Effects of covid-19 pandemic on life expectancy and premature mortality in 2020: time series analysis in 37 countries.
To estimate the changes in life expectancy and years of life lost in 2020 associated with the covid-19 pandemic. Time series analysis. 37 upper-middle and high income countries or regions with reliable and complete mortality data. Annual all cause mortality data from the Human Mortality Database for 2005-20, harmonised and disaggregated by age and sex. Reduction in life expectancy was estimated as the difference between observed and expected life expectancy in 2020 using the Lee-Carter model. Excess years of life lost were estimated as the difference between the observed and expected years of life lost in 2020 using the World Health Organization standard life table. Reduction in life expectancy in men and women was observed in all the countries studied except New Zealand, Taiwan, and Norway, where there was a gain in life expectancy in 2020. No evidence was found of a change in life expectancy in Denmark, Iceland, and South Korea. The highest reduction in life expectancy was observed in Russia (men: -2.33, 95% confidence interval -2.50 to -2.17; women: -2.14, -2.25 to -2.03), the United States (men: -2.27, -2.39 to -2.15; women: -1.61, -1.70 to -1.51), Bulgaria (men: -1.96, -2.11 to -1.81; women: -1.37, -1.74 to -1.01), Lithuania (men: -1.83, -2.07 to -1.59; women: -1.21, -1.36 to -1.05), Chile (men: -1.64, -1.97 to -1.32; women: -0.88, -1.28 to -0.50), and Spain (men: -1.35, -1.53 to -1.18; women: -1.13, -1.37 to -0.90). Years of life lost in 2020 were higher than expected in all countries except Taiwan, New Zealand, Norway, Iceland, Denmark, and South Korea. In the remaining 31 countries, more than 222 million years of life were lost in 2020, which is 28.1 million (95% confidence interval 26.8m to 29.5m) years of life lost more than expected (17.3 million (16.8m to 17.8m) in men and 10.8 million (10.4m to 11.3m) in women). The highest excess years of life lost per 100 000 population were observed in Bulgaria (men: 7260, 95% confidence interval 6820 to 7710; women: 3730, 2740 to 4730), Russia (men: 7020, 6550 to 7480; women: 4760, 4530 to 4990), Lithuania (men: 5430, 4750 to 6070; women: 2640, 2310 to 2980), the US (men: 4350, 4170 to 4530; women: 2430, 2320 to 2550), Poland (men: 3830, 3540 to 4120; women: 1830, 1630 to 2040), and Hungary (men: 2770, 2490 to 3040; women: 1920, 1590 to 2240). The excess years of life lost were relatively low in people younger than 65 years, except in Russia, Bulgaria, Lithuania, and the US where the excess years of life lost was >2000 per 100 000. More than 28 million excess years of life were lost in 2020 in 31 countries, with a higher rate in men than women. Excess years of life lost associated with the covid-19 pandemic in 2020 were more than five times higher than those associated with the seasonal influenza epidemic in 2015.


Effect of a short photoperiod on circadian rhythms of body temperature and motor activity in old rats.
Circadian rhythms of body temperature and motor activity were documented in young and old rats (four 8-week-old and five 22-month-old male Wistars, implanted with telemetric probes and housed in a chronobiological facility) under two different photoperiod conditions. The animals were maintained in a light:dark (LD) cycle of 12 h each (LD 12:12) for 4 weeks and then exposed to a LD 6:18 cycle for 7 weeks to assess the effect of age on the desynchronization of the temporal structure of the rhythms. In old rats under LD 12:12, the power of the 24-h component and the circadian amplitude of body temperature and motor activity were markedly lower than in the young and both rhythms were phase-advanced. After the shift to LD 6:18, the circadian rhythmicity was maintained for both variables and the same phase delay (+5+/-1 h) was observed in both age groups, as was a gradual expansion of the patterns of both functions with the longer night. The photoperiod reduction (6 weeks under LD 6:18) did not modify the power of the 24-h component of body temperature and motor activity in old rats. In young rats, however, the power and amplitude of the 24-h component of motor activity rhythm fell to the levels of those in old rats, while the power of the 24-h component of body temperature rhythm and the amplitude did not change. Our data show that the circadian rhythm of motor activity, but not of body temperature, responds age dependently to a photoperiod reduction.


The specificity of neutralizing antibodies to feline leukaemia viruses.
Feline leukaemia viruses (FeLV) of subgroups A (FeLV-A), B(FeLV-B) and C(FeLV-C) were examined by neutralization. The FeLV-A isolates were monotypic. By contrast, there was antigenic variation within subgroups B and C. There was also considerable cross-reactivity between subgroups. Thus, FeLV-A viruses showed weak cross-reactivity to the standard FeLV-C isolate; four of the subgroup B viruses were identical and cross-reactied with the standard FeLV-C, but not with FeLV-A or the fifth FeLV-B, and this latter virus weakly cros-reacted with FeLV-A but not with the FeLV-C; within subgroup C, one virus was indistinguishable from the standard FeLV-C strain but the other two were very similar to FeLV-A. Therefore, subgroup classification based on interference did not altogether correspond with neutralizing behaviour for subgroups B and C.


Immunologically-mediated acute renal failure of nonglomerular origin in the course of systemic lupus erythematosus [SLE]. Report of two cases.
Acute anuric renal failure was observed in two patients with systemic lupus erythematosus (SLE) during the clinical and serologic active phase of the disease. Renal biopsies, performed during the acute episodes, showed only mild and focal mesangial cell proliferation without deposits. In contrast, tubulointerstitial lesions were predominant. Intense granular immune deposits along the tubular basement membrane, or immunofluorescence examination, were suggestive of immune complex deposition. One of these patients had severe high blood pressure and vascular lesions likely induced by immune complexes. In both, renal function was recovered. Immunologically-mediated tubular and vascular lesions in the course of SLE are discussed.


Mechanical property characterization of resin cement after aqueous aging with and without cyclic loading.
The purpose of this study was to determine changes in flexural properties of resin cement under cyclic loading and aqueous aging. Panavia F flexural modulus and strength were measured by static loading to failure after 48-h, 31-d, and 60-d aqueous aging at 37 degrees C with and without cyclic loading at clinical stress levels. Six specimens were used for each experimental condition. Scanning electron microscopy (SEM) was also used to characterize the morphology of the fractured surfaces to potentially identify resin cement components particularly susceptible to degradation under simulated clinical function. A two-factor ANOVA (p< or =0.05) and Least Significant Difference post hoc test indicated that cyclic loading produced a significant increase in the flexural modulus with no significant effect on the flexural strength. In contrast, aqueous aging time produced a significant decrease in flexural strength with no effect on the flexural modulus. The SEM fracture analysis indicated that resin matrix fracture occurred in static-aqueous specimens; while in the aqueous-cycled specimens, resin matrix fracture occurred in addition to an increasing proportion of filler/resin interface fracture as a result of both increased aqueous aging and increased flexural cycles. Evidence suggests that after aqueous aging with cyclic loading to simulate resin cement clinical function, initial degradation may be related to breakdown of the filler/resin interface bond. Such breakdown is potentially reflective of slow crack propagation that may contribute to in vivo resin cement cohesive failure.


