provides an overview of several available ADHD rating scales and continuous performance tests, and offers a discussion of potential strengths and weaknesses of the instruments. While these tools do not in and of themselves make a diagnosis of ADHD, they can certainly assist in the diagnostic assessment, be crucial in assessing the efficacy of medications in clinical trials, and be a useful adjunct in the clinical management of ADHD.


The lipid composition of hypodermal membranes from the blue crab (Callinectes sapidus) changes during the molt cycle and alters hypodermal calcium permeability.
Crustaceans are covered by a cuticle that does not grow. In order for an individual to grow, the cuticle must periodically be shed (ecdysis). Replacement of the old cuticle with a new one depends on processes that require precise timing and control, yet the nature and location of these controls remain unclear. A candidate site for them is within the hypodermal microvilli. These cellular structures extend through pore canals deep into the acellular cuticular matrix. Changes in the lipid composition of hypodermal microvilli could modulate water and ion fluxes and enzyme activities during critical stages of the molt cycle; however, the lipid composition of these structures has not been assessed during the molt cycle. Data presented here show that phospholipids isolated from hypodermal microvilli of Callinectes sapidus initially have elevated levels of n-6 fatty acids that decline steadily beginning just after ecdysis. Experiments with liposomes reveal that n-6 fatty acids decrease the calcium permeability of membranes, suggesting that the initially elevated levels in the cuticle may function to reduce calcium flux from the cuticle into the hypodermis. In addition, the ratio of cholesterol to phospholipid and the proportion of oleic acid in membrane phospholipids are maximal at 6 h post-ecdysis. It is known that changes in cholesterol and oleic acid content alter membrane permeability to water. It is, therefore possible that water flux through hypodermal membranes is also modulated in the early post-molt cuticle. Changes in microvillar lipid composition might serve importantly to control biomineralization in the post-ecdysal cuticle.


Dynamics of shear-transformation zones in amorphous plasticity: nonlinear theory at low temperatures.
We use considerations of energy balance and dissipation to derive a self-consistent version of the shear-transformation-zone (STZ) theory of plastic deformation in amorphous solids. The theory is generalized to include arbitrary spatial orientations of STZs. Continuum equations for elasto-plastic material and their energy balance properties are discussed.


Cardiovascular disease: much more aggressive in patients with type 2 diabetes.
It is estimated that 80% of individuals with type 2 diabetes die of coronary heart disease. Several factors have been found to contribute to the accelerated atherosclerosis present in diabetic patients. These include hyperglycemia-induced endothelial cell dysfunction, impaired fibrinolysis, increased platelet aggregation, and dysfunctional arterial remodeling. The evidence supports that a healthy lifestyle, statin drugs, angiotensin-converting enzyme inhibitors, and aspirin can modify these factors and slow the atherosclerosis process observed in type 2 diabetes. Because of the high prevalence of cardiovascular disease in people with type 2 diabetes, early cardiac testing is indicated. The optimal strategy for coronary revascularization in diabetic patients remains controversial and is discussed in detail in this review.


Poor prognosis associated with human papillomavirus α7 genotypes in cervical carcinoma cannot be explained by intrinsic radiosensitivity.
To investigate the relationship between human papillomavirus (HPV) genotype and outcome after radiation therapy and intrinsic radiosensitivity. HPV genotyping was performed on cervix biopsies by polymerase chain reaction using SPF-10 broad-spectrum primers, followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse hybridization line probe assay (LiPA25) (version 1) (n=202). PapilloCheck and quantitative reverse transcription-polymerase chain reaction were used to genotype cervix cancer cell lines (n=16). Local progression-free survival after radiation therapy alone was assessed using log-rank and Cox proportionate hazard analyses. Intrinsic radiosensitivity was measured as surviving fraction at 2 Gy (SF2) using clonogenic assays. Of the 202 tumors, 107 (53.0%) were positive for HPV16, 29 (14.4%) for HPV18, 9 (4.5%) for HPV45, 23 (11.4%) for other HPV genotypes, and 22 (10.9%) were negative; 11 (5.5%) contained multiple genotypes, and 1 tumor was HPV X (0.5%). In 148 patients with outcome data, those with HPVα9-positive tumors had better local progression-free survival compared with α7 patients in univariate (P<.004) and multivariate (hazard ratio 1.54, 95% confidence interval 1.11-1.76, P=.021) analyses. There was no difference in the median SF2 of α9 and α7 cervical tumors (n=63). In the cell lines, 9 were α7 and 4 α9 positive and 3 negative. There was no difference in SF2 between α9 and α7 cell lines (n=14). The reduced radioresponsiveness of α7 cervical tumors is not related to intrinsic radiosensitivity.


Carbon monoxide is a major contributor to the regulation of vascular tone in aortas expressing high levels of haeme oxygenase-1.
The contribution of haeme oxygenase-derived carbon monoxide (CO) to the regulation of vascular tone in thoracic aorta was investigated following induction of the inducible isoform of haeme oxygenase (HO-1). Isometric smooth muscle contractions were recorded in isolated rat aortic ring preparations. Rings were incubated in the presence of the nitric oxide (NO) donor S-nitroso-N-acetyl penicillamine (SNAP, 500 microM) for 1 h, then repetitively washed and maintained for a further 4 h prior to producing a concentration-response curve to phenylephrine (PE, 1-3000 nM). Treatment with SNAP resulted in increased mRNA and protein expression of aortic HO-1 and was associated with a significant suppression of the contractile response to PE (P<0.05 vs control). Immunohistochemical staining procedures revealed marked HO-1 expression in the endothelial layer and, to a lesser extent, in smooth muscle cells. Induction of HO-1 in SNAP-treated rings was associated with a higher 14CO release compared to control, as measured by scintillation counting after incubation of aortas with [2-14C]-L-glycine, the precursor of haeme. Guanosine 3',5'-monophosphate (cyclic GMP) content was also greatly enhanced in aortas expressing high levels of HO-1. Incubation of aortic rings with the NO synthase inhibitor, NG-monomethyl-L-arginine (100 microM), significantly (P<0.05) increased the contractile response to PE in controls but failed to restore PE-mediated contractility in SNAP-treated rings. In contrast, the selective inhibitor of haeme oxygenase, tin protoporphyrin IX (SnPP-IX, 10 microM), restored the pressor response to PE in SNAP-treated rings whilst markedly reducing CO and cyclic GMP production. We conclude that up-regulation of the HO-1/CO pathway significantly contributes to the suppression of aortic contractility to PE. This effect appears to be mediated by the elevation of cyclic GMP levels and can be reversed by inhibition of the haeme oxygenase pathway.


