Bilateral toxic epithelial keratopathy following instillation of expired topical eye drops.
Toxic corneal epitheliopathies are common, but the majority are probably so mild that they are subclinical. Clinically significant epithelial keratopathy can occur following a single drop of topical expired carboxymethylcellulose sodium eye drops. This case presents A 34-year-old female who presented to the emergency department with a history of severe ocular pain and reduced vision after bilateral instillation of expired eye drops. Both eyes were diagnosed with toxic epithelial keratopathy. The presenting best corrected visual acuity (BCVA) was 20/100 in the right eye and 20/300 in the left eye. The BCVA at last follow-up was 20/20 in both eyes. The safe use and storage of ophthalmic drugs, including their use before the expiration date, should be reinforced to patients by all healthcare practitioners to avoid complications such as toxic keratopathy.


Proteomics-based identification of secreted protein dihydrodiol dehydrogenase 2 as a potential biomarker for predicting cisplatin efficacy in advanced NSCLC patients.
Cisplatin is the major agent in the standard first-line chemotherapy for NSCLC. However, only a small portion of patients achieve a tumor response to cisplatin-based chemotherapy and eventually develop acquired resistance. The aim of this study was to identify potential biomarkers that could predict the efficacy of cisplatin. Human lung adenocarcinoma cell line A549 was exposed to cisplatin for development of a resistant cell line, A549/DDP, and cisplatin-sensitivity was tested through the MTT assay. The global protein profiles from A549 and A549/DDP were compared using a proteomic approach. Western blot, real-time PCR and immunohistochemistry validated the expression of DDH2 in cell lines and tumor xenografts. Serum levels of DDH2 were measured by ELISA in 105 NSCLC patients treated with cisplatin-based chemotherapy. The resistance of A549/DDP to cisplatin was 8.07-fold higher than that of A549 cells. Proteomic approach identified eight differentially (>5-fold) expressed proteins. Among them, secreted protein DDH2 was further investigated and it was found overexpressed through the method of Western blot, real-time PCR in cell lines, consistent with immunohistochemistry validation in xenograft. Clinical research showed that baseline serum DDH2 level in the patients with a progression disease was significantly higher than the patients of response or stable disease (9.036 vs. 3.529 and 3.982 ng/mL, P<0.001) and serum DDH2 levels were significantly increased after cisplatin-based doublet chemotherapy (5.515 vs. 12.935 vs. 18.406 ng/mL P<0.001, respectively). DDH2 expression might be a potential predictor and monitor of cisplatin efficacy in advanced NSCLC patients.


Vasoactive intestinal peptide stimulates glycolysis in pituitary tumours; 1H-NMR detection of lactate in vivo.
1H- and 31P-NMR spectroscopy has been applied to rats carrying implanted tumours in vivo, and used to observe simultaneous changes in intracellular pH (pHi) and lactate concentration during the stimulatory action of vasoactive intestinal polypeptide (VIP). A maximal decrease in pHi to a mean of 0.29 units below basal values was recorded. At the same time, 11 min after VIP, a maximal increase in tumour lactate was found, with a mean value of 150% of the basal concentration. The magnitude of these changes was compatible with in vitro measurements of basal lactate concentration and buffering capacity made on the same tumour line. It is concluded that VIP stimulates glycolysis by the tumour cells, resulting in an accumulation of lactate and a consequent fall in pHi.


Carboxylesterases from the seeds of an underutilized legume, Mucuna pruriens; isolation, purification and characterization.
Two carboxylesterases (ME-III and ME-IV) have been purified to apparent homogeneity from the seeds of Mucuna pruriens employing ammonium sulfate fractionation, cation exchange chromatography on CM-cellulose, gel-permeation chromatography on Sephadex G-100 and preparative PAGE. The homogeneity of the purified preparations was confirmed by polyacrylamide gel electrophoresis (PAGE), gel-electrofocussing and SDS-PAGE. The molecular weights determined by gel-permeation chromatography on Sephadex G-200 were 20.89 kDa (ME-III) and 31.62 kDa (ME-IV). The molecular weights determined by SDS-PAGE both in the presence and absence of 2-mercaptoethanol were 21 kDa (ME-III) and 30.2 kDa (ME-IV) respectively, suggesting a monomeric structure for both the enzymes. The enzymes were found to have Stokes radius of 2.4 nm (ME-III) and 2.7 nm (ME-IV). The isoelectric pH values of the enzymes, ME-III and ME-IV, were 6.8 and 7.4, respectively. ME-III and ME-IV were classified as carboxylesterases employing PAGE in conjunction with substrate and inhibitor specificity. The K(m) of ME-III and ME-IV with 1-naphthyl acetate as substrate was 0.1 and 0.166 mM while with 1-naphthyl propionate as substrate the K(m) was 0.052 and 0.0454 mM, respectively. As the carbon chain length of the acyl group increased, the affinity of the substrate to the enzyme increased indicating hydrophobic nature of the acyl group binding site. The enzymes exhibited an optimum temperature of 45°C (ME-III) and 37°C (ME-IV), an optimum pH of 7.0 (ME-III) and 7.5 (ME-IV) and both the enzymes (ME-III and ME-IV) were stable up to 120 min at 35°C. Both the enzymes were inhibited by organophosphates (dichlorvos and phosphamidon), but resistant towards carbamates (carbaryl and eserine sulfate) and sulphydryl inhibitors (p-chloromercuricbenzoate, PCMB).


A functional assay for G-protein-coupled receptors using stably transformed insect tissue culture cell lines.
Insect cells are an underexplored resource for functional G-protein-coupled receptor (GPCR) assays, despite a strong record in biochemical (binding) assays. Here we describe the use of vectors capable of creating stably transformed insect cell lines to generate a cell-based functional GPCR assay. This assay employs the luminescent photoprotein aequorin and the promiscuous G-protein subunit Galpha16 and is broadly applicable to human GPCRs. We demonstrate that the assay can quantitate ligand concentration-activity relationships for seven different human GPCRs, can differentiate between partial and full agonists, and can determine rank order potencies for both agonists and antagonists that match those seen with other assay systems. Human Galpha16 improves signal strength but is not required for activity with some receptors. The coexpression of human and bovine betagamma subunits and/or phospholipase Cbeta makes no difference to agonist efficacy or potency. Two different receptors expressed in the same cell line respond to their specific agonists, and two different cell lines (Sf9 and High 5) are able to functionally detect the same expressed GPCR. Sf9 cells have the capability to produce fully functional human receptors, allied to a low background of endogenous receptors, and so are a valuable system for investigating orphan GPCRs and receptor dimerization.


Geographic Region, Racial/Ethnic Disparities, and Late-Life Depression: Results From a Large US Cohort of Older Adults.
To determine associations between geographic region and late-life depression (LLD) severity, item-level symptom burden, and treatment; to evaluate whether racial/ethnic disparities in LLD, previously observed in the overall sample, vary by region. We included 25,502 VITAL (Vitamin D and Omega-3 Trial) participants and administered the Patient Health Questionnaire-8 for depressive symptoms; participants also reported medication and/or counseling care for depression. Multivariable regression analyses were performed. Despite overall lower LLD severity and item-level symptom burden in the Midwest versus Northeast, higher LLD severity and item-level burden were observed among minorities, especially Black and Hispanic adults, compared to non-Hispanic whites in this region. Racial/ethnic disparities in item-level symptoms (e.g., anhedonia, sadness, psychomotor changes) varied by region. There were no significant differences in depression care by region; furthermore, regional variation was not observed in racial disparities in care: e.g., among those with clinician/physician-diagnosed depression, Blacks versus non-Hispanic whites had greater than 50% lower odds of treatment in all regions. LLD varied by geographic region. Furthermore, magnitudes of racial/ethnic disparities in LLD severity and item-level symptom burden, but not depression care, differed by region.


Unusual presentation of brucellosis in a child: acute blindness.
In brucellosis, visual impairment due to optic nerve involvement is rare, and acute onset visual loss is an unusual presenting feature. We report a 15-y-old girl who had pancytopenia and who was admitted to our hospital with acute onset of bilateral blindness and fever. There was no light perception, and anterior segment and fundus examination were normal in both eyes. No other abnormal neurological findings were detected. Increased latencies and decreased amplitudes were found in visual evoked potentials. Cranial MR and CT revealed no abnormality. Blood culture was found to be positive for Brucella melitensis. Anti-Brucella treatment and high-dose metil prednisolon were given. Pancytopenia completely resolved 5 d after anti-Brucella treatment, and at the end of the third month her complaints about impaired vision were resolved. Brucellosis may present with uncommon symptoms in children. Physicians, particularly in areas where the disease is endemic, must consider this in differential diagnosis of a child with acute blindness and pancytopenia.


Gastrointestinal absorption of hydrochlorothiazide enhanced by concomitant intake of food.
Hydrochlorothiazide (hct) 75 mg was administered orally to eight healthy volunteers without (Study I) or together with a standaridized meal (Study II), and plasma and urine concentrations of hct were analyzed by GLC. The plasma levels of hct were higher initially when the tablets were taken on an empty stomach, but after 5 h they were higher in Study II. There was no difference between the two studies in the area under plasma concentration time curves. The urinary recovery of hct totalled 55.6 +/- 4.9 mg when the drug was given with food and 47.4 +/- 6.0 when it was taken on an empty stomach. The difference is significant (p less than 0.01). As the urinary recovery represents the uptake of hct, it appears that the gastrointestinal absorption of hct is enhanced when the drug is given with food.


[Relative abrasion of toothpastes--a toothpaste for everyone].
Since our last publication in this Journal in February 1988, many new dentifrices have appeared on the market, prompting us to revise our scale of relative abrasion for the most current ones. This relative abrasion scale is determined by weight loss of mechanically brushed specimens (methyl methacrylate) with a slurry from each dentifrice.


Timed Up and Go Test: A Reliable and Valid Test in Patients With Chronic Heart Failure.
The timed up and go test (TUGT) is a short-duration functional test frequently used in rehabilitation settings as a measure of balance and mobility. Reliability and validity for patients with chronic heart failure (CHF) has yet to be determined. This prospective cohort study aimed to determine test-retest reliability of the TUGT in patients with CHF, relationships between the TUGT and other variables, including functional tests, and predictors of the TUGT. This was a secondary analysis of data collected in a multicenter randomized controlled trial of exercise training in recently hospitalized patients with heart failure (EJECTION-HF). The TUGT was conducted twice at baseline to determine reliability. Assessments were compared with 6-minute walk distance (6MWD), 10-m walk test time, and other clinical variables. Intraclass correlation coefficient (ICC) was used to determine test-retest reliability and correlations for relationships with other variables. A multiple regression was used to identify predictors of the TUGT. In 278 participants (mean age 62 years), the TUGT demonstrated excellent within-day test-retest reliability (ICC 0.93). A shorter (better) TUGT time was associated with longer 6MWD (r = -0.81; P < .001) and shorter 10-m walk test time (rs = 0.80; P < .001). Best predictors of the TUGT were 6MWD and age, which accounted for 66% of the variance. The TUGT appears to be a reliable and valid functional measurement in patients with CHF.