Direct measurement of in vitro antibody production using an enzyme-linked immunosorbent assay.
A rapid and sensitive enzyme-linked immunoassay is described for quantitation of the secretion of cellular products during short-term (1-20 h) culture in vitro. The method is based on culture of cells, serially diluted in antigen or antibody-coated polystyrene microtitre wells. The wide applicability of this method for measurement of anti-hapten antibody, immunoglobulin and lymphokine production is stressed.


C-reactive protein and white blood cell are associated with frailty progression: a longitudinal study.
Systemic inflammation has been linked to diseases and frailty. However, little is known about the effect of systemic inflammation on frailty progression with a longitudinal study design. This study aimed to investigate the associations of two inflammation indicators, C-reactive protein (CRP) and white blood cell (WBC), with frailty progression. This study utilized data from the China Health and Retirement Longitudinal Study 2011-2018 (wave 1-wave 4). Frailty index (FI) was calculated using 40 items from wave 1 to wave 4 (range: 0 to 1). Two systemic inflammation biomarkers, CRP and WBC, were measured at baseline (wave 1) and logs transformed as continuous variables or grouped using quartiles. Linear mixed-effect models were used to analyze the associations of these two biomarkers with the progression of frailty with adjustment for potential confounding factors. The study enrolled 9111 middle-aged and older participants (52.7% females, mean age 58.8 ± 9.3 years). The median follow-up time was 7.0 years. In a fully adjusted model with further adjustment for baseline FI, higher CRP (β for the interaction with time = 0.239, 95% CI: 0.139 to 0.338) and WBC (β for the interaction with time = 0.425, 95% CI: 0.024 to 0.825) significantly accelerated the rate of increase in the FI during the follow-up period. The associations were more pronounced in younger people (< 60 years) than older people (≥60 years). Higher CRP and WBC accelerated the progression of frailty, particularly in younger groups (< 60 years). The findings suggest the importance of systemic inflammation for the early identification of people at high risk of rapid progression of frailty.


Response of preterm infants to diphtheria-tetanus-pertussis immunizations.
To establish guidelines for the routine use of diphtheria, tetanus, and pertussis (DTP) vaccine in preterm infants, we quantitated antibody responses of preterm infants to DTP and determined the nature and extent of side effects. Twenty-five preterm infants were immunized with 0.5 ml DTP vaccine at routine intervals. Term infants served as controls. Immediately before each immunization and 2 months after the third, DTP-specific antibodies were quantitated. Clinical side effects were determined by parental report. After the second immunization, 100% of preterm infants had evidence of specific antibody production against diphtheria, tetanus, and pertussis. The incidence of side effects was low, but irritability was significantly more common in preterm infants after the second immunization. These observations suggest that the initiation of primary immunization with DTP in preterm infants need not be delayed beyond 2 months of age.


Case duration prediction and estimating time remaining in ongoing cases.
In this issue of the British Journal of Anaesthesia, Jiao and colleagues applied a neural network model for surgical case durations to predict the operating room times remaining for ongoing anaesthetics. We review estimation of case durations before each case starts, showing why their scientific focus is useful. We also describe managerial epidemiology studies of historical data by the scheduled procedure or distinct combinations of scheduled procedures included in each surgical case. Most cases have few or no historical data for the scheduled procedures. Generalizability of observational results such as theirs, and automatic computer assisted clinical and managerial decision-making, are both facilitated by using structured vocabularies when analysing surgical procedures.


Effects of two analgesic opiates (methadone and pentazocine) on the serum prolactin levels in breast cancer.
In 18 female patients affected by advanced breast cancer, the serum prolactin (PRL) levels have been determined under basal conditions and after the administration of analgesic opiates such as methadone and pentazocine. A significant increase of prolactin serum values was found after the use of both drugs. This finding is considered to be of clinical importance.


113mIn-DTPA, a useful compound for the determination of glomerular filtration rate (GFR). The binding of 113mIn to DTPA and a comparison between GFR estimated with 113mIn-DTPA and 125I-iothalamate.
For measurement of glomerular filtration rate the usefulness of diethyl traimino penta acic (DTPA) labelled with 113mIndium has been explored. The labelling procedure is very simple, since eluate from an 113mIn generator can be used directly for labelling DTP. The in vitro and in vivo binding of 113mIn to DTPA in competition with serum proteins was studied by gel-filtration. The radioactivity with the 113mIn-DTPA peak represented 100.6, 107.1 and 99.6% of the amount of radioactivity applied to the gel column for the in vivo studies, and 102.0 and 101.4% for the in vitro studies. Futhermore, the clearance of 113mIn-DTPA was compared to the clearance of 125I-iothalamate using the constant infusion technique. The clearance values were found to be nearly equal (r=0.996). It is concluded that 113mIn is almost entirely bound to DTPA after intravenous injection of the 113mIn-DTPA complex, and that the complex is a suitable agent for determination of glomerular filtration rate.


The source of non-heme iron that binds nitric oxide in cultivated macrophages.
In cultured macrophages (J 774 line) a decrease in iron-sulfur centers (ISC) was not observed after 5 min treatment with nitric oxide (NO) (10(-7) M NO/10(7) cells). The content of these centers was measured by electron spin resonance (ESR) spectroscopy at 16-60 K. However, the appearance of a characteristic ESR signal at g(av) = 2.03 indicated the formation of dinitrosyl iron complex (DNIC) in these cells. These findings suggest that loosely bound non-heme iron (free iron) but not iron from ISC is mainly involved in DNIC formation. ISC might release iron for DNIC formation after their destruction induced by the products of NO oxidation (NO2, N2O3, etc).


Endoscopic release of the carpal ligament: a new technique for carpal tunnel syndrome.
This is a preliminary report outlining an endoscopic technique to release the carpal ligament employing current arthroscopic methods. The technique has been used successfully on 62 hands in 46 patients with no known complications. In some cases, the follow-up period has been rather short. Based on our results, however, there has been rapid recovery with decreased scarring and postoperative pain and no loss of grip or pinch strength, which is sometimes seen with the conventional method of carpal ligament release.