The effects of chronic ganglion blockade and chronic cholinesterase inhibition on the sensitivity of rabbit stomach muscularis to cholinergic and adrenergic agonists.
The EC50 values, KA values and efficacies (e) of selected agonists have been determined in strips of stomach muscularis from control, chlorisondamine-pretreated and O, O-diethyl S[2(ethylthio)ethyl]phosphodithioate (disulfoton)-pretreated rabbits. Strips from chlorisondamine-pretreated animals were supersensitive to carbachol but normosensitive to phenylephrine; the e but the KA of carbachol was affected by this treatment. The KB of atropine was unchanged. Strips from animals treated with disulfoton were subsensitive to phenylephrine but normosensitive to amidephrine and carbachol; both the e and KA of phenylephrine appeared to be elevated by this pretreatment. The KB of phentolamine remained unchanged. These results indicate that the chlorisondamine-induced supersensitivity is the result of a change beyond the level of the cholinergic receptors. In contradistinction, the subsensitivity to phenylephrine after disulfoton pretreatment may result at least in part, from a qualitative change in the alpha adrenergic receptors in the stomach muscularis.


Computational Biomechanical Modeling of Fibrin Networks and Platelet-Fiber Network Interactions.
Fibrin deformation and interaction of fibrin with other blood components play critical roles in hemostasis and thrombosis. In this review, computational and mathematical biomechanical models of fibrin network deformation and contraction at different spatio-temporal scales as well as challenges in developing and calibrating multiscale models are discussed. There are long standing challenges. For instance, applicability of models to identify and test potential mechanisms of the biomechanical processes mediating interactions between platelets and fiber networks in blood clot stretching and contraction needs to be examined carefully. How the structural and mechanical properties of major blood clot components influences biomechanical responses of the entire clot subjected to external forces, such as blood flow or vessel wall deformations needs to be investigated thoroughly.


The survival of patients with bladder tumors treated by surgery: comparative results of an old and a recent series.
A review of a large number of patients with bladder tumors treated primarily by an operation during approximately 4 decades indicates that survival of patients with papillomas and superficial carcinomas essentially was unchanged. Recently, patients with invasive cancers who have been treated have enjoyed a modest improvement in the 5-year survival rate, which was at least in part the result of a diminished postoperative mortality rate.


Rare Complication of Takotsubo Cardiomyopathy: Ventricular Septal Perforation with Septal Dissection.
We describe a rare case of takotsubo cardiomyopathy complicated by acute ventricular septal perforation with ventricular septal dissection. The ventricular perforation was successfully closed by repairing the dissecting site with a bovine pericardial patch.


Blockade of a 5-hydroxytryptophan-induced animal model of depression with a potent and selective 5-HT2 receptor antagonist (LY53857).
To test the hypothesis that a new potent and selective 5-HT2 receptor antagonist would be an excellent blocker of D,L-5-hydroxytryptophan (5-HTP)-induced response suppression in an animal model of depression, we administered LY53857 60 min prior to 5-HTP injections into rats working on an operant schedule for milk reinforcement. As predicted, LY53857 pretreatment significantly blocked 5-HTP depression (90%) in doses as low as 0.1 mg/kg ip. When the dose of LY58357 was further reduced to 0.025 mg/kg, blockade of 5-HTP-induced depression was still greater than 30%. In doses as high as 5.0 mg/kg, LY53857 alone had no effect on the baseline performance of rats working a VI 1 schedule. Pretreatment with desipramine (2.5 mg/kg), an antidepressant characterized as having major noradrenergic effects, did not significantly block the 5-HTP-induced depression. These data suggest that the 5-HTP-induced depression is mediated by serotonergic mechanisms involving 5-HT2 receptors, as LY53857 is a selective antagonist of these receptors. These data also support the suggestion, based on other published data from this laboratory, that some antidepressants are antagonizing 5-HT2 receptors in our animal model of depression and may also act in a similar manner in depressed patients. Thus, this new drug could be of interest as a possible antidepressant agent of the general type that was proposed earlier by Aprison and Hingtgen (1981).


Arterial embolization of bleeding pseudoaneurysm caused by percutaneous renal biopsy.
A pseudoaneurysm of a primary branch of the renal artery with massive hemorrhage developed in a patient who underwent percutaneous needle renal biopsy. He was treated successfully by embolization of the artery with gelatin sponge (Gelfoam).


Studying the integrated functional cognitive basis of sustained attention with a Primed Subjective-Illusory-Contour Attention Task.
Sustained attention plays an important role in everyday life, for work, learning, or when affected by attention disorders. Studies of the neural correlates of attention commonly treat sustained attention as an isolated construct, measured with computerized continuous performance tests. However, in any ecological context, sustained attention interacts with other executive functions and depends on lower level perceptual processing. Such interactions occur, for example, in inhibition of interference, and processing of complex hierarchical stimuli; both of which are important for successful ecological attention. Motivated by the need for more studies on neural correlates of higher cognition, I present an experiment to investigate these interactions of attention in 17 healthy participants measured with high-resolution electroencephalography. Participants perform a novel 2-alternative forced-choice computerised performance test, the Primed Subjective Illusory Contour Attention Task (PSICAT), which presents gestalt-stimuli targets with distractor primes to induce interference inhibition during complex-percept processing. Using behavioural and brain-imaging analyses, I demonstrate the novel result that task-irrelevant incongruency can evoke stronger behavioural and neural responses than the task-relevant stimulus condition; a potentially important finding in attention disorder research. PSICAT is available as an open-source code repository at the following url, allowing researchers to reuse and adapt it to their requirements. https://github.com/zenBen/Kanizsa_Prime/ .


Selected Papers from the pHealth 2021 Conference, Genoa, Italy, 8-10 November 2021.
This Special Issue of the Journal of Personalized Medicine presents extended versions of selected contributions to pHealth 2021, the 18th International Conference on Wearable Micro and Nano Technologies for Personalized Health, held on 8-10 November 2021 in Genoa, Italy [...].


Spontaneous Intracerebral Hemorrhage.
Although commonly arising from poorly controlled hypertension, spontaneous intracerebral hemorrhage may occur secondary to several other etiologies. Clinical presentation to the emergency department ranges from headache with vomiting to coma. In addition to managing the ABCs, the crux of emergency management lies in stopping hematoma expansion and other complications to prevent clinical deterioration. This may be achieved primarily through anticoagulation reversal, blood pressure, empiric management of intracranial pressure, and early neurosurgical consultation for posterior fossa hemorrhage. Patients must be admitted to intensive care. The effects of intracerebral hemorrhage are potentially devastating with very poor prognoses for functional outcome and mortality.


Late asymptomatic atrial lead perforation, a fortuitous finding during lead extraction using thoracoscopic surveillance: a case report and review of the literature.
A 61-year-old male patient was referred for lead extraction of an infected two-chamber pacemaker system first implanted 18 years ago. A new atrial lead was implanted 9 years later because of loss of capture of the original lead. Video-assisted thoracoscopic surgery (VATS) that we use in high-risk cases showed extensive fibrous adhesion between the right atrium wall and the right lung. Dissection of the adhesion revealed the presence of an atrial lead perforated into the lung. After cutting off the lead tip, the residual lead was removed endovascularly from the subclavian site. A literature review of 25 reported cases of late atrial lead perforation was added to the findings in our case report.


