Theoretical assessment of persistence and adaptation in weeds with complex life cycles.
Herbicide-resistant weeds pose a substantial threat to global food security. Perennial weed species are particularly troublesome. Such perennials as Sorghum halepense spread quickly and are difficult to manage due to their ability to reproduce sexually via seeds and asexually through rhizomes. Our theoretical study of S. halepense incorporates this complex life cycle with control measures of herbicide application and tillage. Rooted in the biology and experimental data of S. halepense, our population-based model predicts population dynamics and target-site resistance evolution in this perennial weed. We found that the resistance cost determines the standing genetic variation for herbicide resistance. The sexual phase of the life cycle, including self-pollination and seed bank dynamics, contributes substantially to the persistence and rapid adaptation of S. halepense. While self-pollination accelerates target-site resistance evolution, seed banks considerably increase the probability of escape from control strategies and maintain genetic variation. Combining tillage and herbicide application effectively reduces weed densities and the risk of control failure without delaying resistance adaptation. We also show how mixtures of different herbicide classes are superior to rotations and mono-treatment in controlling perennial weeds and resistance evolution. Thus, by integrating experimental data and agronomic views, our theoretical study synergistically contributes to understanding and tackling the global threat to food security from resistant weeds.


Potential role of Hsp90 inhibitors in overcoming cisplatin resistance of bladder cancer-initiating cells.
For metastatic bladder cancer patients, systemic cisplatin (CDDP)-based combination chemotherapy is the first-line choice of treatment. Although up to 70% of advanced bladder cancer patients initially show good tumor response to this form of combination chemotherapy, over 90% of good responders relapse and eventually die of the disease. According to the cancer stem cell theory, this phenomenon is attributable to the re-growth of bladder cancer-initiating cells (BCICs) that have survived chemotherapy. In this study, the authors have isolated BCICs from cultured human bladder cancer cells to analyze their sensitivity to CDDP and to investigate whether heat-shock protein 90 (Hsp90) inhibitors potentiate the cytotoxicity of CDDP on BCICs. First, the authors have confirmed that a CD44+ subpopulation of 5637 cells met the requirements to be considered tumor-initiating cells. These BCICs were more resistant to CDDP and exhibited more activity in the Akt and ERK oncogenic signaling pathways when compared with their CD44- counterparts. The Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), which simultaneously inactivated both Akt and ERK signaling at noncytocidal concentrations, synergistically potentiated the cytotoxicity of CDDP against BCICs by enhancing CDDP-induced apoptosis in vitro. The potentiating effect of 17-DMAG was more effective than a combination of the two inhibitors specific for the Akt and ERK pathways. Finally, the authors have confirmed that, though human BCIC xenografts exhibited resistance to a single administration of CDDP and the Hsp90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), 17-AAG sensitized them to CDDP in a mouse model. These data encourage clinical trials of Hsp90 inhibitors as they may improve therapeutic outcomes of CDDP-based combination chemotherapy against advanced bladder cancer.


Intravenous amino acid therapy for kidney function in critically ill patients: a randomized controlled trial.
Acute kidney injury (AKI) is characterized by severe loss of glomerular filtration rate (GFR) and is associated with a prolonged intensive care unit (ICU) stay and increased risk of death. No interventions have yet been shown to prevent AKI or preserve GFR in critically ill patients. Evidence from mammalian physiology and small clinical trials suggests higher amino acid intake may protect the kidney from ischemic insults and thus may preserve GFR during critical illness. To determine whether amino acid therapy, achieved through daily intravenous (IV) supplementation with standard amino acids, preserves kidney function in critically ill patients. Multicenter, phase II, randomized clinical trial conducted between December 2010 and February 2013 in the ICUs of 16 community and tertiary hospitals in Australia and New Zealand. Participants were adult critically ill patients expected to remain in the study ICU for longer than 2 days. Random allocation to receive a daily supplement of up to 100 g of IV amino acids or standard care. Duration of renal dysfunction (primary outcome); estimated GFR (eGFR) derived from creatinine; eGFR derived from cystatin C; urinary output; renal replacement therapy (RRT) use; fluid balance and other measures of renal function. 474 patients were enrolled and randomized (235 to standard care, 239 to IV amino acid therapy). At time of enrollment, patients allocated to receive amino acid therapy had higher APACHE II scores (20.2 ± 6.8 vs. 21.7 ± 7.6, P = 0.02) and more patients had pre-existing renal dysfunction (29/235 vs. 44/239, P = 0.07). Duration of renal dysfunction after enrollment did not differ between groups (mean difference 0.21 AKI days per 10 patient ICU days, 95 % CI -0.27 to 1.04, P = 0.45). Amino acid therapy significantly improved eGFR (treatment group × time interaction, P = 0.004), with an early peak difference of 7.7 mL/min/1.73 m(2) (95 % CI 1.0-14.5 mL/min/1.73 m(2), P = 0.02) on study day 4. Daily urine output was also significantly increased (+300 mL/day, 95 % CI 145-455 mL, P = 0.0002). There was a trend towards increased RRT use in patients receiving amino acid therapy (13/235 vs. 25/239, P = 0.062); however, this trend was not present after controlling for baseline imbalance (P = 0.21). Treatment with a daily IV supplement of standard amino acids did not alter our primary outcome, duration of renal dysfunction. anzctr.org.au Identifier: ACTRN12609001015235.


Norovirus prevalence in 'pathogen negative' gastroenteritis in children from periurban areas in Lima, Peru.
Norovirus was detected in 17.4% of 224 diarrhoeal samples from children younger than 24 months of age in Lima, in whom all common pathogens had been excluded (pathogen negative). Norovirus was identified more frequently in children older than 12 months of age than in younger children (34% vs 8%, P<0.001). Among norovirus-positive samples, genogroup II was the predominant group (92%). Compared with rotavirus, norovirus episodes tended to be of shorter duration and less severe. The role of norovirus as a cause of diarrhoea and the ascertainment of its severity in developing countries needs further confirmation by future epidemiological studies.


Antigenic variation and allelic exclusion.
Cells often express only one gene from a set of two or more. African trypanosomes appear to accomplish this monoallelic expression by segregating the selected gene into a specific nuclear body. The possibility that such a structure might explain monoallelic expression in other multigene systems is discussed here.


A multifunctional nanoprobe based on Au-Fe3O4 nanoparticles for multimodal and ultrasensitive detection of cancer cells.
A multifunctional nanoprobe, which can be used for dual modal imaging and the detection of cancer cells, has been reported.


Growth, reproduction and longevity in nematodes from sewage treatment plants.
The growth, reproduction and longevity of Diplogasteritus nudicapitatus, Paroigolaimella bernensis and Rhabditis curvicaudata were investigated under conditions of excess food within the temperature range 5°C-20°C. In all three species growth rate increased with temperature, and in D. nudicapitatus and R. curvicaudata the adult size attained varied significantly with temperature. P. bernensis did not reproduce at 5°C, but showed a progressive increase in reproductive output at higher temperatures. D. nudicaitatus showed increased egg production as temperature increased while R. curvicaudata had maximum egg output at 10°C. Longevity is temperature dependent, decreasing with higher temperatures. Virgin females survived for longer than reproducing females. The data indicate that while D. nudicapitatus and P. bernensis are thermophilic species, R. curvicaudata is adapted to lower temperatures.


Auditory brainstem mechanisms likely compensate for self-imposed peripheral inhibition.
Feedback networks in the brain regulate downstream auditory function as peripheral as the cochlea. However, the upstream neural consequences of this peripheral regulation are less understood. For instance, the medial olivocochlear reflex (MOCR) in the brainstem causes putative attenuation of responses generated in the cochlea and cortex, but those generated in the brainstem are perplexingly unaffected. Based on known neural circuitry, we hypothesized that the inhibition of peripheral input is compensated for by positive feedback in the brainstem over time. We predicted that the inhibition could be captured at the brainstem with shorter (1.5 s) than previously employed long duration (240 s) stimuli where this inhibition is likely compensated for. Results from 16 normal-hearing human listeners support our hypothesis in that when the MOCR is activated, there is a robust reduction of responses generated at the periphery, brainstem, and cortex for short-duration stimuli. Such inhibition at the brainstem, however, diminishes for long-duration stimuli suggesting some compensatory mechanisms at play. Our findings provide a novel non-invasive window into potential gain compensation mechanisms in the brainstem that may have implications for auditory disorders such as tinnitus. Our methodology will be useful in the evaluation of efferent function in individuals with hearing loss.


Further evidence of an intravesicular Ca2+- pump in odontoblasts from rat incisors.
Intracellular vesicles containing alkaline phosphatases were isolated from isolated odontoblasts using several centrifugation techniques, gradient media and filtering procedures. With a combined centrifugation technique using 0.32 M sucrose layered on 1.23 M sucrose, a fraction containing alkaline phosphatases with a 36-40-fold increased specific activity was obtained. This fraction also revealed a high Ca2+-accumulating ability. The vesicle fraction was totally free from mitochondria but to some extent contaminated by lysosomes. Characteristics of Ca2+-uptake were obtained. The Ca2+-uptake was maximal at 37-40 degrees C whereas no Ca2+-accumulated at 4 degrees C. Temperatures above 40 degrees C strongly inhibited Ca2+-uptake. ATP was the most potent stimulator of Ca2+-uptake whereas ITP, GTP, CTP, ADP, PPi and AMP also promoted Ca2+-uptake. Cysteine, EDTA and Triton X-100 were inhibitory to Ca2+-uptake. A correlation between alkaline phosphatases in intracellular vesicles as well as their relation to extracellular matrix vesicles and to the mineralization process is suggested.


Akt inhibition attenuates rasfonin-induced autophagy and apoptosis through the glycolytic pathway in renal cancer cells.
Rasfonin is a fungal secondary metabolite with demonstrated antitumor effects. However, the underlying mechanism of the regulatory role in autophagy initiated by rasfonin is largely unknown. Moreover, the function of Akt to positively mediate the induced autophagy remains elusive. In the present study, we observed that rasfonin induced autophagy concomitant with the upregulation of Akt phosphorylation. Both the inhibition of Akt by small molecule inhibitors and genetic modification partially reduced rasfonin-dependent autophagic flux and PARP-1 cleavage. The overexpression of myrAkts (constant active form) promoted rasfonin-induced apoptosis and autophagy in a cell type- and Akt isoform-specific manner. Using quantitative PCR and immunoblotting, we observed that rasfonin increased the expression of glycolytic gene PFKFB3, and this increased expression can be suppressed in the presence of Akt inhibitor. The inhibition of PFKFB3 suppressed rasfonin-activated autophagy with enhanced PARP-1 cleavage. In the case of glucose uptake was disrupted, which mean the glycolytic pathway was fully blocked, the rasfonin-induced autophagy and PARP-1 cleavage were downregulated. Collectively, these results demonstrated that Akt positively regulated rasfonin-enhanced autophagy and caspase-dependent apoptosis primarily through affecting the glycolytic pathway.