Does the RET variant G691S influence the features of sporadic medullary thyroid carcinoma?
The RET (rearranged during transfection) proto-oncogene G691S variant is over-represented in the germline of patients with sporadic medullary thyroid carcinoma (sMTC) vs. normal controls but so far is not associated with any medical or pathological features of the tumour. The aim of our study was to assess the influence of this variant on the age of onset, clinical, biological and pathological features of sMTC. One hundred patients with histologically proven MTC, for whom the germline genetic analysis of RET was negative and medical records were available, were included in the study. Patients with the heterozygous GS variant or the homozygous SS variant (n = 36) were on average 8.0 years younger than patients with the wild-type GG variant (n = 64, mean age 43.9 vs. 51.9 years, P < 0.01). The former group did not differ from the wild-type group in terms of MTC size, prevalence of C-cell hyperplasia (CCH) or papillary thyroid carcinoma (PTC). However, the prevalence of an increased preoperative basal calcitonin (bCT) level (> 1000 pg/ml) was 2.75-fold higher in the patients with the GS or SS variant than in those with the wild-type variant (P < 0.001). The proportion of patients with lymph node metastases was also higher in the former group (P < 0.05). Multivariate analysis confirmed that the presence of the RET variant is independently associated with higher preoperative bCT values (P = 0.011). Our data demonstrate that the RET G691S variant could modulate the age of onset of sMTC as demonstrated previously for familial tumours. Moreover, this variant is an independent predictor of a higher basal calcitonin synthesis rate in patients with sMTC.


Characterization of [3H]forskolin binding sites in the iris-ciliary body of the albino rabbit.
[3H]Forskolin binding sites were identified using membranes prepared from the iris-ciliary body of adult, albino rabbits. Scatchard analysis of saturation binding experiments demonstrated that [3H]forskolin bound to a single population of high affinity sites. The Kd and Bmax values were 8.7 +/- 0.9 nM and 119.0 +/- 30.9 fmol/mg prot. using membranes prepared from frozen tissue and 17.0 +/- 6.2 nM and 184.4 +/- 47.2 fmol/mg prot. using fresh tissue. The binding of [3H]forskolin was magnesium-dependent. The Bmax was enhanced by sodium fluoride and Gpp(NH)p, a nonhydrolyzable guanine nucleotide analog. Forskolin was the most potent inhibitor of [3H]forskolin binding; two commercially-available analogs were weaker inhibitors. In an adenylate cyclase assay, there was the same rank order of potency to enhance enzyme activity. Based upon binding affinities, magnesium-dependence, sensitivity to sodium fluoride and Gpp(NH)p, rank order of potencies of analogs and correlation of binding with adenylate cyclase activity, these studies suggest that the [3H]forskolin binding site in the iris-ciliary body is similar to the binding site in other tissues.


What can surgeons do to prevent job leave soon after cancer diagnosis? A brief report on colorectal cancer survivors in Japan.
Colorectal cancer is one of the most diagnosed cancers in Japan and the number of cancer survivors has increased. Work-related issues of cancer survivors have been investigated in relation to occupational health, and sufficient evidence in clinical practice is needed to support this. This study aimed to obtain the relevant information, intending to support the employment of patients with colorectal cancer for clinical settings. We conducted a prospective, multicenter cohort study, which included patients who underwent surgery with clinical stage I-III colorectal cancer. An electronic survey was used at the time of hospital admission to collect the patients' occupational information, including job resignation soon after cancer diagnosis. A cross-sectional analysis was performed to evaluate the patients' employment situations. Of 129 eligible patients, 46 (36%) were female. Thirty-nine (30%) were self-employed and 72 (56%) worked at small-sized workplaces, which are not obliged to have occupational physicians. Most patients (89%) expressed their desire to return to work, but eight patients (6%) left their jobs soon after being diagnosed with colorectal cancer before undergoing surgery for several reasons stemming from worries about future treatment and its consequences. Multivariable analyses indicated that nonregular employees and the self-employed might be at a disadvantage in keeping their job at diagnosis. Surgeons should address work-related issues for survivorship, which begins at cancer diagnosis and, when available, collaborate with occupational physicians while being mindful that patients working at smaller companies do not have immediate access to occupational physicians.


Self-reported prevalence and potential factors influencing cardio-cerebral vascular disease among the Chinese elderly: A national cross-sectional study.
Aging is an essential national condition throughout China in the 21st century. Cardio-cerebral vascular disease (CCVD) is a common chronic vascular disease in the elderly. Despite aging becoming an increasingly pressing issue, there has been no comprehensive national investigation into the risk factors, prevalence, and management of CCVD among the elderly population in China. Through the 4th Survey of the Aged Population in Urban and Rural China (SSAPUR), a nationally representative sample of 224,142 adults aged more than 60 years was surveyed using a multistage, stratified sampling method. The 4th SSAPUR was used to investigate CCVD in the elderly. Univariate and multivariate logistic proportional regression analyses explored the risk factors. These risk factors were then entered into a multivariate linear regression model to identify independent predictive factors for CCVD. Disease management was assessed from the self-reported history of physician diagnosis, treatments, and hospital visits among individuals with CCVD. After excluding samples with missing information, 215,041 individuals were included in the analysis. The overall prevalence of CCVD was 26%. Living in a rural area, being older, being female, having low literacy, smoking, getting little sleep, losing a spouse, being single, not getting enough exercise, having a bad financial situation, and not taking part in public welfare programs were the main risk factors for CCVD among the elderly in China (P < 0.05). In the multivariate linear regression model, holding all other variables at any fixed value, CCVD remained associated with "urban and rural" (β = 0.012, P < 0.001), "age" (β = -0.003, P < 0.001), "sex" (β = -0.022, P < 0.001), "education level" (β = -0.017, P < 0.001), "marriage" (β = 0.004, P = 0.047), "smoking" (β = 0.012, P = 0.003), "drinking" (β = -0.015, P = 0.001), and "sleep" (β = 0.008, P = 0.005). There were no collinearity problems among these factors. Major risk factors for prevalent CCVD among the elderly in China include the following: rural residence, female, low literacy level, poor sleep quality, bereavement, non-marriage, living alone, lack of exercise, poor financial situation, and non-participation in public welfare activities. Chinese national policies for preventing, controlling, and managing risk factors for CCVD in the elderly must be urgently developed.


Cloning and expression of rat histidase. Homology to two bacterial histidases and four phenylalanine ammonia-lyases.
Histidase (histidine ammonia-lyase, EC 220.127.116.11) catalyzes the deamination of histidine to urocanic acid. Apart from phenylalanine ammonia-lyase, which is not expressed in animals, histidase is the only enzyme known to have a dehydroalanine residue in its active site. The amino site precursor and the mechanism of formation of dehydroalanine are not known. As an initial step to determining the precursor of dehydroalanine in histidase, we have isolated a functional cDNA clone for histidase from a rat liver cDNA library using an affinity-purified antiserum. The 2.2-kilobase cDNA has a 1,971-base pair open reading frame coding for a 657-amino acid polypeptide with a predicted molecular mass of 72,165 Da. The cDNA has a rare polyadenylation signal (AAUACA) that appears to inefficiently direct polyadenylation in transfected COS monkey kidney cells. Conversion of this sequence to the consensus polyadenylation signal (AAUAAA) resulted in increased levels of stable mRNA. COS cells transfected with a histidase expression vector produce active histidase. The formation of active histidase in cells that have no endogenous histidase activity suggests either that the requisite modifying enzyme is present in these cells or that the dehydroalanine residue forms by an autocatalytic mechanism. Rat histidase was found to have 41 and 43% amino acid identity to Pseudomonas putida and Bacillus subtilis histidases, respectively. Phenylalanine ammonia-lyases from parsley, kidney bean, and two yeast strains were also found to have approximately 20% amino acid identity to rat histidase. On the basis of the similarity of function of histidase and phenylalanine ammonia-lyase, dehydroalanine at the active sites, and the sequence conservation over a large evolutionary distance (mammals, bacteria, yeast, and plants), we propose that the genes for histidase and phenylalanine ammonia-lyase have diverged from a common ancestral gene, of which the most conserved regions are likely to be involved in catalysis or dehydroalanine formation.