Burn injuries in native Canadians: a 10-year experience.
Between 1977 and 1986, 1598 patients were admitted to the Firefighters' Burn Unit of the University of Alberta Hospital in Edmonton, Alberta. One hundred and twenty-five (7.8 per cent) of these patients were Treaty Indians or Metis compared to 4.2 per cent of the general population in the same given area. The data show native people suffered larger total body surface area (TBSA) burns, were hospitalized on average 16.9 days longer and required 0.7 more operations than their non-native counterparts. Natives are also three times more likely to remain within the health care system as inpatients for rehabilitation after acute burn management has been completed. Mortality rates as a result of these burns were similar for natives (4.8 per cent) and non-natives (4.3 per cent). This review indicates that the native population is at higher risk of suffering burn injury even after adjusting for certain demographic variables, consequently impacting the utilization of the health care system.


Development and consensus process for a clinical pathway for the assessment and management of chemotherapy-induced peripheral neuropathy.
Cancer patients treated with neurotoxic chemotherapy are at risk of developing neurological symptoms that can impact functional capacity and quality of life. However, there are no standardised pathways to assess and manage chemotherapy-induced peripheral neurotoxicity (CIPN). This study aimed to determine consensus on statements regarding a CIPN assessment and management clinical pathway. A CIPN clinical pathway (CIPN-path) was developed and reviewed by an expert multi-disciplinary panel and consumers. Agreement with 18 statements regarding four content themes (pretreatment review, screening and assessment, management and referral, and CIPN-path feasibility) were assessed by 70 Australian respondents (68 health professionals, 2 consumers), using a 2-stage Delphi survey process to reach consensus. Respondents rated statements using a 5-point Likert scale to determine the level of agreement, with consensus defined as ≥ 80% of respondents agreeing with each statement. The consensus was reached for 14 of 18 items after stage 1 and all items after stage 2. Feedback was obtained for all items to refine the CIPN-path. There was an agreement on important characteristics of the CIPN-path, including pretreatment screening, regular patient-reported assessment, and a stepped-care approach to investigating and managing symptom burden. There was a lack of agreement on who should oversee CIPN assessment, which may differ according to the structure and resources of each site. There was an overall agreement concerning the CIPN-path to assess and manage CIPN, which may be adapted accordingly to the resources of each clinic. The CIPN-path may assist teams across different health services in identifying CIPN symptoms, aiding decision-making, and reducing morbidity from CIPN.


Adjuvant treatment of endometrial cancer in molecular era: Are we ready to move on?
For many decades, the Bokhman dualist vision was used to stratify endometrial cancer (EC) in good or bad tumors. Nowadays, a more robust and reliable molecular stratification is taking place with the The Cancer Genome Atlas Research Network (TCGA) classification bringing new and important information in the field. Collaborative groups are replicating TCGA using accessible tools with immunohistochemistry. It's time to move on and include this information along with pathology features to better delineate adjuvant treatment in EC.


Immunotherapy preparation guidelines, rules, and regulation.
Allergen immunotherapy has been used to treat allergic diseases for more than 100 years. In the U.S., the preparation of diagnostic and therapeutic extracts requires the cooperation of the extract manufacturer, who provides the individual allergen concentrates, and the practicing physician who formulates, dilutes, and administers the final patient-specific treatment extract. The guidelines, rules, and regulations for these activities have been established and continue to be developed as progress is made. The molecular characterization and standardization of allergenic extracts has allowed for improvements in defining the potency of these products. In turn, these advances have led to improved dosing regimens and formulation practices. This review will describe in detail some of these interactions and will identify issues that require more attention.


Phytochemical and biological studies of Solanum schimperianum Hochst.
Chemical reinvestigation of the aerial parts of Solanum schimperianum Hochst led to the isolation of ten compounds, lupeol (1), β-sitosterol (2), β-sitosterol glucoside (3), oleanolic acid (4), teferidin (5), teferin (6), ferutinin (7), 5-hydroxy-3,7,4'-trimethoxyflavone (8), retusin (9) and kaempferol-3-O-β-d-glucopyranoside (10). Compounds 5-7 were isolated for the first time from Solanaceae and compounds 1-4 and 8-9 for the first time from Solanum schimperianum. The structure elucidation of the isolated compounds was based on careful inspection of spectral data including 1D ((1)H and (13)C NMR), 2D ((1)H-H COSY, HMQC and HMBC, ROESY), UV, MS and IR, in addition to, comparison with literatures. The antimicrobial activity of the extracts as well as the isolated compounds was tested. Only hexane extract showed activity against Bacillus subtilus and Staphylococcus aureus.


Evaluation safety and efficacy of immune checkpoint blockers (ICB) and radiotherapy combination versus ICB in non-small cell lung cancer patients with recurrence or metastasis: A systematic review and meta-analysis.
Currently, immune checkpoint blockers (ICB) and radiotherapy (RT) combination therapy is broadly applied in non-small cell lung cancer (NSCLC) patients. However, meta-analysis about safety and efficacy of RT + ICB versus ICB has not yet been reported. To evaluate safety and efficacy of the combination therapy of ICB and RT in patients with recurrent or metastatic NSCLC and explore factors related to higher response rates, longer lifetime, and lower toxicity, meta-analysis of previous clinical data will be presented in this article. A literature search on patients with recurrent or metastatic NSCLC treated with RT + ICB versus ICB was performed using the Cochrane Library, Embase and PubMed up to December 10, 2022. Suitable quality assessment checklists were selected corresponding to various types of research studies. Comparative and single-arm studies were analyzed using Stata 14.0. 10 comparative studies and 15 arms of combination therapy were included for this meta-analysis. RT significantly improved objective response rate (ORR), disease control rate (DCR), and overall survival (OS) and progression-free survival (PFS) of ICB (I-square value (I2 ) = 0.00%, odds ratio (OR) 1.28, 95% confidence interval (CI) 1.09-1.49, I2 = 0.00%, OR 1.12, 95% CI 1.00-1.25, I2 = 42.1%, OR 0.81, 95% CI 0.72-0.92, I2 = 34.5%, OR 0.80, and 95% CI 0.71-0.89, respectively). Toxicity between combination therapy and ICB monotherapy did not significantly differ in any grade or in ≥3 grade of tr-AEs (I2 = 0.00%, OR 1.05, 95% CI 0.91-1.22, I2 = 0.00%, OR 1.46, 95% CI 0.90-2.37, respectively). Subgroup analyses based on single-arm studies showed that applications of SRS/SBRT, PD-1 inhibitor, and administration of ICB after RT were conducive to a better DCR, longer OS and mild adverse events (heterogeneity between groups (HBG) all p < 0.05). RT can significantly improve ORR, DCR, OS, and PFS of ICB in patients with recurrent or metastatic NSCLC without increasing toxicity. PD-1 inhibitor following SRS/SBRT could be the best option to maximally benefit the patients.