Insulin resistance and bioenergetic manifestations: Targets and approaches in Alzheimer's disease.
Insulin has a well-established role in cognition, neuronal detoxification and synaptic plasticity. Insulin transduction affect neurotransmitter functions, influence bioenergetics and regulate neuronal survival through regulating glucose energy metabolism and downward pathways. A systematic literature review of PubMed, Medline, Bentham, Scopus and EMBASE (Elsevier) databases was carried out with the help of the keywords like "Alzheimer's disease; Hypometabolism; Oxidative stress; energy failure in AD, Insulin; Insulin resistance; Bioenergetics" till June 2020. The review was conducted using the above keywords to collect the latest articles and to understand the nature of the extensive work carried out on insulin resistance and bioenergetic manifestations in Alzheimer's disease. The article sheds light on insulin resistance mediated hypometabolic state on pathological progression of AD. The disrupted insulin signaling has pathological outcome in form of disturbed glucose homeostasis, altered bioenergetic state which increases build-up of senile plaques (Aβ), neurofibrillary tangles (τ), decline in transportation of glucose and activation of inflammatory pathways. The mechanistic link of insulin resistant state with therapeutically explorable potential transduction pathways is the focus of the reviewed work. The present work opines that the mechanism by which the insulin resistance mediates dysregulation of bioenergetics and progresses to neurodegenerative state holds the tangible potential to succeed in the development of novel dementia therapies. Further, hypometabolic complications and altered insulin signaling may be explored as a mechanistic relation between bioenergetic deficits and AD.


Comparison of the effects of calmidazolium, morphine and bupivacaine on N-methyl-D-aspartate- and septide-induced nociceptive behaviour.
We have recently shown that spinal calmodulin inhibitors (W-7 and calmidazolium) dose-dependently inhibit the nociceptive reaction (biting, scratching, licking, BSL) evoked by intrathecal N-methyl-D-aspartate (NMDA) and septide, an agonist of the neurokinin (NK) NK1 receptor. To compare this effect with that induced by standard analgesics, we now report a study of the effects of calmidazolium (14420 nmol), bupivacaine (29-582 nmol) and morphine (26-260 nmol) when coadministered intrathecally with either NMDA (4 microg) or septide (0.5 microg). Calmidazolium had the highest potency for inhibiting septide-induced nociceptive behaviour, acting over a dose range of 34-130 nmol (dose eliciting a half-maximal response, ED50, 67 nmol) lower than that of bupivacaine [ED50 234 (115-475) nmol]. Only the highest dose of morphine (260 nmol) inhibited septide-evoked BSL [ED50=133 (69-255) nmol]. Higher doses of morphine could not be tested due to the appearance of an excitatory aversive reaction. Both calmidazolium [ED50=232 (138-388) nmol] and bupivacaine [ED50=123 (59-256) nmol] dose-dependently reduced NMDA-induced BSL reaching an almost maximal inhibition at the highest doses assayed (420 and 291 nmol, respectively). In contrast, morphine had less effect on NMDA-induced behaviour, inducing only a partial reduction of BSL even with the highest dose assayed (260 nmol). Overall, it can be concluded that the calmodulin inhibitor calmidazolium inhibits septide- and NMDA-evoked nociceptive behaviour with a potency and efficacy at least as high as those of morphine and bupivacaine.


Complete genome sequence analysis of a reassortant strain of bluetongue virus serotype 16 from Italy.
The complete genome sequence of a reassortant field strain of bluetongue virus serotype 16 (BTV-16), isolated from cattle in the Apulia region of Italy in 2002, has been determined by Illumina sequencing. Sequence comparisons of segment 1 (Seg-1) to Seg-10, except Seg-5, show that BTV-16 strain ITL2002 belongs to the major eastern topotype of BTV.


Plasmin/plasminogen system in colorectal cancer.
Pericellular proteolysis plays a crucial role in tumor cell invasion. The controlled degradation of the extracellular matrix by tumor cell-associated proteases allows tumor cells to invade surrounding tissues and gain access to the circulation. One of the main protease systems involved in tumor cell invasion and metastasis is the plasminogen/plasmin system (PPS). The components of the PPS include the urokinase plasminogen activator (uPA), its cell surface receptor urokinase plasminogen activator receptor (uPAR), and its naturally occurring inhibitors, plasminogen activator inhibitors 1 and 2 (PAI-1 and PAI-2). Increases in tumor and serum levels of uPA, uPAR, and PAI-1 are associated with a worse prognosis in patients with colon cancer. Use of these proteins as either tumor or serum markers may allow more accurate determination of the prognosis in colon cancer patients. Furthermore, these proteins appear to be attractive as targets for the biologic therapy of colon cancer.


Haloperidol, raclopride, and eticlopride induce microcatalepsy during operant performance in rats, but clozapine and SCH 23390 do not.
The purpose of this work was (1) to assess the ability of selected antipsychotic and comparison drugs to induce arrest of movement phenomena during operant responding and (2) to evaluate the capacity of muscarinic anitcholinergics to block such effects. The effects of haloperidol (0.02-0.12 mg/kg, i.p., 45 min), raclopride (0.05-0.80 mg/kg, i.p., 30 min) eticlopride (0.02-0.16 mg/kg, i.p., 45 min), clozapine (1.0-8.0 mg/kg, i.p., 60 min) and SCH 23390 (0.01-0.16 mg/kg, i.p., 30 min) were administered to rats for 4 weeks in a between-groups dosing design. Operant responses in 15 min and the maximum duration of the rat's muzzle entry into the reinforcement dipper well (the measure of arrest of movement that reflected microcatalepsy) were the quantitative measures of behavior. The D2 antagonists dose-relatedly decreased operant responding and increased maximum muzzle duration, effects that were significantly reversed by the anticholinergic scopolamine (0.1 mg/kg) or atropine (6.0 mg/kg). Although the atypical antipsychotic drug clozapine and the selective D1 antagonist SCH 23390 both significantly reduced operant responding, these drugs did not produce microcatalepsy. The results suggested that microcatalepsy expressed in the context of ongoing operant behavior may model low-dose extrapyramidal side effects.


Invasive methicillin-resistant Staphylococcus aureus infections among patients on chronic dialysis in the United States, 2005-2011.
Approximately 15 700 invasive methicillin-resistant Staphylococcus aureus (MRSA) infections occurred in US dialysis patients in 2010. Frequent hospital visits and prolonged bloodstream access, especially via central venous catheters (CVCs), are risk factors among hemodialysis patients. We describe the epidemiology of and recent trends in invasive MRSA infections among dialysis patients. We analyzed population-based data from 9 US metropolitan areas from 2005 to 2011. Cases were defined as MRSA isolated from a normally sterile body site in a surveillance area resident who received dialysis, and were classified as hospital-onset (HO; culture collected >3 days after hospital admission) or healthcare-associated community-onset (HACO; all others). Incidence was calculated using denominators from the US Renal Data System. Temporal trends in incidence and national estimates were calculated controlling for age, sex, and race. From 2005 to 2011, 7489 cases were identified; 85.7% were HACO infections, and 93.2% were bloodstream infections. Incidence of invasive MRSA infections decreased from 6.5 to 4.2 per 100 dialysis patients (annual decrease, 7.3%) with annual decreases of 6.7% for HACO and 10.5% for HO cases. Among cases identified during 2009-2011, 70% of patients were hospitalized in the year prior to infection. Among hemodialysis cases, 60.4% of patients were dialyzed through a CVC. The 2011 national estimated number of MRSA infections was 15 169. There has been a substantial decrease in invasive MRSA infection incidence among dialysis patients. Most cases had previous hospitalizations, suggesting that efforts to control MRSA in hospitals might have contributed to the declines. Infection prevention measures should include improved vascular access and CVC care.


Exercise-induced ST-segment elevation in patients with a recent acute myocardial infarction treated by primary percutaneous coronary intervention.
To get insight in the mechanism of exercise-induced ST-segment elevation (STE) in patients with Q/QS waves at the electrocardiogram (ECG). We performed exercise stress test in 13 patients with anterior acute myocardial infarction treated by successful primary percutaneous coronary intervention (PCI). Compared to rest, an additional STE > or = 1 mm in one or more precordial ECG leads during exercise occurred in nine patients (69%), in the absence of symptoms. In acute myocardial infarction (MI) patients, treated by primary PCI and showing optimal coronary blood flow restoration at angiography, STE can still be induced by exercise in Q/QS wave ECG leads. This finding lends further support to the theory that exercise-induced STE in this clinical context is unlikely to represent by itself transient myocardial ischemia or viability.


Efficacy of olfactory training in patients with olfactory loss: a systematic review and meta-analysis.
Olfactory loss is a challenging clinical problem with few proven therapeutic options. Early experimental results with olfactory training suggest that this novel therapy may be an effective intervention for olfactory dysfunction of multiple etiologies. The aim of this study was to systematically review currently available studies that assess the efficacy and outcomes of olfactory training in patients with olfactory loss. A comprehensive systematic literature review was performed with the assistance of a reference librarian using the PubMed, PsycInfo, Google Scholar, EMBASE, and Proquest databases. Eligible studies were extracted based on defined inclusion criteria and the effect of olfactory training on objective olfactory function was evaluated qualitatively and by meta-analysis. A total of 10 studies with 639 patients were identified and systematically reviewed. Sufficient data for meta-analysis was available for 3 studies. Patients receiving olfactory training experienced a statistically significant improvement in the Threshold, Discrimination, Identification (TDI) score compared to control patients (mean difference [MD] 3.77; 95% confidence interval [CI], 2.28 to 5.26). Improvement in olfactory function was observed in discrimination (MD 1.92; 95% CI, 1.13 to 2.71) and identification (MD 1.61; 95% CI, 0.55 to 2.68), but not in olfactory thresholds (MD -0.01; 95% CI, -0.42 to 0.39). Olfactory training is a promising modality for the treatment of olfactory dysfunction. Results of this systematic review and meta-analysis suggest that it may be an effective treatment for olfactory dysfunction due to multiple etiologies. Additional high-quality studies are needed to define indications, outcomes, and duration of therapy for this novel therapy.