Short-term antihypertensive therapy lowers the C-reactive protein level.
There is a growing body of data concerning significant interactions between markers of inflammation and cardiovascular diseases such as hypertension accompanied by elevated levels of plasma C-reactive protein (CRP). Therefore CRP is thought to be an independent risk factor of cardiovascular diseases. The aim of this study was to evaluate the effects of antihypertensive therapy (perindopril, bisoprolol and combined therapy) on plasma CRP concentration in 67 subjects with mild or moderate hypertension who have been treatment-naive and otherwise healthy. The results show a correlation between CRP level and blood pressure values. BP reduction was associated with a decrease in CRP concentration. The CRP-lowering effect of perindopril and bisoprolol was comparable and the degree of reduction might reflect their similar influence on blood pressure. Combined treatment influenced the CRP level to a greater extent than both monotherapies. Plasma CRP level was lowered by antihypertensive therapy independently of the drug applied. The CRP level did not normalize completely in moderate hypertensive patients.


Binding of cytochalasin B to platelets.
The binding of cytochalasin B (CB) to human platelets and to isolated platelet cytosol and membranes has been analyzed with [3H]CB. High- and low affinity classes of saturable binding sites were associated with intact platelets. Binding at very low concentrations of CB (i.e., high-affinity binding) was partially prevented by 100 mM D-galactose or D-glucose and to a much lesser extent by L-glucose. Binding to platelet cytosol also involved two classes of sites with affinities and capacities similar to those observed with the whole cells. None of this binding, however, was affected by 100 mM D-galactose. Saturable binding to platelet membranes occurred at sites with a uniform binding affinity. Approximately 52% of this binding was prevented by 1 M D-galactose and another 15% by cytochalasin E (CE). We hypothesize that binding in the cytosol is to monomeric (low-affinity) and polymerized (high-affinity) actin, whereas membrane binding (high-affinity only) occurs primarily at sites involved with galactose transport.


Formaldehyde emission monitoring from a variety of solid wood, plywood, blockboard and flooring products manufactured for building and furnishing materials.
The measurements of formaldehyde emission (FE) from solid wood, plywood, flooring and blockboard used for building and furnishing materials were obtained using the European small-scale chamber (EN 717-1) and gas analysis (EN 717-2) methods to identify the major sources of formaldehyde among construction and wood products in the Czech Republic. The differences in the FE values reported for various wood products were a function of their structural differences. These results showed that the wood species, plywood type and thickness significantly affected the FE measured by EN 717-2 (P<0.001). The FE values from solid wood ranged between 0.0068 and 0.0036ppm and 0.084-0.014mg/m(2)h. The initial FE ranged from 0.006mg/m(3) for engineered flooring with polyvinyl acetate (PVAc) to 0.048mg/m(3) for painted birch blockboard. Furthermore, the FE dropped noticeably by the end of the measuring period, ranging between 0.006mg/m(3) for engineered flooring with PVAc and 0.037mg/m(3) for painted beech blockboard. Additionally, the initial FE was higher for the painted blockboard (0.035-0.048mg/m(3)) than for the uncoated boards (0.022-0.032mg/m(3)). In the first week after manufacturing, the FE was high, but the decrease in FE was noticeable at the two-week measurement for all of the materials, especially for the painted blockboards.


Retinal ganglion cell response to axotomy and nerve growth factor in the regenerating visual system of the newt (Notophthalmus viridescens): an ultrastructural morphometric analysis.
Nerve growth factor (NGF) treatment, given as a single 200 BU intraocular injection at the time of optic nerve transection, was found to significantly accelerate the retinal ganglion cell response to axotomy in the newt (Notophthalmus viridescens). In the control series the per cent of neurons in the retinal ganglion layer demonstrating nuclear reactivity (i.e. chromatin changes) reaches a peak by 14 days post axotomy (14 DPA), plateaus through 21 DPA and falls thereafter, returning to control levels by 90 DPA. NGF treatment is shown to significantly accelerate the entrance of responding retinal ganglion cells into the reactive nuclear phase between 1 and 7 DPA, and by 7 DPA nuclear reactivity has reached a peak, in contrast to 14 DPA for control values. Consequently, NGF treatment causes retinal ganglion cells to be in the nuclear reactive state a week longer than controls but reactivity diminishes after 21 DPA as in controls. Electron microscopic morphometric analysis further substantiates these observations by demonstrating that NGF treatment can elicit certain cellular organelle changes a week earlier (i.e. at 7 DPA) than they would normally occur (i.e. at 14 DPA) in response to axotomy. In addition to eliciting cellular hypertrophy at 7 DPA, NGF treatment significantly increases Golgi field densities in the neuronal perikaryal cytoplasm as well as a doubling of the number of nucleoli per nucleus and stimulating a significant increase in nucleolar cross-sectional areas. A dose-response relationship exists between the per cent of retinal ganglion cells demonstrating nuclear reactivity at 7 DPA and various NGF concentrations which compares favorably with the dose response study involving the number of regenerating axons per nerve cross-section at 14 DPA. Studies to determine if the NGF mediated responses were a specific effect elicited by this protein molecule or whether they are also produced by other peptides which share some properties in common with NGF demonstrate that only NGF is capable of eliciting these responses.


Collapsin response mediator protein-4 regulates F-actin bundling.
Collapsin response mediator proteins (CRMPs) form a family of cytosolic phosphoproteins which are involved in the signal transduction of semaphorin 3A leading to growth cone collapse. These proteins interact with a variety of cytosolic proteins including tubulin heterodimers. Here, we show that CRMP-4 co-localizes with F-actin in regular rib-like structures within lamellipodia of B35 neuroblastoma cells. Furthermore, depolymerization of actin fibers changed the distribution of GFP-CRMP-4 in vivo. In vitro, recombinant CRMP-4 formed homo-oligomers, bound to F-actin and organized F-actin into tight bundles. Both oligomerization and F-actin bundling depended on the C-terminal part of CRMP-4. The stoichiometry of actin and CRMP-4 in bundles was approximately 1:1 and the apparent equilibrium constant of the microfilament-CRMP-4 interaction was estimated from bundling assays as K(app) = 730 mM(-1). CRMP-4 was abundant in the cytosol of B35 neuroblastoma cells and its concentration was measured as approximately 1.7 microM. Overexpression of CRMP-4 inhibited the migration of B35 neuroblastoma cells, while knockdown of CRMP-4 enhanced cell migration and disturbed rib-like actin-structures in lamellipodia. Taken together, our data indicate that CRMP-4 promotes bundling of F-actin in vitro, that it is an important component of rib-like actin bundles in lamellipodia in vivo and that it functionally regulates the actin cytoskeleton in motile cells. These findings suggest a specific regulatory role of CRMP-4 towards the actin cytoskeleton which may by be relevant for growth cone collapse.


Plasma neurofilament light chain level is not a biomarker of Charcot-Marie-Tooth disease progression: Results of 3-year follow-up study.
Charcot-Marie-Tooth disease (CMT) is a hereditary, slowly progressive neuropathy. Currently, there are no effective pharmacological treatments or sensitive disease activity biomarkers available. The aim of this study was to demonstrate the change in plasma neurofilament light chain (NfL) over time in a CMT cohort and analyse the association between CMT severity and NfL level. Initially, 101 CMT patients and 64 controls were enrolled in the study. Repeated evaluation was performed in 73 patients and 28 controls at a 3-year interval. Disease severity assessment included clinical evaluation with CMT Neuropathy Score version 2 (CMTNSv2). Plasma NfL concentration was measured using the Simoa (single molecule array) NfL assay. Plasma NfL concentration was increased in the CMT group compared with controls (p < 0.001). Overall NfL level increased over the 3-year interval in both CMT (p = 0.012) and control (p = 0.001) groups. However, in 22 of 73 CMT patients and seven of 28 controls, the NfL level decreased from the baseline. Analysing the association between 3-year change in plasma NfL and disease severity (CMTNSv2), there was no correlation in the CMT group (r = 0.228, p = 0.052) or different CMT subgroups. Our study verifies increased plasma NfL concentrations in patients with CMT compared with controls. Longitudinal 3-year data showed a variable change in NfL levels between CMT subtypes. There was no association between change in NfL over time and disease severity. These findings suggests that NfL is not a biomarker for CMT progression.


Transoral laser microsurgery for the unknown primary: role for lingual tonsillectomy.
We conducted a retrospective review of patients with unknown primary head and neck cancer who underwent a transoral laser microsurgery (TLM)-assisted search for an occult tumor. Fifty-two patients at a single center with unknown primaries of squamous cell carcinoma (SCC) were treated with a surgical algorithm. The overall rate of primary tumor identification was 75% (39 of 52 patients). When selecting those cases in which a TLM algorithm with lingual tonsillectomy was utilized, the detection rate was 86% (31 of 36). Tumors were most commonly found in the lingual (65.0%) and palatine tonsils (27.5%). When directed biopsies did not locate a tumor, a higher yield was obtained with the addition of a lingual tonsillectomy in 8 patients. A surgical algorithm for the unknown primary that includes TLM-assisted techniques, including a lingual tonsillectomy, offers the greatest likelihood of successfully detecting the location of occult primary tumors.


Glucocorticoid receptor cleavage by leupeptin-sensitive enzymes in rat kidney cytosol.
The proteolytic origin of small fragments of both the glucocorticoid and mineralocorticoid receptors in rat kidney cytosol was inferred from the effects of leupeptin, a bacterial tripeptide that inhibits many proteases [Sherman, M.R. et al., (1978). Federation Proc. 37:167--173]. In the present study, the smallest fragment of the glucocorticoid receptor containing the steroid-binding site, the mero-receptor, was characterized with respect to the Stokes radius (RS = 23 +/- 3 A) and the isoelectric point (pI = 5.9 at 4 degrees). Chromatography of cytosol labeled with [3H]triamcinolone acetonide on Sephadex LH-20 (Pharmacia) in aqueous buffer resolved the steroid-receptor complex from the unmodified free steroid and from steroid metabolites and contaminants. This technique facilitated analyses of the leupeptin-stabilized receptor form by isoelectric focusing (pU = 5.9 at 4 degrees) and centrifugation in glycerol gradients (s20,w = 9--11 S in 50mM KCl). When this large complex in fresh cytosol was analyzed on Agarose (Bio-Rad) at a high flow rate, it had RS congruent to 60 A in 50 mM KCl and RS congruent to 30 A in 400 mM KCl. These analytical studies with leupeptin indicate the need for inexpensive, irreversible inhibitors of proteolytic enzymes for the purification of intact receptors, holo-receptors, from kidney and other tissues. Specific proteases can then be applied to dissect the holo-receptor into the globular mero-receptor, proximal to the steroid-binding site, and the asymmetric region(s), distal segment(s), that may be involved in the nuclear interactions.