Conditioned medium from BV2 microglial cells having polyleucine specifically alters startle response in mice.
Repeat-associated non-AUG translation (RAN translation) is observed in transcripts that are causative for polyglutamine (polyQ) diseases and generates proteins with mono amino acid tracts such as polyalanine (polyA), polyleucine (polyL) and polyserine (polyS) in neurons, astrocytes and microglia. We have previously shown that microglia with aggregated polyQ led to defective differentiation and degeneration of neuron-like cells. However, it has not been determined whether only microglia containing a specific RAN product, but not other RAN products, is harmful in vitro and in vivo. Here we show that polyL-incorporating microglia specifically led to altered startle response in mice. Aggregated polyA, polyS and polyL induced aberrant differentiation of microglia-like BV2 cells. Differentiated PC12 cells treated with conditioned medium (CM) of polyS- and polyL- but not polyA-incorporating microglia-like BV2 cells showed retraction of neurites and loss of branch of neurites. Injection of the polyL-CM, but not polyA-CM and polyS-CM, into the lateral ventricle lowered startle response in mice. Consistently, polyL induced the highest expression of CD68 in BV2 cells. The lowered startle response was replicated in mice given the polyL-CM in the caudal pontine reticular nucleus (PnC), the key region of startle response. Thus, endogenous RAN proteins having polyL derived from polyQ diseases-causative genes in microglia might specifically impair startle response.


The 5-HT6 receptor interactome: New insight in receptor signaling and its impact on brain physiology and pathologies.
The serotonin (5-HT)6 receptor is a Gs-coupled receptor exclusively expressed in the central nervous system. Highest receptor densities are found in brain regions implicated in mnemonic functions where the receptor is primarily but not exclusively located in the primary cilium of neurons. The 5-HT6 receptor continues to raise particular interest for neuropharmacologists, given the pro-cognitive effects of antagonists in a wide range of cognitive impairment paradigms in rodents and human. The 5-HT6 receptor also finely controls key neuro-developmental processes including neuron migration and differentiation. However, its influence upon neurodevelopment and cognition is not solely mediated by its coupling to the Gs-adenylyl cyclase pathway, suggesting alternative signal transduction mechanisms. This prompted studies aimed at characterizing the receptor interactome that identified 125 candidate receptor partners, making the 5-HT6 receptor one of the G protein-coupled receptors with the most extensively characterized interactome. These studies showed that the receptor localization at the plasma membrane and, consequently, its signal transduction, are finely modulated by several receptor partners. They demonstrated that prefrontal 5-HT6 receptors engage the mTOR pathway to compromise cognition in neurodevelopmental models of schizophrenia, and a role of the 5-HT6-mTOR pathway in temporal epilepsy. Finally, they revealed that the receptor activates Cdk5 signaling in an agonist-independent manner through a mechanism involving receptor phosphorylation by the associated Cdk5 and highlighted its key role in the migration of neurons and neurite growth. These new receptor-operated signaling mechanisms should be considered in the future development of drugs acting on 5-HT6 receptors. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.


An n-level field theory of biological neural networks.
An n-level field theory, based on the concept of "functional interaction", is proposed for a description of the continuous dynamics of biological neural networks. A "functional interaction" describes the action from one substructure of a network to another at several levels of organization, molecular, synaptic, and neural. Because of the continuous representation of neurons and synapses, which constitute a hierarchical system, it is shown that the property of non-locality leads to a non-local field operator in the field equations. In a hierarchical continuous system, the finite velocity of the functional interaction at the lower level implies non-locality at the higher level. Two other properties of the functional interaction are introduced in the formulation: the non-symmetry between sources and sinks, and the non-uniformity of the medium. Thus, it is shown that: (i) The coupling between topology and geometry can be introduced via two functions, the density of neurons at the neuronal level of organization, and the density-connectivity of synapses between two points of the neural space at the synaptic level of organization. With densities chosen as Dirac functions at regularly spaced points, the dynamics of a discrete network becomes a particular case of the n-level field theory. (ii) The dynamics at each of the molecular and synaptic lower level are introduced, at the next upper level, both in the source and in the non-local interaction of the field to integrate the dynamics at the neural level. (iii) New learning rules are deduced from the structure of the field equations: Hebbian rules result from strictly local activation; non-Hebbian rules result from homosynaptic activation with strict heterosynaptic effects, i.e., when an activated synaptic pathway affects the efficacy of a non-activated one; non-Hebbian rules and/or non-linearities result from the structure of the interaction operator and/or the internal biochemical kinetics.


Added value of multiphase CTA imaging for thrombus perviousness assessment.
Thrombus perviousness has been associated with favorable functional outcome in acute ischemic stroke (AIS) patients. Measuring thrombus perviousness on CTA may be suboptimal due to potential delay in contrast agent arrival in occluded arteries at the moment of imaging. Dynamic sequences acquired over time can potentially overcome this issue. We investigate if dynamic CTA has added value in assessing thrombus perviousness. Prospectively collected image data of AIS patients with proven occlusion of the anterior or posterior circulation with thin-slice multi-phase CTA (MCTA) and non-contrast CT were co-registered (n = 221). Thrombus attenuation increase (TAI; a perviousness measure) was measured for the arterial, venous, and delayed phase of the MCTA and time-invariant CTAs (TiCTA). Associations with favorable clinical outcome (90-day mRS ≤ 2) were assessed using univariate and multivariable regressions and calculating areas under receiver operating curves (AUC). TAI determined from the arterial phase CTA was superior in the association with favorable outcome with OR = 1.21 per 10 HU increase (95%CI 1.04-1.41, AUC 0.62, p = 0.014) compared to any other phase (venous 1.14(95%CI 1.01-1.30, AUC 0.58, p = 0.033), delayed 1.046(95%CI 0.919-1.19, AUC 0.53, p = 0.50)), and TiCTA (1.15(95%CI 1.02-1.30, AUC 0.60, p = 0.022). In the multivariable model, only TAI on arterial phase was significantly associated with favorable outcome (aOR 1.59, 95%CI 1.04-2.43, p = 0.032). Association between TAI with functional outcome was optimal on arterial-phase CTA such that dynamic CTA imaging has no additional benefits in current thrombus perviousness assessment, thereby suggesting that the delay of contrast arrival at the clot is a key variable for patient functional outcome.