Synthesis of Altenuene Backbones through Iodine(III)-Participated Umpolung Diesterification and Insights into the General [1,5]-H Shift in para-Dearomatization of Phenols via Quantum Chemical Calculations.
Through PhI(OAc)2-oxidized dearomatization and diesterification of 3'-hydroxy-[1,1'-biphenyl]-2-carboxylic acids, a series of polycyclic compounds possessing an altenuene backbone were obtained in moderate to good yields. The Umpolung diesterification reaction was completed under mild reaction conditions without an additional nucleophilic reagent. This work offers a concise method for the synthesis of diverse natural altenuene analogues. The mechanism was proposed, and the [1,5]-H shift was studied in isomerization from the ketone-form structure to a phenol employing computational studies.


A novel PGD(2) receptor expressed in eosinophils.
PGD(2) is a major product of arachidonic acid metabolism by mast cells and is released in the lungs following allergen challenge. Activation of the classic PGD(2) receptor (DP receptor) results in stimulation of adenylyl cyclase, resulting in inhibition of platelet aggregation and smooth muscle relaxation. A second PGD(2) receptor has recently been identified and designated as the DP(2) receptor, or chemoattractant receptor-homologous molecule expressed on Th2 cells. PGD(2) acts through the DP(2) receptor to induce eosinophil chemotaxis, actin polymerization, calcium mobilization, and adhesion molecule expression. The most potent DP(2) receptor agonist yet identified is 15R-methyl-PGD(2), which has the unnatural R configuration at C(15). 15-Deoxy-Delta(12,14)-PGJ(2) is also a potent DP(2) receptor agonist that activates eosinophils at concentrations much lower than those required for its anti-inflammatory effects. Because of its critical location in the lung and its potent effects on eosinophils, PGD(2) may be an important proinflammatory mediator in asthma.


Sensitivity and specificity of death certificates for diabetes: as good as it gets?
Diabetes is the sixth leading cause of death in U.S adults, which may be an underestimate because of under-reporting on death certificates. In this study we examined death certificate sensitivity and specificity for diabetes, as well as the factors related to better reporting, in a community-based sample. Death certificates were obtained for 3,209 decedents who were enrolled in the Rancho Bernardo cohort in 1972-1974 and followed through 2003. Diabetes status was reassessed at periodic clinic visits and annual mailed surveys during an average follow-up of 15.2 +/- 7.6 years. Diabetes reported anywhere on death certificates was abstracted. Sensitivity and specificity calculations among diabetic participants were stratified by age, sex, year, place, cause of death, and diabetes medication use. Among 1,641 men and 1,568 women, 378 decedents had a history of diabetes, 168 of whom had diabetes listed anywhere on their death certificates. The sensitivity and specificity were 34.7 and 98.1%. Diabetes reporting on death certificates did not improve over time or vary significantly by age and sex, but sensitivity for diabetes reporting was better for recent (1992-2003) cardiovascular disease (CVD) deaths compared with any other causes of death (48.9 vs. 28.6%, respectively, P < 0.05). Although diabetes reporting on death certificates did not improve over time, sensitivity was better for diabetes in the context of CVD deaths, probably reflecting the increasing recognition that diabetes is a major cardiovascular risk factor.


Cell analysis in cerebrospinal fluid (CSF) using Sysmex® hematology analyzers XT-4000i and XE-5000: evaluation with CSF controls of the Joint German Society for Clinical Chemistry and Laboratory Medicine (DGKL).
In cerebrospinal fluid (CSF) analysis, hematology analyzers (HAs) Sysmex® XT-4000i and XE-5000, equipped with flow cytometry (FCM), were used to count cells and differentiate leukocytes into mononuclear and polymorphonuclear cells (MNCs, PMCs) applying body fluid mode. FCM was evaluated with 20 DGKL CSF controls containing viable human leukocytes and erythrocytes. HA values were compared with reference values by Passing/Bablok regression analysis to reveal conformity. Conformity of white blood cells (WBCs) was obtained with native leukocytes, counted in calibrated Fuchs-Rosenthal chamber as reference; red blood cell counts proved inaccurate. CV <40% with WBC counts <20 per μL impairs accuracy. Reference WBC differentiation was assayed using FACS Canto II™ and FC-500 SN with anti-CD45, anti-CD14, anti-CD16, anti-CD16/56 [Becton Dickinson (BD); Beckman Coulter (BC)]. BD FACS lysing solution®-no-wash-procedure was applied. BC pretreatment with Versalyse lysing solution was not recommended. MNCs (lymphocytes + monocytes) were significantly lower (∼14%) on both HAs; PMCs (granulocytes or sum of neutrophils + eosinophils + basophils: range 1-86 M/L) were significantly higher (∼2.2-fold). WBC HA differentiation is not reliable because MNC/PMC differentiation yielded lower and higher values than FACS-FCM references, respectively. This is attributed to incorrect discrimination of leukocytes with rounded/nonrounded nuclei; adding leukocytes with nonrounded nuclei to too low HA MNCs (about 40% not-activated) yielded P/B conformity; subtraction of leukocytes with nonrounded nuclei from elevated HA PMCs showed conformity (about 85% activated). Nucleus/activation state of leukocytes was assessed using microhistology. Sysmex XT-4000i and XE-5000 HAs systems are inappropriate for complete CSF cell analysis.


Sevoflurane does not alter norepinephrine-induced intracellular Ca²(+) changes in the diabetic rat aorta.
The effect of volatile anesthetics on the mechanism(s) of vascular contraction in diabetes mellitus (DM) has not been fully understood. The current study was designed to determine the effects of sevoflurane on the norepinephrine (NE)-induced changes in contractile state and intracellular Ca²(+) concentrations ([Ca²(+)](i)) in the spontaneously developing type 2 DM rat. The effects of sevoflurane on NE (10⁻⁶M)-induced vasoconstriction and increase in [Ca²(+)](i) in the aortas from Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 DM model, and from age-matched control Long-Evans Tokushima Otsuka (LETO) rats were investigated using an isometric force transducer and fluorometer with fura-2 as an indicator of [Ca²(+)](i). Norepinephrine-induced increases in tension and [Ca²(+)](i) in OLETF rats were 54.8%, 95% confidence interval (CI) 36.9-72.6% and 58.8%, 95% CI 51.5-66.1%, respectively, and in LETO rats they were 46.4%, 95% CI 39.0-53.7% and 53.8%, 95% CI 46.9-60.7%, respectively, when expressed as the percentage relative to that induced by KCl 30 mM. In LETO rats, sevoflurane at a concentration of 3.4% inhibited the vascular contraction (9.4%, 95% CI 6.3-12.6%; P < 0.001) and the increase in [Ca²(+)](i) (33.3%, 95% CI 27.4-39.2%; P = 0.002). In OLETF rats, however, sevoflurane failed to affect either the NE-induced contraction (43.6%, 95% CI 28.3-58.9%; P = 0.68) or the elevation in [Ca²(+)](i) (60.5%, 95% CI 56.3-64.8%; P = 0.93). Sevoflurane at clinically relevant concentrations inhibited the NE-induced increase in [Ca²(+)](i) in the aortic smooth muscle from normal rats but not in that from type 2 DM rats. Thus, a Ca²(+)- signalling pathway resistant to sevoflurane appears to exist in the type 2 DM rat aorta.


Receptor-mediated label-transfer assay (RELAY): a novel method for the detection of plasma tumor necrosis factor at attomolar concentrations.
We have exploited the extremely high binding specificity of the 55 kDa human tumor necrosis factor (TNF) receptor in an assay designed to detect TNF with sensitivity limited only by limits in the detection of 131I. Bivalent derivatives of the 55 kDa TNF receptor (referred to here as the TNF binding protein), in which the extracellular domain is coupled to an IgG heavy chain, ordinarily bind TNF with very high affinity as a result of the fact that they interact with two separate sites on the trimer surface. The TNF binding protein is radioiodinated to a high specific activity and then added to plasma at a saturating concentration, so that it binds all active TNF present in the solution. Covalent adducts between molecules of TNF and molecules of the binding protein are then produced by crosslinking with disuccinimidyl suberate (DSS). The complexes are swept out of solution using sepharose beads to which polyclonal anti-TNF antibodies have been affixed. On electrophoresis, the complex presents itself as a band of M(r) = 200 kDa (as distinct from the uncomplexed binding protein, which has a size of 120 kDa and which in any case is removed by washing). As little as 50 fg of active TNF (600,000 trimers) can be detected in a 5 ml sample of plasma using this approach, corresponding to the detection of TNF at a 200 aM concentration. Notably, no TNF is detectable in normal plasma specimens, indicating that normal plasma contains active TNF at a concentration beneath 200 aM.


Effects of age, seasonality, and reproductive status on the gut microbiome of Southern White Rhinoceros (Ceratotherium simum simum) at the North Carolina zoo.
Managed southern white rhinoceros (Ceratotherium simum simum) serve as assurance populations for wild conspecifics threatened by poaching and other anthropocentric effects, though many managed populations experience subfertility and reproductive failure. Gut microbiome and host health are inextricably linked, and reproductive outcomes in managed southern white rhinoceros may be mediated in part by their diet and gut microbial diversity. Thus, understanding microbial dynamics within managed populations may help improve conservation efforts. We characterized the taxonomic composition of the gut microbiome in the managed population of female southern white rhinoceros (n = 8) at the North Carolina Zoo and investigated the effects of seasonality (summer vs. winter) and age classes (juveniles (n = 2; 0-2 years), subadults (n = 2; 3-7 years), and adults (n = 4; >7 years)) on microbial richness and community structure. Collection of a fecal sample was attempted for each individual once per month from July-September 2020 and January-March 2021 resulting in a total of 41 samples analyzed. Microbial DNA was extracted and sequenced using the V3-V4 region of the 16S rRNA bacterial gene. Total operational taxonomic units (OTUs), alpha diversity (species richness, Shannon diversity), and beta diversity (Bray-Curtis dissimilarity, linear discriminant analysis effect size) indices were examined, and differentially enriched taxa were identified. There were differences (p < 0.05) in alpha and beta diversity indices across individuals, age groups, and sampling months. Subadult females had higher levels of Shannon diversity (Wilcoxon, p < 0.05) compared to adult females and harbored a community cluster distinct from both juveniles and adults. Samples collected during winter months (January-March 2021) possessed higher species richness and statistically distinct communities compared to summer months (July-September 2020) (PERMANOVA, p < 0.05). Reproductively active (n = 2) and currently nonreproductive adult females (n = 2) harbored differentially enriched taxa, with the gut microbiome of nonreproductive females significantly enriched (p = 0.001) in unclassified members of Mobiluncus, a genus which possesses species associated with poor reproductive outcomes in other animal species when identified in the cervicovaginal microbiome. Together, our results increase the understanding of age and season related microbial variation in southern white rhinoceros at the North Carolina Zoo and have identified a potential microbial biomarker for reproductive concern within managed female southern white rhinoceros.