Introduction of calcium chelators into isolated rat pancreatic acini inhibits amylase release in response to carbamylcholine.
The Ca2+ chelators, EGTA and BAPTA, have been introduced into intact, isolated rat pancreatic acini using a hypotonic swelling method. This resulted in complete inhibition of amylase release, stimulated by carbamylcholine at a submaximal concentration and 82 - 85% inhibition at maximal concentrations. Acini swollen in the absence of Ca2+ chelators showed similar secretory responses to those of unswollen acini. Treatment of unswollen acini with chelators inhibited the maximum response to carbamylcholine by only 23%. The inhibitory effect of intracellular chelators was not due to ATP depletion or a lowering of the total cell Ca2+ content. Thus, these results provide the first direct demonstration that an increase in intracellular Ca2+ concentration is necessary for the stimulation of enzyme release from pancreatic acinar cells.


[Validity and limits of invasive pharmacological tests in the treatment of malignant ventricular hyperkinetic arrhythmias].
Programmed stimulation can now be safely performed for the evaluation of therapy for recurrent ventricular tachyarrhythmia. The initiation of ventricular tachycardia appears closely related to its actual spontaneous clinical occurrence. Serial electrophysiologic studies can be performed and are effective in prospectively evaluating the response to antiarrhythmic drugs. The efficacy of therapy based on the results of programmed stimulation appears to be good. On the other hand, Amiodarone can be effective in the chronic treatment as well as in patients with ineffective acute drug test.


Prehabilitation: high-quality evidence is still required.
Prehabilitation comprises multidisciplinary healthcare interventions, including exercise, nutritional optimisation, and psychological preparation, which aim to dampen the metabolic response to surgery, shorten the period of recovery, reduce complications, and improve the quality of recovery and quality of life. This editorial evaluates the potential benefits and limitations of and barriers to prehabilitation in surgical patients. The results of several randomised clinical trials and meta-analyses on prehabilitation show differing results, and the strength of the evidence is relatively weak. Heterogeneity in patient populations, interventions, and outcome measures, with a wide range for compliance, contribute to this variation. Evidence could be strengthened by the conduct of large-scale, appropriately powered multicentre trials that have unequivocal clinically relevant and patient-centric endpoints. Studies on prehabilitation should concentrate on recruiting patients who are frail and at high risk. Interventions should be multimodal and exercise regimens should be tailored to each patient's ability with longitudinal measurements of impact.


Crowd-out of defence and health spending: is Israel different from other industrialised nations?
Does high defence spending limit the growth of public health investment? Using comparative data from 31 OECD countries between 1980 and 2010, we find little evidence that defence crowds out public health spending. Whether measured in terms of long-term levels or short-term changes, per capita defence and health spending positively and significantly correlate. To investigate the possibility that countries with high security needs such as Israel exhibit differing patterns, we also compare crowd-out among countries experiencing violent conflicts as well as current high military-spending countries. We observed a greater positive correlation between changes in health and defence spending among conflict-countries (r = 0.65, p < 0.01) than in non-conflict countries (r = 0.12, p = 0.01). However, similar to other high-military spending countries, Israel's politicians reduced defence spending while increasing health expenditure during its recent recession. These analyses reveal that while Israel's politicians have chronically underinvested in public health, there are modest steps being taken to rectify the country's unique and avoidable crowding out of public health from its high military spending.


Anisomycin inhibits Coxsackievirus B replication by promoting the lysosomal degradation of eEF1A1.
Group B Coxsackieviruses (CVB) are non-enveloped small RNA viruses in the genus Enterovirus, family Picornaviridae. CVB infection causes diverse conditions from common cold to myocarditis, encephalitis, and pancreatitis. No specific antiviral is available for the treatment of CVB infection. Anisomycin, a pyrrolidine-containing antibiotic and translation inhibitor, was reported to inhibit the replication of some picornaviruses. However, it is unknown if anisomycin can act as an antiviral against CVB infection. Here we observed that anisomycin showed potent inhibition on CVB type 3 (CVB3) infection with negligible cytotoxicity when applied at the early stage of virus infection. Mice infected with CVB3 showed markedly alleviated myocarditis with reduced viral replication. We found that CVB3 infection significantly increased the transcription of eukaryotic translation elongation factor 1 alpha 1 (eEF1A1). CVB3 replication was suppressed by EEF1A1 knockdown, while elevated by EEF1A1 overexpression. Similar to the effect of CVB3 infection, EEF1A1 transcription was increased in response to anisomycin treatment. However, eEF1A1 protein level was decreased with anisomycin treatment in a dose-dependent manner in CVB3-infected cells. Moreover, anisomycin promoted eEF1A1 degradation, which was inhibited by the treatment of chloroquine but not MG132. We demonstrated that eEF1A1 interacted with the heat shock cognate protein 70 (HSP70), and eEF1A1 degradation was inhibited by LAMP2A knockdown, implicating that eEF1A1 is degraded through chaperone-mediated autophagy. Taken together, we demonstrated that anisomycin, which inhibits CVB replication through promoting the lysosomal degradation of eEF1A1, could be a potential antiviral candidate for the treatment of CVB infection.


Moderate exercise improves gait stability in disabled elders.
Decreased muscle strength impedes elders' functional performance in daily activities such as gait. The mechanisms whereby increased strength improves gait are unknown. A prospective, blinded, randomized trial of moderate intensity strength exercise was conducted and its impact was measured on functional mobility during gait in 132 functionally limited elders. Lower extremity strength was measured, including hip abductor, hip extensor, and knee extensor strength. Of the 132 subjects, 120 subjects (mean age, 75.1 yrs) completed 6 months of elastic band resistance training at least 3 times a week or served as no-exercise controls. Subjects increased their lower extremity strength in the exercise and control groups, by 17.6% and 7.3% (p < .01), respectively. Gait stability improved significantly more in the exercise group than in the control group (p < .05). Increases in forward gait velocity were not significantly different between groups. Peak mediolateral velocity and base of support improved in the exercise group, but not in the control group. Change in lower extremity strength correlated significantly but weakly with many of the gait variables. Gait stability, especially mediolateral steadiness, improved in the exercise group but not in the control group. These results show that even moderate strength gains benefit gait performance in elders and thus provide a sound basis for encouraging low-intensity strength training for elders with functional limitations.


Epilepsy and metaphors in literature.
This topic has two different aspects: seizures and epilepsy used as metaphors and seizures described in metaphors. Whereas some metaphors are unique and have high literary value, others can be categorized in prototypical groups. These include sexual metaphors; metaphors of strong emotions, of life crises and breakdown, and also of exultation; religious metaphors; and metaphors of weakness which mostly belong to older literature. Writers with epilepsy, in their literary texts, rarely talk about seizures in metaphors. Authors who do this sometimes seem to use reports that they have received from afflicted persons. The most common metaphors for seizures belong to the realms of dreams and of strong sensory impressions (visual, auditory). More rarely, storm and whirlwind are used as literary metaphors for seizures. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity".


Spread of extended-spectrum beta-lactamase-producing Escherichia coli from a swine farm to the receiving river.
The dissemination of drug-resistant bacteria into different environments has posed a grave threat to public health, but data on the spread of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) from animal farms to the receiving river are limited. Here, 57 ESBL-producing E. coli isolated from a pig farm and the receiving river were analyzed in terms of drug resistance, ESBL genes, and enterobacterial repetitive intergenic consensus (ERIC). The results showed that ESBL-producing E. coli from swine feces and downstream water of the pig farm outfall overlapped substantially in drug resistance and ESBL genes. Additionally, six ESBL-producing E. coli from the downstream water exhibited 100 % genetic similarity with strains from the swine feces. In conclusion, effluents of animal farms are a likely contributor to the presence of ESBL-producing E. coli in aquatic environments.


S-nitrosylation of the thioredoxin-like domains of protein disulfide isomerase and its role in neurodegenerative conditions.
Correct protein folding and inhibition of protein aggregation is facilitated by a cellular "quality control system" that engages a network of protein interactions including molecular chaperones and the ubiquitin proteasome system. Key chaperones involved in these regulatory mechanisms are the protein disulfide isomerases (PDI) and their homologs, predominantly expressed in the endoplasmic reticulum of most tissues. Redox changes that disrupt ER homeostasis can lead to modification of these enzymes or chaperones with the loss of their proposed neuroprotective role resulting in an increase in protein misfolding. Misfolded protein aggregates have been observed in several disease states and are considered to play a pivotal role in the pathogenesis of neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral sclerosis. This review will focus on the importance of the thioredoxin-like CGHC active site of PDI and how our understanding of this structural motif will play a key role in unraveling the pathogenic mechanisms that underpin these neurodegenerative conditions.


Enhancing central nervous system remyelination in multiple sclerosis.
Recent studies on adult neural stem cells and the developmental biology of myelination have generated the expectation that neural precursors can repair the damaged central nervous system of multiple sclerosis patients where the endogenous remyelination process has failed. As a result, many laboratories are engaged in translational studies in which the goal is to design ways to promote remyelination and repair. Here we raise issues highlighted by prior experimental and human work that should be considered lest these studies become "lost in translation."


CTCF in parvalbumin-expressing neurons regulates motor, anxiety and social behavior and neuronal identity.
CCCTC-binding factor (CTCF) is a regulator of chromatin organization and has direct effects on gene transcription. Mutations in CTCF have been identified in individuals with neurodevelopmental conditions. There are wide range of behaviors associated with these mutations, including intellectual disabilities, changes in temperament, and autism. Previous mice-model studies have identified roles for CTCF in excitatory neurons in specific behaviors, particularly in regards to learning and memory. However, the role of CTCF in inhibitory neurons is less well defined. In the current study, specific knockout of CTCF in parvalbumin-expressing neurons, a subset of inhibitory neurons, induced a specific behavioral phenotype, including locomotor abnormalities, anxiolytic behavior, and a decrease in social behavior. The anxiolytic and social abnormalities are detected before the onset of locomotor abnormalities. Immunohistochemical analysis revealed a disbalance in parvalbumin-expressing and somatostatin-expressing cells in these mice. Single nuclei RNA sequencing identified changes in gene expression in parvalbumin-expressing neurons that are specific to inhibitory neuronal identity and function. Electrophysiology analysis revealed an enhanced inhibitory tone in the hippocampal pyramidal neurons in knockout mice. These findings indicate that CTCF in parvalbumin-expressing neurons has a significant role in the overall phenotype of CTCF-associated neurodevelopmental deficits.


