Compartment-specific, differential regulation of eukaryotic elongation factor 2 and its kinase within Aplysia sensory neurons.
Long-term facilitation (LTF) in Aplysia is a leading model for elucidating the biochemical mechanisms of synaptic plasticity underlying learning. LTF requires translational control downstream of target of rapamycin complex 1. Our lab has previously shown that treatment with the facilitating neurotransmitter, 5-hydroxytryptamine (5-HT), causes a target of rapamycin complex 1-mediated decrease in phosphorylation of eukaryotic elongation factor 2 (eEF2) within the neurites of sensory neurons involved in LTF. Here, we characterize the Aplysia orthologue of eEF2 kinase (eEF2K). We show that the Aplysia eEF2K orthologue contains an S6 kinase phosphorylation site and that a serine-to-alanine mutation at this site blocks the ability of 5-HT to decrease eEF2 phosphorylation in neurites. We also show that within the soma, 5-HT has the opposite effect, decreasing eEF2K phosphorylation at the S6 kinase site and, concomitantly, increasing eEF2 phosphorylation. Surprisingly, while eEF2K over-expression inhibits translation of a marker for internal ribosome entry site-dependent translation, it stimulates the translation of a marker for cap-dependent translation. This study demonstrates that eEF2 is differentially regulated in separate compartments and contributes to a growing body of evidence that inhibition of elongation can stimulate the translation of certain transcripts.


[Parathion axial teratogenesis after giving several compounds with known anti-teratogenic or antitoxic properties in vertebrate adults or embryos after exposure to organic phosphates. Study in the quail embryo (Coturnix coturnix japonica)].
Axial abnormalities, highly specific of parathion, are prevented by pyridine aldoximes P2S, 2-PAM and TMB4. Atropine, well known as an antimuscarinic agent is ineffective and so it is for tryptophan and DMSO, compounds having protective effect on some morphogenetic disturbances induced by organic phosphates. These results point out the specificity of pyridine aldoximes as alleviating agents on the characteristic axial deformities induced by parathion.


Effect of bacterial lipopolysaccharide on growth of murine bladder cancer, MBT-2.
Intradermal palpable MBT-2 tumor responded with bacterial lipopolysaccharide to hemorrhagic necrosis (LPS) in C3H/HeN (endotoxin sensitive) mice. We have tested LPS fractions isolated from E. coli, Klebsiella pneumoniae, Salmonella minnesota, Pseudomonas aeruginosa and Serratia culture filtrates. All these LPS preparations showed tumor necrotizing activity accompanied by toxicity (body weight loss) in C3H/HeN mice. However, MBT-2 tumors grown in an endotoxin-resistant strain (C3H/HeJ) of mice did not respond to LPS, even at a very high dose. In vitro, the LPS showed no cytotoxic effect on MBT-2 cells. For comparison, systemic administration of tumor necrosis factor (cachexin ) did not affect the i.d. tumor growth. These data indicate that host reactions to LPS (endotoxicity) plays a pivotal role in the expression of tumor necrosis. Accordingly, comparisons of tumor response between endotoxin sensitive and resistant mice avoid potential overestimation of the therapeutic value of certain bacterial products and/or LPS contaminated agents.


Reduced Synaptic Density in Patients with Lewy Body Dementia: An [11 C]UCB-J PET Imaging Study.
Patients with Parkinson's disease (PD) often develop dementia, but the underlying substrate is incompletely understood. Generalized synaptic degeneration may contribute to dysfunction and cognitive decline in Lewy body dementias, but in vivo evidence is lacking. The objective of this study was to assess the density of synapses in non-demented PD (nPD) subjects (N = 21), patients with PD-dementia or Dementia with Lewy bodies (DLB) (N = 13), and age-matched healthy controls (N = 15). Using in vivo PET imaging and the novel synaptic-vesicle-glycoprotein 2A (SV2A) radioligand [11C]UCB-J, SUVR-1 values were obtained for 12 pre-defined regions. Volumes-of-interest were defined on MRI T1 scans. Voxel-level between-group comparisons of [11C]UCB-J SUVR-1 were performed. All subjects underwent neuropsychological assessment. Correlations between [11C]UCB- J PET and domain-specific cognitive functioning were examined. nPD patients only demonstrated significantly reduced SUVR-1 values in the substantia nigra (SN) compared to HC. DLB/PDD patients demonstrated reduced SUVR-1 values in SN and all cortical VOIs except for the hippocampus and amygdala. The voxel-based analysis supported the VOI results. Significant correlation was seen between middle frontal gyrus [11C]UCB-J SUVR-1 and performance on tests of executive function. Widespread cortical reduction of synaptic density was documented in a cohort of DLB/PDD subjects using in vivo [11C]UCB-J PET. Our study confirms previously reported synaptic loss in SN of nPD patients. [11C]UCB-J binding in selected cortical VOIs of the DLB/PDD patients correlated with their levels of cognitive function across relevant neuropsychological domains. These findings suggest that the loss of synaptic density contributes to cognitive impairment in nPD and DLB/PDD. © 2021 International Parkinson and Movement Disorder Society.


Pediatric caustic ingestion and parental cocaine abuse.
To report two cases in which toddlers drank a caustic liquid which their parents had been using to prepare free-base and crack cocaine. Case series. Two toddlers presented with first- and second-degree burns of the oral cavity, pharynx and esophagus from caustic ingestion. The first had drunk ammonia from an unmarked clear plastic container the morning after "a party at a friend's house". The second had drunk potassium hydroxide from a clear plastic container which was labelled "pH UP" and had a small "Danger" sign. Both children were treated with intravenous hydration, steroids, antibiotics and analgesics. Fortunately, neither child suffered long-term physical sequelae. When questioned, the parents of both children admitted to using these alkalis to prepare free-base and crack cocaine. Appropriate steps were taken by social services to protect these children from further neglect. Despite federal legislation and public education, pediatric caustic ingestion remains a significant problem. These cases suggest that, in certain cases of pediatric caustic ingestion, caregivers should be questioned regarding possible drug abuse. Larger warning labels and further public education might help prevent many cases of pediatric caustic ingestion.


The mathematical expression of damage law of museum lighting on dyed artworks.
Dyed artworks are highly sensitive to light and are easily affected by museum lighting, resulting in irreversible permanent color damage such as fading and discoloration. Exposure, light source spectrum and material properties are the three indicators causing damage to artworks. Therefore, it is the basis for effective lighting protection to reveal the quantitative influence of exposure and light source spectrum composition on the damage degree of different pigments and establish a mathematical model that can accurately express the above rules. At present, the color damage calculation model of dyed artworks under three parameters' coupling action is missing. This research established a visual three-dimensional change surface of the color difference values of 23 pigments varying with the spectral wavelength and exposure through experimental methods. The relative responsivity function ΔEn = fn(λ, Q), where n = 1 ~ 23, was obtained for 23 pigments under the coupling effects of exposure and light source spectra. Furthermore, a mathematical model [Formula: see text] calculating the color damage of pigments in the range of visible light was proposed. The proposed model was verified by the experimental method, which realizes the mathematical expression of the damage law of museum lighting on dyed artworks.


Accelerometer-Measured Daily Activity in Heart Failure With Preserved Ejection Fraction: Clinical Correlates and Association With Standard Heart Failure Severity Indices.
Daily physical activity assessed by accelerometers represents a novel method to assess the impact of interventions on heart failure (HF) patients' functional status. We hypothesized that daily activity varies by patient characteristics and correlates with established measures of HF severity in HF with preserved ejection fraction. In this ancillary study of the NEAT-HFpEF trial (Nitrate's Effects on Activity Tolerance in HF With Preserved Ejection Fraction), average daily accelerometer units (ADAU) and hours active per day were assessed during a 14-day period before starting isosorbide mononitrate or placebo (n=110). Baseline ADAU was negatively associated with age, female sex, height, and body mass index, and these variables accounted for 28% of the variability in ADAU (P<0.007 for all). Adjusting for these factors, patients with lower ADAU were more likely to have had an HF hospitalization, orthopnea, diabetes mellitus and anemia, be treated with β-blockers, have higher ejection fraction, relative wall thickness and left atrial volume, and worse New York Heart Association class, HF-specific quality of life scores, 6-minute walk distance, and NT-proBNP (N-terminal pro-B-type natriuretic peptide; P<0.05 for all). Associations between hours active per day and clinical characteristics were similar. Relative to baseline, there were no significant associations between changes in ADAU or hours active per day and changes in standard functional assessments (New York Heart Association, quality of life, 6-minute walk distance, and NT-proBNP) with isosorbide mononitrate. Daily activity is a measure of HF-related and global functional status in HF with preserved ejection fraction. As compared with intermittently assessed standard HF assessments, change in daily activity may provide unique information about the impact of HF interventions on functional status. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02053493.


Type 2 diabetes, breast cancer specific and overall mortality: Associations by metformin use and modification by race, body mass, and estrogen receptor status.
While type 2 diabetes (T2D) has been associated with increased all-cause mortality among women diagnosed with breast cancer (BC), the association between T2D and breast cancer-specific (BCS) mortality is unresolved. The goal of this study was to examine the association between T2D and BCS mortality and examine the influence of metformin treatment on mortality rates. A retrospective cohort study was conducted between 2002 and 2008 at Emory University Hospitals among non-Hispanic black and white women who had confirmed diagnosis of stage I-III BC and known diabetes status (T2D: n = 73; non-T2D: n = 514). Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Compared to non-T2D patients, T2D women had almost a 2-fold increase in BCS mortality after adjusting for covariates (HR = 2.01; 95%CI = 1.02-3.98). Though attenuated, the increased hazard of death was also observed for all-cause mortality (HR = 1.74; 95%CI = 1.06-2.87). T2D patients who were not on metformin had substantially higher hazard of BCS mortality compared to non-diabetic patients (HR = 4.54; 95%CI = 1.98-10.44), whereas the association among T2D patients treated with metformin was weak (HR = 1.20; 95%CI = 0.36-3.97) and included the null. Among women with BC, T2D is associated with increased BCS mortality. Metformin treatment for T2D during the initial diagnosis of BC may improve outcomes.