Modeling solubilization of oil mixtures in anionic microemulsions II. Mixtures of polar and non-polar oils.
Polar/amphiphilic oils, called lipophilic linkers, are sometimes added to oil-water-ionic surfactant microemulsions in order to increase the solubilization of hydrophobic oils. The solubilization increase has been well documented for a number of systems. However, mathematical models to calculate the solubilization increase have been proposed only for optimum microemulsions (i.e., middle phase microemulsions solubilizing equal volumes of oil and water). In this paper we propose a model, which predicts solubilization enhancement for non-optimum microemulsion systems as well. The model is an extension of the net-average curvature model of microemulsion. The net-average curvature model is combined with a surface activity model to account for the increased palisade layer solubilization due to the presence of the polar/amphiphilic oil component. New non-linear mixing rules are also incorporated to account for the optimum salinity and the characteristic length variation of the anionic surfactant microemulsion as a function of the lipophilic linker concentration. The model predicts the effect of the lipophilic linker and the electrolyte concentration on the oil solubilization in accordance with the experimental results.


Comparison of LED and LASER Colonoscopy About Linked Color Imaging and Blue Laser/Light Imaging of Colorectal Tumors in a Multinational Study.
In light-emitting diode (LED) and LASER colonoscopy, linked color imaging (LCI) and blue light/laser imaging (BLI) are used for lesion detection and characterization worldwide. We analyzed the difference of LCI and BLI images of colorectal lesions between LED and LASER in a multinational study. We prospectively observed lesions with white light imaging (WLI), LCI, and BLI using both LED and LASER colonoscopies from January 2020 to August 2021. Images were graded by 27 endoscopists from nine countries using the polyp visibility score: 4 (excellent), 3 (good), 2 (fair), and 1 (poor) and the comparison score (LED better/similar/LASER better) for WLI/LCI/BLI images of each lesion. Finally, 32 lesions (polyp size: 20.0 ± 15.2 mm) including 9 serrated lesions, 13 adenomas, and 10 T1 cancers were evaluated. The polyp visibility scores of LCI/WLI for international and Japan-expert endoscopists were 3.17 ± 0.73/3.17 ± 0.79 (p = 0.92) and 3.34 ± 0.78/2.84 ± 1.22 (p < 0.01) for LED and 3.30 ± 0.71/3.12 ± 0.77 (p < 0.01) and 3.31 ± 0.82/2.78 ± 1.23 (p < 0.01) for LASER. Regarding the comparison of lesion visibility about between LED and LASER colonoscopy in international endoscopists, a significant difference was achieved not for WLI, but for LCI. The rates of LED better/similar/LASER better for brightness under WLI were 54.5%/31.6%/13.9% (International) and 75.0%/21.9%/3.1% (Japan expert). Those under LCI were 39.2%/35.4%/25.3% (International) and 31.3%/53.1%/15.6% (Japan expert). There were no significant differences in the diagnostic accuracy and the comparison score of BLI images between LED and LASER. The differences of lesion visibility for WLI/LCI/BLI between LED and LASER in international endoscopists could be compared to those in Japanese endoscopists.


Trocar guided laparoscopic feeding jejunostomy: a simple new technique.
Several techniques of laparoscopic feeding jejunostomy have been described. Most of them require costly commercial kits. Here we present a novel, simple, low-cost method for laparoscopic jejunostomy tube placement. This technique involves 4 ports. A left lateral "guide" trocar is used as a landmark for tube placement. A jejunal loop is selected and 4 vicryl sutures are placed in a diamond shape on the antimesenteric side of the intestine and left untied. These 4 stitches are extracted using a transabdominal suture grasper inserted through 4 small incisions around the left lateral guide trocar. After an enterotomy is made in the center of these 4 stitches using cautery device, the left lateral trocar is removed and a 12 Fr Foley catheter is inserted in the trocar site and introduced into the bowel. The 4 stitches are pulled toward the abdominal wall and gently tied without additional suturing. Eight patients who underwent this procedure between 2007 and 2009 were reviewed. The procedure was successful in all patients. The median operative time was 70.5 minutes. There were no postoperative complications with respect to infection, bleeding, or bowel obstruction, and no perioperative mortality. Our trocar-guided approach for laparoscopic feeding jejunostomy placement is a simple, cost-effective, safe, and effective method.


Phyllodes tumor of the breast: diagnosis, management and outcome during a 10-year experience.
Phyllodes tumor is a very rare tumor of the breast, incidence being 0.3-0.9% of all breast tumors. Phyllodes tumors are classified into three grades: benign, borderline or malignant. The aim of this study was to investigate patient characteristics, imaging characteristic findings, surgical treatment and outcome of phyllodes tumor. This is a retrospective review of phyllodes tumor patients who had undergone surgical management between 1 January 2006 and 31 December 2015 in Head, Neck and Breast Unit, Department of Surgery, Chiang Mai University Hospital. A total of 188 phyllodes tumor patients were included in this study. The average age of the patients was 35.6 years. The majority of the tumors were of lobulated shape. Tumor morphology from imaging: lobulated shaped tumor 112 cases, oval-shape 37 cases, round shape 8 cases and irregular 5 cases. Surgical management is the standard procedure for treatment of phyllodes tumors. A wide local excision was performed in 147 cases, mastectomy in 20 cases (modified radical mastectomy in 2 cases) and wide excision followed by mastectomy 21 cases. The final pathological diagnoses of the phyllodes tumors were: benign 118 cases (62%), borderline 33 cases (18%) and malignant in 37 cases (20%). The margin did not affect recurrence in all types. The most frequent is a benign phyllodes tumor. Surgical treatment to remove the tumor with a free margin is acceptable with no recurrence difference from a wider margin. However, younger age and malignant phyllodes tumor are the two highest risk factors for recurrence.


Bimetallic bionic taste sensor for perception of the synergistic effect of umami substances.
Synergistic effect is one of the main properties of umami substances, elucidating the synergistic effect of umami is of great significance in the food industry. In this study, a bimetallic bionic taste sensor was developed to evaluate the synergistic effect of umami substances based on the perceptual mechanism of the human taste system. The Venus flytrap domain of T1R1 which is in charge of recognizing umami ligands was employed as the sensing element and self-assembled on the bimetallic nanomaterial (MoS2-PtPd) by Au-S bonding, the binding of receptors and ligands is characterized by changes of electrical signals. The sensor had good linearity (R2 > 0.99) and wide detection range in the detection of different kinds of umami substances (amino acids, nucleotides, organic acids, umami peptides) with detection limits as low as 0.03 pM. Comparing with electronic tongues, the sensor owned multiple characteristics of human taste system and could recognize the presence of synergistic effect of umami substances in a variety of real samples. Moreover, the differences in synergistic effect at different concentrations and ratios were also explored, the findings showed that the synergistic effect was more obvious at lower concentrations and balanced ratios of multiple umami substances added. The strategy would afford a promising platform for in-depth research on the mechanism of synergistic effect and multifunctional industrial applications.