Measurement of the graft angles for the anterior cruciate ligament reconstruction with transtibial technique using postoperative magnetic resonance imaging in comparative study.
The aims of this study were to quantify the angle and placement of an anterior cruciate ligament (ACL) grafted with a single incision ACL reconstruction technique using postoperative magnetic resonance imaging (MRI), and to compare the results with those with a native ACL. Between February 1996 and May 2004, 96 consecutive patients, who had undergone postoperative MRI of the knee followed by an arthroscopically assisted ACL reconstruction with either a hamstring tendon or bone-patellar tendon-bone (BTB) autograft, were enrolled in this study. The femoral tunnel was drilled using the transtibial technique. The patients were divided into two groups; the hamstring tendon graft group (group H; 50 patients) and the BTB graft group (group B; 46 patients). All the patients including both groups in this study underwent postoperative MRI and were followed up for a minimum of 2 years. The control group (group C) consisted of 50 patients whose meniscus tear had been operated on by arthroscopy and whose ACL was intact. The orientation of the ACL ligament or graft was measured using three different methods: the sagittal ACL angle, the ACL-Blumensaat line angle, and the coronal ACL angle. The mean sagittal ACL angle in group C (58.7 +/- 3.8 degrees ) was significantly lower than in groups H (64.6 +/- 4.2 degrees ) and B (71.3 +/- 6.0 degrees ). The mean ACL-Blumensaat line angle in group C (8.6 +/- 3.6 degrees ) was also significantly lower than in groups H (12.8 +/- 5.2 degrees ) and B (18.0 +/- 5.3 degrees ). The mean coronal ACL angle in group C (65.9 +/- 4.4 degrees ) was lower than that in groups H (73.5 +/- 2.4 degrees ) and B (75.2 +/- 2.9 degrees ). The grafted ACL of the hamstring tendon and BTB grafts on the postoperative MRI showed a significant vertical angle in the coronal and sagittal plane compared with the native ACL. In the sagittal plane, the hamstring tendon graft was positioned more obliquely than the BTB graft, which had a larger angle of the tibial tunnel, in an attempt to prevent a graft-tunnel mismatch. The postoperative MRI study showed that the more horizontally the angle of the tibial tunnel can be placed in a single incision ACL reconstruction, the more efficiently it can produce a graft closer to the native ACL.


Synthesis and biological evaluation of oxazinonaphthalene-3-one derivatives as potential anticancer agents and tubulin inhibitors.
In the present study, a new series of oxazinonaphthalene-3-one analogs was designed and synthesized as novel tubulin inhibitors. The cytotoxic activity of the synthesized compounds was evaluated against four human cancer cell lines including A2780 (human ovarian carcinoma), A2780/RCIS (cisplatin resistant human ovarian carcinoma), MCF-7 (human breast cancer cells), and MCF-7/MX (mitoxantrone resistant human breast cancer cells), those compounds which demonstrated the most antiproliferative activity in the MTT test were selected to investigate their tubulin inhibition activity and their effects on cell cycle arrest (at the G2/M phase). Moreover, molecular docking studies of the selected compounds in the catalytic site of tubulin (PDB ID: 4O2B) were carried out to describe the results of biological experiments. Most of our compounds exhibited significant to moderate cytotoxic activity against four human cancer cell lines. Among them, Compounds 4d, 5c, and 5g, possessing trimethoxy phenyl, showed the most antiproliferative activity with IC50 values ranging from 4.47 to 52.8 μM. The flow cytometric analysis of A2780 cancer cell line treated with compounds 4d, 5c, and 5g showed that these compounds induced cell cycle arrest at the G2/M phase. Compound 5g, the most antiproliferative compound, inhibited tubulin polymerization in a dose-dependent manner. Molecular docking studies of 5g into the colchicine-binding site of tubulin displayed a possible mode of interaction between this compound and tubulin.


Exploring the experience of undergraduate nursing students following placement at psychiatric units in China: A phenomenological study.
To explore undergraduate nursing students' experiences of psychiatric placements. Placement is an important learning phase for undergraduate nursing students and the placement experiences may affect their career choices. However, nursing students' experiences of psychiatric placements have not been fully explored in China. This study adopted a descriptive, phenomenological design. After psychiatric placement, a semi-structured interview was conducted in June 2022 among 22 final-year undergraduate nursing students using purposive sampling. The data were analysed using Colaizzi's seven-step analysis method. Five themes were identified: i) destigmatising mental illness; ⅱ) beneficial communication; ⅲ) gaining confidence; iv) disappointment and sadness; and v) fear and discomfort. Nursing students experienced various positive experiences and negative emotions during their psychiatric placement. Further research should explore and validate appropriate educational strategies to optimise students' placement experiences to increase their career interest in psychiatric nursing.


Alpha-Catulin Co-Localizes With Vimentin Intermediate Filaments and Functions in Pulmonary Vascular Endothelial Cell Migration via ROCK.
The ubiquitous α-catulin acts as a scaffold for distinct signalosomes including RhoA/ROCK; however, its function is not well understood. While α-catulin has homology to the cytoskeletal linkers α-catenin and vinculin, it appears to be functionally divergent. Here we further investigated α-catulin function in pulmonary vascular endothelial cells (VEC) on the premise that α-catulin has a unique cytoskeletal role. Examination of endogenous α-catulin intracellular localization by immunofluorescence revealed a highly organized cytosolic filamentous network suggestive of a cytoskeletal system in a variety of cultured VEC. Double-immunofluorescence analyses of VEC showed endogenous α-catulin co-localization with vimentin intermediate filaments. Similar to vimentin, α-catulin was found to distribute into detergent-soluble and -insoluble fractions. Treatment of VEC with withaferinA, an agent that targets vimentin filaments, disrupted the α-catulin network distribution and altered α-catulin solubility. Vimentin participates in cell migration, and withaferinA was found to inhibit VEC migration in vitro; similarly, α-catulin knock-down reduced VEC migration. Based on previous reports showing that ROCK modulates vimentin, we found that ROCK depletion attenuated VEC migration; furthermore, α-catulin depletion was shown to reduce ROCK-induced signaling. These findings indicate that α-catulin has a unique function in co-localization with vimentin filaments that contributes to VEC migration via a pathway that may involve ROCK signaling. J. Cell. Physiol. 231: 934-943, 2016. © 2015 Wiley Periodicals, Inc.


Contingency-based delay to reinforcement following functional communication training for autistic individuals: A multilevel meta-analysis.
Functional communication training, an intervention for challenging behavior rooted in principles of applied behavior analysis, has copious empirical support dating back to the mid-1980s for autistic individuals. Recently, there has been a concerted effort to thin reinforcement delivery during functional communication training using contingency-based delays that, in turn, are designed to enhance practicality and feasibility while not compromising efficacy. In this synthesis, we meta-analyzed the literature base with the goal of investigating both combined and across type effectiveness of contingency-based delays. We also aimed to investigate moderating variables that might impact intervention outcomes. Findings showed that contingency-based delays were effective for individuals with an autism spectrum disorder diagnosis and most effective when the delay incorporated some form of positive reinforcement. In addition, differential reinforcement of alternative-based delays was overall more effective when compared to differential reinforcement of other behavior-based delays. Noteworthy moderating variables found to impact contingency-based delay efficacy included the intervention dosage and the topography of behavior. We discuss these findings and highlight directions where additional empirical research is warranted to improve our understanding about contingency-based delays for individuals diagnosed with autism spectrum disorder.


Establishment of a biomarker model for predicting bone metastasis in resected stage III non-small cell lung cancer.
This study was designed to establish a biomarker risk model for predicting bone metastasis in stage III non-small cell lung cancer (NSCLC). The model consists of 105 cases of stage III NSCLC, who were treated and followed up. The patients were divided into bone metastasis group (n = 45) and non-bone metastasis group (other visceral metastasis and those without recurrence) (n = 60). Tissue microarrays were constructed for immunohistochemical study of 10 molecular markers associated with bone metastasis, based on which a model was established via logistic regression analysis for predicting the risk of bone metastases. The model was prospectively validated in another 40 patients with stage III NSCLC. The molecular model for predicting bone metastasis was logit (P) = - 2.538 + 2.808 CXCR4 +1.629 BSP +0.846 OPN-2.939 BMP4. ROC test showed that when P ≥ 0.408, the sensitivity was up to 71% and specificity of 70%. Model validation in the 40 cases in clinical trial (NCT 01124253) demonstrated that the prediction sensitivity of the model was 85.7%, specificity 66.7%, Kappa: 0.618, with a high degree of consistency. The molecular model combining CXCR4, BSP, OPN and BMP4 could help predict the risk of bone metastasis in stage IIIa and IIIb resected NSCLC.


The lateralized readiness potential and P300 of stimulus-set switching.
The present study aimed at investigating whether stimulus-set switching involves the same stages of information processing as response-set switching. A pair-wise task switching paradigm in which the trial sequences comprised only two tasks was used. The effect of preparation was manipulated so that the participants performed only the repeat trials in some blocks and only the switch trials in other blocks, or both the repeat and switch trials were randomly mixed within a single block. P300 peak latency and stimulus- and response-locked lateralized readiness potential intervals were used to indicate the processing stage of stimulus identification, response selection and motor execution, respectively. The results demonstrated that the stimulus-set switching involves stages of information processing following stimulus identification and before motor execution.


Sm Doped ZnO Nanowires@PAN Nanofibrous Membranes for Photocatalytic Degradation of Dye.
Wastewater involving a lot of contaminants like organic dyes from the textile finishing industry causes a greater adverse impact on human beings. There are many patents on nanofibers involved metallic oxides, this paper studies photocatalytic degradation of free-pollution Zinc Oxide (ZnO) nanomaterials on dye decontamination. Polyacrylonitrile (PAN) nanofibrous membranes loaded with Zinc Oxide (ZnO) nanowires were fabricated and evaluated for photocatalytic degradation. In this work, Polyacrylonitrile (PAN) nanofibrous membranes loaded with ZnO seeds were prepared by electrospinning PAN/Zn (Ac)2 solution followed by a thermal decomposition process. ZnO nanowires were hydrothermally grown on the surface of PAN nanofibers. The effects of the ratio of PAN and zinc acetate in a solution, decomposition temperature and ammonia (NH4OH) on the morphologies of ZnO nanowires were observed. ZnO nanowires showed the optimum morphologies when the ratio of PAN/Zn (Ac)2 was 10:1.5. The decomposition temperature was 150oC, and NH4OH was added in the hydrothermal reaction. The photocatalytic degradation of Rhodamine B solution under UV irradiation was used as a model reaction. The photodegradation ability of the ZnO @PAN membrane doped with cerium (Sm) was also investigated. Slight Sm doping increased the photocatalytic degradation rate from 57% to 89% under ultraviolet light irradiation for 2h. After 5 times of cycling under the same conditions, it still maintained the dye decolorization rate that was above 65%. Sm doped ZnO nanowires @PAN nanofibrous membranes were easily produced and could provide a novel process for the degradation of dye decontamination.