Influence of superstition on the date of hospital discharge and medical cost in Japan: retrospective and descriptive study.
To determine the influence of superstition about Taian (a lucky day)-Butsumetsu (an unlucky day) on decision to leave hospital. To estimate the costs of the effect of this superstition. Retrospective and descriptive study. University hospital in Kyoto, Japan. Patients who were discharged alive from Kyoto University Hospital from 1 April 1992 to 31 March 1995. Mean number, age, and hospital stay of patients discharged on each day of six day cycle. The mean number, age, and hospital stay of discharged patients were highest on Taian and lowest on Butsumetsu (25.8 v 19.3 patients/day, P=0.0001; 43.9 v 41.4 years, P=0.0001; and 43.1 v 33.3 days, P=0.0001 respectively). The effect of this difference on the hospital's costs was estimated to be 7.4 million yen (¿31 000). The superstition influenced the decision to leave hospital, contributing to higher medical care costs in Japan. Although hospital stays need to be kept as short as possible to minimise costs, doctors should not ignore the possible psychological effects on patients' health caused by dismissing the superstition.


Cell line models for drug discovery in PIK3CA-mutated colorectal cancers.
Colorectal cancer remains a major cause of cancer-related morbidity and mortality. Metastatic disease is still incurable in most cases. New therapies based on a better understanding of the pathogenesis are needed to improve outcomes. Mutations in the catalytic sub-unit of kinase PI3K encoded by gene PIK3CA are common in colorectal cancer cell lines and patient samples. The characteristics of colorectal cancer cell lines from the Cancer Cell Line Encyclopedia (CCLE), with and without PIK3CA mutations, were evaluated and compared. A panel of colorectal cancer cell lines with and without PIK3CA mutations were compared for their sensitivity to PIK3 inhibitors. Concomitant molecular abnormalities of sensitive versus resistant cell lines were identified. Colorectal cancer cell lines with PIK3CA mutations are commonly diploid and have microsatellite instability (MSI) and a high tumor mutation burden (TMB), compared with cell lines without PIK3CA mutations. Cell lines with PIK3CA mutations tend to have higher sensitivity to some but not all PI3K inhibitors tested and display variability in sensitivity. Both cell lines with MSI and microsatellite stable (MSS) are among the most sensitive to PI3K inhibitors. Multiple concomitant mutations in the PI3K/AKT and KRAS/BRAF/MEK/ERK pathways are often observed in sensitive cell lines. In concordance with patient samples, colorectal cancer cell lines with PIK3CA mutations display more commonly MSI and tend to be more sensitive to PI3K inhibitors. Variability in sensitivity of PIK3CA-mutated cell lines suggests that additional molecular abnormalities contribute to sensitivity.


A social network analysis model approach to understand tuberculosis transmission in remote rural Madagascar.
Quality surveillance data used to build tuberculosis (TB) transmission models are frequently unavailable and may overlook community intrinsic dynamics that impact TB transmission. Social network analysis (SNA) generates data on hyperlocal social-demographic structures that contribute to disease transmission. We collected social contact data in five villages and built SNA-informed village-specific stochastic TB transmission models in remote Madagascar. A name-generator approach was used to elicit individual contact networks. Recruitment included confirmed TB patients, followed by snowball sampling of named contacts. Egocentric network data were aggregated into village-level networks. Network- and individual-level characteristics determining contact formation and structure were identified by fitting an exponential random graph model (ERGM), which formed the basis of the contact structure and model dynamics. Models were calibrated and used to evaluate WHO-recommended interventions and community resiliency to foreign TB introduction. Inter- and intra-village SNA showed variable degrees of interconnectivity, with transitivity (individual clustering) values of 0.16, 0.29, and 0.43. Active case finding and treatment yielded 67%-79% reduction in active TB disease prevalence and a 75% reduction in TB mortality in all village networks. Following hypothetical TB elimination and without specific interventions, networks A and B showed resilience to both active and latent TB reintroduction, while Network C, the village network with the highest transitivity, lacked resiliency to reintroduction and generated a TB prevalence of 2% and a TB mortality rate of 7.3% after introduction of one new contagious infection post hypothetical elimination. In remote Madagascar, SNA-informed models suggest that WHO-recommended interventions reduce TB disease (active TB) prevalence and mortality while TB infection (latent TB) burden remains high. Communities' resiliency to TB introduction decreases as their interconnectivity increases. "Top down" population level TB models would most likely miss this difference between small communities. SNA bridges large-scale population-based and hyper focused community-level TB modeling.


Perceived Stress and Mild Cognitive Impairment among 32,715 Community-Dwelling Older Adults across Six Low- and Middle-Income Countries.
Perceived stress may be a modifiable risk factor for mild cognitive impairment (MCI) and ultimately dementia, but studies on this topic from low- and middle-income countries (LMICs) are lacking. We assessed the association between perceived stress and MCI in six LMICs (China, Ghana, India, Mexico, Russia, and South Africa) using nationally representative data. Cross-sectional, community-based data on individuals aged ≥50 years from the World Health Organization's Study on Global Ageing and Adult Health were analyzed. The definition of MCI was based on the National Institute on Ageing-Alzheimer's Association criteria. A perceived stress score (range 0 [lowest stress] to 10 [highest stress]) was computed based on two questions from the Perceived Stress Scale. Multivariable logistic regression analysis was conducted to assess the as-sociation between perceived stress and MCI. The mean (SD) age of the 32,715 participants was 62.1 (15.6) years and 51.7% were females. After adjustment for potential confounders including depression, in the overall sample, a one-unit increase in the perceived stress score was associated with a 1.14 (95% CI = 1.11-1.18) times higher odds for MCI. The association was similar among those aged 50-64 and ≥65 years. Countrywise analysis showed that there was a moderate level of between-country heterogeneity in this association (I2 = 59.4%), with the strongest association observed in Russia (OR = 1.33, 95% CI = 1.15-1.55). If our study results are confirmed in prospective studies, addressing perceived stress may have an impact in reducing the risk for MCI and subsequent dementia in LMICs.


Examining Land Use Changes to Evaluate the Effects of Land Management in a Complex, Dynamic Landscape.
Anthropogenic alterations to landscapes have increased as the human population continues to rise, leading to detrimental changes in natural habitats. Ecological restoration assists in recovery by altering habitats to improve conditions and foster biodiversity. We examined land cover changes over time within a complex, dynamic region in the Midwest to assess the long-term effects of conservation. We used Landsat 8 bands for a 15-class land cover map of Oak Openings Region using supervised classification. We validated our map and achieved an overall accuracy of 71.2% from correctly classified points out of total visited points. Change over 10 years, from 2006 to 2016, was explored by comparing class statistics from FRAGSTATS between our map and original land cover map. We found that natural land, i.e., forest and early successional, covered 33%, with 10% permanently protected, while human-modified land, i.e., agricultural and developed, covered 67% of the region. Over 10 years, natural classes increased, and cultural classes decreased by 5.8%. There were decreases for the three forest communities and increases for the two early successional communities. These changes are likely the result of natural recovery and disturbance, and conservation efforts by the Green Ribbon Initiative. Changes in habitat also came with distribution changes, e.g., increased fragmentation for some classes, which was readily visible. Our useful method measured functionality by emphasizing changes in composition and configuration. Our approach provides a tool for assessing cumulative regional-scale effects from site-level management and conservation. This large-scale view for conservation is needed to effectively mitigate future changes.


Characteristics of patients with brain metastases from human epidermal growth factor receptor 2-positive breast cancer: subanalysis of Brain Metastases in Breast Cancer Registry.
Up to 40% of patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer develop brain metastases (BMs). Understanding of clinical features of these patients with HER2-positive breast cancer and BMs is vital. A total of 2948 patients from the Brain Metastases in Breast Cancer registry were available for this analysis, of whom 1311 had primary tumors with the HER2-positive subtype. Patients with HER2-positive breast cancer and BMs were-when compared with HER2-negative patients-slightly younger at the time of breast cancer and BM diagnosis, had a higher pathologic complete response rate after neoadjuvant chemotherapy and a higher tumor grade. Furthermore, extracranial metastases at the time of BM diagnosis were less common in HER2-positive patients, when compared with HER2-negative patients. HER2-positive patients had more often BMs in the posterior fossa, but less commonly leptomeningeal metastases. The median overall survival (OS) in all HER2-positive patients was 13.2 months (95% confidence interval 11.4-14.4). The following factors were associated with shorter OS (multivariate analysis): older age at BM diagnosis [≥60 versus <60 years: hazard ratio (HR) 1.63, P < 0.001], lower Eastern Cooperative Oncology Group status (2-4 versus 0-1: HR 1.59, P < 0.001), higher number of BMs (2-3 versus 1: HR 1.30, P = 0.082; ≥4 versus 1: HR 1.51, P = 0.004; global P = 0.015), BMs in the fossa anterior (HR 1.71, P < 0.001), leptomeningeal metastases (HR 1.63, P = 0.012), symptomatic BMs at diagnosis (HR 1.35, P = 0.033) and extracranial metastases at diagnosis of BMs (HR 1.43, P = 0.020). The application of targeted therapy after the BM diagnosis (HR 0.62, P < 0.001) was associated with longer OS. HER2-positive/hormone receptor-positive patients showed longer OS than HER2-positive/hormone receptor-negative patients (median 14.3 versus 10.9 months; HR 0.86, P = 0.03), but no differences in progression-free survival were seen between both groups. We identified factors associated with the prognosis of HER2-positive patients with BMs. Further research is needed to understand the factors determining the longer survival of HER2-positive/hormone receptor-positive patients.


Genotyping and plant-derived glycan utilization analysis of Bifidobacterium strains from mother-infant pairs.
Bifidobacteria are important probiotics; some of the beneficial effects of bifidobacteria are achieved by the hydrolysis of glycans in the human gut. However, because the diet of breastfed infants typically lacks plant-derived glycans, in the gut environment of mothers and their breastfed infants, the mother will intake a variety of plant-derived glycans, such as from onions and bananas, through her diet. Under this assumption, we are interested in whether the same species of bifidobacteria isolated from mother-infant pairs present a distinction in their hydrolysis of plant-derived carbohydrates. Among the 36 Bifidobacterium strains, bifidobacterial carbohydrate utilization showed two trends related to the intestinal environment where the bacteria lived. Compared with infant-type bifidobacterial strains, adult-type bifidobacterial strains preferred to use plant-derived glycans. Of these strains, 10 isolates, 2 Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), 2 Bifidobacterium pseudolongum (B. pseudolongum), 2 Bifidobacterium bifidum (B. bifidum), 2 Bifidobacterium breve (B. breve), and 2 Bifidobacterium longum (B. longum), were shared between the mother-infant pairs. Moreover, the repetitive sequence-based polymerase chain reaction (rep-PCR) results illustrated that B. pseudolongum and B. bifidum showed genotypic similarities of 95.3 and 98.2%, respectively. Combined with the carbohydrate fermentation study, these results indicated that the adult-type strains have a stronger ability to use plant-derived glycans than infant-type strains. Our work suggests that bifidobacterial carbohydrate metabolism differences resulted in the selective adaptation to the distinct intestinal environment of an adult or breastfed infant. The present study revealed that the different gut environments can lead to the differences in the polysaccharide utilization in the same strains of bifidobacterial strains, suggesting a further goal of investigating the exact expression of certain enzymes in response to specific carbon sources.