The laboratory diagnosis of mycobacterial diseases. Challenges and common sense.
The laboratory diagnosis of mycobacterial diseases is reviewed. It is re-emphasized that the diagnosis of mycobacterial diseases, especially tuberculosis (TB), is primarily clinical. With proper collection techniques and an appropriate number of sputa specimens acid-fast smears of concentrated sputa can still result in the detection of the majority of patients with cavitary TB who are responsible for the majority of TB transmission. Finally, the techniques used in the laboratory to diagnose mycobacterial diseases should be matched to the resources available to the laboratory and the incidence of those diseases in the area served by the laboratory.


Implementation of tuberculosis infection control measures in designated hospitals in Zhejiang Province, China: are we doing enough to prevent nosocomial tuberculosis infections?
Tuberculosis (TB) infection control measures are very important to prevent nosocomial transmission and protect healthcare workers (HCWs) in hospitals. The TB infection control situation in TB treatment institutions in southeastern China has not been studied previously. Therefore, the aim of this study was to investigate the implementation of TB infection control measures in TB-designated hospitals in Zhejiang Province, China. Cross-sectional survey using observation and interviews. All TB-designated hospitals (n=88) in Zhejiang Province, China in 2014. Managerial, administrative, environmental and personal infection control measures were assessed using descriptive analyses and univariate logistic regression analysis. The TB-designated hospitals treated a median of 3030 outpatients (IQR 764-7094) and 279 patients with confirmed TB (IQR 154-459) annually, and 160 patients with TB (IQR 79-426) were hospitalised in the TB wards. Most infection control measures were performed by the TB-designated hospitals. Measures including regular monitoring of TB infection control in high-risk areas (49%), shortening the wait times (42%), and providing a separate waiting area for patients with suspected TB (46%) were sometimes neglected. N95 respirators were available in 85 (97%) hospitals, although only 44 (50%) hospitals checked that they fit. Hospitals with more TB staff and higher admission rates of patients with TB were more likely to set a dedicated sputum collection area and to conduct annual respirator fit testing. TB infection control measures were generally implemented by the TB-designated hospitals. Measures including separation of suspected patients, regular monitoring of infection control practices, and regular fit testing of respirators should be strengthened. Infection measures for sputum collection and respirator fit testing should be improved in hospitals with lower admission rates of patients with TB.


Mechanisms of pelvic floor muscle training for managing urinary incontinence in women: a scoping review.
Pelvic floor muscle training is recommended as first line treatment for urinary incontinence in women based on three proposed theorized mechanisms: 'Enhanced Pelvic Floor Muscle Strength,' 'Maximized Awareness of Timing,' and 'Strengthened Core Muscles'. The purpose of this scoping review was to systematically map evidence for and against theorized mechanisms through which pelvic floor muscle training interventions work to reduce urinary incontinence in women. The scoping review is based upon a comprehensive search of relevant literature published from 1990 to 2020 in PubMed, CINAHL, PsycINFO, ClinialTrials.gov, reference lists from review articles, and hand searches of articles by known researchers in the field. We included English-language, peer-reviewed articles on pelvic floor muscle training as an intervention for adult women if they provided empirical evidence to testing the theorized intervention mechanisms. Two independent reviewers screened articles for inclusion and extracted data to describe details of each study (author, year, country, design, sampling), measures of pelvic floor muscle strength and urinary incontinence, statistical analysis of linkage between changes in the measures, and pelvic floor muscle training regimens. Data were summarized to facilitate the integration of diverse evidence to draw conclusions on supporting or refuting the three proposed theorized mechanisms for managing urinary incontinence in women. Of the 278 articles identified with the search, 13 (4.7%) met inclusion criteria. There was weak to no evidence for the mechanism of enhanced pelvic floor muscle strength, equivocal support for maximized awareness of timing, and no evidence for strengthened core muscles. This review revealed extremely limited data supporting the proposed theorized mechanisms underlying pelvic floor muscle training programs to manage urinary incontinence in women. Such evidence is needed to help women and clinicians understand how, why and when a woman benefits from pelvic floor muscle training. Future studies should specifically state and report statistical analysis that relates the theorized mechanisms to the training outcomes observed.


Cost of intraocular lens versus contact lens treatment after unilateral congenital cataract surgery: retrospective analysis at age 1 year.
To describe the differences in treatment costs for infants randomized to contact lens correction versus primary intraocular lens (IOL) implantation after unilateral cataract surgery in the Infant Aphakia Treatment Study (IATS). Retrospective cost analysis of a prospective, randomized clinical trial based on Georgia Medicaid data and the actual costs of supplies used. The IATS is a randomized, multicenter (n=12) clinical trial comparing treatment of aphakia with a primary IOL or contact lens in 114 infants with unilateral congenital cataract. Infants underwent cataract surgery with or without placement of an IOL. The mean cost of cataract surgery and all additional surgeries, examinations, and supplies used up to 12 months of age. The mean cost of treatment for a unilateral congenital cataract with primary IOL implantation was $14 752 versus $10 726 with contact lens correction. The initial cataract surgery accounted for approximately 50% of the treatment costs for both groups. Contact lens costs accounted for 15% ($1600/patient) in the aphakic group, whereas glasses costs represented only 4% ($535/patient) in the IOL group. The increased costs in the IOL group were primarily due to the higher cost of cataract surgery in this group ($7302 vs. $5357) and the cost of additional operations. For IATS patients up to 12 months of age, cataract surgery coupled with IOL implantation and spectacle correction was 37.5% (∼$4000) more expensive than cataract surgery coupled with contact lens correction. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Fabrication of transition metal dichalcogenides quantum dots based on femtosecond laser ablation.
As heavy metal-free quantum dots, transition metal dichalcogenides (TMDs) and boron nitride (BN) quantum dots (QDs) have aroused great interest due to features such as good thermal conductivity, chemical stability, and unique optical properties. Although TMDs have been synthesized using different methods, most of these methods require time-consuming or complex steps, limiting the applications of TMDs. We propose a fast and simple method for the synthesis of high-quality molybdenum disulfide (MoS2) QDs and tungsten disulfide (WS2) QDs based on femtosecond laser ablation and sonication-assisted liquid exfoliation. The prepared MoS2 QDs and WS2 QDs were characterized by transmission electron microscopy, atomic force microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. The resulting products possessed few-layered thickness with an average size of 3.7 nm and 2.1 nm. Due to the abundance of functional groups on their surface, the MoS2 QDs and WS2 QDs showed bright blue-green luminescence under UV irradiation. Our method offers a facile and novel synthetic strategy for TMDs QDs and other two-dimensional nanomaterial quantum dots, such as boron nitride quantum dots (BNQDs).