Blood-sucking bugs as a gentle method for blood-collection in water budget studies using doubly labelled water.
During doubly-labelled water (DLW) experiments, blood collection by venous puncture may traumatize animals and consequently affect the animals' behaviour and energy budget. Recent studies have shown that blood-sucking bugs (Triatominae; Heteroptera) can be used instead of conventional needles to obtain blood from animals. In this paper, we validate the bug method in captive nectar-feeding bats, Glossophaga soricina, for water budget analysis by comparing the daily water flux estimated with the DLW method with values measured by an energy balance method. As the mean daily water flux of the DLW method was not significantly deviating from the expected value, blood-sucking bugs may substitute more invasive methods of blood collection in DLW experiments. Based on the DLW estimates, daily energy and water intake rates were calculated and compared to values measured with the energy balance method. The DLW method and the energy balance method yielded on average similar results regarding the daily energy intake (DLW method: 48.8+/-14.2 kJ d(-1) versus energy balance method: 48.1+/-9.9 kJ d(-1)) and daily water intake (DLW method: 13.7+/-2.4 mL d(-1) versus energy balance method: 14.7+/-3.0 mL d(-1)). Based on the calculated water and sugar intake per day, we estimated the sugar concentration of ingested nectar to equal on average 16.2+/-2.4% (mass/mass), which fell close to the measured sugar concentration of 17% (mass/mass) bats fed on during the experiment. We conclude that it is possible to extrapolate mean daily energy and water intake for animal groups, populations and species based on DLW estimates, but due to the large variance of results (low accuracy), it seems inadequate to calculate values for single individuals.


[Clinical application of robotic tele-manipulation system in stereotactic surgery].
To assess the clinical usefulness, accuracy, and safety of tele-manipulation for frameless stereotactic surgery using the CAS-R-5 robot system. We prospectively evaluated 32 patients underwent tele-manipulation of frameless stereotactic operations from Sep. 2005 to Sep. 2006. Tele-manipulations were performed via a digital data network by a neurosurgeon in Beijing while the patients were located in Yan'an. The distance is 1300 kilometers away. The accuracy of location and improvement of symptom were observed after operation. The period of follow-up was from 3 to 14 months (the average was 12 months). The surgical operations in 32 cases were successful. Remote fiducial registration was performed with a mean accuracy of 1. 50 mm and the standard difference were 0.32 mm between the planned and actual target. There were no complications. Diagnosis and treatment for intracranial disease by tele-manipulation frameless stereotactic surgeries are reliable and safe.


Effect of ultrafiltration process on physico-chemical, rheological, microstructure and thermal properties of syrups from male and female date palm saps.
This study investigates the effect of the ultrafiltration process on physicochemical, rheological, microstructure and thermal properties of syrups from male and female date palm sap. All the studied syrups switched from pseudoplastic rheological behaviour (n=0.783) to Newtonian behaviour (n∼1) from 10 to 50 °C respectively and present similar thermal profiles. Results revealed that the ultrafiltration process significantly affects the rheological behaviour of the male and female syrups. These differences on rheological properties are attributed to the variation of chemical composition between sap and sap permeate syrups. Furthermore, the effect of temperature on viscosity of the syrups was investigated during heating and cooling processes at the same shear rate (50s(-1)). This study provides idea of the stability of the syrup by evaluating the area between heating and cooling curves. Actually, the syrup prepared from male sap permeate is the most stable between the four studied syrups.


The genus Speleocola lipovsky (Acari: Trombiculidae) with descriptions of two new species from Venezuela.
Speleocola Lipovsky 1952 is redescribed. New species S. clangula off Rhipidomys sp., Venezuela, and S. nolae off Peropteryx kappleri, Venezuela, are described. A key to the 5 included species is given.


The effects of various diphosphonates on a rat model of cardiac calciphylaxis.
Seven diphosphonate analogs were treated for their effects on myocardial and cardiovascular degeneration and calcification in an experimental model of cardiac calciphylaxis. A single oral dose of dihydrotachysterol (DHT) administered to rats induced myocardial and vascular degeneration, focal myocarditis and vasculitis, and myocardial and vascular mineralization. The results demonstrated a considerable variation among the various diphosphonates in their ability to block the pathological changes observed in this model. Ethane-1-hydroxy-1,1-diphosphonate (EHDP) was the most effective diphosphonate in reducing myocardial and vascular degeneration and calcification, whereas diphosphonates such as ethane-1-amino-1,1-diphosphonate (EADP) and hydroxymethylene diphosphonate (HMDP) had little or no effect compared to saline controls. For those diphosphonates which were effective, e.g., EHDP, the tissue-protective effects were observed whether the rats were treated with drug prior to the administration of DHT, or whether drug treatment commenced after DHT administration. The results are discussed in terms of the known biological properties of the diphosphonate drugs.


Increased bone contact to a calcium-incorporated oxidized commercially pure titanium implant: an in-vivo study in rabbits.
The aim of this study was to evaluate the bone response to an oxidized titanium implant (Ox) and a calcium-incorporated oxidized titanium implant (Ca). A blasted titanium implant (Bl) was used as control. The implants were topographically characterized using an optical interferometer and placed: one in each distal femoral metaphysis and two in each proximal tibial metaphysis in rabbits. The rabbits were killed 12 weeks after implant insertion, and the implants and their surrounding tissues were removed en bloc for histomorphometrical evaluations. Topographical evaluation revealed three different surfaces: average height deviation (S(a), microm) values for Ca:Ox:Bl implants were 0.3:0.6:0.9, developed surface area ratios (%) 17:44:31, number of summits per microm(2) 208:136:118, and core fluid retention index values 1.33:1.33:1.38. The mean percentages of bone contact to the implants placed in the tibia (Ca:Ox:Bl) were 47:30:34 and to the implants placed in the femur (Ca:Ox) 32:20. The mean percentages of surrounding bone area for the implants placed in the tibia were 40:47:37 and for the implants placed in the femur 43:46. A significant increase in bone contact was found for smooth (S(a) <0.5 microm) but more densely peaked calcium-incorporated oxidized implants when compared to slightly rougher (S(a)=0.5-1.0 microm) oxidized or blasted implants.


Transmission control of schistosomiasis japonica: implementation and evaluation of different snail control interventions.
The great progress made in the control of schistosomiasis japonica in China is to some extent explained by successful intermediate host snail control, in particular with environmental management commencing some 50 years ago. By 1995, interruption of Schistosoma japonicum transmission had been achieved in five of the 12 schistosome-endemic provinces while endemic areas in the remaining provinces had been reduced significantly, and snail habitats had decreased by 74%. In this paper, we review the role and approaches towards control and give an account of compounds toxic to snails. Mid- and long-term national plans for schistosomiasis control are discussed, including integrated snail control approaches as an important measure. It is anticipated that implementation of these plans will accelerate snail control, which in turn will consolidate and mutually reinforce other control measures, most notably praziquantel-based chemotherapy. The ultimate aim is to eliminate schistosomiasis as a public health problem in China.


Supramolecular dimerisation of middle-chain Phe pentapeptides via CB[8] host-guest homoternary complex formation.
Pentapeptides containing a Phe residue in the middle of the sequence exhibit ternary complex formation in the presence of cucurbit[8]uril, thus opening new perspectives on supramolecular peptide dimerisation studies.


GABA(B) receptor agonists for the treatment of drug addiction: a review of recent findings.
A growing preclinical and clinical literature suggests that GABA(B) receptor agonists promote abstinence and reduce the use of cocaine, heroin, alcohol and nicotine. The purpose of this paper is to critically review these data. GABA(B) receptor agonists, such as baclofen, appear to reduce the reinforcing effects of abused drugs in animal models under multiple experimental procedures. This occurs at doses that have little effect on responding for other positive reinforcers such as food or water. We review evidence that these potential therapeutic effects may be mediated by modulation of mesolimbic dopamine neurons. This review also examines the preliminary clinical data from studies of the efficacy of baclofen for treatment of cocaine, alcohol, and nicotine dependence. We suggest that these preliminary data provide a rationale for conducting more systematic studies of the effects of GABA(B) receptor agonists as treatment for drug abuse. This line of research may also improve our understanding of the neurochemical mechanisms underlying the drug dependence process.


Dissociations within association cortex.
The parietal lobes of nonhuman primates have been well characterized by single neuron recordings, yet clear partitioning of the human parietal lobes has not been clearly demonstrated. An elegant new fMRI study by Simon and colleagues (this issue of Neuron) suggests that parietal cortex does indeed contain dissociable subregions, each specialized for a particular visuomotor or cognitive function.


Characterization of spatiotemporal dynamics in EEG data during picture naming with optical flow patterns.
In this study, we investigate the spatiotemporal dynamics of the neural oscillations by analyzing the electric potential that arises from neural activity. We identify two types of dynamics based on the frequency and phase of oscillations: standing waves or as out-of-phase and modulated waves, which represent a combination of standing and moving waves. To characterize these dynamics, we use optical flow patterns such as sources, sinks, spirals and saddles. We compare analytical and numerical solutions with real EEG data acquired during a picture-naming task. Analytical approximation of standing waves helps us to establish some properties of pattern location and number. Specifically, sources and sinks are mainly located in the same location, while saddles are positioned between them. The number of saddles correlates with the sum of all the other patterns. These properties are confirmed in both the simulated and real EEG data. In particular, source and sink clusters in the EEG data overlap with each other with median percentages around 60%, and hence have high spatial correlation, while source/sink clusters overlap with saddle clusters in less than 1%, and have different locations. Our statistical analysis showed that saddles account for about 45% of all patterns, while the remaining patterns are present in similar proportions.