Bacterial lipases: A review on purification and characterization.
Lipase (E.C.188.8.131.52) belongs to the hydrolases and is also known as fat splitting, glycerol ester hydrolase or triacylglycerol acylhydrolase. Lipase catalyzes the hydrolysis of triglycerides converting them to glycerol and fatty acids in an oil-water interface. These are widely used in food, dairy, flavor, pharmaceuticals, biofuels, leather, cosmetics, detergent, and chemical industries. Lipases are of plant, animal, and microbial origin, but microbial lipases are produced at industrial level and represent the most widely used class of enzymes in biotechnological applications and organic chemistry. Phylogenetic analysis and comparison of residues around GxSxG motif provided an insight to the diversity among bacterial lipases. A variety of para-Nitrophenyl (p-NP) esters having C2 to C16 (p-NP acetate to p-NP palmitate) in their fatty acid side chain can be hydrolyzed by bacterial lipases. Large heterogeneity has been observed in molecular and catalytic characteristics of lipases including molecular mass; 19-96 kDa, Km; 0.0064-16.58 mM, Kcat; 0.1665-1.0 × 104 s-1 and Kcat/Km; 26.02-7377 s-1/mM. Optimal conditions of their working temperature and pH have been stated 15-70 °C and 5.0-10.8, respectively and are strongly associated with the type and growth conditions of bacteria. Surface hydrophobicity, enzyme activity, stability in organic solvents and at high temperature, proteolytic resistance and substrate tolerance are the properties of bacterial lipases that have been improved by engineering. Bacterial lipases have been extensively studied during last decade. However, their wider applications demand a detailed review on purification, catalytic characterization and applications of lipases.


The dsRNA mycovirus ChNRV1 causes mild hypervirulence in the fungal phytopathogen Colletotrichum higginsianum.
The genus Colletotrichum comprises a large number of filamentous fungi responsible for anthracnose diseases in many tropical and subtropical fruits and vegetables. In particular, Colletotrichum higginsianum infects Brassicaceae species, including Arabidopsis. The C. higginsianum strain IMI349063A is naturally infected with a dsRNA virus, named Colletorichum higginsianum non-segmented virus (ChNRV1). Here, we investigated the biological effect of ChNRV1 in C. higginsianum by comparing strains with and without the virus. ChNRV1 does not have an effect on C. higginsianum growth under salt and cell-wall stress conditions. However, thermal stress reduced C. higginsianum growth rate, this effect being more evident in the wild-type C. higginsianum strain containing the virus. Although ChNRV1 had no effect in conidiation, conidia were narrower when the virus is present. More importantly, ChNRV1 causes a mild increase in C. higginsianum virulence (hypervirulence) when infecting Arabidopsis plants. These findings indicated that, whereas the ChNRV1 mycovirus does not impair growth and conidiation of C. higginsianum, it confers hypervirulence to the fungal host. These findings will help in future research on the effect of mycoviral infection on pathogenic fungi in plant species of agronomical relevance.


Liver transplantation for metabolic disorders.
Liver transplantation for metabolic disorders continues to be an expanding field, both in the range of indications and patient numbers. In most large series it accounts for approximately 7% of all adult transplants and 29% of all childhood transplants. As the results of medical therapy are improved so too are the results of liver transplantation, and hence more patients are being considered for the latter therapy. The benefits of this treatment are not only the prolongation of and improvement in the quality of life for the patient, it has also given insight into the basic metabolic defects of many disorders.


Relationship between phosphorylation of sperm-specific antigen and prognosis of lung adenocarcinoma.
Lung cancer is generally considered as a highly malignant cancer. A major challenge for the management of lung adenocarcinoma patients is to predict the clinical course of the disease after resection. We analyzed the different levels of phosphorylation of proteins in lung adenocarcinoma tissues between a poor prognosis (PP) group, in which six patients exhibited recurrence within five years after surgery, and a good prognosis (GP) group, in which seven patients did not exhibit recurrence within five years after surgery. We found that phosphorylation at Ser92 of the sperm-specific antigen 2 (SSFA2) [phospho-SSFA2(pS92)] was stimulated in the PP group. Using samples from a total of 46 patients, we investigated the utility of phospho-SSFA2(pS92) to discriminate patients of GP and PP groups, with multiple reaction monitoring (MRM) mass spectrometry. Consequently, we confirmed that the PP group had significantly elevated phospho-SSFA2(pS92) levels. Additionally, no expression of SSFA2 recognized in the normal lung tissues. From these results, we demonstrate that phospho-SSFA2 (pS92) is related to the prognosis of early resected lung adenocarcinomas. Therefore, we suggest that phosphorylation of this protein indicates its role as a potential biomarker and new therapeutic target. Lung adenocarcinoma patients often experience a high rate of recurrence after surgery. It is important to discover biomarkers for prognostic prediction and therapeutic targets for treatment of early-stage lung adenocarcinoma. In this study, using tissue samples obtained from patients with lung adenocarcinoma that had been stored for five years at -80°C, we identified 13 unique phosphorylated peptides, which were differentially expressed between poor and good prognosis groups. We confirmed that phosphorylation at Ser92 of the sperm-specific antigen 2 (SSFA2)[phospho-SSFA2 (pS92)], was related to poor prognosis. Our study demonstrates that prognostic prediction of early-stage lung adenocarcinoma is possible, and suggests new therapeutic targets for its treatment.


Lung abscess complicating pneumococcal pneumonia: a causal role of non-steroidal anti-inflammatory drugs?
Pulmonary abscess is a distinctly uncommon complication of pneumococcal pneumonia in immunocompetent adults that has recently been reported to occur following administration of non-steroidal anti-inflammatory drugs (NSAIDs). We report herein the case of a 24-year-old patient with no predisposing risk factor who developed a lung abscess after NSAIDs exposure, further illustrating this potentially severe complication of NSAIDs use, especially in the absence of associated antibiotic therapy.


Low-level laser therapy decreases levels of lung neutrophils anti-apoptotic factors by a NF-kappaB dependent mechanism.
Low-level laser therapy (LLLT) is a known modulator of inflammatory process. Herein we studied the effect of 660 nm diode laser on mRNA levels of neutrophils anti-apoptotic factors in lipopolysaccharide (LPS)-induced lung inflammation. STUDY DESIGN/METHODOLOGY: Mice were divided into 8 groups (n=7 for each group) and irradiated with energy dosage of 7.5 J/cm(2). The Bcl-xL and A1 mRNA levels in neutrophils were evaluated by Real Time-PCR (RT-PCR). The animals were irradiated after exposure time of LPS. LLLT and an inhibitor of NF-kappaB nuclear translocation (BMS 205820) attenuated the mRNA levels of Bcl-xL and A1 mRNA in lung neutrophils obtained from mice subjected to LPS-induced inflammation. LLLT reduced the levels of anti-apoptotic factors in LPS inflamed mice lung neutrophils by an action mechanism in which the NF-kappaB seems to be involved.