Two fucosylated chondroitin sulfates from the sea cucumber Eupentacta fraudatrix.
Two fucosylated chondroitin sulfates EF1 and EF2 were isolated from the sea cucumber Eupentacta fraudatrix. Separation of the polysaccharides was performed using anion-exchange chromatography on DEAE-Sephacel by elution of 0.75M and 1.0M NaCl solutions. The structures of biopolymers were determined by chemical and NMR spectroscopic methods. The backbone of EF1 was found to be composed of chondroitin sulfate A and E units in a ratio of about 1:1. The core of EF2 along with chondroitin sulfate A and E fragments contained unusual disaccharide repeating units →4)-β-d-GlcpA2S3S-(1→3)-β-d-GalpNAc6S-(1→. The main type of branches in both polysaccharides was α-l-Fucp3S4S unit attached to O-3 of GlcA residues. Another type of branches was found to be the disaccharide fragment α-l-Fucp-(1→2)-α-l-Fucp3S4S-(1→ linked to O-3 of GlcA. The presence of structurally different fucosylated chondroitin sulfates in one species of sea cucumber is rather unusual and has not been described previously.


Infectious Bronchitis Virus California Variant CA1737 Isolated from a Commercial Layer Flock with Cystic Oviducts and Poor External Egg Quality.
False layer syndrome is a condition in which the reproductive tract of chicks is infected with infectious bronchitis virus (IBV) strains that cause permanent damage to the oviduct. These chickens subsequently develop cystic oviducts and do not lay eggs, and affected flocks fail to reach expected egg production peaks. The California Animal Health and Food Safety laboratory, Turlock Branch, received four separate case submissions from a 25-to-28-wk-old commercial ISA Brown layer flock. Birds were submitted for diagnostic evaluation due to suboptimal egg production and vent pecking. Submissions totaled 31 birds and consisted of live layers, recent mortality, and a flat of eggs. No clinical signs were observed in the submitted live birds. The most common gross findings included cystic left oviducts, signs of vent pecking, ovarian regression, and yolk coelomitis. The eggs were abnormally shaped with irregular, white, gritty deposits on the surface of the shell. Microscopically, there was atrophy of the oviducts, glandular hypoplasia, and lymphocytic salpingitis. In addition, lymphoplasmacytic tracheitis was observed, and renal tubules were dilated with multifocal areas of mineralization. IBV was identified by reverse transcription quantitative PCR from cecal tonsil tissue pools and tracheal swab pools. Sequencing of the S1 hypervariable region of IBV and whole-genome IBV sequencing were 97% homologous to the California variant CA1737/04. Definitive proof of the CA1737 strain's causing reproductive abnormalities will require challenge studies with fulfillment of Koch's postulates and evaluation of confounding and risk factors.


Unilateral proptosis.
Unilateral proptosis is not uncommonly encountered by the otolaryngologist. A thorough understanding of the potential causes and the appropriate diagnostic evaluation will ensure a successful outcome.


A Biological Imitation Game.
The digital reconstruction of a slice of rat somatosensory cortex from the Blue Brain Project provides the most complete simulation of a piece of excitable brain matter to date. To place these efforts in context and highlight their strengths and limitations, we introduce a Biological Imitation Game, based on Alan Turing's Imitation Game, that operationalizes the difference between real and simulated brains.


Biochemical Characterization and Substrate Specificity of Autophagin-2 from the Parasite Trypanosoma cruzi.
The genome of the parasite Trypanosoma cruzi encodes two copies of autophagy-related cysteine proteases, Atg4.1 and Atg4.2. T. cruzi autophagin-2 (TcAtg4.2) carries the majority of proteolytic activity and is responsible for processing Atg8 proteins near the carboxyl terminus, exposing a conserved glycine. This enables progression of autophagy and differentiation of the parasite, which is required for successful colonization of humans. The mechanism of substrate hydrolysis by Atg4 was found to be highly conserved among the species as critical mutations in the TcAtg4.2, including mutation of the conserved Gly-244 residue in the hinge region enabling flexibility of the regulatory loop, and deletion of the regulatory loop, completely abolished processing capacity of the mutants. Using the positional scanning-substrate combinatorial library (PS-SCL) we determined that TcAtg4.2 tolerates a broad spectrum of amino acids in the P4 and P3 positions, similar to the human orthologue autophagin-1 (HsAtg4B). In contrast, both human and trypanosome Atg4 orthologues exhibited exclusive preference for aromatic amino acid residues in the P2 position, and for Gly in the P1 position, which is absolutely conserved in the natural Atg8 substrates. Using an extended P2 substrate library, which also included the unnatural amino acid cyclohexylalanine (Cha) derivative of Phe, we generated highly selective tetrapeptide substrates acetyl-Lys-Lys-Cha-Gly-AFC (Ac-KKChaG-AFC) and acetyl-Lys-Thr-Cha-Gly-AFC (Ac-KTChaG-AFC). Althoughthese substrates were cleaved by cathepsins, making them unsuitable for analysis of complex cellular systems, they were recognized exclusively by TcAtg4.2, but not by HsAtg4B nor by the structurally related human proteases SENP1, SENP2, and UCH-L3.


Idiopathic infantile arterial calcification with cardiac, renal and central nervous system involvement.
Idiopathic infantile arterial calcification was diagnosed in a 2 week old infant with failure to thrive associated with neurological, renal and cardiac signs. Therapy with diphosphonate resulted in a complete resolution of vascular calcifications. At the age of 2 years the child is doing well but requires medical treatment for arterial hypertension.


[Histone antibodies: significance in the diagnosis of SLE in comparison to dsDNA antibodies and antibodies to extractable nuclear antigens].
Antibodies to histones of the IgG-class are specific for SLE and can be shown in 23% of the sera. They are not associated with clinical symptoms of SLE, but with dsDNA-antibodies.


Infection prophylaxis in pulmonary surgery: a randomized prospective study.
A prospective randomized study to evaluate the efficacy of antibiotic prophylaxis against postoperative infections was carried out on 120 patients undergoing pulmonary operations. The patients were randomized into two groups of 60 patients each. One group received doxycycline (deoxytetracycline) prophylaxis for five days, and the other received cefuroxime (a second-generation cephalosporin) for one day. The groups were comparable with regard to age, sex, common risk factors, diagnosis, and operative procedures. A reduction in the infection rate was noted in the cefuroxime group (10/60) compared with the doxycycline group (19/60), but the difference was not statistically significant (p = 0.055). In major infections (empyema and pneumonia) there was no difference between the groups (4/60 in the cefuroxime group and 5/60 in the doxycycline group), but a significant (p less than 0.05) reduction was noted in minor infections (6/56 and 14/55, respectively) such as lower respiratory tract infections and prolonged fever. There were no wound infections in the two study groups. There were significantly (p less than 0.05) fewer postoperative fever reactions (axillary temperature greater than 37.5 degrees C) in the cefuroxime group (30/60) compared with the doxycycline group (44/60). Both antibiotics were effective in preventing wound infections, but cefuroxime may also be beneficial in preventing minor respiratory infections. The bactericidal effect of cefuroxime may explain this finding.


[Thermal-temporal patterns and temporal program of development of poikilothermic animals in the light of the data obtained using dimensionless criteria of duration of development (tau(n)/tau(0))].
An attempt was undertaken to generalize and interpret the data on thermal-temporal patterns of development of the poikilothermic animals obtained using relative criteria of development duration.


PKU as a factor in the development of self-esteem.
Self-esteem of ten children with phenylketonuria was compared with that of seven unaffected siblings of children with PKU in a total of 11 families. Ages of the nine girls and eight boys ranged from 8 to 15 years. The study examined several variables that might affect self-esteem. From this study, it appears that PKU status and lowered IQ together contribute to lowered self-concept and that PKU status alone (i.e. with the effects of IQ removed) has a strong tendency to influence self-esteem.


Comparative evaluation of a bioabsorbable collagen membrane and connective tissue graft in the treatment of localized gingival recession: A clinical study.
Gingival recession (GR) can result in root sensitivity, esthetic concern to the patient, and predilection to root caries. The purpose of this randomized clinical study was to evaluate (1) the effect of guided tissue regeneration (GTR) procedure using a bioabsorbable collagen membrane, in comparison to autogenous subepithelial connective tissue graft (SCTG) for root coverage in localized gingival recession defects; and (2) the change in width of keratinized gingiva following these two procedures. A total of 10 cases, showing at least two localized Miller's Class I or Class II gingival recession, participated in this study. In a split mouth design, the pairs of defects were randomly assigned for treatment with either SCTG (SCTG Group) or GTR-based collagen membrane (GTRC Group). Both the grafts were covered with coronally advanced flap. Recession depth (RD), recession width (RW), width of keratinized gingiva (KG), probing depth (PD), relative attachment level (RAL), plaque index (PI), and gingival index (GI) were recorded at baseline, 3 and 6 months postoperatively. Six months following root coverage procedures, the mean root coverage was found to be 84.84% ± 16.81% and 84.0% ± 15.19% in SCTG Group and GTRC Group, respectively. The mean keratinized gingival width increase was 1.50 ± 0.70 mm and 2.30 ± 0.67 mm in the SCTG and GTRC group, respectively, which was not statistically significant. It may be concluded that resorbable collagen membrane can be a reliable alternative to autogenous connective tissue graft in the treatment of gingival recession.


Postoperative improvement in DASH score, clinical findings, and nerve conduction velocity in patients with cubital tunnel syndrome.
We investigated a recovery pattern in subjective and objective measures among 52 patients with cubital tunnel syndrome after anterior subcutaneous transposition of the ulnar nerve. Disabilities of the Arm, Shoulder and Hand (DASH) score (primary outcome), numbness score, grip and pinch strength, Semmes-Weinstein (SW) score, static 2-point discrimination (2PD) score, and motor conduction velocity (MCV) stage were examined preoperatively and 1, 3, 6, 12, and ≥24 months postoperatively. Statistical analyses were conducted to evaluate how each variable improved after surgery. A linear mixed-effects model was used for continuous variables (DASH score, numbness, grip and pinch strength), and a proportional odds model was used for categorical variables (SW and 2PD tests and MCV stages). DASH score significantly improved by 6 months. Significant recovery in numbness and SW test scores occurred at 1 month. Grip and pinch strength, 2PD test scores, and MCV stage improved by 3 months. DASH scores and numbness recovered regardless of age, sex, or disease severity. It was still unclear if both subjective and objective measures improved beyond 1-year postoperatively. These data are helpful for predicting postoperative recovery patterns and tend to be most important for patients prior to surgery.