Oxygen dependence of metabolism and cellular adaptation in vertebrate muscles: a review.
The key roles the cardiovascular system play in the complex distribution of blood, and consequently oxygen, have been extensively studied in vertebrates. Numerous studies have also revealed the complex and varied ways in which tissues cope with compromised oxygen supply. The links between these two processes are the subject of much current research. This article aims to review how blood supply influences tissue oxygenation and affects metabolism, and how this might have played a role in the evolution of the complex muscle arrangements which characterise vertebrates. Muscle tissue is the greatest proportion of body mass in most vertebrates and undergoes dramatic alterations in metabolism and associated oxygen flux. Special attention is given to the myotome of fishes, in which the partitioning of the fibre types contrasts with the mosaic arrangement of tetrapods. This gives us the opportunity to study pure whole vascularised muscle blocks, rather than single fibres, and further explore the interrelationship between oxygen supply and tissue energetics.


Self-assembled FeS-based cascade bioreactor with enhanced tumor penetration and synergistic treatments to trigger robust cancer immunotherapy.
Major challenges for cancer treatment are how to effectively eliminate primary tumor and sufficiently induce immunogenic cell death (ICD) to provoke a robust immune response for metastasis control. Here, a self-assembled cascade bioreactor was developed to improve cancer treatment with enhanced tumor penetration and synergistic therapy of starvation, chemodynamic (CDT) and photothermal therapy. Ultrasmall FeS-GOx nanodots were synthesized with glucose oxidase (GOx) as template and induced by paclitaxel (PTX) to form self-assembling FeS-GOx@PTX (FGP) via hydrophobic interaction. After accumulated at tumor sites, FGP disassembles to smaller FeS-GOx for enhanced deep tumor penetration. GOx maintains high enzymatic activity to catalyze glucose with assistant of oxygen to generate hydrogen peroxide (H2O2) as starvation therapy. Fenton reaction involving the regenerated H2O2 in turn produced more hydroxyl radicals for enhanced CDT. Following near-infrared laser at 808 nm, FGPs displayed pronounced tumor inhibition in vitro and in vivo by the combination therapy. The consequent increased exposure to calreticulin amplified ICD and promoted dendritic cells maturation. In combination with anti-CTLA4 checkpoint blockade, FGP can absolutely eliminate primary tumor and avidly inhibit distant tumors due to the enhanced intratumoral infiltration of cytotoxic T lymphocytes. Our work presents a promising strategy for primary tumor and metastasis inhibition.


Painful hepatic hemangioma: report of a case with an emphasis on sonographic findings.
Hepatic hemangiomas are usually asymptomatic and very rarely produce abdominal symptoms. We report a painful 10 × 9 cm hemangioma situated at the hepatic surface of segment 6. The lesion showed a heterogeneous internal structure, composed irregularly of hyperechoic and hypoechoic areas, and it also showed weak posterior echo enhancement. Contrast-enhanced US showed the so-called fill-in pattern, leading to the diagnosis of hepatic hemangioma. The patient's abdomen showed no other abnormal findings, which stressed the relationship between the hemangioma and the patient's symptoms. When the diagnosis of hepatic hemangioma is conclusive, surgical therapy is indicated only in patients with severe symptoms. Our patient was considered to be a candidate for enucleation of the lesion. Histopathologically, the lesion included no areas of hemorrhage or necrosis, and the patient's abdominal pain was likely due to distension of the liver capsule. After surgery, the patient was completely free of symptoms, and enucleation was considered to be appropriate.


Cladophialophora bantiana brain abscess and concurrent pulmonary cryptococcus neoformans infection in a patient twenty years after renal transplantation.
Recipients of solid organ transplants are at risk for a variety of infections due to their immunocompromised status. The types of infections are often correlated to the timing from their transplant. After about six to twelve months, transplant recipients remain at risk for typical community acquired pathogens, late viral infections, and fungal infections including atypical molds such as Cladophialophora bantiana. C. bantiana is a dematiaceous fungus that has a predilection for infecting the brain and is the most common cause of cerebral phaeohyphomycosis - a term used to describe infections caused by molds that produce dark cell walls. Patients with cerebral abscesses due to C. bantiana infections have an estimated mortality of about 70%. Improved outcomes have been seen in patients who receive both surgical and antifungal therapy. While there are no clear guidelines on antifungal therapy, most cases have been treated with combination amphotericin B, a triazole (itraconazole, voriconazole, or posaconazole) with flucytosine sometimes in conjunction as well. This case describes a patient with C. bantiana brain abscess and concurrent Cryptococcus neoformans pulmonary infection that occurred twenty years after his kidney transplantation. He was treated successfully with two craniotomies for cerebral abscess debridement and liposomal amphotericin B followed by planned lifelong voriconazole.


Decay of Salmonella enterica, Escherichia coli and bacteriophage MS2 on the phyllosphere and stored grains of wheat (Triticum aestivum).
Cereal crops grown in the biosolids-amended soil can potentially become contaminated with pathogenic micro-organisms during growth and at the time of harvesting. There is small but unquantified potential risk of transfer of enteric pathogens to humans and animals from contaminated plants and grains. This study examined decay of Escherichia coli, Salmonella enterica serovar Typhimurium and bacteriophage MS2 on the wheat phyllosphere and on stored grains. This was done to assess the health implications of cereal crops contaminated from land application of biosolids. E. coli, S. enterica and MS2 were inoculated onto the leaves, spikelets and grains of wheat. The change in the numbers of inoculated micro-organisms was determined over time to calculate the respective 90% reduction time (T90 ) in each of these environments. A rapid inactivation (T90 <1-3 days) of E. coli and S. enterica and MS2 from the plant phyllosphere was observed, particularly from the spikelets. The decay rates were influenced by micro-organism type and location on the plant phyllosphere. Decay times on the stored grains were longer (T90 9-71 days), with some observed influence of grain variety on pathogen decay times. Results of this study suggest that there is very limited potential of enteric pathogens survival on wheat phyllosphere and grains. Therefore, the risk of transfer of enteric pathogens from biosolids-amended soil to consumers of grain products is considered to be low. This study has important implications for the grains industry, as the results suggest that chances of preharvest contamination of grains with enteric pathogens from biosolids-amended soil are low.


On the investigation of the bilayer functionalities of 1,2-di-oleoyl-sn-glycero-3-phosphatidylcholine (DOPC) large unilamellar vesicles using cationic hemicyanines as optical probes: a wavelength-selective fluorescence approach.
The behavior of the cationic hemicyanines trans-4-[4-(dimethylamino)-styryl]-1-methylpyridinium iodide (HC) and 4,(4-(dihexadecylamino)styryl-N-methyl-pyridinium iodide (DIA) were studied in large unilamellar vesicles (LUV) of 1,2-di-oleoyl-sn-glycero-3-phosphatidylcholine (DOPC) using absorption, emission, depolarization and time resolved spectroscopies. Also, thorough spectroscopic studies were performed in homogeneous media to investigate the different interactions that the dyes can experience with its microenvironment. These results help us to comprehend the dye performance under different media and, consequently find interesting features of the DOPC membrane properties. The studies in homogeneous media analyzed by the Kamlet and Taft's solvatochromic comparison method demonstrate, for the first time, that the cationic hemycianines undergo specific interactions with the medium through the solvents ability to donate an electron pair as measured by the beta parameter. Thus, the absorption bands shifts bathochromically with beta while, the emission band shifts hypsochromically. In addition, for the relaxed hemicyanines the 00 energy, nu00, is invariant with the solvent properties. The results in LUV of DOPC show that, DIA undergoes a strong association with the vesicle bilayer while HC partitions between the water and the bilayer pseudophases. To monitor directly the microenvironment and dynamics around HC and DIA inside the DOPC bilayer, we use the wavelength-selective fluorescence approach, which is based on the red edge effect in fluorescence spectroscopy, in addition with the nu00 energy of the hemicyanines. The results show that the fluid state of the DOPC bilayer resembles the microenvironment of sodium bis (2-ethylhexyl) sulfosuccinate (AOT) reverse micelles at W=[H2O]/[AOT] below 10 where there is no free water forming the water pool. Moreover, it is demonstrated for the first time, that the region of the bilayer close to the polar head of DOPC is a powerful electron donor environment.


Hypoattenuated Leaflet Thickening After Implantation of the ACURATE neo or the ACURATE neo2 Transcatheter Heart Valve.
Subclinical leaflet thrombosis, identified as hypoattenuated leaflet thickening (HALT) on cardiac computed tomography scan, has been observed after transcatheter aortic valve replacement (TAVR). However, data on HALT after the implant of the supra-annular ACURATE neo/neo2 prosthesis are limited. This study aimed to determine the prevalence and risk factors for the development of HALT after TAVR with the ACURATE neo/neo2. A total of 50 patients who received the ACURATE neo/neo2 prosthesis were prospectively enrolled. Patients underwent a contrast-enhanced multidetector row cardiac computed tomography scan at before, after, and 6 months after TAVR. At the 6-month follow-up, HALT was detected in 16% (8 of 50 patients). These patients had a lower implant depth of the transcatheter heart valve (8 ± 2 mm vs 5 ± 2 mm, p = 0.001), less calcified native valve leaflets, a better expansion of the frame at the level of the left ventricular outflow tract, and were less often hypertensive. Thrombosis of the sinus of Valsalva occurred in 18% (9/50). There was no difference in the anticoagulation regimen between patients with and without thrombotic findings. In conclusion, HALT was present in 16% of patients at 6 months follow-up, patients presenting with HALT had a lower implant depth of the transcatheter heart valve, and HALT was detected in patients on oral anticoagulation therapy.


The effects of mindfulness meditation versus CBT for anxiety on emotional distress and attitudes toward seeking mental health treatment: a semi-randomized trial.
Older adults often avoid seeking psychological treatment, thus challenging their ability to cope effectively with anxiety, stress, and depression. The current study aimed to compare the effects of a mindfulness intervention with cognitive behavioral therapy (CBT) on measures of emotional distress and attitudes toward seeking mental health treatment among older adults. Twenty-four seniors were assigned to three groups: (1) Mindfulness-based intervention for seniors (MBIS), (2) CBT for anxiety, or (3) a care-as-usual control group. Participants in the two intervention groups of eight weekly sessions were randomly assigned. Results showed that attitudes toward seeking psychological treatment and depression, anxiety, and worry levels were evaluated before and after the interventions. Following both interventions, participants considered the prospect of utilizing psychological treatment more positively, whereas no changes were observed in the control group. Interestingly, worry levels were eased only in the MBIS group, and anxiety levels were eased only in the CBT group. Our findings support the understanding that cognitive group interventions can effectively achieve their intended aim (decreasing worry or anxiety) and positively impact attitudes toward psychological treatment.Trial registration: clinicaltrials, NCT04165005, 15/11/19.