Appearance of a transient inv(14)(q11q32) in a case of B cell chronic lymphocytic leukemia.
The inv(14)(q11q32) has been reported to be a specific chromosome aberration in T-cell chronic lymphocytic leukemia (T-CLL) and different types of T-cell lymphomas. Here, the first case of B-CLL with a clonal inv(14)(q11q32) in a phytohemagglutinin-stimulated bone marrow culture is presented. In a subsequent study 9 months later, tetradecanoyl-o-phorbol-13-acetate stimulated blood and bone marrow cultures revealed a clone with a t(1;11)(p13.2;q23.1) and an aberrant chromosome 17.


Structural and functional peculiarities of mast cells in undifferentiated connective tissue dysplasia.
We performed an immunomorphological study of mast cells from undamaged skin in women with phenotypical evidence of undifferentiated connective tissue dysplasia syndrome, patients of cosmetological clinics. It was found that the numerical density of mast cells containing chymase granules in this condition 1.7-fold surpassed the corresponding parameter in patients without signs of connective tissue dysplasia syndrome, which probably was a result of compensatory and adaptive reaction aimed at activation of the synthesis of the connective tissue extracellular matrix components. It was hypothesized that increased content of chymase-positive mast cells in the skin of patients with connective tissue dysplasia syndrome contributed to the formation of associated arterial hypertension.


Increases in the concentration of brain derived neurotrophic factor in the lumbar spinal dorsal horn are associated with pain behavior following chronic constriction injury in rats.
Animals exhibiting thermal hyperalgesia as a sign of neuropathic pain 7 days after loose ligation of the sciatic nerve exhibited a significant increase in the concentration of brain derived neurotrophic factor (BDNF) in their lumbar spinal dorsal horn. In contrast, following the disappearance of thermal hyperalgesia 28 days after loose ligation of the sciatic nerve, there were no differences in BDNF levels between control animals and those with sciatic ligations. These data suggest a close association in the timeline of the development and disappearance of behavioral signs of neuropathic pain with changes in BDNF levels in the lumbar spinal dorsal horn, and lend further support to the notion that plasticity in the processing of sensory information in the spinal dorsal horn may contribute to the development of persistent pain.


Malignant fibrous histiocytoma of the renal capsule. Light and electron microscopic study of a rare tumor.
This light microscopically pleomorphic tumor, which occurred in the renal capsule of 35-year-old female was diagnosed as a malignant fibrous histiocytoma. Ultrastructurally, the tumor showed two major components; fibroblast-like and histiocyte-like cells. This report stresses the rarity of such neoplasm in the kidney and also the usefulness of electron microscopy in establishing the diagnosis.


Phosphatase production by microorganisms isolated from diverse types of soils.
Qualitative and quantitative nature of phosphatases produced by various fungal, bacterial, and actinomycetes isolates from diverse soils was examined. Soil fungi, particularly those belonging to the genera Aspergillus and Penicillium, were found to be most effective in producing phosphatases intra- and extracellularly. None of the 16 bacterial isolates produced acid phosphatase, but most of them did produce neutral phosphatase. Actinomycetes produced only negligible quantities of phosphatases.


A predator-prey model with predators using hawk and dove tactics.
In this work we present a predator-prey model that incorporates individual behavior of the predators. A classical Lotka-Volterra model with self-limiting prey describes the predator-prey interaction. Predator individuals can use two behavioral tactics to dispute a prey when they meet, the classical hawk and dove tactics. Each individual can use both tactics along its life. The predator behavioral change is described by means of a game dynamic model based upon the replicator equations, where the gain depends on prey density. We assume that the demographic process, predator-prey interactions, acts at a slow time scale in comparison with the evolution of the behavior of the predator population. The existence of two time scales allows studying the complete system from a reduced one, which describes the dynamics of the total predator and prey densities at the slow time scale. The aim of this work is to study the effects of individual predator behavior on the dynamics of the predator-prey system. The main conclusion that emerges from this study is the existence of a relationship between prey density and the strategy adopted by predators: aggressive behavior is connected to high prey and low predator densities, whereas a polymorphism dove-hawk is found at low prey and high predator densities.


A metagenomic study of the gut microbiome in PTB'S disease.
There is an abundant link between the gut microbiota and human health and it plays a critical role in the clinic. It is recognized that microbial dysregulation contributes to the pathogenesis of tuberculosis (TB) but the underlying mechanisms remain unclear. In this study, we investigated the association of gut microbiome composition with TB as well as its possible roles in the development of this disease. Fecal samples were collected from 10 TB patients and 20 healthy control samples. DNA extracted from fecal samples was subjected to 16S rDNA gene sequencing analysis on the Illumina MiSeq platform. Compared with healthy control samples, the gut microbiome of patients with TB was characterized by the decreased Alpha diversity. Perhaps, the decrease of microbial diversity which results in microbial dysregulation is the reason for clinical patients with more symptoms. The PTB group showed the most unique microbiota by higher abundance of Bifidobacteriaceae, Bifidobacteriales, Coriobacteriaceae, Coriobacteriales, Actinobacteria, Caulobacteraceae, Phyllobacteriaceae, Rhizobiales, Burkholderiaceae, Burkholderiaceae. Inflammatory status in PTB patients may be associated with the increased abundance of Clostridia and decreased abundance of Prevotella. We found that the abundance of Solobacterium and Actinobacteria was higher in the patients. There were 4 significant differences (p < 0.05) in the two groups which belonged to four metabolic categories, including endocytosis, phosphotransferase system (PTS), toluene degradation, and amoebiasis. We applied the approach of metagenomic sequencing to characterize the features of gut microbiota in PTB patients. The present study provided a detailed analysis of the characterization of the gut microbiota in patients based on the clinic. According to the metagenome analysis, our results indicated that the gut microbiota in PTB patients was significantly different from healthy control samples as characterized by the bacteria and metabolic pathway. The richness of the gut microbiota in patients was revealed. It was hypothesized that the above-mentioned changes of the gut microbiota could exert an impact on the development of PTB through the downstream regulation of the immune status of the host by way of the gut-lung axis.