New grading system for angiographic evaluation of arterial occlusions and recanalization response to intra-arterial thrombolysis in acute ischemic stroke.
The Thrombolysis in Myocardial Infarction (TIMI) grading scheme and other classification systems are limited because they do not account for occlusion location or collateral circulation. A new scheme for angiographic classification of arterial occlusion and recanalization response to intra-arterial thrombolysis in acute ischemic stroke was designed because of limitations in existing grading systems. The proposed scheme assigns a score from 0 to 5 on the basis of occlusion site and collateral supply. The pre- and post-thrombolysis angiograms of 15 patients with acute ischemic stroke were independently graded by three neurointerventionists according to TIMI perfusion grade (0-3), a grading scheme developed by Mori et al. (Mori E, Tabuchi M, Yoshida T, Yamadori A: Intracarotid urokinase with thromboembolic occlusion of the middle cerebral artery. Stroke 19:802-812, 1988) (0-4), and the proposed scheme (0-5); and interobserver agreement was assessed. The effect of severity of initial arterial occlusion on outcomes of good recovery (National Institutes of Health Stroke Scale score of < or =4) or death at 7 days after thrombolysis according to the proposed and TIMI grading schemes was also assessed in 60 patients with acute ischemic stroke. Multivariate analyses were performed to assess these relationships after adjusting for patient age, sex, time interval between symptom onset and treatment, and thrombolytic agent used. Interobserver agreement was higher for pre- and posttreatment grading of angiographic images using the new classification scheme (kappa = 0.73) than with either TIMI perfusion grade (kappa = 0.68) or Mori et al. grade (kappa = 0.68). The proposed grading scheme was inversely associated with good recovery at 7 days (odds ratio, 0.4; 95% confidence interval, 0.2-0.9) and directly associated with 7-day mortality (odds ratio, 2.0; 95% confidence interval, 1.1-3.6) after treatment. Initial TIMI grade did not correlate with either good recovery or death at 7 days. An inverse trend was observed between initial severity of angiographic occlusion as determined by the proposed scheme and complete recanalization after treatment (odds ratio, 0.6; 95% confidence interval, 0.4-1.02). Application of the new classification scheme for assessing pretreatment occlusion and response to intra-arterial thrombolysis resulted in high interobserver agreement and correlated with 7-day outcomes. The six grades used in this scheme allowed precise angiographic evaluation of perfusion changes.


Decolourization of dye-containing effluent using mineral coagulants produced by electrocoagulation.
The colour and colour causing-compounds has always been undesirable in water for any use, be it industrial or domestic wastewaters. The discharge of such effluents causes excessive oxygen demand in the receiving water and then a treatment is required before discharge into ecosystems. This study examined the possibility to remove colour causing-compounds from effluent by chemical coagulation, in comparison with direct electrocoagulation. The inorganic coagulants (C1, C2 and C3) in the form of dry powder tested, were respectively produced from electrolysis of S1=[NaOH (7.5 x 10(-3)M)], S2=[NaCl (10(-2)M)], and S3=[NaOH (7.5 x 10(-3)M)+NaCl (10(-2)M)] solutions, using sacrificial aluminium electrodes operated at an electrical potential of 12 V. Reactive textile dye (CI Reactive Red 141) was used as model of colour-causing compound prepared at a concentration of 50 mgl(-1). The best performances of dye removal were obtained with C(2) having a chemical structure comprised of a mixture of polymeric specie (Al45O45(OH)45Cl) and monomeric species (AlCl(OH)2.2H2O and Al(OH)3). The removal efficiency (R(A)) evaluated by measuring the yields of 540 nm-absorbance removal varied from 41 to 96% through 60 min of treatment by imposing a concentration of C2 ranging from 100 to 400 mg l(-1). The effectiveness of the treatment increased and the effluent became more and more transparent while increasing C(2) concentration. The comparison of chemical treatment using C2 coagulant and direct electrocoagulation of CI Reactive Red 141 containing synthetic solution demonstrated the advantage of chemical treatment during the first few minutes of treatment. A yield of 88% of absorbance removal was recorded using C2 coagulant (400 mg l(-1)) over the first 10 min of treatment, compared to 60% measured using direct electrocoagulation while imposing either 10 or 15 V of electrical potential close to the value (12 V) required during C2 production. However, at the end of the treatment (after 60 min of treatment), CI Reactive Red 141 pollutant was completely removed from solution (540 nm-absorbance removal of 100%) using direct electrochemical treatment, compared to 96.4% of absorbance removed while treating dye-containing synthetic solution by means of C2 coagulant.


Number of good quality embryos on day 3 is predictive for both pregnancy and implantation rates in in vitro fertilization/intracytoplasmic sperm injection cycles.
To evaluate the predictive value for implantation and pregnancy rates of the number of embryos that reach the eight-cell stage with less than 20% fragmentation (good quality embryos) on day 3. Prospective observational study. Private IVF center. One hundred eighty-nine women undergoing IVF, or intracytoplasmic sperm injection with at least four zygotes, who have had three embryos transferred on day 3. None. Pregnancy rate and implantation rate. All patients (n = 189) had 3 embryos transferred. The patients were divided in five groups according to the number of good quality embryos on day 3 (0, 1, 2, 3, >3; respectively). For the five groups, the pregnancy rates were 2.9%, 33.3%, 45.5%, 39.4%, and 64.3%; the implantation rates were 2.0%, 17.0%, 20.5%, 19.3%, and 35.7%. No statistically significant differences in pregnancy rate or implantation rate were found for groups 1, 2, and 3 (when 1, 2, or 3 good quality embryos were present). The data were also analyzed after pooling these three groups. A statistically significant difference in pregnancy rate and implantation rate was found for group 0 (no good quality embryos), groups 1, 2, and 3 (1, 2, or 3 good quality embryos), and group >3 (>3 good quality embryos). The number of good quality embryos available on day 3 is a strong predictive value for both pregnancy rate and implantation rate. When good quality embryos are present on day 3, only two embryos should be transferred to minimize multiple pregnancies.


Molecular diagnosis of colorectal tumors by expression profiles of 50 genes expressed differentially in adenomas and carcinomas.
Most colon cancers are thought to develop through the 'adenoma-to-carcinoma sequence' model. To elucidate the mechanisms underlying this pathway, we analysed gene-expression profiles of 20 colorectal tumors (nine adenomas and 11 differentiated adenocarcinomas) by means of a cDNA microarray representing 23,040 genes coupled with laser-capture microdissection. A two-dimensional hierarchical clustering analysis of expression profiles of the 20 tumors correctly separated the carcinoma group from the adenoma group. Furthermore we identified 51 genes whose expression was commonly up-regulated, 376 that were commonly down-regulated in both types of tumors as opposed to normal colonic epithelium and 50 whose expression levels were significantly different between adenomas and carcinomas. On the basis of expression profiles of the 50 discriminating genes, we established a scoring system to separate adenomas from carcinomas. Application of this scoring system for evaluating five additional colorectal tumors correctly predicted their histological features. The genome-wide information reported here should contribute to a more profound understanding of colorectal tumorigenesis, particularly of adenoma-carcinoma progression, and provide indicators for developing novel strategies to diagnose, treat, and ultimately prevent colorectal carcinomas.


Long-term treatment response and fluorodopa positron emission tomographic scanning of parkinsonism in a family with dopa-responsive dystonia.
Dopa-responsive dystonia (DRD) is one form of childhood-onset idiopathic torsion dystonia. Adult-onset parkinsonism has appeared in several previously unaffected members in families with DRD suggesting that this may be an additional phenotypical expression of the disease. We report a family with DRD in which 2 women and 1 man, unaffected by dystonia, developed tremor-onset parkinsonism after age 50 years. The women continue on a low dosage of levodopa after 9 and 13 years of treatment, with a stable, nearly complete, symptomatic response. This contrasts to the typical long-term treatment complications observed in patients with Parkinson's disease. We assessed nigrostriatal dopaminergic function in the proband, with typical DRD, and the 2 women with parkinsonism using 6-[18F]fluoro-L-dopa positron emission tomography. All 3 had normal striatal 6-[18F]fluoro-L-dopa uptake. These observations provide compelling evidence that "benign" adult-onset parkinsonism may be an expression of the disease in some members of families with DRD and does not support consideration of the DRD gene as a risk factor for development of Parkinson's disease. There may be considerable clinical heterogeneity in DRD depending on the age at onset.


TIMP-1 inhibits microvascular endothelial cell migration by MMP-dependent and MMP-independent mechanisms.
It was reported over a decade ago that tissue inhibitor of metalloproteinases-1 (TIMP-1) suppresses angiogenesis in experimental models but the mechanism is still incompletely understood. This in vitro study focused on the molecular basis of TIMP-1-mediated inhibition of endothelial cell (EC) migration, a key step in the angiogenic process. Both recombinant human TIMP-1 and the synthetic MMP inhibitors, GM6001 and MMP-2-MMP-9 Inhibitor III, suppressed migration of human dermal microvascular endothelial cells (HDMVEC) in a dose-dependent fashion. The MMP-dependent inhibition of migration was associated with increased expression of the junctional adhesion proteins, VE-cadherin and PECAM-1, and VE-cadherin accumulation at cell-cell junctions. TIMP-1 also caused MMP-independent dephosphorylation of focal adhesion kinase (FAK) (pY397) and paxillin, which was associated with reduced number of F-actin stress fibers and focal adhesions. Moreover, TIMP-1 stimulated expression of PTEN that has been shown to reduce phosphorylation of FAK and inhibit cell migration. Our data suggest that TIMP-1 inhibits HDMVEC migration through MMP-dependent stimulation of VE-cadherin and MMP-independent stimulation of PTEN with subsequent dephosphorylation of FAK and cytoskeletal remodeling.


Scleritis after glaucoma filtering surgery with mitomycin C.
Adjunctive intraoperative mitomycin C increases the success of glaucoma filtering surgery, but also the postoperative complications. This is the first report of scleritis after its use. In five patients, scleritis developed 3 to 24 weeks after inferior trabeculectomy with mitomycin C. The onset was characterized by acute pain, redness of the eye, and decreased vision. Three patients had anterior scleritis and two had posterior scleritis. Infection or bleb leakage was not seen in any patient. All patients responded to a course of topical steroids and oral ibuprofen or prednisone. Anterior and posterior scleritis may complicate the use of topical mitomycin C during trabeculectomy, Prompt diagnosis and treatment reverses the inflammation, maintaining the success of the surgical procedure.


Risk of future depression in people who are obese but metabolically healthy: the English longitudinal study of ageing.
There is some evidence to suggest that obesity is a risk factor for the development of depression, although this is not a universal finding. This discordance might be ascribed to the existence of a 'healthy obese phenotype'--that is, obesity in the absence of the associated burden of cardiometabolic risk factors. We examined whether the association of obesity with depressive symptoms is dependent on the individual's metabolic health. Participants were 3851 men and women (aged 63.0±8.9 years, 45.1% men) from the English Longitudinal Study of Ageing, a prospective study of community dwelling older adults. Obesity was defined as body mass index ≥30 kg m(-2). Based on blood pressure, high-density lipoprotein cholesterol, triglycerides, glycated haemoglobin and C-reactive protein, participants were classified as 'metabolically healthy' (0 or 1 metabolic abnormality) or 'unhealthy' (≥2 metabolic abnormalities). Depressive symptoms were assessed at baseline and at 2 years follow-up using the 8-item Centre of Epidemiological Studies Depression (CES-D) scale. Obesity prevalence was 27.5%, but 34.3% of this group was categorized as metabolically healthy at baseline. Relative to non-obese healthy participants, after adjustment for baseline CES-D score and other covariates, the metabolically unhealthy obese participants had elevated risk of depressive symptoms at follow-up (odds ratio (OR)=1.50; 95% confidence interval (CI), 1.05-2.15), although the metabolically healthy obese did not (OR=1.38; 95% CI, 0.88-2.17). The association between obesity and risk of depressive symptoms appears to be partly dependent on metabolic health, although further work is required to confirm these findings.