Efficacy and Safety of Gastrointestinal Tumour Site Marking with da Vinci-Compatible Near-Infrared Fluorescent Clips: A Case Series.
The conventional near-infrared fluorescent clip (NIRFC) ZEOCLIP FS® has been used successfully in marking tumour sites during laparoscopic surgeries. However, this clip is difficult to observe with the Firefly imaging system equipped with the da Vinci® surgical system. We have been involved in the modification of ZEOCLIP FS® and development of da Vinci-compatible NIRFC. This is the first prospective single-centre case series study verifying the usefulness and safety of the da Vinci-compatible NIRFC. Twenty-eight consecutive patients undergoing da Vinci®-assisted surgery for gastrointestinal cancer (16 gastric, 4 oesophageal, and 8 rectal cases) between May 2021 and May 2022 were enrolled. Tumour location was identified by the da Vinci-compatible NIRFCs in 21 of 28 (75%) patients, which involved 12 gastric (75%), 4 oesophageal (100%), and 5 rectal (62%) cancer cases. No adverse events were observed. Tumour site marking with da Vinci-compatible NIRFC was feasible in 28 patients enrolled in this study. Further studies are warranted to substantiate the safety and improve the recognition rate.


[SNaPshot technique for detection of single-nucleotide polymorphisms (SNPs) in HBV polymerase gene region of HBV gene].
To establish a rapid specific method to identify the single-nucleotide polymorphisms (SNPs) of HBV polymerase gene region which are the methionine residue of the conserved YMDD motif. Two specific primers were designed to amplify interested gene region involved in SNPs which were also used as HBV DNA identification. Specific primers of SNaPshot were designed to detect 741A-G (YVDD), 743G-T (YIDD). The different fluorescent dye labeled ddNTP was used to further extend the strand of PCR product and was detected by ABI PRISM 310 Genetic Analyzer. Sera from 13 patients with chronic hepatitis B after lamivudine treatment were analyzed. Aside from mutation of YMDD, there were mutations of 514C-A, 523C-A, 562T-A, 667C-A. The 13 samples were simultaneously tested with SNaPshot and DNA sequencing, the same results were obtained. The method of SNaPshot showed high specificity. Mutation of YMDD results in the changes of ATG codon, and there are new ATG codon in the upper strand of YMDD. SNaPshot technique is rapid, specific and accurate for the SNPs monitoring of HBV DNA mutation during lamivudine therapy. Two samples were determined by SnaPshot technique, identifying the co-existence of the mixed wild type and mutant type HBV infection.


Ultrasound for Suspected Acute Appendicitis in Adult Women Under Age 40: An Evaluation of On-Call Radiology Resident Scanning.
At our institution, on-call radiology residents perform emergent ultrasounds (US) outside of departmental working hours. The aim of the study was to evaluate radiology resident-performed US for clinically suspected acute appendicitis in women under the age of 40. Retrospective review of 104 consecutive US scans outside of departmental working hours by radiology residents, and 104 consecutive US studies scanned during departmental working hours by sonographers, in women under the age of 40 for clinically suspected appendicitis . Appendix visualization rate was 27% for the resident group (sonographer group: 30%, p = 0.759). The sensitivity and specificity of US for appendicitis were 63% (95% confidence interval: 41%-81%) and 98% (95% CI: 91%-100%), respectively for the resident group (sonographer group: 69% [95% CI: 41%-89 %] and 98% [95% CI: 92%-100%], respectively). An alternative cause for right lower quadrant pain was offered in 17% of resident group cases (sonographer group: 21%, p = 0.598). Follow-up CT or MRI was performed in 47% of resident cases (sonographer group: 44%, p = 0.781). Residents performed more focused US (i.e. not imaging the pelvic organs), at 34% (sonographer group: 1%, p < 0.001). When only focused scanning was performed by residents, there was a trend toward increased downstream imaging (CT or MRI), odds ratio = 2.76 (95% CI: 0.99-7.70). Out-of-hours US scans performed by radiology residents had similar performance characteristics compared to departmental sonographers. We discovered an increased rate of downstream imaging in cases in which residents performed limited scans and did not document visualization of the pelvic organs.


Metronomic adjuvant chemotherapy improves treatment outcome in nasopharyngeal carcinoma patients with postradiation persistently detectable plasma Epstein-Barr virus deoxyribonucleic acid.
To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.


Integrated analysis of multiple methods reveals characteristics of the immune microenvironment in medulloblastoma.
To explore the characteristics of the immune microenvironment (IME) of medulloblastoma (MB) by four methods: flow cytometry (FCM), immunohistochemical (IHC), bulk RNA expression and single cell RNA sequencing (scRNA-seq), we collected the intraoperative specimens of MB, ependymoma (EPN), high-grade glioma (HGG), and low-grade glioma (LGG) to make a cross-cancer comparison. The specimens were subjected to FCM and IHC respectively, and deconvolution from bulk RNA expression data and scRNA-seq analysis were performed in MB from the GEO database. FCM and IHC analysis found that the proportion of lymphocytes (LC) and T cells between MB and other brain tumors were significantly different. The deconvolution of bulk RNA expression data showed that only the proportion of cell types in MCPCOUNTER changed greatly. scRNA-seq found that the proportion of various immune cells in the IME of MB differed between different subtypes. Techniques such as FCM, IHC, bulk RNA expression, and scRNA-seq can sort out different immune cell subsets to a certain extent and quantify their proportions. The four methods have their own strengthens and limitations, but for highly heterogeneous tumor such as MB, integrated analysis of multiple methods is a better choice.


The CR1 C5507G polymorphism is not involved in susceptibility to idiopathic pulmonary fibrosis in two European populations.
Idiopathic pulmonary fibrosis (IPF), a severe lung disease with unknown aetiology, is thought to have an important genetic component. Single nucleotide polymorphism, C5507G, of the complement receptor 1 (CR1) gene, which affects the number of CR1 molecules on erythrocytes, has been associated with susceptibility to IPF in a single European population. To replicate this finding, 53 Czech IPF patients with 203 Czech healthy control subjects and 70 English IPF patients with 149 English controls were investigated. In both populations, there were no significant differences in distribution of CR1 C5507G variants between IPF patients and their appropriate control groups. In conclusion, the association of the CR1 C5507G polymorphism with susceptibility to IPF was not reproducible in Czech and English populations.


Cerebral autoregulation during deep hypothermic nonpulsatile cardiopulmonary bypass with selective cerebral perfusion in dogs.
We evaluated effects of hypothermic cardiopulmonary bypass on the cerebral circulation and metabolism of six dogs over a temperature range of 37 degrees to 20 degrees C under alphastat acid-base regulation (uncorrected for body temperature). Cerebral metabolic rate for oxygen was determined from the difference between arterial and sagittal sinus blood oxygen contents, and direct cerebral blood flow measurements of the venous outflow from the isolated sagittal sinus. After core cooling at a constant perfusion flow rate of 80 ml/kg/min, cerebral blood flow significantly reduced to 10.0 +/- 1.1 ml/100 gm/min at 20 degrees C (20% +/- 2% of that at 37 degrees C) because of an increase in the cerebral vascular resistance (339% +/- 48%). Cerebral metabolic rate for oxygen reduced to 18% +/- 2%. The upper body vascular resistance decreased to a greater extent than the lower body resistance (37% +/- 4% versus 82% +/- 12%). In the selective cerebral perfusion system at 20 degrees C, when perfusion pressure (mean carotid arterial pressure minus central venous pressure) was lowered from 90 mm Hg by graded reduction of the perfusion flow rate, cerebral blood flow remained constant down to a perfusion pressure of 40 mm Hg, then steeply declined. Cerebral metabolic rate for oxygen also kept a constant level down to 30 mm Hg, then fell abruptly. Definite autoregulatory response was detected even in profound hypothermic nonpulsatile cardiopulmonary bypass. These results suggest that cerebral perfusion flow should be regulated so as to keep the perfusion pressure within the range of cerebral autoregulation to prevent cerebral ischemia or hyperperfusion, especially during selective cerebral perfusion for operations on the aortic arch.


Frizzled-7 and limb mesenchymal chondrogenesis: effect of misexpression and involvement of N-cadherin.
Products of the Frizzled family of tissue polarity genes have been identified as putative receptors for the Wnt family of signaling molecules. Wnt-signaling is implicated in the regulation of limb mesenchymal chondrogenesis, and our recent study indicates that N-cadherin and related activities are functionally involved in Wnt-7a-mediated inhibition of chondrogenesis. By using an in vitro high-density micromass culture system of chick limb mesenchymal cells, we have analyzed the spatiotemporal expression patterns and the effects on chondrogenesis of RCAS retroviral-mediated misexpression of Chfz-1 and Chfz-7, two Frizzled genes implicated in chondrogenic regulation. Chfz-1 expression was localized at areas surrounding the cartilaginous nodules at all time points examined, whereas Chfz-7 expression was limited to cellular aggregates during initial mesenchymal condensation, and subsequently was down-regulated from the centers toward the periphery of cartilage nodules at the time of chondrogenic differentiation, resembling the pattern of N-cadherin expression. Chondrogenesis in vitro was inhibited and limited to a smaller area of the culture upon misexpression of Chfz-7, but not affected by Chfz-1 misexpression. Analyses of cellular condensation and chondrogenic differentiation showed that the inhibitory action of Chfz-7 is unlikely to be at the chondrogenic differentiation step, but instead affects the earlier precartilage aggregate formation event. At 24 hr, expression of N-cadherin, a key component of the cellular condensation phase of chondrogenesis, was delayed/suppressed in Chfz-7 misexpressing cultures, and was limited to a significantly smaller cellular condensation area within the entire culture at 48 hr, when compared with control cultures. Chfz-1 misexpressing cultures appeared similar to control cultures at all time points. However, neither Chfz-1 nor Chfz-7 misexpression affected mesenchymal cell proliferation in vitro. These results suggest that Chfz-7 is active in regulating N-cadherin expression during the process of limb mesenchymal chondrogenesis and that Chfz-1 and Chfz-7 are involved in different Wnt-signaling pathways.


Decision regret 3 and 6 months after treatment for head and neck cancer: Observational study of associations with clinicodemographics, anxiety, and quality of life.
While quality of life (QOL), psychosocial health, and adverse treatment outcomes have been studied in head and neck cancer (HNC) patients, decision regret is an important and understudied complication that can negatively impact future health care decision making. Data collected using a HNC patient registry with questionnaires administered at initial consultation visits plus 3 and 6 months after treatment completion was retrospectively analyzed. A visual analog anxiety scale and the University of Washington Quality of Life were given at clinic visits. Decision regret was determined using a validated scale. Demographic and clinical variables were collected retrospectively and at baseline. Patients with higher anxiety and lower self-reported QOL had higher concurrent regret at 3-month (n = 140) and at 6-month (n = 82) post-treatment. Later disease stage at presentation, nonprimary surgical treatment, and lower health literacy were associated with greater regret. Decision regret was highest in HNC patients with high anxiety, low QOL, and more advanced disease.