Weipixiao attenuate early angiogenesis in rats with gastric precancerous lesions.
Angiogenesis is a pathobiological hallmark of gastric cancer. However, rare studies focus on angiogenesis in gastric precancerous lesions (GPL). Weipixiao (WPX), a Chinese herbal preparation, is proved clinically effective in treating GPL. Here, we evaluated WPX's anti-angiogenic potential for GPL, and also investigated the possibility of its anti-angiogenic mechanisms. HPLC analysis was applied to screen the major chemical components of WPX. After modeling N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced GPL in male Sprague-Dawley rats, different doses of WPX were administrated orally for 10 weeks. Next, we performed histopathological examination using routine H&E staining and HID-AB-PAS staining. In parallel, we assessed angiogenesis revealed by microvessel density (MVD) using CD34 immunostaining, and subsequently observe microvessel ultrastructure in gastric mucosa under Transmission Electron Microscope. Finally, we detect expression of angiogenesis-associated markers VEGF and HIF-1α using immunohistochemistry. Moreover, mRNA expressions of ERK1, ERK2, Cylin D1 as well as HIF-1α in gastric mucosa were determined by quantitative real-time reverse transcription- polymerase chain reaction. We observed the appearance of active angiogenesis in GPL rats, and demonstrated that WPX could reduce microvascular abnormalities and attenuate early angiogenesis in most of GPL specimens with a concomitant regression of most intestinal metaplasia (IM) and a portion of gastric epithelial dysplasia (GED). In parallel, WPX could suppress HIF-1α mRNA expression (P < 0.01) as well as protein expression (although without statistical significance), and could markedly inhibit VEGF protein expression in GPL rats. Mechanistically, WPX intervention, especially at low dose, caused a significant decrease in the ERK1 and Cylin D1 mRNA levels. However, WPX might probably have no regulatory effect on ERK2 amplification. WPX could attenuate early angiogenesis and temper microvascular abnormalities in GPL rats. This might be partly achieved by inhibiting on the angiogenesis-associated markers HIF-1α and VEGF, and on the ERK1/Cylin D1 aberrant activation.


Lymphadenectomy for gastric cancer in clinical trials: update.
The controversy over the value of extended lymph node dissection for treatment of gastric cancer is fiercely debated. Whereas Japanese surgeons claim that the superior survival rates in their series are due to extensive resection (D2 resection), many Western authorities believe that their results only reflect differences in the prevalence of prognostic factors, inconsistencies between Japanese and Western staging systems, and the phenomenon of "stage migration," which occurs with extensive resection. Two small randomized prospective trials from Hong Kong and Cape Town showed a tendency toward high morbidity with extensive lymph node dissection but no survival benefit. In contrast, the recently completed prospective German Gastric Carcinoma Study demonstrated a clear survival advantage with D2 resection for tumor stages II and IIIa with no increase in perioperative morbidity or mortality. The long-term results of the still ongoing randomized MRC and Dutch trials are therefore eagerly awaited.


[The clinical value of miniature ultrasonic probes on diagnosis and treatment of digestive tract diseases].
To investigate the clinical value of miniature ultrasonic probes (MUP) in the diagnosis and treatment of digestive tract diseases. 537 patients who were indicated for endoscopic ultrasorography (EUS) underwent EUS with 7.5 - 20 MHz MUP and double-cavity electronic endoscope. According to the diagnoses of MUP, those patients who presented the indication of treatment were treated by endoscopic resection or surgical excision respectively, the postoperative histological results were compared with the preoperative diagnoses of MUP. A follow-up with MUP was periodically made for a few patients without endoscopic resection or surgical excision. Among the 537 patients the diagnosis of gastrointestinal submucosal lesions was made in the 256 cases, polyp in 56 cases, inflammatory prominence in 37 cases, extrinsic compression 53 cases, digestive tract cancer 50 cases, peptic ulcer 17 cases, cholecystolithiasis 11 cases, chronic pancreatitis in 8 cases, and achalasia 2 cases and 47 cases were diagnosed as normal, After examination of MUP, 220 patients were treated by endoscopic resection or surgical excision respectively, the postoperative histological results of 211 patients were completely consistent with the preoperative diagnosis of MUP, and diagnostic accuracy of MUP was 95.9%. The result of follow-up with MUP indicated that gastrointestinal leiomyoma, lipoma, phlebangioma and cyst were unchanged within 1 - 2 years. The patients who were treated by endoscopic resection or centesis showed no complication. EUS with MUP is a valuable method in diagnosis of gastrointestinal submucosal lesions, staging of digestive tract cancer and diagnosis of biliary-pancreatic diseases. It plays a very important role for making scientific, effective, safe and economic therapeutic plan.


Effect of Pheromone-Mediated Mating Disruption on Pest Population Density of Maruca vitrata (Fabricius) (Crambidae: Lepidoptera).
The legume pod borer (Maruca vitrata) is one of the most serious legume pests due to its wide host range and high damage potential. Pheromone components on M. vitrata have been previously identified, allowing research on more environmentally friendly IPM tools for its control. M. vitrata produces a three-component pheromone blend containing (E, E)-10,12-hexadecadienal (major), (E, E)-10,12-hexadecadienol (minor), (E)-10-hexadecenal (minor). This study focused on the efficacy of synthetic pheromone lures and their blend components for mating disruption in M. vitrata. Under laboratory conditions, the mating behavior of M. vitrata pairs was observed from 18:00 to 02:00 h in an interval of 20 min to assess the efficacy of different pheromone lures. The scotophase behavior results show that the complete pheromone blend (E, E)-10,12-hexadecadienal + (E, E)-10,12-hexadecadienol + (E)-10-hexadecenal with a blend ratio of 1:1:1 effectively disrupted mating. The impact on mating disruption was evident from the lower fecundity and egg hatch/eclosion. The same lures were evaluated in a small-scale caged field study. The results show that the pheromone blend of (E, E)-10,12-hexadecadienal + (E, E)-10,12-hexadecadienol + (E)-10-hexadecenal in a1:1:1 ratio significantly disrupted the normal mating, leading to lower flower and pod damage and higher mung bean yield.


Generation of Artificial Thymic Organoids from Human and Murine Hematopoietic Stem and Progenitor Cells.
The generation of T cells is a complex, carefully orchestrated process that occurs in the thymus. The ability to mimic T cell differentiation in vitro has opened up avenues to better understand different stages of thymopoiesis but has also enabled the in vitro production of mature T cells suitable for immunotherapy. Among existing protocols, the artificial thymic organoid (ATO) system has been shown to be the most efficient at producing mature conventional T cells. In this serum-free model, human or murine hematopoietic stem and progenitor cells (HSPCs) are combined with a murine stromal cell line expressing a Notch ligand in a 3D cell aggregate. In ATOs, although only simple medium changes are required throughout the cultures, HSPCs differentiate into T cells with kinetics and phenotypes similar to those of endogenous thymopoiesis. This article describes protocols for the generation of ATOs from human and murine HSPCs. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Expansion and preparation of MS5-hDLL4 or MS5-mDLL4 cells Basic Protocol 2: Isolation of human hematopoietic stem and progenitor cells (HSPCs; CD34+ cells) Support Protocol 1: Transduction of human HSPCs (CD34+ cells) Basic Protocol 3: Production of thymic progenitors and mature T cells from human HSPCs in artificial thymic organoids (ATOs) Support Protocol 2: Phenotype analysis of human ATO cells by flow cytometry Basic Protocol 4: Isolation of murine HSPCs (Lin- Sca1+ cKit+; LSK) and hematopoietic stem cells (LSK CD150+ CD48-) Basic Protocol 5: Production of thymic progenitors and mature T cells from murine HSPCs in ATOs Support Protocol 3: Phenotype analysis of murine ATO cells by flow cytometry Alternate Protocol: Generation of ATOs from single HSPCs.