Chronological difference in walking impairment among Japanese group A xeroderma pigmentosum (XP-A) patients with various combinations of mutation sites.
Almost all Japanese group A xeroderma pigmentosum (XP-A) patients have nonsense and/or nonsense codon-leading mutations in the XP group A (XPA) gene, and develop neurological abnormalities. Walking ability is one of the most important neuromuscular functions of the patients, because it determines their daily activities. We studied the correlation between the various combinations of mutations found by PCR-RFLP in Japanese XP-A patients and their chronological walking impairment. We classified these patients into six groups. Group I: A patient who was homozygous for the mutation at codon 116 in exon 3 (Type 1 mutation) could never walk unaided. Group III: Typical patients who were homozygous for the mutation at intron 3 (Type 2 mutation) could walk unaided till 7-16 years of age. Group V: Patients who were compound heterozygous for Type 2 mutation and for the mutation at codon 228 in exon 6 (Type 3 mutation) began to develop some walking difficulty at 5-13 years of age and became unable to walk at 25-28 years of age. Group VI: A patient who was homozygous for Type 3 mutation could walk unaided without any difficulty till the age of 21. The walking ability of group II and IV patients is not known yet.


Radiologic adjacent segment degeneration 2 years after lumbar fusion for degenerative spondylolisthesis.
Lumbar fusion is now a currently accepted treatment for degenerative lumbar spondylolisthesis (DLSP), but may induce adjacent segment degeneration (ASD). The present study hypothesis was that there are radiological parameters associated with ASD. The study objective was to determine predictive factors of ASD. A single-center retrospective study included patients operated on between 2006 and 2013 for DLSP. Radiological parameters were analyzed on preoperative, immediate postoperative and final follow-up lateral X-ray. ASD was defined by the following adjacent segment criteria:>3mm anteroposterior translation,>10° segmental kyphosis, or>50% loss of disc height. One hundred and seven patients were included: 79% female; mean age, 67±10.2 years. Fusion involved 1 level in 67% of cases and 2 or more in 33%, with transforaminal lumbar interbody fusion (TLIF) in 27% of cases. There was overall significant gain in lumbar lordosis (mean, 3.1°; P=0.04). At a mean 27.8 months' follow-up, 29% of cases showed ASD and 10% required surgical reintervention. Preoperative anterior imbalance and long fusion (>2 levels) were significantly associated with ASD (OR=2.81, 95% CI [1.17-6.74] versus OR=2.76, 95% CI [1.15-6.63]). There were no significant differences according to postoperative radiological parameters, or to TLIF (OR=1.8, 95% CI [0.7-4.4]). Twenty-nine percent of patients developed ASD, with a surgical revision rate of 10%. ASD risk factors comprised high number of instrumented levels and preoperative sagittal imbalance. IV, retrospective cohort.


Comparison of phenolic compounds contained in Aquilaria leaves of different species.
Leaves of Aquilaria plants contain a variety of phenolic compounds such as iriflophenone glycosides, mangiferin, and genkwanin. Previous studies showed that Aquilaria leaf extracts exhibit many pharmacological activities, including antidiabetic and laxative effects. However, a few studies have reported differences in the chemical content and compositions of Aquilaria species. Here, three Aquilaria species were identified using matK and trnL-trnF sequences and their leaves were analyzed by HPLC and LC/MS. Comparison of the chemical components and α-glucosidase inhibition activity of the three species showed that the level of iriflophenone glycosides in A. rugosa was higher than in A. sinensis and A. crassna. There was no difference in the α-glucosidase inhibition activity of leaf extracts of the three species, but the strength of the inhibition activity can possibly be explained by the total sum of active compounds in the leaf extracts.


[A transition zone phenomenon of the skin in cadavers lying in bath water].
In three cases a phenomenon is reported, seen on the skin of bodies found dead after a longer time of lying in bathtubs filled with water. The sign was parallel to the surface of the water and showed a breadth up to about 1 cm. Contrary to the surrounding skin, the mark was characterized by paleness and clearly les distinct formation of postmortem alterations as put-refaction. Searching for an explanation, temperature measurements were performed in model. The results showed the marginal paleness of the skin to be a thermal phase transition phenomenon. This mark has a forensic message too: it demonstrates a longer remaining of the corpse in the corresponding position, is a statement concerning the high of the water level, and allows a reconstruction of the original situation after manipulation, but is no sign of vital reaction.


A bioinformatics approach to the identification of novel deleterious mutations of human TPMT through validated screening and molecular dynamics.
Polymorphisms of Thiopurine S-methyltransferase (TPMT) are known to be associated with leukemia, inflammatory bowel diseases, and more. The objective of the present study was to identify novel deleterious missense SNPs of TPMT through a comprehensive in silico protocol. The initial SNP screening protocol used to identify deleterious SNPs from the pool of all TPMT SNPs in the dbSNP database yielded an accuracy of 83.33% in identifying extremely dangerous variants. Five novel deleterious missense SNPs (W33G, W78R, V89E, W150G, and L182P) of TPMT were identified through the aforementioned screening protocol. These 5 SNPs were then subjected to conservation analysis, interaction analysis, oncogenic and phenotypic analysis, structural analysis, PTM analysis, and molecular dynamics simulations (MDS) analysis to further assess and analyze their deleterious nature. Oncogenic analysis revealed that all five SNPs are oncogenic. MDS analysis revealed that all SNPs are deleterious due to the alterations they cause in the binding energy of the wild-type protein. Plasticity-induced instability caused by most of the mutations as indicated by the MDS results has been hypothesized to be the reason for this alteration. While in vivo or in vitro protocols are more conclusive, they are often more challenging and expensive. Hence, future research endeavors targeted at TPMT polymorphisms and/or their consequences in relevant disease progressions or treatments, through in vitro or in vivo means can give a higher priority to these SNPs rather than considering the massive pool of all SNPs of TPMT.


Gastric versus postpyloric feeding.
Feeding into the small bowel is often recommended to improve nutrient delivery for critically ill patients, and thus improve outcome and reduce complications associated with enteral feeding. Risks and benefits of gastric feeding, use of motility agents, postpyloric feeding, and obtaining small bowel access are discussed here. Randomized clinical trials directly comparing postpyloric with gastric feeds are also evaluated. These small, underpowered studies demonstrate small but clinically important differences in important outcomes (pneumonia), but are weakened by significant heterogeneity. Current evidence does not support routine use of postpyloric feeding in the critically ill. A standardized approach to optimizing benefits and minimizing risks with enteral nutrition delivery will help clinicians identify patients who would benefit from small bowel feeding.


Genetic structure and characteristics of Tibetan chickens.
Tibetan chicken is one of the most common and widely distributed highland breeds, and is often used as a model organism for understanding genetic adaptation to extreme environments in Tibet. Despite its apparent geographical diversity and large variations in plumage patterns, the genetic differences within breed were not accounted for in most studies and have not been systematically investigated. In order to reveal and genetically differentiate the current existing TBC sub-populations that might have major implications for genomic research in TBCs, we systematically evaluated the population structure and demography of current TBC populations. Based on 344 whole-genome sequenced birds including 115 Tibetan chickens that were mostly sampled from family-farms across Tibet, we revealed a clear separation of Tibetan chickens into 4 sub-populations that broadly aligns with their geographical distribution. Moreover, population structure, population size dynamics, and the extent of admixture jointly suggest complex demographic histories of these sub-populations, including possible multiple origins, inbreeding, and introgressions. While most of the candidate selected regions found between the TBC sub-populations and Red Jungle fowls were nonoverlapping, 2 genes RYR2 and CAMK2D were revealed as strong selection candidates in all 4 sub-populations. These 2 previously identified high altitude associated genes indicated that the sub-populations responded to similar selection pressures in an independent but functionally similar fashion. Our results demonstrate robust population structure in Tibetan chickens that will help inform future genetic analyses on chickens and other domestic animals alike in Tibet, recommending thoughtful experimental design.


Current and evolving treatment strategies in adult immune thrombocytopenia.
Immune thrombocytopenia (ITP) is an acquired autoimmune phenomenon resulting in low platelet count and increased bleeding risk. Goals of upfront management include prompt control of severe bleeding-which is rare-as well as induction and maintenance of a hemostatic platelet count. Thus, optimal management of ITP patients is often challenging and requires a highly individualized approach. Many patients may not suffer significant bleeding despite severe thrombocytopenia and the risk of toxicity associated with treatment may outweigh its benefit. Most patients treated with standard first-line regimen of glucocorticoids achieve an initial response. However, the rate of long-term remission remains low and multiple lines of therapy are often required. Current investigations aim at defining the subgroup of patients at risk of relapse and providing intensified risk-balanced induction regimens to improve long-term disease control. This short review summarizes current and emerging treatment strategies in adult ITP.


Deferoxamine reduces and nitric oxide synthase inhibition increases neutrophil-mediated myotube injury.
We tested the contribution of reactive oxygen species (ROS), reactive nitrogen species (RNS) and the beta 2 integrin CD18 to neutrophil-mediated myotube injury. Human myotubes were cultured with human neutrophils in the presence or absence of inhibitors directed against ROS, RNS, and CD18. Muscle injury was assessed by a (51)Cr release assay. The inclusion of superoxide dismutase (50-500 U/ml) in the culture medium did not affect myotube injury. A significant protective effect was provided by including catalase (600-2400 U/ml), deferoxamine (1-2 mM), or anti-CD18 antibody (10 microg/ml) in the culture medium. S-Ethylisothiourea (500-1000 microM), an inhibitor of nitric oxide synthase (NOS), significantly increased myotube injury and reduced nitric oxide (NO) in cultures consisting of only myotubes. In conclusion, neutrophil-mediated skeletal muscle injury appears to be largely dependent on CD18-mediated neutrophil adhesion and iron-dependent hydroxyl radical production. In addition, skeletal muscle NOS activity may protect skeletal muscle against the injury caused by neutrophils.


MRI of silicone vitreous ocular implants with phantom correlation.
We imaged two patients who had silicone oil injected their vitreous cavities. The images demonstrated an increased chemical shift artifact. We developed and tested an in vitro silicone oil model in an attempt to explain this. To our knowledge, this artifact has not been previously described. We constructed a phantom using medication cups containing water, lard and two types of silicone. Background control baths of water and lard were used to simulate different local environments. The phantoms were imaged with T1-and T2-weighted and T1-weighted fat suppression sequences. The artifacts were due to the pronounced chemical shift of silicone in relation to intraconal fat. Our model accurately reproduced our clinical images. Spectral analysis of the silicone model revealed different resonating frequencies for fat/silicone, thereby explaining the pronounced chemical shift artifact.