Peer evaluations of the competence of children vulnerable to psychopathology.
Peer evaluations of the behavior of 75 children of schizophrenic mothers, 57 children of depressed mothers, and 153 controls were collected using the Pupil Evaluation Inventory. The children, both boys and girls, were in grades 2 through 9. Both male and female children of schizophrenics were viewed more deviantly than controls on Aggression and Unhappiness-Withdrawal factors. Only the female children of schizophrenics were viewed as less likable than controls. In general, children of schizophrenics did not differ from children of depressives. The exception was the older daughters of schizophrenics, who were rated as more deviant than members of both the remaining groups.


Weight gain and work comp: A growing problem in the workers' compensation rehabilitation system.
Obesity has become a major public health concern in the United States, and has ultimately affected occupational health, including Workers' Compensation. Obesity has been determined to contribute to work-related injury. This analysis examined weight change post-injury during the Workers' compensation rehabilitation process, and specifically how it relates to perceived mental health need, perceived dietary habits, food stamp usage, and the amount of time since the work injury. Archival data analysis was conducted examining Workers' Compensation claimants over a four year period. Data was collected from 1,864 valid Workers' Compensation claims and analyzed using descriptive statistics and a backwards elimination multiple regression analysis to examine predictive relationships between the variables of interest. Approximately 2/3 of the sample reported weight gain post-injury, with the additional 1/3 reporting weight loss or no change. Both perceived benefit from mental health services and perceived healthy dietary habits were significantly predictive of weight gain. Clinical psychological distress, such as depression and anxiety, may be contributory factors to weight gain, and poor perceptions in food quality and caloric estimations may also relate to this problem. Suggestions for future research, including intervention studies, are also included.


Coccidioidomycosis of the extensor tenosynovium of the wrist. A case report.
A 59-year-old man had isolated coccidioidomycosis infestation of the tenosynovium of the wrist extensor tendons resistent to surgical and amphotericin chemotherapy. Some improvement has been noted on Miconazole chemothearapy, but neither the long term side effects nor clinical results are known.


Alterations in cat cerebrocortical capillary morphometrical parameters following K+-induced cerebrocortical swelling.
Histochemical, electron microscopic, and morphometrical techniques were employed in the determination of the effects attributed to K+-induced cerebrocortical swelling on cat cerebrocortical capillary diameter, length, surface area, volume, and minimal intercapillary distance. Bilaterally exposed and intact temporoparietal cerebral cortices of 4 conditioned adult cats were simultaneously superfused with isotonic, artificial CSF containing 3.5 mM K+ (control) and 54 mM K+ experimental), for 1h at 37 degrees C with monitoring of systemic vital function, hematocrit, arterial blood gases, and determination of cerebrocortical tissue water content. The mean values for cerebrocapillary diameter were 5% (P less than 0.05) greater in swollen tissues when compared with comparable mean values determined for controls. The values for minimal intercapillary distance determined from control and experimental animals plotted as relative frequency histograms represented two distinct populations (P less than 0.005). The significance of altered capillary morphometric parameters are discussed in relation to K+-induced cerebrocortical swelling.


Association between anxiety disorders and substance use disorders among young persons: results of a 21-year longitudinal study.
To examine the linkages between anxiety disorders and the development of substance use disorders in a birth cohort of young people studied to young adulthood. Data were gathered over the course of a longitudinal study of a birth cohort of over 1000 New Zealand born young people. Over the course of the study, data were gathered on: (a) anxiety disorders and substance use disorders at ages 16-18 and 18-21; (b) a range of potential confounding factors including measures of childhood, social, and family factors. Young people with anxiety disorders had odds of substance dependence that were between 1.3 and 3.9 times higher than young people without anxiety disorders. These associations were largely explained by a series of covariate factors relating to: (a) childhood and family factors; (b) prior substance dependence; (c) comorbid depression; (d) peer affiliations. After adjustment for these factors, anxiety disorder was unrelated to all measures of substance use. Young people with anxiety disorders are at increased risk of substance dependence. However, this association appears to be largely or wholly non causal and reflects the associations between childhood factors, prior substance dependence, comorbid depression, peer affiliations and the development of anxiety disorders.


Quantitative determination of farnesyl and geranylgeranyl diphosphate levels in mammalian tissue.
Farnesyl diphosphate (FPP) and geranylgeranyl diphosphate (GGPP) are branch point intermediates of isoprenoid biosynthesis. Inhibitors of isoprenoid biosynthesis, such as the statins and bisphosphonates, are widely used therapeutic agents. However, little is known about the degree to which they alter levels of upstream and downstream isoprenoids, including FPP and GGPP. Therefore, we developed a method to isolate and quantify FPP and GGPP from mammalian tissues. Tissues from mice were collected, snap frozen in liquid nitrogen, and stored at -80 degrees C. FPP and GGPP were isolated by a combined homogenization and extraction procedure and were purified with a C18 solid phase extraction column. Farnesyl protein transferase (FTase) or geranylgeranyl protein transferase I (GGTase I) were used to conjugate FPP and GGPP with fluorescent dansylated peptides. FPP and GGPP were quantified by high-performance liquid chromatography (HPLC). The respective concentrations of FPP and GGPP are as follows: 0.355+/-0.030 and 0.827+/-0.082 units of nmol/g wet tissues in brain, 0.320+/-0.019 and 0.293+/-0.035 units of nmol/g wet tissues in kidney, 0.326+/-0.064 and 0.213+/-0.029 units of nmol/g wet tissues in liver, and 0.364+/-0.015 and 0.349+/-0.023 units of nmol/g wet tissues in heart (means+/-SEM). This method allows for determination of FPP and GGPP concentrations in any tissue type and is sensitive enough to detect changes following treatment with inhibitors of isoprenoid biosynthesis.


On-cartridge derivatisation using a calixarene solid-phase extraction sorbent for facile, sensitive and fast determination of formaldehyde in beer.
This work demonstrates the successful application of an on-cartridge derivatisation procedure for facile, fast and sensitive determination of formaldehyde in beer by HPLC-UV. The derivatisation and solid-phase extraction (SPE) were integrated into a novel calixarene SPE sorbent: tetraazacalix[2]arene[2]triazine bonded silica gel. Specifically, 2,4-dinitrophenylhydrazine was adsorbed onto the sorbent in advance, based on the charge-transfer interaction between the macrocyclic molecule and nitrobenzenes. The method was optimised and validated: under the optimal conditions of derivatisation, SPE and HPLC separation, good linearity was obtained in the range of 0.080-3.2μgmL(-1) with a correlation coefficient of 0.9939, the limit of detection was 3.0ngmL(-1) (S/N=3), the limit of quantification was 10ngmL(-1) (S/N=10), and the recovery level using this method was desirable at 75-84%. The developed method was successfully applied to determine formaldehyde content in real beer samples; the results were in the range of 0.11-1.1μgmL(-1).


Selective in vitro labeling of white blood cells using 99mTc-labeled liposomes.
We describe a method by which endocytosis-based radiolabeling of WBC is achieved using 99mTc-liposomes of optimal size and charge, and of a composition that assures both in vitro (whole blood) and intracellular stability of the radiopharmaceutical. In our study, excellent in vitro stability of 99mTc-liposomes with 95% labeling efficiency was observed with >90% stability up to 6 h and a minimum of 85% after 24 h of incubation either in normal saline or serum. Total WBC labeling efficiency using 99mTc-liposomes determined by radio-thin layer chromatographic analysis was 30.6 +/- 2.21%, 20.89 +/- 1.31% for monocytes and 9.7 +/- 1.74% for polymorphonuclears. Negligible activity was bound to red blood cells. The procedure did not affect the cell viability and the separation of the free 99mTc-liposomes from the cells was done by centrifugation.


Intensive care of haematological patients.
This article presents the treatment results of 320 consecutive patients with malignant haematological diagnoses admitted to a tertiary intensive care unit at a Danish University hospital over a six-year period (2005-2010). With reference to international publications, we describe the development in treatment. This was a retrospective observational study. The median age was 59 years. The median intensive care unit (ICU) stay was six days. A total of 88% required mechanical ventilation, and 72% received vasopressor treatment. The median Simplified Acute Physiology Score II score was 58. The ICU and one-year mortality rates were 44% and 77%, respectively, but mortality was significantly lower for patients aged 0-20 years. For patients aged 20-80 years, the mortality risk was independent of age. For the group of patients admitted acutely to the ICU with other diagnoses, the ICU- and the one-year mortality rate was 13% and 33%, respectively. Despite progress, the mortality rate for haematological patients in ICUs is high. We lack valid tools that allow us to differentiate between those who can benefit from intensive care and those for whom transfer to an ICU is futile. One patient out of five is alive after one year. This supports a strategy offering haematological patients intensive care on an equal footing with other patients. Follow-up studies of survivors, clarification of function level and quality of life are needed. not relevant. not relevant.


Values for αβ and γδ T-lymphocytes and CD4+, CD8+, and CD56+ subsets in healthy adult subjects: assessment by age and gender.
Normal reference values in healthy subjects for T-lymphocytes for both types of receptors, αβ and γδ, and their subsets are yet to be defined. The aim of this study was to measure peripheral blood αβ and γδ total T-lymphocytes and their subsets in a population of healthy subjects, in order to obtain valid reference values for studies in human pathology. We studied a total of 157 healthy subjects, 78 men and 79 women, establishing their levels of CD3+, CD4+, CD8+, CD56+, αβCD3+, αβCD3+CD4+, αβCD3+CD8+, αβCD3+CD56+, γδCD3+, γδCD3+CD4-CD8-, γδCD3+CD8+, and γδCD3+CD56+ T-cells by flow cytometry. The T-cell subsets were compared for different age and gender groups. A significant decrease in CD3+, CD3+CD4+, CD3+CD4+ αβ, and CD3+ γδ T-cells was observed in elderly subjects. CD3+, CD3+ αβ, and CD3+CD4+ αβ T-cells increased in women, while CD3+CD56+ αβ T-cells increased in men. CONCLUSIONS.: These reference values could be useful in further research studies for assessing changes that occur in the different αβ and γδ T subsets in human pathology.