Drug persistency of two cholinesterase inhibitors: rivastigmine versus donepezil in elderly patients with Alzheimer's disease.
To compare persistency rates and persistency days in patients with Alzheimer's disease (AD) who initiated therapy with either rivastigmine or donepezil, and to identify factors influencing persistency in a real-world setting. This study used data collected by MarketScan from 1 January 1999 to 31 December 2002. Patients were included if they were newly diagnosed with AD and filled at least one prescription for rivastigmine or donepezil between 1 July 2000 and 30 June 2001, were > or =65 years of age on the index prescription date, and had continuous health and prescription insurance during the entire study period. Patients were excluded if they filled a prescription for any cholinesterase inhibitor during the 18 months prior to initiation of the study drugs. Patients who refilled their initial cholinesterase inhibitor prescription within a permissible gap of 60 days after depleting the drug supply from the prior prescription were considered to be persistent. Sensitivity analysis was performed to test the robustness of the persistency definition. The Kaplan-Meier method was used to determine persistency rates across time and Cox proportional hazards models were used to estimate relative risks of discontinuation or switch with adjustment for other covariates, and to identify factors significantly influencing persistency of the study drugs. Of the newly treated AD patients, the proportion of rivastigmine and donepezil patients who continued their medication was the same (47%; p = 0.5). On average, rivastigmine users continuously used their medication for 234 days (median 312 days) while those taking donepezil used their medication for 235 days (median 315 days) [p = 0.91]. Patients were more likely to discontinue or switch their initial cholinesterase inhibitor if they used a central nervous system (CNS) medication before initiation of therapy (relative risk [RR] = 1.23; 95% CI 1.01, 1.51 without adjustment for study variables; RR = 1.30; 95% CI 1.05, 1.60 with adjustment for study variables). On the other hand, patients were less likely to discontinue their cholinesterase inhibitor if they visited their physician office frequently (RR = 0.24; 95% CI 0.18, 0.32 without adjustment; RR = 0.23; 95% CI 0.17, 0.30 with adjustment) or if they were hospitalised after initiation of their cholinesterase inhibitor therapy (RR = 0.60; 95% CI 0.39, 0.91 without adjustment; RR = 0.65; 95% CI 0.42, 0.99 with adjustment). Patients who were newly diagnosed with AD and initiated therapy with either rivastigmine or donepezil had similar levels of persistency with their initial AD therapy in a real-world setting.


Changes in global food consumption increase GHG emissions despite efficiency gains along global supply chains.
Greenhouse gas (GHG) emissions related to food consumption complement production-based or territorial accounts by capturing carbon leaked through trade. Here we evaluate global consumption-based food emissions between 2000 and 2019 and underlying drivers using a physical trade flow approach and structural decomposition analysis. In 2019, emissions throughout global food supply chains reached 30 ±9% of anthropogenic GHG emissions, largely triggered by beef and dairy consumption in rapidly developing countries-while per capita emissions in developed countries with a high percentage of animal-based food declined. Emissions outsourced through international food trade dominated by beef and oil crops increased by ~1 Gt CO2 equivalent, mainly driven by increased imports by developing countries. Population growth and per capita demand increase were key drivers to the global emissions increase (+30% and +19%, respectively) while decreasing emissions intensity from land-use activities was the major factor to offset emissions growth (-39%). Climate change mitigation may depend on incentivizing consumer and producer choices to reduce emissions-intensive food products.


[A case-control study on the efficacy and the optimum interval of mass screening for prostatic cancer].
The efficacy and the optimum interval of mass screening for prostatic cancer were investigated by a case-control study. A matched pairs analysis by 1:5 was conducted between 31 cases of advanced prostatic cancer in stage C and D detected by mass screening and 155 controls of normal subjects selected at random. In all cases and controls, the history of taking part of the mass screening for last 3 years, then the estimates of odds ratios (OR) and 95% confidence intervals (95% CI) were calculated on discordant pairs of the matched analysis. OR to suffer from advanced prostatic cancer was 0.22 (95% CI: 0.07-0.70) in the group to submit to mass screening 1 year ago in comparison with the group not to submit once for 3 years. According to the analysis on the interval of submission to mass screening, the effect of screening to prevent the progression to advanced stages might be valied for 1 year. Mass screening for prostatic cancer every year might be efficient to reduce the number of patients progressing to advanced stages.


Steric-hindrance effect and self-sacrificing template behavior induced PDA@SnO2-QDs/N-doped carbon hollow nanospheres: Enhanced structural stability and reaction kinetics for long-cyclic Li-ion half/full batteries.
Tin-based anode materials with high theoretical specific capacity are subject to huge volume expansion and poor reaction reversibility, leading to degradation of battery performance. Herein, the steric-hindrance effect and self-sacrificing template behavior of polydopamine were firstly developed to induce the formation of hollow nanospheres assembled by ultrafine SnO2 quantum dots (SnO2-QDs) and nitrogen-doped carbon (NC), containing residual polydopamine (PDA) cores. The PDA@SnO2-QDs/NC hollow nanospheres could effectively accommodate the volume expansion and maintain structural stability. More importantly, the PDA core could capture oxygen free radicals produced by the charge/discharge process and be involved in the evolution of the SEI layer, achieving enhanced electrochemical reaction kinetics. The optimized PDA@SnO2-QDs/NC anode shows a specific capacity of 898 mAh g-1 after 300 cycles at 0.3 A g-1, and scarcely capacity attenuation after 1500 cycles at 1 A g-1. The long-cyclic life is up to 3000 cycles at 3 A g-1. Even after 200 cycles, the anode in the PDA@SnO2-QDs/NC||LFP full battery gives a reversible capacity of 489 mAh g-1 at 0.3 A g-1, with a capacity retention of 77 %. This work casts new light on tin-based anode materials and interface optimization.