Marked losses of computed tomography-derived skeletal muscle area and density over the first month of a critical illness are not associated with energy and protein delivery.
Changes in muscularity during different phases of critical illness are not well described. This retrospective study aimed to describe changes in computed tomography (CT)-derived skeletal muscle area (SMA) and density (SMD) across different weeks of critical illness and investigate associations between changes in these parameters and energy and protein delivery. Thirty-two adults admitted to the intensive care unit (ICU) who had ≥2 CT scans at the third lumbar area performed ≥7 d apart were included in the study. CT-derived SMA (cm2) and SMD (Hounsfield units) were determined using specialized software. A range of clinical and nutrition variables were collected for each day between comparator scans. Associations were assessed by Pearson or Spearman correlations. There was a significant decrease in SMA between the two comparator scans where the first CT scan was performed in ICU wk 1 (n = 20; P < .001), wk 2 (n = 11; P < .007), and wk 3 to 4 (n = 7; P = .012). There was no significant change in SMA beyond ICU wk 5 to 7 (P = .943). A significant decline in SMD was observed across the first 3 wk of ICU admission (P < .001). Overall, patients received a mean 24 ± 6 kcal energy/kg and 1.1 ± 0.4 g protein/kg per study day and 83% of energy and protein requirements according to dietitian estimates. No association between SMA or SMD changes and nutrition delivery were found. Critically ill patients experience marked losses of SMA over the first month of critical illness, attenuated after wk 5 to 7. Energy and protein delivery were not associated with degree of muscle loss.


Phospholipids alter tau conformation, phosphorylation, proteolysis, and association with microtubules: implication for tau function under normal and degenerative conditions.
Discerning the in situ functions of the microtubule-associated protein (MAP) tau is of interest both in terms of neuronal differentiation and homeostasis as well as in terms of neurodegenerative conditions such as Alzheimer's disease. In the present study, exposure to excess phosphatidyl serine (PS) for < 1 min induced antigenic alterations in multiple N-terminal, C-terminal and central epitopes of purified human brain tau. Notably, "AD-like" epitopes (PHF-1, ALZ-50, AT-8) were decreased by PS; other epitopes (e.g., 5E2, Tau-1) increased and others remained relatively unchanged. Inclusion of gamma-AT[32P] during incubations did not reveal any contaminating kinase activity. Direct addition of chloroform:methanol (CM; the initial PS solvent) demonstrated that these changes were not derived from CM-mediated tau denaturation. Phosphatidyl choline induced similar antigenic changes, while phosphatidyl inositol did not. PS inhibited MAP-kinase generation of phospho-dependent tau epitopes and incorporation of phosphates by tau. Inclusion of PS during coincubation of tau and tubulin reduced the extent of cosedimentation of tau with MTs. Finally, PS enhanced the ability of calpain-mediated tau proteolysis. These data suggest that tau antigenicity in situ may be derived from phospholipid-dependent alterations in tau conformation in addition to tau phosphorylation state. These data further suggest that disruption of the normal association of tau with phospholipids may foster accumulation of tau and, in doing so, render tau more susceptible to hyperphosphorylation.


Experimental data showing the effect of wetting on soil structure transformations: 3D images.
Structure of the pore network of the soil controls many processes in the soil. Soil moistening have a profound impact on soil structure, which may affect a soil functions. This dataset presents the non-destructive three-dimensional (3D) visualization of the same soil sample under two different saturation conditions: air-dried and saturated beyond the field capacity [1]. The data were obtained by X-ray computed tomography and stored as three-dimensional 8-bit grayscale arrays. Two reconstructed images of the same sample were produced for future research. This dataset provides a valuable and unique insight for the qualitative and quantitative analysis.


A community-driven resource for genomic epidemiology and antimicrobial resistance prediction of Neisseria gonorrhoeae at Pathogenwatch.
Antimicrobial-resistant (AMR) Neisseria gonorrhoeae is an urgent threat to public health, as strains resistant to at least one of the two last-line antibiotics used in empiric therapy of gonorrhoea, ceftriaxone and azithromycin, have spread internationally. Whole genome sequencing (WGS) data can be used to identify new AMR clones and transmission networks and inform the development of point-of-care tests for antimicrobial susceptibility, novel antimicrobials and vaccines. Community-driven tools that provide an easy access to and analysis of genomic and epidemiological data is the way forward for public health surveillance. Here we present a public health-focussed scheme for genomic epidemiology of N. gonorrhoeae at Pathogenwatch ( https://pathogen.watch/ngonorrhoeae ). An international advisory group of experts in epidemiology, public health, genetics and genomics of N. gonorrhoeae was convened to inform on the utility of current and future analytics in the platform. We implement backwards compatibility with MLST, NG-MAST and NG-STAR typing schemes as well as an exhaustive library of genetic AMR determinants linked to a genotypic prediction of resistance to eight antibiotics. A collection of over 12,000 N. gonorrhoeae genome sequences from public archives has been quality-checked, assembled and made public together with available metadata for contextualization. AMR prediction from genome data revealed specificity values over 99% for azithromycin, ciprofloxacin and ceftriaxone and sensitivity values around 99% for benzylpenicillin and tetracycline. A case study using the Pathogenwatch collection of N. gonorrhoeae public genomes showed the global expansion of an azithromycin-resistant lineage carrying a mosaic mtr over at least the last 10 years, emphasising the power of Pathogenwatch to explore and evaluate genomic epidemiology questions of public health concern. The N. gonorrhoeae scheme in Pathogenwatch provides customised bioinformatic pipelines guided by expert opinion that can be adapted to public health agencies and departments with little expertise in bioinformatics and lower-resourced settings with internet connection but limited computational infrastructure. The advisory group will assess and identify ongoing public health needs in the field of gonorrhoea, particularly regarding gonococcal AMR, in order to further enhance utility with modified or new analytic methods.


Safety Assessment on Serious Adverse Events of Targeted Therapeutic Agents Prescribed for RAS Wild-Type Metastatic Colorectal Cancer: Systematic Review and Network Meta-Analysis.
Despite substantially elevated risk of serious adverse events (SAEs) from targeted therapy in combination with chemotherapy, comprehensive pharmacovigilance research is limited. This study aims to systematically assess SAE risks of commonly prescribed targeted agents (bevacizumab, cetuximab, and panitumumab) in patients with rat sarcoma viral oncogene homolog (RAS) wild-type metastatic colon cancer. Keyword searches of Cochrane Library, Clinical Key and MEDLINE were conducted per PRISMA-NMA guidelines. Frequentist network meta-analysis was performed with eight randomized controlled trials to compare relative risk (RR) of 21 SAE profiles. The risks of hematological, gastrointestinal, neurological SAE were insignificant among targeted agents (p > 0.05). The risk of serious hypertension was substantially elevated in bevacizumab-based chemotherapy (p < 0.05), whereas panitumumab-based chemotherapy had markedly elevated risk of serious thromboembolism (RR 3.65; 95% CI 1.30−10.26). Although both cetuximab and panitumumab demonstrated increased risk of serious dermatological and renal toxicities, panitumumab-based chemotherapy has relatively higher risk of skin toxicity (RR 15.22; 95% CI 7.17−32.35), mucositis (RR 3.18; 95% CI 1.52−6.65), hypomagnesemia (RR 20.10; 95% CI 5.92−68.21), and dehydration (RR 2.81; 95% CI 1.03−7.67) than cetuximab-based chemotherapy. Thus, further studies on risk stratification and SAE management are warranted for safe administration of targeted agents.


Kinetics of IgG subclasses and their effects on the incidence of infection after allogeneic hematopoietic stem cell transplantation.
The impact of the reconstitution of IgG subclasses after allogeneic hematopoietic cell transplantation (allo-HCT) on the outcomes is unclear. We investigated the effects of stem cell source on the levels of serum IgG subclasses and their influence on the infection risk and prognosis. The levels of serum IgG, IgG2 and IgG4 were measured chronologically in 100 patients who underwent allo-HCT at our institute. The median levels of serum IgG, IgA and IgM and the number of total B-cells were determined up to one year after allo-HCT. The serum IgG2 levels decreased within one year. A multiple linear regression analysis identified lymphoid malignancy, cord blood, and days after allo-HCT as significant risk factors for low serum IgG2 levels. There were no significant differences in the level of IgG or IgG2 at 90 days after allo-HCT between the late bacterial infection group (≥90 days following allo-HCT) and the control group (P = 0.34 and 0.45, respectively). There was no significant impact of the IgG, IgG2 or IgG4 levels on the survival or non-relapse mortality. The results suggest that cord blood transplantation might affect humoral immune reconstitution, including the IgG2 level, after allo-HCT.


The prognostic importance of the number of dissected lymph nodes after induction chemoradiotherapy for esophageal cancer.
Analyses of adequacy of lymph node dissection during resection of esophageal cancer are based on patients who have not undergone induction chemoradiotherapy. We sought to determine the minimum number of dissected lymph nodes necessary to ensure adequate staging after induction chemoradiotherapy. A prospectively maintained thoracic surgery database was queried to identify consecutive patients undergoing postinduction esophagectomy from 1996 to 2010. Cox proportional hazard and recursive partitioning survival analyses were performed. Complete lymph node data were available for 395 patients. Mean age was 59.5 years, and 64 patients (16%) were female. The median number of dissected lymph nodes was 8 (range, 0 to 63). When pathologic (p)T stage, pN stage, and the number of dissected lymph nodes were used as predictors, only pN stage (odds ratio, 1.3; 95% confidence interval, 1.2 to 1.7) and age (odds ratio, 1.03; 95% confidence interval, 1.01 to 1.04) independently predicted survival. Recursive partitioning was performed on 262 pN0 patients using T stage and the number of dissected lymph nodes as predictors. No pN0 patient with 28 lymph nodes dissected died during follow-up. For patients with fewer than 28 lymph nodes dissected, the next prognostic factor was T stage. For pT1-2 N0 patients, the number of lymph nodes dissected did not affect survival. For pT3-4 N0 patients, a significant survival decrement was noted for patients with fewer than 7 lymph nodes dissected compared with those with more than 7 lymph nodes dissected. T stage determines prognosis in postinduction pN0 patients with fewer than 28 lymph nodes evaluated. Postinduction pT3N0 patients with fewer than 7 lymph nodes evaluated are understaged.