Risk assessment of patients with clinical manifestations of cardiac sarcoidosis with positron emission tomography and magnetic resonance imaging.
Prior studies have shown that late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) and fluorodeoxyglucose (FDG) positron emission tomography (PET) confer incremental risk assessment in patients with cardiac sarcoidosis (CS). However, the incremental prognostic value of the combined use of LGE and FDG compared to either test alone has not been investigated, and this is the aim of the present study. Retrospective observational study of 56 symptomatic patients with high clinical suspicion for CS who underwent LGE-CMR and FDG-PET and were followed for the occurrence of death and/or malignant ventricular arrhythmias (VA). The combination of PET and CMR yielded the following groups: 1) LGE-negative/normal-PET (n=20), 2) LGE-positive/abnormal-FDG (n=20), and 3) LGE-positive/normal FDG (n=16). After a median follow-up of 2.6years (IQR 1.2-4.1), 16 patients had events (7 deaths, 10 VA). All, but 1, events occurred in patients with LGE. LGE-positive/abnormal-FDG (7 events, HR 10.1 [95% CI 1.2-84]; P=0.03) and LGE-positive/normal-FDG (8 events, HR 13.3 [1.7-107]; P=0.015) patients had comparable risk of events compared to the reference LGE-negative/normal-PET group. In adjusted Cox-regression analysis, presence of LGE (HR 18.1 [1.8-178]; P=0.013) was the only independent predictor of events. CS patients with LGE alone or in association with FDG were at similar risk of future events, which suggests that outcomes may be driven by the presence of LGE (myocardial fibrosis) and not FDG (inflammation).


Genome-wide DNA methylation profiles changes associated with constant heat stress in pigs as measured by bisulfite sequencing.
Heat stress affects muscle development and meat quality in food animals; however, little is known regarding its regulatory mechanisms at the epigenetic level, such as via DNA methylation. In this study, we aimed to compare the DNA methylation profiles between control and heat-stressed pigs to identify candidate genes for skeletal muscle development and meat quality. Whole-genome bisulfite sequencing was used to investigate the genome-wide DNA methylation patterns in the longissimus dorsi muscles of the pigs. Both groups showed similar proportions of methylation at CpG sites but exhibited different proportions at non-CpG sites. A total of 57,147 differentially methylated regions were identified between the two groups, which corresponded to 1,422 differentially methylated genes. Gene ontogeny and KEGG pathway analyses indicated that these were mainly involved in energy and lipid metabolism, cellular defense and stress responses, and calcium signaling pathways. This study revealed the global DNA methylation pattern of pig muscle between normal and heat stress conditions. The result of this study might contribute to a better understanding of epigenetic regulation in pig muscle development and meat quality.


Stereoselective analysis of fenoprofen and its metabolites.
Reversed-phase high-performance liquid chromatographic assays have been developed to quantitate simultaneously fenoprofen and its major metabolites as well as to distinguish between their R- and S- enantiomers following a single oral dose of 600 mg racemic fenoprofen to healthy volunteers. The compounds are extracted from plasma (after precipitation of plasma protein) or assayed directly in diluted urine samples employing a gradient solution on a C18 column and ultraviolet detection. Two internal standards, ketoprofen and flunoxaprofen, are used to allow measurement of very low (0.05 microgram/ml) and high (70 microgram/ml) concentrations in each sample. R- and S-fenoprofen glucuronides can be separated directly; the 4'-hydroxyfenoprofen conjugates are measured via an indirect method by comparing the concentration of 4'-hydroxyfenoprofen before and after hydrolysis. The R- and S-enantiomers of both parent and 4'-hydroxy metabolite are derivatized with L-leucinamide via an ethyl chloroformate intermediate and subsequently analyzed on a C18 column. Concentrations of metabolites found in plasma were low when compared to parent drug. The S/R ratio of fenoprofen in plasma always exceeds 1 and increases with time after dosage while the S/R ratio of its 4'-hydroxy metabolite remains almost unchanged at 1.1. R-Fenoprofen glucuronide disappears rapidly from plasma as compared to its S-antipode; a less pronounced difference is noted between R- and S-4'-hydroxyfenoprofen conjugates. Fenoprofen is almost completely excreted as its S-acyl glucuronides; the renal clearance of unchanged drug is very low.


Rigid fixation as a treatment for hypertrophic non-union.
A series of 17 cases of non-union in which the one common factor in treatment was rigid fixation, resulted in union.


Denosumab in postmenopausal women with low bone mineral density.
Receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162) binds RANKL with high affinity and specificity and inhibits RANKL action. The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density (T score of -1.8 to -4.0 at the lumbar spine or -1.8 to -3.5 at the proximal femur). Subjects were randomly assigned to receive denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 210 mg), open-label oral alendronate once weekly (at a dose of 70 mg), or placebo. The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase. Denosumab treatment for 12 months resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent (as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo), at the total hip of 1.9 to 3.6 percent (as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo), and at the distal third of the radius of 0.4 to 1.3 percent (as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo). Near-maximal reductions in mean levels of serum C-telopeptide from baseline were evident three days after the administration of denosumab. The duration of the suppression of bone turnover appeared to be dose-dependent. In postmenopausal women with low bone mass, denosumab increased bone mineral density and decreased bone resorption. These preliminary data suggest that denosumab might be an effective treatment for osteoporosis. (ClinicalTrials.gov number, NCT00043186.).


2-Pyridinyl-3-(4-methylsulfonyl)phenylpyridines: selective and orally active cyclooxygenase-2 inhibitors.
A series of novel 2-pyridinyl-3-(4-methylsulfonyl)phenylpyridines has been synthesized and evaluated with respect to their ability to inhibit the isozymes of cyclooxygenase, COX-1, and COX-2. Optimum COX-2 activity is observed by introduction of a substituent at C5 of the central pyridine. 5- Chloro-3-(4-methylsulfonyl)phenyl-2-(2-methyl-5-pyridinyl)pyridine 33 was identified as the optimum compound in this series.


One monitored case of sudden death.
A 90-year-old female had a Holter monitoring recording because of a syncopal episode. She developed a fatal cardiac arrest during the recording. A severe bradycardia was the initiating fatal dysrhythmia. This was followed by ventricular tachycardia and fibrillation and finally cardiac standstill.