A solution to the problem of undictated operative reports by residents.
The objective of this study was to reduce the number of operative reports assigned to the surgical residents but not dictated within 48 hours by 80% within 6 months. A before-after trial was conducted in a teaching hospital (part of a major academic medical center) in an urban setting, of a complex intervention based on a theoretical framework for behavioral change. Data were collected for more than 6 months before the intervention, and then in three separate time periods during the next 18 months. The intervention, lasting 41 weeks, and directed specifically at undictated operative reports, comprised the following: educational sessions, posting of residents' names with delinquency rates, attending/resident interactions, telephone reminders, rewards, and punishments. The population studied comprised every resident who rotated through the general surgery service over a 2-year period 1995 to 1997. The mean (+/-SD) number of undictated operative reports declined progressively from 72 (+/-8.3) to 6 (+/-2.6). This 92% reduction was statistically significant (P <0.00005). The mean number of undictated discharge summaries declined progressively from 54 (+/-11.2) to 13 (+/-8.1). This 76% reduction was also statistically significant (P <0.00005). There was a close correlation between the operative reports and the discharge summaries (r = 0.82). The performance of residents on the surgical service in respect to operative report dictation can be profoundly influenced by a carefully targeted set of interventions based on behavioral theory. The improved performance can be maintained with simple reminders and the halo effect of the intervention extends to the dictation of discharge summaries.


Treatment of experimental renal osteodystrophy with pamidronate.
We evaluated the effects of the bisphosphonate pamidronate on bone histomorphometry, structure and strength in male rats with uninephrectomy or with chronic renal disease induced by 5/6 nephrectomy. In rats with chronic renal disease the plasma urea, phosphate and parathyroid hormone levels were significantly increased compared to rats with a uninephroctomy and none of these parameters was affected by pamidronate treatment. In the femoral midshaft, chronic renal disease reduced cortical bone mineral density and content. No difference was observed in the breaking load of the femoral midshaft. In the distal femur, a high-turnover renal osteodystrophy was found but pamidronate suppressed this bone turnover and increased bone mineral content. Treatment had no effect on chronic disease-induced augmentation of osteoid volume or fibroblast surface. These studies show that in this model of stage 3 renal disease, pamidronate increased mineral content in the femoral midshaft and distal metaphysis primarily by adding bone to endocortical and trabecular surfaces but did not reduce osteitis fibrosa.


A comparison of aquaporin function in mediating stomatal aperture gating among drought-tolerant and sensitive varieties of rice (Oryza sativa L.).
Climate change drastically affects the cultivation of rice, and its production is affected significantly by water stress. Adaptation of a plant to water deficit conditions is orchestrated by efficient water uptake and a stringently regulated water loss. Transpiration remains the major means of water loss from plants and is mediated by microscopic pores called stomata. Stomatal aperture gating is facilitated by ion channels and aquaporins (AQPs) which regulate the turgidity of the guard cells. In a similar manner, efficient water uptake by the roots is regulated by the presence of AQPs in the plasma membrane of root cells. In this study, we compare the efficiency of transmembrane water permeability in guard cells and root protoplasts from drought-tolerant and sensitive varieties of Oryza sativa L. In this report, we studied the transmembrane osmotic water permeability (Pos) of guard cell and root protoplasts of drought-sensitive and tolerant cultivars. The guard cells isolated from the drought-sensitive lowland rice variety ADT-39 show significant low osmotic permeability than the drought-tolerant rice varieties of Anna (lowland) and Dodda Byra Nellu (DBN) (upland local land rice). There is no significant difference in relative gene expression patterns of PIPs (Plasma membrane Intrinsic Proteins "PIP1" and "PIP2" subfamilies) in guard cells isolated from ADT-39 and Anna. While the expression levels of AQP genes remain the same between ADT-39 and Anna, there is a drastic difference in their osmotic permeability in the guard cells in spite of a higher number of stomata in Anna and DBN, hinting at a more efficient gating mechanism of AQP in the stomata of the drought-tolerant varieties studied.


Combinations of ketamine and atropine are neuroprotective and reduce neuroinflammation after a toxic status epilepticus in mice.
Epileptic seizures and status epilepticus (SE) induced by the poisoning with organophosphorus nerve agents (OP), like soman, are accompanied by neuroinflammation whose role in seizure-related brain damage (SRBD) is not clear. Antagonists of the NMDA glutamate ionotropic receptors are currently among the few compounds able to arrest seizures and provide neuroprotection even during refractory status epilepticus (RSE). Racemic ketamine (KET), in combination with atropine sulfate (AS), was previously shown to counteract seizures and SRBD in soman-poisoned guinea-pigs. In a mouse model of severe soman-induced SE, we assessed the potentials of KET/AS combinations as a treatment for SE/RSE-induced SRBD and neuroinflammation. When starting 30min after soman challenge, a protocol involving six injections of a sub-anesthetic dose of KET (25mg/kg) was evaluated on body weight loss, brain damage, and neuroinflammation whereas during RSE, anesthetic protocols were considered (KET 100mg/kg). After confirming that during RSE, KET injection was to be repeated despite some iatrogenic deaths, we used these proof-of-concept protocols to study the changes in mRNA and related protein contents of some inflammatory cytokines, chemokines and adhesion molecules in cortex and hippocampus 48h post-challenge. In both cases, the KET/AS combinations showed important neuroprotective effects, suppressed neutrophil granulocyte infiltration and partially suppressed glial activation. KET/AS could also reduce the increase in mRNA and related pro-inflammatory proteins provoked by the poisoning. In conclusion, the present study confirms that KET/AS treatment has a strong potential for SE/RSE management following OP poisoning. The mechanisms involved in the reduction of central neuroinflammation remain to be studied.


Healing with the needles.
A child's spontaneous desire to help her mother during an office visit prompts me to reflect upon the multidimensional nature of healing and how, as family physicians, we often encounter these unique moments in our day-to-day practice.


11C-L-methionine positron emission tomography in the clinical management of cerebral gliomas.
Positron emission tomography (PET) using L-[methyl-(11)C]-methionine (MET) is the most popular amino acid imaging modality in oncology, although its use is restricted to PET centers with an in-house cyclotron facility. This review focuses on the role of MET-PET in imaging of cerebral gliomas. The biological background of tumor imaging with methionine is discussed with particular emphasis on cellular amino acid transport, amino acid utilization in brain, normal metabolism of methionine, and its alterations in cancer. The role of MET-PET in clinical management of cerebral gliomas in initial diagnosis, differentiation of tumor recurrence from radiation injury, grading, prognostication, tumor-extent delineation, biopsy planning, surgical resection and radiotherapy planning, and assessment of response to therapy is also reviewed in detail.


Oral Viral Infections: Diagnosis and Management.
This article focuses on common viral infections in the oral cavity with associated systemic manifestations. Discussed are the clinical features, histopathology, diagnosis, treatment, and prevention of viral infections in oral cavity. This will be a useful aid for general practitioners and other dental personnel wanting to expand their pathologic knowledge. This article discusses herpes simplex, varicella zoster, mononucleosis, cytomegalovirus, enteroviruses, rubeola, rubella, mumps, and human papillomavirus. After reviewing this topic, the dentist or hygienist will minimally be competent to diagnose the appropriate oral cavity viral infectious diseases and help patients get the appropriate care they need.