Antibiotic export by efflux pumps affects growth of neighboring bacteria.
Cell-cell interactions play an important role in bacterial antibiotic resistance. Here, we asked whether neighbor proximity is sufficient to generate single-cell variation in antibiotic resistance due to local differences in antibiotic concentrations. To test this, we focused on multidrug efflux pumps because recent studies have revealed that expression of pumps is heterogeneous across populations. Efflux pumps can export antibiotics, leading to elevated resistance relative to cells with low or no pump expression. In this study, we co-cultured cells with and without AcrAB-TolC pump expression and used single-cell time-lapse microscopy to quantify growth rate as a function of a cell's neighbors. In inhibitory concentrations of chloramphenicol, we found that cells lacking functional efflux pumps (ΔacrB) grow more slowly when they are surrounded by cells with AcrAB-TolC pumps than when surrounded by ΔacrB cells. To help explain our experimental results, we developed an agent-based mathematical model, which demonstrates the impact of neighbors based on efflux efficiency. Our findings hold true for co-cultures of Escherichia coli with and without pump expression and also in co-cultures of E. coli and Salmonella typhumirium. These results show how drug export and local microenvironments play a key role in defining single-cell level antibiotic resistance.


Adrenal adenoma with bilateral adrenocortical nodular change in a patient with Cushing's syndrome.
We report a 57-year-old male patient with adrenocorticotrophin (ACTH)-independent Cushing's syndrome and long-standing hypertension. Both abdominal computed tomographic scan and magnetic resonance imaging revealed bilateral adrenal enlargement with the presence of a tumour in the left adrenal. Marked uptake of 131I-6 beta-iodomethyl-19-norcholesterol was observed only in the left adrenal gland. Left adrenalectomy and biopsy of the right adrenal gland were subsequently performed. Histological examination revealed the presence of an adrenocortical adenoma in the left adrenal with multiple adrenocortical nodules in both left and right non-neoplastic adrenals. Peri- and intraadrenal arteries and arterioles demonstrated marked arteriosclerotic vascular changes. Immunoreactivity for several steroidogenic enzymes was present in the tumour and markedly diminished in the non-neoplastic adrenals. This patient with Cushing's adenoma is considered to have developed adrenocortical nodules in the nonneoplastic adrenal possibly as a result of localized compensatory overgrowth of adrenocortical cells in response to ischaemic changes due to arteriopathy. When examining patients with Cushing's syndrome and bilateral adrenal enlargement, the possibility of concomitant adenoma and adrenocortical nodule formation should also be considered in the differential diagnosis


Schedule-dependent synergistic action of tiazofurin and dipyridamole on hepatoma 3924A cells.
Tiazofurin is an oncolytic nucleoside analog that has shown therapeutic activity in end-stage acute non-lymphocytic leukemia and in chronic granulocytic leukemia in blast crisis. Tiazofurin is anabolized to the active metabolite, TAD, which inhibits IMP dehydrogenase activity, leading to a reduction in guanylate pools and to the cessation of neoplastic cell proliferation. The drug exhibits potent cytostatic and cytotoxic activity against hepatoma 3924A cells in culture. In growth-inhibition and clonogenic assays, the 50% inhibitory concentration of tiazofurin was 3.8 and 4.2 microM, respectively. Dipyridamole, an inhibitor of nucleoside transport, curtails the salvage of nucleosides and bases for nucleotide biosynthesis. Dipyridamole exhibited cytotoxicity against hepatoma 3924A cells, with an LC50 of 24 microM and an IC50 of 29 microM being recorded. A combination of tiazofurin and dipyridamole provided synergistic cytotoxicity in hepatoma 3924A cells in culture. This synergistic activity was dependent on the order of addition of the drugs. Simultaneous addition of the two drugs produced antagonism, whereas preincubation of cells with tiazofurin or dipyridamole followed by addition of the second drug resulted in synergy. TAD concentrations were significantly higher (129% and 135%) in cells that had been pretreated with tiazofurin or dipyridamole before the addition of the second agent as compared with cells that had been treated simultaneously (113%). These studies indicate the importance of the order of the addition of drugs to obtain a synergistic response in combination chemotherapy and suggest the need for a careful selection of drug modulation in clinical trials of tiazofurin and dipyridamole.


Fatal Lucio's phenomenon in 2 patients with previously undiagnosed leprosy.
We report 2 cases of Lucio's phenomenon, a rare, aggressive, occasionally fatal type 2 reaction occurring in the diffuse nonnodular type of lepromatous leprosy. The clinical diagnosis of Lucio's phenomenon is difficult, and there are no known predictive or prognostic factors. Despite institution of aggressive treatment after diagnosis, our 2 cases had fatal outcomes.


Does the UK undergraduate medical curriculum prepare students in Oral and Maxillofacial Surgery? A scoping review.
Oral and Maxillofacial Surgery (OMFS) is one of 10 surgical specialties recognised by the General Medical Council (GMC). The GMC states that newly qualified doctors should be familiar with a wide range of specialties and should refer patients appropriately. However, inadequate awareness of and exposure to OMFS in UK medical schools have been widely reported. Two independent investigators conducted a scoping review of all published articles that have evaluated the preparation of students in OMFS in UK undergraduate medical curricula. Our inclusion criteria were UK studies, articles published since inception, OMFS education, and relevance for undergraduate medical students. Data were extracted in accordance with recommendations by the National Health Service (NHS) Centre for Reviews and Dissemination. These were then analysed by qualitative synthesis. Our initial search yielded a total of 351 articles. Following application of the exclusion criteria according to PRISMA guidelines, 11 articles were included in the final analysis. Four main themes were identified: exposure to OMFS in the medical school curriculum, knowledge of OMFS conditions, knowledge of OMFS career progression, and ability to refer OMFS conditions appropriately. A consistent finding was that most medical students felt that they had insufficient exposure to and awareness of the specialty. All the papers recommended the need for change in the existing undergraduate medical curriculum. This review shows an overwhelming need for further development of OMFS in undergraduate medical curricula in the UK. However, there is insufficient primary research to show how best to achieve this. We propose that future research should focus on improvements in the quality of the current teaching methods and the adoption of new innovations to inspire and educate future doctors.


Lower Success in Trabeculectomies in Exfoliation Compared With Primary Open-angle Glaucoma Patients in Sweden.
In a Sweden-based study, a lower success rate in exfoliation than in open-angle glaucoma patients was found in a 5-year follow-up after trabeculectomy. The present study aimed to compare the success of trabeculectomies in exfoliation versus open-angle glaucoma patients. Data were gathered through a retrospective chart review. Included patients underwent primary trabeculectomy from January 1 2009 till December 31, 2014 (6 y). All included patients were operated on at the Eye Department, Skaraborg Hospital, Sweden, and followed for at least 5 years after surgery. Included patients had primary open-angle glaucoma (POAG) or exfoliation glaucoma (EXFG). The study followed the recommendations of the World Glaucoma Association (WGA). Successful result: criterion A: eye pressure ≤18 mm Hg and pressure reduction ≥30% without medications (complete success: A1), with or without medications (qualified success: A2). Criterion B: eye pressure ≤15 mm Hg and pressure reduction ≥40% without medications (complete success: B1), with or without medications (qualified success: B2). A total of 147 patients were included in this study, 92 in the EXFG and 55 in the POAG group. At the baseline, only 3 variables (intraocular pressure, number of medications, and the number of laser treatments) showed a significant difference between EXFG and POAG patients. Complete and qualified success for both criterion A (A1 and A2) and B (B1 and B2) were significantly lower in the EXFG compared with the POAG group (Mantel-Cox test, P<0.0001, P=0.01, P<0.001, P=0.008). Trabeculectomies in EXFG seem to have a lower success rate than in POAG patients. EXFG patients should be checked often after trabeculectomy to detect the failure of the surgery.


Intestinal pneumatosis: differential diagnosis.
Intestinal pneumatosis (IP) is an infrequent radiological sign defined as pathological gas infiltration into the bowel wall. It may be associated to different underlying clinical conditions-inflammatory bowel diseases, malignancies, chemotherapy, infections, immune deficiency status, trauma, intestinal ischemia, and necrosis-that are often related to emergency state and require a prompt diagnosis. All the imaging techniques, especially abdominal radiography and Computed Tomography, could detect the presence of IP and discern the forms related to emergency conditions. The differential diagnosis is essential to start an immediate clinical or surgical management and treatment. The aim of this article is to review the radiological features of IP in different illnesses, with particular attention to differential diagnosis.


Seasonal variations of particle number concentration and its relationship with PM2.5 mass concentration in industrial-residential airshed.
The smaller particles that dominate the particle number concentration (PNC) in the ambient air only contribute to a small percentage of particulate matter (PM) mass concentration although present in high particle number concentration. These small particles may be neglected upon assessing the health impacts of the PM. Hence, the knowledge on the particle number concentration size distribution deserves greater attention than the particulate mass concentration. This study investigates the measurement of the particle mass concentrations (PM2.5) and PNC of 0.27 μm < Dp < 4.50 μm during the southwest (SW), inter-monsoon (IM) and northeast (NE) monsoons in the industrial-residential airshed of Skudai, Johor Bahru, Malaysia. The PM2.5 mass concentrations and PNC were measured using a multi-channel GRIMM Environmental Dust Monitor (GRIMM EDM-SVC 365) equipped with a global positioning system. Diurnal variations, statistical analysis and regression plots were utilised from a six-month hourly data set to examine the patterns of the PNC size distributions and its relationships with the PM2.5 mass concentration. The overall mean PM2.5 mass concentration was 21.85 μg m-3, with the 24 h mean values of 26.80 μg m-3, 26.08 μg m-3 and 13.76 μg m-3 for the SW, IM and NE monsoons, respectively. It was found that the hourly mean of PNC was recorded at the highest concentration during the SW monsoon (373.20 # cm-3). The particles in the accumulation mode (Dp < 1.0 μm) were the prevalent form of the particle number concentration (94-98%). The scatter plots between the PM2.5 mass concentration and particle number size distribution showed that the PNC mode of 0.27 < Dp < 1.0 μm has the highest correlation value of r2 = 0.87 due to the emission from the anthropogenic activities. The results of this study highlight the importance of the PNC measurement in the seasonal variations of the PM2.5 pollution, indicating the significance of the regional-scale emission control actions in the local air quality management.