Dose-response association of polycyclic aromatic hydrocarbon with self-reported trouble sleeping in adults: evidence from the National Health and Nutrition Examination Survey.
Previous epidemiological evidence from large population-based studies on the association between polycyclic aromatic hydrocarbons (PAH) exposure and the risk of sleep disorders is inadequate. To comprehensively examine the relationship between independent and combined PAHs and trouble sleeping, we analyzed data from 8194 participants from the National Health and Nutrition Survey (NHANES) cycles. Multivariate adjusted logistic regression and restricted cubic spline models were applied to assess the relationship between PAH exposure and the risk of trouble sleeping. Bayesian kernel machine regression and weighted quantile sum regression models were used to estimate the combined association of urinary PAHs with trouble sleeping. In the single-exposure analyses, compared with the lowest level, the respective adjusted odds ratios (ORs) for trouble sleeping among subjects from the highest quartile were 1.34 (95% CI, 1.15, 1.56), 1.23 (95% CI, 1.05, 1.44), 1.31 (95% CI, 1.11, 1.54), 1.35 (95% CI, 1.15, 1.58), and 1.29 (95% CI, 1.08, 1.53) for 1-hydroxynaphthalene (1-NAP), 2-hydroxynaphthalene (2-NAP), 3-hydroxyfluorene (3-FLU), 2-hydroxyfluorene(2-FLU), and 1-hydroxypyrene(1-PYR). An overall positive correlation between the PAH mixture and trouble sleeping was observed when the mixture was at the 50th percentile or higher. The current study reveals that PAH metabolites (1-NAP, 2-NAP, 3-FLU, 2-FLU, and 1-PYR) may be detrimental to trouble sleeping. PAH mixture exposure was positively associated with trouble sleeping. The results suggested the potential impacts of PAHs and expressed concerns regarding the potential impact of PAHs on health. More intensive research and monitoring of environmental pollutants in the future will contribute to preventing environmental hazards.


Preparation of PEGylated uricase attached magnetic nanowires and application for uric acid oxidation.
The present study aims to immobilize the uricase enzyme on magnetic nanowires and to examine its potential for use in the treatment of gout. For this, Au/Ni/Au nanowires were synthesized using a polycarbonate membrane template by the sequential electrodeposition of Au, Ni, and Au, respectively. The uricase enzyme was covalently attached to these nanowires and was also coated with PEG. Optimum enzymatic conditions, kinetic parameters, thermal, storage, and operational stability were determined by performing enzymatic activity tests of free and immobilized uricase. Additionally, the efficacy of both enzyme preparations in artificial human serum and the presence of protease was also investigated. Experimental results showed that immobilized uricase showed higher stability than free uricase in all studied conditions. The potential of immobilized uricase to oxidize uric acid in artificial serum was also investigated and it was found that immobilized preparation demonstrated approximately 6 times higher activity than that of the free enzyme. The results of this study showed that uricase-attached nanowires oxidized uric acid effectively and are promising in the treatment of gout.


Sex and age-related differences in chronic rhinosinusitis with nasal polyps electing ESS.
Sex and age of patients are variables affecting across the board all chronic rhinosinusitis with nasal polyps (CRSwNP) endotypes. The main aim of this investigation was to compare the clinical, laboratory, pathological and prognostic characteristics of CRSwNP in male vs female patients stratified according to age (young-adult [20 years ≤ age ≤ 40 years], and elderly [age ≥ 65 years]). This is the first study that analyzed the association of the above-mentioned features with age and sex combination in CRSwNP electing endoscopic sinus surgery (ESS). One hundred and five consecutive young-adult patients (62 males and 43 females) and 67 elderly patients (44 males and 23 females) with CRSwNP who had undergone ESS were enrolled. The recurrence rate resulted associated with the age and sex combination (p = 0.0165). Young-adult males' recurrence rate (29.0%) was higher than young-adult females (11.6%) and elderly males (4.5%). Allergy resulted associated with age and sex combination (p = 0.0158). Young-adult males' allergy rate (50.0%) was higher than elderly males' (29.5%) and elderly females' (13%). Moreover, allergy rate was higher in young-adult females (41.9%) than in elderly females. Our data suggest the possibility of an interaction between sex and age in the recurrence of nasal polyposis after ESS. More studies are needed to understand the role of sex hormones in pathogenesis and prognosis of CRSwNP.


Homogeneous chemiluminescent assays for free choline in human plasma and whole blood.
Choline was oxidized in the presence of choline oxidase and the hydrogen peroxide generated was detected using a chemiluminescent acridinium-9-carboxamide. The dose response for choline (0-150 microM) was established in buffer and was validated for the quantification of choline in human plasma and whole blood. This homogeneous assay was performed in a 96-well microplate format and required minimal sample volume (4 microL) and short analysis time (<5s per well). The new assay(s) correlated well (R>0.98, plasma; R>0.97, whole blood) with LC-MS/MS.


Winning the Microbial Battle, but Not the War.
An effective immune response leads to rapid elimination of infectious agents, with seemingly little long-term impairment to the host. New findings by Morais da Fonseca et al. reveal that acute infections may result in permanent disruption of tissue homeostasis and immune dysfunction, long after clearance of a pathogen.


Society of Family Planning Guidelines: Postplacental insertion of intrauterine devices.
Postplacental intrauterine device (IUD) placement, defined as IUD placement within 10 min after delivery of the placenta, is an appealing strategy for increasing access to postpartum IUDs because it does not require a separate postpartum visit. These guidelines present an evidence-based assessment of postplacental IUD placement after vaginal and cesarean delivery. Postplacental IUD insertion is safe and does not have higher risks of complications than interval insertion. Most studies find that the risk of IUD expulsion is higher after postplacental insertion than after interval insertion for both vaginal and cesarean deliveries. Most studies find higher rates of expulsion after vaginal delivery than after cesarean delivery. However, expulsion rates vary widely across studies, without clear evidence about the factors that may influence expulsion. In settings where replacement of expelled IUDs is available, patient populations with low rates of return for the postpartum visit are most likely to benefit from provision of postplacental IUD placement with appropriate counseling about risks and benefits.


Variant clinical courses in children with immune thrombocytopenic purpura: Sixteen year experience of a single medical center.
Immune thrombocytopenic purpura (ITP) is the most common cause of acquired thrombocytopenia in children. The objective of this study was to evaluate the presenting features, variation in the clinical courses, initial response rate to therapy, and long-term outcome in patients with ITP. Three hundred and fifty out of 491 newly diagnosed patients with ITP between the initial diagnosis ages of 6 months to 16 years were included in this retrospective, descriptive study. Patients with acute vs chronic ITP, acute vs recurrent ITP and chronic vs recurrent ITP were compared in terms of age at diagnosis, gender, initial platelet count, response rate to initial therapy, long-term outcome, and total duration of follow-up. The clinical courses of the patients were determined as acute, chronic and recurrent in 63.8%, 29.1%, and 7.1%, respectively. Platelet count >20x109/L and initial diagnosis age >10 years were found to increase the probability of chronic outcome by at least two-fold. It is concluded that ITP in childhood is a common disease with low morbidity and mortality. In addition to the acute and chronic form, a rare recurrent form, which accounts for about 4-7% of all ITP patients, should be considered.


Comparison of eltanolone and thiopental in anaesthesia for termination of pregnancy.
Eltanolone, a new steroid hypnotic, was compared to thiopental in short anaesthesia. Sixty unpremedicated, Asa 1-2 women were randomized to receive eltanolone 0.6 (group E1) or 0.8 mg.kg-1 (group E2) or thiopental 4 mg.kg-1 (group T) for induction of anaesthesia. One minute before induction glycopyrrolate 0.2 mg and alfentanil 15 micrograms.kg-1 i.v. were administered. If induction failed, additional boluses of the test drug were given. Anaesthesia was maintained with 67% nitrous oxide in oxygen, and additional bolus doses of the test drug were given in a standardized fashion, if needed. Recovery was assessed by a research nurse blinded to the agent used. Mean +/- s.d. induction doss were 0.7 +/- 0.1 mg.kg-1 (group E1), 0.8 +/- 0.1 mg.kg-1 (group E2) and 4.0 +/- 0.0 mg.kg-1 (group T). Induction time was prolonged in the group E1 compared to the other two groups (P < 0.05). Side effects were few in all groups, but involuntary muscle movements or hypertonus occurred in 23% of the patients in the eltanolone and in 3% in the thiopental groups (n.s). Early recovery (eye opening, orientation and sitting) was slower in both eltanolone groups compared to the thiopental group (P < 0.01). No differences between the groups were found in toleration of oral fluids, walking, voiding, postoperative analgesic requirements or postoperative nausea and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)


Manipulating Selective Metal-to-Metal Electron Transfer to Achieve Multi-Phase Transitions in an Asymmetric [Fe2 Co]-Assembled Mixed-Valence Chain.
Manipulation of multi-functions in molecular materials is promising for future switching and memory devices, although it is currently difficult. Herein, we assembled the asymmetric {Fe2 Co} unit into a cyanide-bridged mixed-valence chain {[(Tp)Fe(CN)3 ]2 Co(BIT)} ⋅ 2CH3 OH (1) (Tp=hydrotris(pyrazolyl)borate and BIT=3,4-bis-(1H-imidazol-1-yl)thiophene), which showed reversible multi-phase transitions accompanied by photo-switchable single-chain magnet properties and a dielectric anomaly. Variable-temperature X-ray structural studies revealed thermo- and photo-induced selective electron transfer (ET) between the Co and one of the Fe ions. Alternating-current magnetic susceptibility studies revealed that 1 displayed on and off single-chain magnet behavior by alternating 946-nm and 532-nm light irradiation. A substantial anomaly in the dielectric constant was discovered during the electron transfer process, which is uncommon in similar ET complexes. These findings illustrate that 1 provided a new platform for multi-phase transitions and multi-switches adjusted by selective metal-to-metal ET.


Granuloma Coinfection with Mycobacterium bovis, Mycobacterium avium subsp. paratuberculosis, and Corynebacterium pseudotuberculosis in Five Hunted Red deer (Cervus elaphus) in Portugal.
We report granulomatous lymphadenitis in red deer (Cervus elaphus) in Portugal caused by coinfection with Corynebacterium pseudotuberculosis, Mycobacterium bovis, and Mycobacterium avium subsp. paratuberculosis, as demonstrated by molecular methods.


Effects of central administration of insulin in normal and VMH (ventromedial hypothalamus) lesioned rats on food intake.
Central effects of insulin on 20 min. food intake were studied in rats. Insulin administration in the lateral ventricular cerebrospinal fluid (CSF) did not alter food intake in the intact or lesioned ventromedial hypothalamus (VMH) rats. Whereas, after insulin injection in VMH there was a decrease in food intake. In VMH lesioned rats, subcutaneous injection of insulin increased food intake.