Diethylstilbestrol and 11 derivatives: a mutagenicity study with Salmonella typhimurium.
Diethylstilbestrol was tested for mutagenicity with his- S. typhimurium strains under 10 different matabolic situations (no exogenous metabolizing system; S9 mix from liver homogenate of rats induced with Aroclor 1254, with or without inhibition of epoxide hydratase; liver and/or kidney S9 mix from control or hamsters treated with Aroclor 1254; horse-radish peroxidase + H2O2). Under none of these conditions did diethylstilbestrol give any indication of a mutagenic effect. Furthermore, 11 metabolites and other derivatives of diethylstilbestrol, 2 of them potent inducers of sister-chromatid exchange in cultured fibroblasts, were not mutagenic with any of the 4 tester strains (S. typhimurium TA100, TA98, TA1537, TA1535) in the presence or absence of S9 mix from liver homogenate of rats induced with Aroclor 1254. Thus, one of the few known human carcinogens is very resistant to detection by the mammalian enzyme-mediated Salmonella typhimurium mutagenicity test (Ames test). This is especially remarkable since the metabolizing systems used included: (1) some of very high metabolic activity (S9 mix from liver homogenate of rats and hamsters induced with Aroclor 1254); (2) metabolizing systems from organs susceptible to the carcinogenic activity of diethylstilbestrol (hamster kidney); as well as (3) a mixture of (1) and (2) in case both activities are required for the carcinogenic effect in the whole animal.


Pathophysiologic features of a pneumoperitoneum at laparoscopy: a swine model.
The aim of this study was to examine local and systemic reactions of the body to a pneumoperitoneum to elucidate potential dangers and risks of laparoscopic procedures. Laparoscopy was performed on 25 pigs. The pigs were divided into five groups by level of intraabdominal pressure (14 and 18 mm Hg) and gas used (carbon dioxide and air). The effects of the pneumoperitoneum on cardiopulmonary condition and the peritoneal milieu were observed. These effects should be the result of various changes as the mechanical, ventilatory, cellular, hormonal, and immunologic levels. In this animal study marked changes in the peritoneal milieu were observed, and we demonstrated that these changes were dependent on the gas used, intraabdominal pressure, and duration of application. Locally these changes are manifest in the development of severe peritoneal acidosis, hypercapnia, and the release of various mediators. Systemic changes, in particular cardiopulmonary changes, also depend on the intraabdominal pressure and the gas used. During conventional pneumoperitoneum the peritoneum might change to a large extent so that the development of new risks are possibly encouraged. A reduction in intraabdominal pressure with the use of carbon dioxide as the insufflation gas should result in normal acid-base balance.


Heterogeneous levamisole receptors: a single-channel study of nicotinic acetylcholine receptors from Oesophagostomum dentatum.
A muscle vesicle preparation from Oesophagostomum dentatum, a 5 mm parasitic nematode, was developed for single-channel recording. Properties of nicotinic acetylcholine receptors activated by the anthelmintic levamisole (10 microM) were investigated using cell-attached and isolated inside-out patches. The current-voltage relationships of the single-channel currents were linear with conductances in the range 24.6-57.7 pS (mean 39.5 pS). The distributions of open times were fitted with a single exponential and mean open times were in the range 0.98-4.43 ms (mean 2.2 ms). The distributions of conductances and open times of the channels showed that the receptors could not be described as a single homogeneous population. There were two main channel subtypes: one subtype, designated G35, had a mean conductance of 35.2 pS and mean open time of 1.6 ms: another subtype designated G45, had a mean conductance of 44.6 pS and mean open time of 2.7 ms. A channel with a conductance near 25 pS. designated G25, and a channel with a conductance near 55 pS. designated G55, were also observed. The designations were based on the mean conductances. G. of the channel subtypes. A model for the heterogeneous population of nicotinic acetylcholine channels predicting four subtypes of receptor separated by their conductance is discussed and related to the development of levamisole resistance.


Fungal wood-degrading enzymes in esca-diseased grapevine and effects of carbohydrate environment on fungal development.
In esca disease affecting grapevines, Phaeomoniella chlamydospora and Phaeoacremonium minimum colonize the woody parts of the trunks and arms, where they obtain nutrition from xylem sap and, potentially, from residues resulting from the enzymatic breakdown of lignified cell walls, particularly osidic residues. We quantified the secretion of lignin peroxidase, manganese peroxidase and laccase by these fungi in woody tissues of selectively infected cuttings using immunolabeling and transmission electron microscopy. Our results indicated that the detection of these enzymes was generally higher in tissues infected with Phaeoacremonium minimum. These data were confirmed through immunodetection of enzymes secreted by hyphae of fungi grown in vitro. Additionally, we observed that the supply of various carbohydrates (mono, di, tri and tetrasaccharides and polymers) differentially influenced fungal growth and polypeptide secretion. Since some secreted polypeptides display detrimental effects on grapevine cells, these results raise the question of whether the carbohydrate environment could be a factor affecting the aggressiveness of these pathogens.


Do baseline atrial electrocardiographic and infarction patterns predict new-onset atrial fibrillation after ST-elevation myocardial infarction? Insights from the Assessment of Pexelizumab in Acute Myocardial Infarction Trial.
Atrial infarction reportedly occurs in 0.7% to 52% of ST-elevation myocardial infarctions (STEMIs), up to two thirds of whom develop atrial fibrillation and flutter (AF). Prospective validation of electrocardiographic atrial infarction patterns is lacking. Hence, in STEMI patients treated with primary percutaneous coronary intervention, we examined whether baseline atrial electrocardiographic changes or atrial infarction patterns predicted new AF or mortality. Within the Assessment of Pexelizumab in Acute Myocardial Infarction trial, a nested case-control study was conducted. Patients with new AF were matched 1:1 with controls, and baseline atrial electrocardiographic variables were examined. Abnormal P wave morphology (Liu minor criterion for atrial infarction) was significantly associated with new AF (adjusted odds ratio, 1.68; 1.03-2.73). This was also independently associated with 90-day mortality in the overall case-control cohort (adjusted hazard rate, 1.90; 1.04-3.46) and among patient with new-onset AF (adjusted hazard rate, 2.43; 1.22-4.84). Abnormal P wave morphology significantly predicted new AF and 90-day mortality in STEMI patients.


The antiblastogram.
The antiblastogram allows the specific determination within a few days of the effect of single and combined chemotherapeutic agents upon the cells of a given tumor, informing about their action, summation, antagonism and synergism. It permits to evaluate the activity of both hydrosoluble and liposoluble products, giving information about the possible activation or inactivation of chemotherapeutic agents by different substances and subcellular fractions.


Nutritional Physiology and Biochemistry of Dairy Cattle under the Influence of Heat Stress: Consequences and Opportunities.
: Higher milk yield and prolificacy of the modern dairy cattle requires high metabolism activities to support them. It causes high heat production by the body, which coupled with increasing environmental temperatures results in heat stress (HS). Production, health, and welfare of modern cattle are severely jeopardized due to their low adaptability to hot conditions. Animal activates a variety of physiological, endocrine, and behavioral mechanisms to cope with HS. Traditionally, decreased feed intake is considered as the major factor towards negative energy balance (NEBAL) leading to a decline in milk production. However, reciprocal changes related to insulin; glucose metabolism; failure of adipose mobilization; and skeletal muscle metabolism have appeared to be the major culprits behind HS specific NEBAL. There exists high insulin activity and glucose become preferential energy fuel. Physiological biochemistry of the heat stressed cows is characterized by low-fat reserves derived NEFA (non-esterified fatty acids) response, despite high energy demands. Besides these, physiological and gut-associated changes and poor feeding practices can further compromise the welfare and production of the heat-stressed cows. Better understanding of HS specific nutritional physiology and metabolic biochemistry of the dairy cattle will primarily help to devise practical interventions in this context. Proper assessment of the HS in cattle and thereby applying relevant cooling measures at dairy seems to be the basic mitigation approach. Score of the nutritional strategies be applied in the eve of HS should target supporting physiological responses of abatement and fulfilling the deficiencies possessed, such as water and minerals. Second line of abatement constitutes proper feeding, which could augment metabolic activities and synergizes energy support. The third line of supplemental supports should be directed towards modulating the metabolic (propionates, thiazolidinediones, dietary buffers, probiotics, and fermentates) and antioxidant responses (vitamins). Comprehensive understanding of the energetic metabolism dynamics under the impact of incremental heat load and complete outlook of pros and cons of the dietary ameliorating substances together with the discovery of the newer relevant supplementations constitutes the future avenues in this context.


Anatomic specificity in the diagnosis and treatment of internal rectal prolapse.
Distal bowel evacuation was studied by cinedefecography in 85 women with obstinate constipation, tenesmus, and incomplete evacuation in whom a diagnosis of internal rectal intussusception was clinically suspect. Sixty-five patients showed radiographic evidence of intussusception--mostly of the distal rectum, without rectosacral separation. Patients with distal intussusception who did not respond to nonoperative measures were treated by Delorme's transrectal excision with excellent results. Internal rectal intussusception is a real and demonstrable entity which may be symptomatically disabling and whose documentation may be integral to effective and anatomically specific treatment. The syndromes of perineal descent, solitary rectal ulcer, levator syndrome and so-called recurrent hemorrhoids may be diagnostic intermediaries in the evolution of internal rectal intussusception.


The correlation between various types of intraocular lens and laser wavelength.
To analyze effects of the composition and the color of intraocular lenses (IOLs) on laser wavelength. A case control study. Laser light rays at wavelengths ranging from 0.1 to 0.5 W were directed at a polymethymethacrylate ocular model fitted consecutively with three types of IOLs at various refractive powers. A laser detector was placed on the model beneath the lenses. The laser beam was passed through the IOLs and the output measured by a sensor. Attenuation rate was calculated. The colored IOL caused significantly more attenuation than did the noncolored IOLs (p <.01). A 30-diopter colored IOL showed an attenuation rate of up to 15% at a wavelength of 488 + 514 nm. Consideration of the wavelength and the output of a laser for a particular IOL is required when laser photocoagulation of the retina is performed in patients with pseudophakia.


Acute renal failure in the neonate.
With advances in diagnostic technology, the diagnosis of renal failure from prerenal and renal causes is being made more frequently. With better clinical understanding of etiologic causes, early prevention and diagnostic and therapeutic measures can be taken. Proper and controlled use of fluids, calories, and drugs is essential. Because of its relative ease, peritoneal dialysis is usually preferred over hemodialysis when renal failure cannot be handled more conservatively. Although the incidence of renal failure has apparently increased with the advent of neonatal intensive care, survival rates are increasing and the potential for prevention is better.


p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype.
Cellular senescence suppresses cancer by forcing potentially oncogenic cells into a permanent cell cycle arrest. Senescent cells also secrete growth factors, proteases, and inflammatory cytokines, termed the senescence-associated secretory phenotype (SASP). Much is known about pathways that regulate the senescence growth arrest, but far less is known about pathways that regulate the SASP. We previously showed that DNA damage response (DDR) signalling is essential, but not sufficient, for the SASP, which is restrained by p53. Here, we delineate another crucial SASP regulatory pathway and its relationship to the DDR and p53. We show that diverse senescence-inducing stimuli activate the stress-inducible kinase p38MAPK in normal human fibroblasts. p38MAPK inhibition markedly reduced the secretion of most SASP factors, constitutive p38MAPK activation was sufficient to induce an SASP, and p53 restrained p38MAPK activation. Further, p38MAPK regulated the SASP independently of the canonical DDR. Mechanistically, p38MAPK induced the SASP largely by increasing NF-κB transcriptional activity. These findings assign p38MAPK a novel role in SASP regulation--one that is necessary, sufficient, and independent of previously described pathways.


Neuropeptide Y2 receptors are involved in enhanced neurogenic vasoconstriction in spontaneously hypertensive rats.
1. The present study addressed the role of neuropeptide (NPY) Y2 receptors in neurogenic contraction of mesenteric resistance arteries from female spontaneously hypertensive rats (SHR). Arteries were suspended in microvascular myographs, electrical field stimulation (EFS) was performed, and protein evaluated by Western blotting and immunohistochemistry. 2. In vasopressin-activated endothelium-intact arteries, NPY and fragments with selectivity for Y1 receptors, [Leu31,Pro34]NPY, Y2 receptors, NPY(13-36), and rat pancreatic polypeptide evoked more pronounced contractions in segments from SHR than in Wistar Kyoto (WKY) arteries, even in the presence of the Y1 receptor antagonist, BIBP3226 (0.3 microM, (R)-N(2)-(diphenacetyl)-N-[(4-hydroxyphenyl)methyl]D-arginineamide). 3. In the presence of prazosin and during vasopressin activation, EFS-evoked contractions were larger in arteries from SHR compared to WKY. EFS contractions were enhanced by the Y2 receptor selective antagonist BIIE0246TF (0.5 microM, (S)-N2-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6h)-oxodibenz[b,e]azepin-11-y1]-1-piperazinyl]-2-oxoethyl]cyclo-pentyl-N-[2-[1,2-dihydro-3,5 (4H)-dioxo-1,2-diphenyl-3H-1,2,4-triazol-4-yl]ethyl]-argininamide), reduced by BIBP3226, and abolished by the combination of BIBP3226 and BIIE0246TF. 4. Immunoblotting showed NPY Y1 and Y2 receptor expression to be similar in arteries from WKY and SHR, although a specific Y2 receptor band at 80 kDa was detected only in arteries from WKY. 5. Immunoreaction for NPY was enhanced in arteries from SHR. In contrast to arteries from WKY, BIIE0246TF increased NPY immunoreactivity in EFS-stimulated arteries from SHR. 6. The present results suggest that postjunctional neuropeptide Y1 and Y2 receptors contribute to neurogenic contraction of mesenteric small arteries. Moreover, both enhanced NPY content and altered neuropeptide Y1 and Y2 receptor activation apparently contribute to the enhanced neurogenic contraction of arteries from SHR.


Diagnosis and categorization of small bowel neoplasms: role of computed tomography.
A retrospective study of 35 patients with small bowel neoplasms studied by computed tomography (CT) was performed. The tumor detection rate was 80%. Using the findings reported in the literature, an adequate histological diagnosis could be performed in 69% of the cases by CT. Lipomas, leiomyomas, leiomyosarcomas, and carcinoid tumors were well-recognized, but adenocarcinomas and lymphomas were often mistaken one for the other. An accurate preoperative staging was performed in 61% of the cases. CT failed to detect 75% of the invaded lymph nodes, 25% of the liver metastases, and 25% of the tumoral growth beyond the bowel wall. Despite major limitations in preoperative staging, a good detection rate and some features allowing a specific diagnosis advocate using CT along with the barium examination when clinical history suggests a small bowel tumor.


[The social worker, a partner in nursing care].
Social workers play a pivotal role in the care of domestic violence victims. Their support consists in facilitating access to housing, health services, justice and helping the victims obtain suitable assistance. Social services are present in hospitals and across the territories. One of the social worker's missions is to guarantee the protection of children.


Maxillary sinus elevation by lateral window approach: evolution of technology and technique.
The maxillary sinus elevation procedure has become an important pre-prosthetic surgical procedure for the creation of bone volume in the edentulous posterior maxilla for the placement of dental implants. Research and clinical experience over the past 30 years has increased the predictability of this procedure as well as reduced patient morbidity. Data on grafting materials and implant survival rates comes from 10 published evidence-based reviews that include all relevant published data from 1980 to 2012. Supporting clinical material comes from the experience of the authors. The evidence-based reviews report and compare the implant survival rates utilizing various grafting materials, implant surfaces, and the use or non-use of barrier membranes over the lateral window. Clinical studies report on complication rates utilizing piezoelectric surgery and compare them to complication rates with rotary instrumentation. The conclusions of all the evidence-based reviews indicate that the utilization of bone replacement grafts, rough-surfaced implants, and barrier membranes result in the most positive outcomes when considering implant survival. Further, the utilization of piezoelectric surgery, rather than rotary diamond burs, for lateral window preparation and membrane separation leads to a dramatic reduction in the occurrence of the intraoperative complications of bleeding and membrane perforation.


Vascularized bone transfer for tibial pseudarthrosis. Part I: Vascularized fibula transplantation. A report of 4 cases in the treatment of traumatic bone defects of the tibia.
The limited experience of reconstruction of four cases of large tibial defects with free vascularized fibular grafts is presented. Healing occurred in three of the four patients, and one developed a distal pseudarthrosis. One graft fractured twice but healed with a hypertrophic callus.


A macroscopic object passively cooled into its quantum ground state of motion beyond single-mode cooling.
The nature of the quantum-to-classical crossover remains one of the most challenging open question of Science to date. In this respect, moving objects play a specific role. Pioneering experiments over the last few years have begun exploring quantum behaviour of micron-sized mechanical systems, either by passively cooling single GHz modes, or by adapting laser cooling techniques developed in atomic physics to cool specific low-frequency modes far below the temperature of their surroundings. Here instead we describe a very different approach, passive cooling of a whole micromechanical system down to 500 μK, reducing the average number of quanta in the fundamental vibrational mode at 15 MHz to just 0.3 (with even lower values expected for higher harmonics); the challenge being to be still able to detect the motion without disturbing the system noticeably. With such an approach higher harmonics and the surrounding environment are also cooled, leading to potentially much longer mechanical coherence times, and enabling experiments questioning mechanical wave-function collapse, potentially from the gravitational background, and quantum thermodynamics. Beyond the average behaviour, here we also report on the fluctuations of the fundamental vibrational mode of the device in-equilibrium with the cryostat. These reveal a surprisingly complex interplay with the local environment and allow characteristics of two distinct thermodynamic baths to be probed.


Acute and long-term hemodynamic effects of oral pirbuterol in patients with chronic severe congestive heart failure: randomized double-blind trial.
In 20 patients with severe congestive heart failure (CHF), we studied the effects of the beta-adrenergic agonist pirbuterol compared to placebo in both an acute double-blind randomized trial and after long-term treatment. Acutely, pirbuterol patients (n = 10) demonstrated a significant rise in cardiac index (2.2 +/- 0.14 to 3.2 +/- 0.32 L/min/m2), stroke index (26 +/- 2.6 to 35 +/- 2.9 ml/beat/m2), stroke work index (22 +/- 2.4 to 30 +/- 2.7 gm X m/m2), and ejection fraction (22 +/- 4 to 30 +/- 5%). These hemodynamic variables did not significantly change in placebo patients (n = 10). After 3 weeks of pirbuterol therapy, 14 patients (70%) were symptomatically improved and were continued on the drug for another 3 weeks; 13 of 14 patients who were symptomatically improved underwent restudy. Compared to pretreatment baseline, there was continued improvement in cardiac index (2.5 +/- 0.16 to 3.2 +/- 0.24 L/min/m2), stroke index (30 +/- 2.5 to 38 +/- 2.9 ml/beat/m2), stroke work index (26 +/- 2.3 to 35 +/- 3.1 gm X m/m2), and ejection fraction (24 +/- 1 to 28 +/- 4%). Patients more frequently improved were those with nonischemic cardiomyopathy and those with higher initial ejection fractions. These results demonstrate the acute beneficial effects of oral pirbuterol versus placebo in a double-blind randomized trial. Improvement was maintained during long-term therapy in the majority of CHF patients.


Effects of genome-wide neuroticism-associated variants on five-factor model personality traits in schizophrenia.
Patients with schizophrenia (SCZ) have characteristic personality traits compared with healthy subjects. Genome-wide significant variants for neuroticism have been reported in healthy subjects. However, the associations of these genome-wide neuroticism-associated variants with five-factor personality traits in patients with SCZ are less clear. We investigated the influences of nine independent genome-wide significant variants for neuroticism on five-factor personality traits (neuroticism, extraversion, openness, agreeableness, and conscientiousness) assessed by the NEO Five-Factor Inventory (NEO-FFI) in 107 patients with SCZ and 119 healthy controls (HCs). As expected, patients with SCZ scored significantly higher for neuroticism and lower for extraversion, openness, agreeableness and conscientiousness than HCs (p < 0.05). Of nine neuroticism-associated variants, the T allele at rs4653663 related to lower neuroticism was only significantly associated with lower neuroticism in patients with SCZ (β = -0.27, p = 3.88 × 10-3) and in combined subjects (β = -0.15, p = 0.026). Furthermore, of other personality traits, the genetic variant was significantly associated with higher agreeableness in combined subjects (β = 0.17, p = 9.41×10-3), higher conscientiousness in patients with SCZ (β = 0.21, p = 0.031) and lower conscientiousness in HCs (β = -0.20, p = 0.034), and nominally associated with higher extraversion in patients with SCZ (β = 0.18, p = 0.056) and in combined subjects (β = 0.13, p = 0.051). These outcomes were not affected by clinical variables. We suggest that genome-wide neuroticism-associated variant could be associated with neuroticism as well as other personality traits in schizophrenia.


Headache among medical and psychology students.
Headaches occur frequently and thus are a key component of sociocentric medical education. To study headaches among students of medicine and psychology in a single university. This was a questionnaire-based survey of a cohort of students of medicine and psychology. The overall lifetime prevalence of headache was 98% and over the last year, 91%. Tensional headache accounted for 59% and migraine 22% in medicine; and 48.5% and 32% respectively in psychology. Forty-five percent reported that headaches had a variable sporadic impact on their productivity. The self-medication rate was 77%. Thirty-six percent reported worsening since admission to the university. The prevalence of headaches was very high. Tension-type headaches predominated in males and migraine in females. Tension-type was more frequent among medical students than among psychology students; migraine was more frequent in psychology (more females) than in medicine. Both kinds of students reported that headaches caused low interference with daily activities. The students reported that their symptoms had worsened since admission to the university.