Adherence screening and monitoring.
Patient adherence is an essential goal of pharmaceutical care and can be an initial focus for cognitive services in a traditional pharmacy. Pharmacists are well placed to manage adherence programs. Activities associated with adherence include screening or assessment, follow-up monitoring, and use of memory aids or refill reminders. Technology is available in many forms to assist pharmacists in this role. The pharmacist's role in adherence should focus on achieving desirable patient outcomes. Services associated with adherence programs need not be attached to distribution activities. Producing cost-effective drug therapy outcomes will continue to be of critical value to patients, health care systems, and third party providers.


Return to Work, Fatigue and Cancer Rehabilitation after Curative Radiotherapy and Radiochemotherapy for Pelvic Gynecologic Cancer.
Pain, fatigue, and depression are a common cluster of symptoms among cancer patients that impair quality of life and daily activities. We aimed to evaluate the burden of cancer rehabilitation and return-to-work (RTW) rates. Tumor characteristics, lifestyle and household details, treatment data, the use of in-house social services and post-treatment inpatient rehabilitation, and RTW were assessed for 424 women, diagnosed with cervical, uterine, or vaginal/vulvar cancer, receiving curative radio(chemo)therapy. Progression-free RTW rate at 3 months was 32.3%, and increased to 58.1% and 63.2% at 12 and 18 months, respectively. Patients with advanced FIGO stages and intensified treatments significantly suffered more from acute pain and fatigue. A higher Charlson-Comorbidity-Index reliably predicted patients associated with a higher risk of acute fatigue during RT. Aside from the presence of children, no other household or lifestyle factor was correlated with increased fatigue rates. Women aged ≤ 45 years had a significantly higher risk of developing depression requiring treatment during follow-up. Post-treatment inpatient cancer rehabilitation, including exercise and nutrition counseling, significantly relieved fatigue symptoms. The burdens for recovery from cancer therapy remain multi-factorial. Special focus needs to be placed on identifying high-risk groups experiencing fatigue or pain. Specialized post-treatment inpatient cancer rehabilitation can improve RTW rates.


Detection of nuclear factor-kappaB and inducible nitric oxide synthase in the lungs of pigs naturally infected with Actinobacillus pleuropneumoniae.
Activated nuclear factor-kappaB (NF-kappaB) and inducible nitric oxide synthase (iNOS) were detected immunohistochemically in pleuropneumonic lungs from 20 pigs naturally infected with Actinobacillus pleuropneumoniae. NF-kappaB was detected mainly in nuclei of inflammatory cells, confirming its activation. Intense immunolabelling for NF-kappaB and iNOS was seen within the lung lesions, but labelling was minimal in unaffected portions of the lung of infected pigs and in normal lung from uninfected (control) pigs. Examination of serial sections from the 20 infected lung samples demonstrated a close association between NF-kappaB and iNOS. This suggests that NF-kappaB plays a key role in triggering the activation of iNOS in porcine pleuropneumonia.


Radiologic Findings of Mesonephric-Like Adenocarcinoma of the Uterine Corpus: A Case Report.
According to the 2020 World Health Organization classification, mesonephric-like adenocarcinoma (MLA) is newly categorized as a subtype of endometrial carcinoma and remains a relatively unknown disease owing to its rarity. To the best of our knowledge, radiological findings of MLA have not been reported in the English literature. The uterine MLAs show a worse clinical prognosis and a more aggressive biological behavior than the usual endometrial carcinoma. Herein, we present the imaging findings of a 65-year-old female with a MLA in the uterine corpus. The tumor was a solid endometrial mass with deep myometrial invasion, poor contrast enhancement, and moderate diffusion restriction.


Neural correlates of inhibition of socially relevant stimuli in adults with autism spectrum disorder.
Adults with autism spectrum disorder (ASD) can demonstrate difficulties with inhibiting inappropriate social responses. Presently, little research has utilized socially relevant stimuli to explore the modulatory effects of emotion on cognitive control in this population. To assess neural mechanisms of inhibiting social stimuli, we presented images of happy or sad facial expressions in a Go/NoGo task to unmedicated adults with ASD and to controls during functional magnetic resonance imaging (fMRI). Groups did not differ on behavioral measures. Brain activation in response to NoGo vs. Go trials revealed differing regional patterns of activation within groups. Controls recruited brain regions involved in inhibition (dorsal- [DLPFC] and ventro-lateral prefrontal cortices [VLPFC], anterior cingulate cortex [ACC]), response suppression (parietal lobe), interoceptive awareness (insula), and also the fusiform and middle temporal gyri. Adults with ASD only recruited the VLPFC and right fusiform gyrus, and weakly activated the ACC and insula. Between-group comparisons indicated that controls activated the DLPFC, while adults with ASD relied on the VLPFC and the fusiform gyrus to inhibit responses. Adults with ASD may have relied more on visual association cortex, possibly as a means of recruiting additional neural processes that could act as a compensatory mechanism.


A Comparison of Back Pain Functional Scale With Roland Morris Disability Questionnaire, Oswestry Disability Index, and Short Form 36-Health Survey.
A comparison study of Back Pain Functional Scale (BPFS) with Roland Morris Questionnaire (RMQ), Oswestry Disability Index (ODI), and Short Form 36-Health Survey (SF-36). The aim of this study is to investigate the correlation of BPFS with RMQ, ODI, and SF-36. The primary goal in the treatment of patients with low back pain is to improve the patients' levels of activities and participation. Many questionnaires focusing on function have been developed in patients with low back pain. BPFS is one of these questionnaires. No studies have investigated the correlation of BPFS with ODI and SF-36. This study was conducted with 120 patients receiving outpatient and inpatient treatment in physiotherapy and rehabilitation units of a state hospital. BPFS, RMQ, ODI, and SF-36 questionnaires were used to assess the disability in low back pain. Spearman and Pearson Correlation were used to compare the data obtained in the study. There was a good correlation among the 5 functional outcome measures (correlation r = -0.693 for BPFS/RMQ, r = -0.794 for BPFS/ODI, r = 0.697 for BPFS/SF-36 Physical function and r = 0.540 for BPFS/SF-36 Pain). BPFS demonstrated good correlation with RMQ, ODI, SF-36 physical function, and SF-36 pain. 2.


Monolayer supertubes of Carbon-Armored platinum nanocrystals enabling robust oxygen reduction electrocatalysis.
Self-assembled superstructures composed of nanocrystals (NCs) have shown immense potential for enhancing the performance in electrocatalytic applications. However, there has been limited research on the self-assembly of platinum (Pt) into low-dimensional superstructures as efficient electrocatalysts for oxygen reduction reaction (ORR). In this study, we designed a unique tubular superstructure composed of monolayer or sub-monolayer carbon-armored platinum nanocrystals (Pt NCs) using a template-assisted epitaxial assembly approach. The organic ligands on the surface of Pt NCs were in situ carbonized, resulting in few-layer graphitic carbon shells that encapsulate Pt NCs. Due to their monolayer assembly and tubular geometry, the Pt utilization of the supertubes was 1.5 times higher than that of conventional carbon-supported Pt NCs. As a result, such Pt supertubes exhibit remarkable electrocatalytic performance for the ORR in acidic media, with a high half-wave potential of 0.918 V and a high mass activity of 181 A g-1Pt at 0.9 V, which are comparable to commercial carbon-supported Pt (Pt/C) catalysts. Furthermore, the Pt supertubes demonstrate robust catalytic stability, as confirmed by long-term accelerated durability tests and identical-location transmission electron microscopy. This study presents a new approach to designing Pt superstructures for highly efficient and stable electrocatalysis.


Expression of Epstein-Barr virus genes and of lymphocyte activation molecules in undifferentiated nasopharyngeal carcinomas.
Previous studies investigating the role of Epstein-Barr virus (EBV) in undifferentiated nasopharyngeal carcinoma (NPC) have been performed on extracts from biopsies. The authors analyzed expression and localization of viral gene products in 18 undifferentiated NPCs at the cellular level using immunohistology and in situ hybridization. All cases were EBV-positive. The small nuclear EBV-encoded RNAs, EBERs, were regularly expressed whereas the latent membrane protein, LMP1, and EBV was detectable only in four cases (22%) and the nuclear antigen 2 was not detectable. The BZLF-1 protein of EBV which disrupts viral latency, was not detectable, confirming that the virus is latent in the tumor cells. Although the expression of the CD23 antigen in transplantable NPCs has been reported, our study demonstrates that expression of this antigen in human undifferentiated NPCs is rare. In contrast, almost all cases expressed the CDw70 antigen. Since in normal tissues this antigen is present only in activated lymphoid blasts, this finding may be relevant for the differential diagnosis of undifferentiated NPCs.


The role of resistance training in influencing insulin resistance among adults living with obesity/overweight without diabetes: A systematic review and meta-analysis.
The purpose of this study was to systematically examine the independent effect of resistance training (RT) on markers of insulin resistance (IR) (fasting insulin and HOMA-IR) among individuals with overweight/obesity without diabetes. PubMed, SPORTdiscus, SCOPUS, Prospero, and clinicaltrials.gov were searched through December 19, 2022. Article screening was conducted in three phases: title screen (n = 5020), abstract screen (n = 202), and full text screen (n = 73). A total of 27 studies with 402 individual data points were used for the meta-analysis. Comprehensive Meta-Analysis software version 3.0 was used to interpret pre- and post-IR measurements with a random-effects model. Exploratory sub-analyses were conducted on studies for only females, only males, and age (< 40 and ≥ 40 years). RT had a significant effect on fasting insulin (- 1.03, 95 % CI - 1.03, - 0.75 p < 0.001) and HOMA-IR (- 1.05, 95 % CI - 1.33, - 0.76, p < 0.001). Sub-analyses revealed that males had a more pronounced effect compared to females and those < 40 years of age had a more pronounced effect compared to those ≥ 40 years. The results of this meta-analysis illustrate that RT plays an independent role in improving IR among adults with overweight/obesity. RT should continue to be recommended as part of preventive measures among these populations. Future studies examining the effect of RT on IR should consider dose centered on the current U.S. physical activity guidelines.


Inhibition of bovine mononuclear cell proliferation, interleukin-2 synthesis, protein-tyrosine kinase and leukotriene B4 production by a protein-tyrosine kinase inhibitor, genistein.
Genistein, an isoflavanoid compound, a selective inhibitor of protein-tyrosine kinase (PTK), inhibited PHA-stimulated bovine peripheral blood mononuclear cell proliferation (PBMC), interleukin-2 (IL-2) production, phosphorylation of PTK p56lck. Further, genistein also inhibited leukotriene B4 production from A-23187 stimulated cultures. Our data suggest that the PTK plays an important role in the signal transduction of bovine PBMC proliferation.