Phytochemical analysis, antioxidant and in vitro β-galactosidase inhibition activities of Juniperus phoenicea and Calicotome villosa methanolic extracts.
Juniperus Phoenicea (JP) and Calicotome Villosa (CV) are used by Jordanian populations as herbal remedies in traditional medicine. Herein, the phytochemical contents of their methanolic extracts were analyzed and their antioxidant as well as in vitro anti- β-Galactosidase activities were evaluated; their effect on β-Galactosidase enzyme kinetics was evaluated and the thermodynamic of the enzyme was determined. The antioxidant activity of JP and CV crude methanolic extracts was evaluated using 1,1-diphenyl,2-picrylhydrazyl (DPPH) free radical scavenging and ferric reducing antioxidant power (FRAP) assays; however, the effect of the plants' crude extracts on β-Galactosidase activity and kinetics was evaluated in vitro. Moreover, total phenolic, flavonoids, and flavonols content in plants' extracts were determined and expressed in Gallic acid equivalent (mg GAE/g dry extract) or rutin equivalent (mg RE/g dry extract). Phytochemical screening of the crude extracts of JP and CV leaves revealed the presence of phenols, alkaloids, flavonoids, terpenoids, anthraquinones, and glycosides. Flavonoids and flavonols contents were significantly higher in JP than in CV (p < 0.05). Furthermore, an analogous phenolic content was detected in both JP and CV methanolic extracts (103.6 vs 99.1 mg GAE/g extract). The ability of JP extract to scavenge DPPH radicals was significantly higher than that of CV extract with IC50 = 11.1 μg/ml and 15.6 μg/ml, respectively. However, their extracts revealed relatively similar antioxidant capacities in FRAP assay; their activity was concentration dependent. The JP extract inhibited β-galactosidase enzyme activity with a significant IC50 value compared to CV extract; they exhibited their inhibitory activities at IC50 values 65 µg/ml and 700 µg/ml, respectively. Rutin revealed anti-β-galactosidase activity at IC50 = 75 µg/ml. The mode of inhibition of β-galactosidase by JP, CV, and rutin was non-competitive, mixed, and competitive inhibition, respectively. Thermodynamic and enzyme inactivation kinetics revealed that β-galactosidase has a half-life time of 108 min at 55 °C, activation energy of 208.88 kJ mol-1 and the inactivation kinetics follows a first-order reaction with k-values 0.0023-0.0862 min-1 and positive entropy of inactivation (∆S°) values at various temperatures, indicating non-significant processes of aggregation. The methanolic extracts of JP and CV possess anti-hyperglycemic and antioxidant activities with potential pharmaceutical applications.


DNA damage-signaling, homologous recombination and genetic mutation induced by 5-azacytidine and DNA-protein crosslinks in Escherichia coli.
Covalent linkage between DNA and proteins produces highly toxic lesions and can be caused by commonly used chemotherapeutic agents, by internal and external chemicals and by radiation. In this study, using Escherichia coli, we investigate the consequences of 5-azacytidine (5-azaC), which traps covalent complexes between itself and the Dcm cytosine methyltransferase protein. DNA protein crosslink-dependent effects can be ascertained by effects that arise in wild-type but not in dcmΔ strains. We find that 5-azaC induces the bacterial DNA damage response and stimulates homologous recombination, a component of which is Dcm-dependent. Template-switching at an imperfect inverted repeat ("quasipalindrome", QP) is strongly enhanced by 5-azaC and this enhancement was entirely Dcm-dependent and independent of double-strand break repair. The SOS response helps ameliorate the mutagenic effect of 5-azaC but this is not a result of SOS-induced DNA polymerases since their induction, especially PolIV, seems to stimulate QP-associated mutagenesis. Cell division regulator SulA was also required for recovery of QP mutants induced by 5-azaC. In the absence of Lon protease, Dcm-dependent QP-mutagenesis is strongly elevated, suggesting it may play a role in DPC tolerance. Deletions at short tandem repeats, which occur likewise by a replication template-switch, are elevated, but only modestly, by 5-azaC. We see evidence for Dcm-dependent and-independent killing by 5-azaC in sensitive mutants, such as recA, recB, and lon; homologous recombination and deletion mutations are also stimulated in part by a Dcm-independent effect of 5-azaC. Whether this occurs by a different protein/DNA crosslink or by an alternative form of DNA damage is unknown.


Autosomal Dominant Tubulointerstitial Kidney Disease HNF1B With Maturity-Onset Diabetes of the Young: A Case Report With Kidney Biopsy.
Autosomal dominant tubulointerstitial kidney disease subtype hepatocyte nuclear factor 1β (ADTKD-HNF1B) is a hereditary disease caused by variants of HNF1B that is characterized by a family history of tubulointerstitial nephropathy with concomitant diabetes mellitus. We report on a Japanese man in his early 40s who had ADTKD-HNF1B diagnosed. He had a reduced glomerular filtration rate, borderline diabetes mellitus, multiple small cysts in his bilateral kidneys, and pancreatic hypoplasia. He also had a family history of diabetes and kidney cystic lesions. These phenotypes represent ADTKD-HNF1B and genetic analysis revealed a missense variant of HNF1B. Kidney biopsy demonstrated not only tubulointerstitial fibrosis but also abnormal mitochondrial morphology in tubular cells, a novel finding.


[Barriers to referral to pulmonary rehabilitation in COPD patients from the perspective of general practitioners].
In spite of recommendations of the highest level of proof (rank A), the respiratory rehabilitation remains very widely sub-prescribed by general practitioners, who are nevertheless in the front line in the care and the follow-up of the patients affected by BPCO. Semi-qualitative study with the general practitioners installed in the city of Montauban (Tarn-et-Garonne). The rate of answer was 57%. Eighty-six percent of the patients BPCO followed in general medicine have never participated in a respiratory rehabilitation program. Eighty percent of the questioned general practitioners declared not to know the last recommendations of the HAS. A total of 66.7% of the questioned general practitioners considered that prescription of respiratory rehabilitation comes within their remit. Eighty seven percent of the general practitioners declare not to know the existing respiratory programs of rehabilitation in their region. The main barrier for prescription of respiratory rehabilitation for patients BPCO in general medicine could be the misunderstanding of the local existing programs. The distribution of existing tools such as the map of the programs of respiratory rehabilitation established by the group Alvéole of the Society of Pneumology of French language (SPLF) could so be a facilitating factor.


Unsupervised home-based resistance training for community-dwelling older adults: A systematic review and meta-analysis of randomized controlled trials.
We aimed to summarize evidence on the safety, adherence and effectiveness of home-based resistance training (UHBRT) for improving health-related endpoints in community-dwelling older adults. Randomized controlled trials of UHBRT in older adults (≥60yrs) were included after a systematic search (PubMed, CINAHL, PsycInfo, SPORTDiscus, Web of Science, MEDLINE, Cochrane Central Register of Controlled Trials) until 02/19/2021. Adverse events and adherence rates were assessed as indicators of feasibility. Other endpoints included physical (muscle strength, muscle power, balance, physical performance) and mental-related measures (cognition, quality of life [QoL]) as well as other health-related variables (body composition, physical activity levels, falls). 21 studies (N = 4,053) were included. No major adverse events were reported, with adherence averaging 67 % (range 47-97 %). UHBRT significantly improved lower-limb muscle strength (Hedges' g = 0.33; 95 % confidence interval [CI] = 0.11-0.57), muscle power measured through the sit-to-stand test (g = 0.44; 95 %CI = 0.06-0.84), and balance (assessed with the postural sway, g = 0.32; 95 %CI = 0.16-0.49). No benefits were found for other strength indices (handgrip strength), balance (single leg stance and functional reach test), physical performance (walking speed, TUG and SPPB), QoL, nor for the risk or rate of falls (all p > 0.05, g<0.61). No meta-analysis could be performed for the remaining endpoints. Although efforts are needed to increase adherence, preliminary evidence suggests that UHBRT can be safe and modestly effective for improving some measures of lower-limb muscle strength, balance, and muscle power in community-dwelling older adults. However, no benefits were found for other physical fitness measures, QoL or falls. More evidence is therefore needed to draw definite conclusions.


Context-specific territorial behavior in urban birds: no evidence for involvement of testosterone or corticosterone.
Testosterone produced by the gonads is a primary mediator of seasonal patterns of territoriality and may directly facilitate territorial behavior during an encounter with a potential intruder. Costs and benefits associated with territoriality can vary as a function of habitat, for example through differences in resource distribution between areas occupied by different individuals. We investigated behaviors in response to simulated territorial intrusions (hereafter territorial behaviors) in urban (Phoenix, Arizona) and nearby desert populations of two Sonoran Desert birds (Curve-billed Thrasher and Abert's Towhee). We also examined the degree to which these behaviors are mediated by testosterone (T) and the adrenal steroid, corticosterone (CORT), which can interact with T in territorial contexts. In both species, urban birds displayed more territorial behaviors than their desert conspecifics, but this difference was not associated with variation in either plasma total or in plasma free (i.e., unbound to binding globulins) T or CORT. In addition, neither plasma T nor plasma CORT changed as a function of duration of the simulated territorial intrusion. Urban Abert's Towhees displayed more territorial behaviors in areas where their population densities were high than in areas of low population densities. Urban Curve-billed Thrashers displayed more territorial behaviors in areas with a high proportion of desert-type vegetation, particularly in areas that differed in vegetation composition from nearby randomly sampled areas, than in areas with a high proportion of exotic or non-desert type vegetation. Associations between territorial behavior and habitat characteristics were not related to plasma T or CORT. Understanding the hormonal processes underlying these associations between behavior and habitat may provide insight into how free-ranging animals assess territorial quality and alter their defensive behavior accordingly.


Chronic lymphatic leukemia diagnosed through histological evaluation of resected prostatic tissue.
Chronic lymphatic leukemia was diagnosed through routine histological evaluation of resected prostatic tissue. Two cases are presented.


Investigation of Behavioural Pain Scale, Critical Care Pain Observation Tool, nociceptive flexion reflex and pupillary dilatation reflex as predictors of behavioural reactions to nociceptive procedures in critically ill patients unable to self-report pain.
Procedural pain is a common burden in critical care treatment and the prediction of nociceptive reactions remains challenging. Thus, we investigated the Behavioural Pain Scale (BPS), the Critical Pain Observational Tool (CPOT), the nociceptive flexion reflex (NFR), the pupillary dilation reflex (PDR) and the Richmond Agitation-Sedation Scale (RASS) as predictors of behavioural reactions to nociceptive procedures. In this monocentric, prospective, observational study, we analysed data of 128 critically ill adults unable to self-report pain to investigate the predictability of behavioural reactions to two procedures: endotracheal suctioning and turning. Next to routine clinical data, CPOT, BPS, PDR, NFR, RASS, propofol and sufentanil doses were recorded before the procedures. For endotracheal suctioning, NFR, BPS, CPOT and RASS showed predictive performances significantly better than chance, but none of them performed significantly better than the sufentanil dose rate. For turning, BPS, CPOT and RASS showed predictive performances significantly better than chance, but only the RASS performed significantly better than the propofol dose rate. Behavioural reactions to both investigated clinical procedures can be predicted by observational scales or nociceptive reflexes. For endotracheal suctioning, none of the predictors performed superior to using the sufentanil dose rate as a predictor. As using sufentanil as a predictor requires no extra effort in contrast to the other predictors, none of the here investigated tools seem advisable for predicting behavioural reactions to endotracheal suctioning. For patient turning, the RASS predicts reactions better than any other tool. In this observational study, we demonstrate that behavioural reactions to potentially nociceptive procedures in critical care treatment can be predicted by observational scales and nociceptive reflexes. However, for endotracheal suctioning, none of the predictors is superior to using the opioid dose rate as a predictor. For patient turning, the RASS predicts reactions better than any other parameters.


Control programs for strongyloidiasis in areas of high endemicity: an economic analysis of different approaches.
Implementation of control programmes for Strongyloides stercoralis infection is among the targets of the World Health Organization Roadmap to 2030. Aim of this work was to evaluate the possible impact in terms of economic resources and health status of two different strategies of preventive chemotherapy (PC) compared to the current situation (strategy A, no PC): administration of ivermectin to school-age children (SAC) and adults (strategy B) versus ivermectin to SAC only (strategy C). The study was conducted at the IRCCS Sacro Cuore Don Calabria hospital, Negrar di Valpolicella, Verona, Italy, at the University of Florence, Italy, and at the WHO, Geneva, Switzerland, from May 2020 to April 2021. Data for the model were extracted from literature. A mathematical model was developed in Microsoft Excel to assess the impact of strategies B and C in a standard population of 1 million subjects living in a strongyloidiasis endemic area. In a case base scenario, 15% prevalence of strongyloidiasis was considered; the 3 strategies were then evaluated at different thresholds of prevalence, ranging from 5 to 20%. The results were reported as number of infected subjects, deaths, costs, and Incremental-Effectiveness Ratio (ICER). A 1-year and a 10-year horizons were considered. In the case base scenario, cases of infections would reduce dramatically in the first year of implementation of PC with both strategy B and C: from 172 500 cases to 77 040 following strategy B and 146 700 following strategy C. The additional cost per recovered person was United States Dollar (USD) 2.83 and USD 1.13 in strategy B and C, respectively, compared to no treatment in the first year. For both strategies, there was a downtrend in costs per recovered person with increasing prevalence. The number of adverted deaths was larger for strategy B than C, but cost to advert one death was lower for strategy C than B. This analysis permits to estimate the impact of two PC strategies for the control of strongyloidiasis in terms of costs and adverted infections/deaths. This could represent a basis on which each endemic country can evaluate which strategy can be implemented, based on available funds and national health priorities.


[A cermet X-ray tube for mammography].
Characteristics of a new cermet X-ray tube for mammography are considered. The results of experimental testing of the tube are described.


Capillary electrophoresis-based separation of transferrin sialoforms in patients with carbohydrate-deficient glycoprotein syndrome.
The heterogeneity associated with protein glycoforms has been a challenge to analytical chemists and the subject of structure-function studies for biochemists since their presence in biological systems had been confirmed some three decades ago. Initial investigations led to discoveries of synthetic and degradative pathways, and brief forays into functional determination of the "glyco" portion on the protein activity in glycoproteins. Only recently has it come to our understanding that variations from the "normal" glycosylation patterns might be indicative of pathological states. The presence of certain transferrin (Tf) glycoforms in human serum has been shown to correlate with certain clinical syndromes. Hence, the ability to separate and quantitatively measure the various forms of human Tf has become increasingly important. It this study, we demonstrate that a simple method utilizing a DB-17-coated capillary to slow endoosmotic flow and a sieving buffer containing hydroxyethyl cellulose allows for the resolution of sialoforms of transferrin. An analysis time of less than eight minutes allows for baseline resolution of the lower sialoforms of Tf, presenting a simple, rapid test for carbohydrate-deficient transferrin (CDT). We demonstrate the utility of this methodology for the facile diagnosis of carbohydrate-deficient glycoprotein syndrome, and postulate that it may allow for the detection of other carbohydrate-deficient protein-related disease states.


Selective regulation of nerve growth factor expression in developing cutaneous tissue by early sensory innervation.
In the developing vertebrate peripheral nervous system, the survival of sympathetic neurons and the majority of sensory neurons depends on a supply of nerve growth factor (NGF) from tissues they innervate. Although neurotrophic theory presupposes, and the available evidence suggests, that the level of NGF expression is completely independent of innervation, the possibility that innervation may regulate the timing or level of NGF expression has not been rigorously investigated in a sufficiently well-characterized developing system. To address this important question, we studied the influence of innervation on the regulation of NGF mRNA expression in the embryonic mouse maxillary process in vitro and in vivo. The maxillary process receives its innervation from predominantly NGF-dependent sensory neurons of the trigeminal ganglion and is the most densely innervated cutaneous territory with the highest levels of NGF in the embryo. When early, uninnervated maxillary processes were cultured alone, the level of NGF mRNA rose more slowly than in maxillary processes cultured with attached trigeminal ganglia. In contrast to the positive influence of early innervation on NGF mRNA expression, the levels of brain-derived neurotrophic factor (BDNF) mRNA and neurotrophin-3 (NT3) mRNA rose to the same extent in early maxillary processes grown with and without trigeminal ganglia. The level of NGF mRNA, but not BDNF mRNA or NT3 mRNA, was also significantly lower in the maxillary processes of erbB3-/- mice, which have substantially fewer trigeminal neurons than wild-type mice. This selective effect of initial innervation on target field NGF mRNA expression provokes a re-evaluation of a key assertion of neurotrophic theory that the level of NGF expression is independent of innervation.


Genetic variation of 15 STR loci (D3S1358, vWA, FGA, TH01, TPOX, CSF1PO, D5S818, D13S317, D7S820, D16S539, D2S1338, D8S1179, D21S11, D18S51, and D19S433) in populations of north and central Poland.
Allele frequencies for 15 short tandem repeats (STRs) included in AmpFlSTR Profiler and AmpFlSTR SGM Plus kits were obtained from populations of Pomorze Gdanskie, Wielkopolska, Kujawy, Pomorze Zachodnie, Mazury and Mazowsze regions of Poland.


Efficacy of an Infrared Radiator for Hypothermia Prevention in a Simulated Setup of Entrapped Vehicle Accident Victims.
Prolonged extrication of entrapped patients after road traffic accidents increases the risk of sustained hypothermia. Accident-related hypothermia increases mortality in severely injured patients, and prehospital efforts to prevent hypothermia are essential. We evaluated various warming measures regarding their preclinical suitability and efficacy for patient warming, tested in realistically-simulated road traffic accident scenarios under cold ambient conditions in a climate chamber. The effects of a chemical warming blanket (CWB), forced-air warming (FAW) device, or infrared radiator (IRR) on the core body and skin surface temperature of a subject previously exposed to a cold environment (5°C for 12 minutes) was recorded via temperature sensors and thermographically, respectively. Physiological parameters such as oxygen saturation, blood pressure, and heart rate were also monitored. Under cold environmental conditions, all devices were able to compensate or overcompensate the cooling of body parts directly exposed to the heating measure. In the body areas that were not directly warmed (back, lower extremities), only the CWB limited further cooling. FAW and IR irradiation rapidly and effectively warmed the heat-exposed areas (head and arms). However, both methods - but especially the IRR - led to a noticeably accelerated cooling in body parts not directly exposed to heat (back, legs). The increased mortality associated with hypothermia in severely injured crash victims during prolonged vehicle extrication has intensified efforts to prevent sustained hypothermia. The use of a CWB, FAW or IRR are in principle all suitable for reducing or compensating for heat loss. The ongoing cooling of those body parts not directly exposed to the heat source was interpreted as a steal phenomenon in regional blood flow. However, the practicality and effectiveness of these measures, combined with their logistical requirements, must be evaluated in real extrication scenarios.


Phase Evolution on the Hydrogen Adsorption Kinetics of NiFe-Based Heterogeneous Catalysts for Efficient Water Electrolysis.
Transition metal layered double hydroxides, especially nickel-iron layered double hydroxide (NiFe-LDH) shows significant advancement as efficient oxygen evolution reaction (OER) electrocatalyst but also plays a momentous role as a precursor for NiFe-based hydrogen evolution reaction (HER) catalysts. Herein, a simple strategy for developing Ni-Fe-derivative electrocatalysts via phase evolution of NiFe-LDH under controllable annealing temperatures in an argon atmosphere is reported. The optimized catalyst annealed at 340 o C (denoted NiO/FeNi3 ) exhibits superior HER properties with an ultralow overpotential of 16 mV@10 mA cm-2 . Density functional theory simulation and in situ Raman analyses reveal that the excellent HER properties of the NiO/FeNi3 can be attributed to the strong electronic interaction at the interface of the metallic FeNi3 and semiconducting NiO, which optimizes the H2 O and H adsorption energies for efficient HER and OER catalytic processes. This work will provide rational insights into the subsequent development of related HER electrocatalysts and other corresponding compounds via LDH-based precursors.


Ouabain and Digoxin Activate the Proteasome and the Degradation of the ERα in Cells Modeling Primary and Metastatic Breast Cancer.
Estrogen receptor α expressing breast cancers (BC) are classically treated with endocrine therapy. Prolonged endocrine therapy often results in a metastatic disease (MBC), for which a standardized effective therapy is still lacking. Thus, new drugs are required for primary and metastatic BC treatment. Here, we report that the Food and Drug Administration (FDA)-approved drugs, ouabain and digoxin, induce ERα degradation and prevent proliferation in cells modeling primary and metastatic BC. Ouabain and digoxin activate the cellular proteasome, instigating ERα degradation, which causes the inhibition of 17β-estradiol signaling, induces the cell cycle blockade in the G2 phase, and triggers apoptosis. Remarkably, these effects are independent of the inhibition of the Na/K pump. The antiproliferative effects of ouabain and digoxin occur also in diverse cancer models (i.e., tumor spheroids and xenografts). Additionally, gene profiling analysis reveals that these drugs downregulate the expression of genes related to endocrine therapy resistance. Therefore, ouabain and digoxin behave as 'anti-estrogen'-like drugs, and are appealing candidates for the treatment of primary and metastatic BCs.


Direct C-H Carboxylation Forming Polyfunctionalized Aromatic Carboxylic Acids by Combined Brønsted Bases.
CO2 fixation into electron-deficient aromatic C-H bonds proceeds with the combined Brønsted bases LiO-t-Bu and LiO-t-Am/CsF/18-crown-6 (t-Am = CEtMe2) under a CO2 atmosphere to afford a variety of polyfunctionalized aromatic carboxylic acids.