Exploring the excess mortality due to depressive symptoms in a community-based sample: The role of Alzheimer's Disease.
Depression has been associated with increased risk of death. However, there is lack of studies exploring such relationship in the context of dementia. Given the high prevalence of both depression and Alzheimer's Disease (AD), investigating their temporal association with mortality is of public health relevance. Longitudinal data from the WHICAP study were analyzed (1958 individuals aged ≥65 years). Depressive symptoms were assessed with the 10-item Center for Epidemiologic Studies Depression Scale (CES-D). Respondents were identified as having AD if they satisfied the criteria of the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Cox regressions analyses were performed to determine the association between depressive symptoms and risk of all-cause mortality using the overall sample, and by AD status. Depressive symptoms were significantly associated with higher mortality risk after adjusting for all potential covariates in the overall sample (HR=1.22; 95% CI=1.02, 1.46) and in individuals with incident AD (HR=1.88; 95% CI=1.12, 3.18). The CES-D does not measure clinical depression but depressive symptomatology. Since those who were exposed to known risk factors for mortality are likely to die prematurely, our results may have been skewed to the individuals with longer survival. Strategies focusing on prevention and early treatment of depression in the elderly may have a beneficial effect not only on patient quality of life and disability, but may also increase survival in the context of AD.


High-throughput analytical model to evaluate materials for temperature swing adsorption processes.
In order for any material to be considered in a post-combustion carbon capture technology, it must have high working capacities of CO₂ from flue gas and be regenerable using as little energy as possible. Shown here is an easy to use method to calculate both working capacities and regeneration energies and thereby predict optimal desorption conditions for any material.


Enhancement of solar-driven photocatalytic activity of oxygen vacancy-rich Bi/BiOBr/Sr2LaF7:Yb3+,Er3+ composites through synergetic strategy of upconversion function and plasmonic effect.
For better use of solar energy, the development of efficient broadband photocatalyst has attracted extraordinary attention. In this study, a ternary composite consisting of Sr2LaF7:Yb3+,Er3+ upconversion (UC) nanocrystals and Bi nanoparticles loaded BiOBr nanosheets with oxygen vacancies (OVs, SLFBB) was designed and synthesized by multistep solvent-thermal method. Mechanisms of in-situ formation of Bi nanoparticles and OVs in BiOBr/Sr2LaF7:Yb3+,Er3+ composites (SFLB) are clarified. The Bi metal and OVs enhanced the light-harvesting capacity in the region of visible-near-infrared (Vis-NIR), and promoted the separation of electron-hole (e-/h+) pairs. Furthermore, the surface plasmon resonance (SPR) effect of Bi metal can improve the energy transfer from Sr2LaF7:Yb3+,Er3+ to BiOBr via nonradiative energy transfer process, resulting in enhancing the light utilization from upconverting NIR into Vis light. Due to the synergistic effects of UC function, SPR and OVs, the SFLBB exhibited obviously enhanced photocatalytic ability for the degradation of BPA with a rate of 8.9 × 10-3 min-1, which is about 2.78 times higher than 3.2 × 10-3 min-1 of BiOBr (BOB) under UV-Vis-NIR light irradiation. This work provides a novel strategy for the project of high-efficiency Bismuth-based broadband photocatalysts, which is helpful to further understand the mechanism of enhanced photocatalysis by UC function and plasmonic effect.


Metabolic changes in avian blood and their effects on determination of blood gases and pH.
Oxygen consumption. MO2 and CO2 production rates, Cco2, of duck blood samples anaerobically stored at 41 degrees C were 0.041 and 0.036 mMol (L blood)minus 1 min minus 1, respectively, and were independent of O2 saturation in the range of 100 to 10% saturation; the resulting metabolic respiratory quotient of blood was 0.88. The pH decreased linearly with time at a rate of 0.0014 unit min minus 1. The lactic acid production rate was independent of Po2, and was about 0.033 MMol L minus 1 min minus 1. Errors were assessed that may be introduced in blood gas analysis when the high metabolic activity of avian blood is not accounted for. Thus the O2 dissociation curve established using the Van Slyke analysis will be shifted to the right; however, the displacement around P50 is only about 1 torr for a time lag of 5 min between sampling and analysis and is even less at higher Po2 values. When using electrodes, P02 will be underestimated and PCO2 overestimated. The magnitude of these errors depends on both delay time and slope of the dissociation curves. It is concluded that the standard blood gas analytical methods are applicable to avian blood, but that in some cases corrections for metabolic effects are neccessary. Any delay between blood sampling and analysis should be kept as short as possible; storage, if neccessary, should be on ice.


Development of high-radiation-sensitive polymer gel for magnetic resonance imaging in three-dimensional dosimetry.
We developed a high radiation sensitive polymer gel by modifying the amounts of the gel components and the temperature for the gel preparation. We evaluated its relaxation time linearity against dose and compared the measured dose distribution with the calculated one. For the relaxation time-dose linearity, irradiations were carried out with a linear accelerator using 6 MV photons and doses ranging from 0-5.0 Gy. The relationship between dose and R(2) value (reciprocal of T(2) relaxation time) was measured and it had good linearity over a wide range (0.3-5 Gy). The measured dose distributions were in good agreement with calculated ones. Since the present gel has higher sensitivity and it is synthesized more easily at lower cost than conventional polymer gels, we expect to see improved three-dimensional (3D) dosimetry using it.


Randomised controlled trial demonstrating the impact of behaviour change intervention provided by dental professionals to improve gingival health.
To determine impact of oral hygiene behaviour change intervention compared to the prevailing standard of oral hygiene advice provided in general dental practice, on bleeding on probing (BOP) in gingivitis patients, over 3-months. The effect of providing power-brushes was also evaluated. NHS dental practices were cluster-randomised to intervention or control (2:1). Dentists at intervention sites received behaviour modification training. Participants were stratified to high (≥20% BOP) or low (<20% BOP) presence of gingivitis and a subset assigned a power-brush. BOP and plaque scores were assessed at baseline and 3-months. A total of 538 participants (369:169; intervention: control) completed the study. BOP reduced in both gingivitis groups with significantly greater reduction in intervention compared to control group (BOP:38% vs 19%, p = 0.0236); Borderline significance favouring the intervention was demonstrated for the low gingivitis group (BOP:37% vs 15%, p = 0.0523). A highly significant reduction in BOP (intervention vs control) was demonstrated for volunteers who swapped from manual to power-brush (44% vs 37%, p = 0.0039). Plaque score improved more in control than intervention group (Plaque:37% vs 44%, p = 0.00215). Behaviour change techniques were readily mastered by the dental professional researchers. The introduction of an oral hygiene behaviour change intervention significantly reduced gingivitis in volunteer patients compared to control at 3 months. Swapping to a power-brush significantly favoured BOP reduction compared to manual brush continuation although plaque reduction did not follow expectation in comparison to BOP scores. Behaviour change techniques should routinely be considered in patient care. Plaque-induced gingivitis is highly prevalent in the UK despite being preventable with good oral hygiene. Its continuum, periodontitis, negative impacts quality of life. This study suggests oral hygiene behavioural interventions (GPS) significantly reduce gingivitis and that GPS introduction will improve oral health and may improve quality of life.


Evaluation of a dacitic (rhyolitic) tuff breccia use on performance, inflammatory, and antioxidant responses in broilers mildly challenged with Eimeria spp.
The objective of the study was to investigate the effects of a dacitic tuff breccia (DTB) on Eimeria-infected broilers. A total of 600 one-day-old Cobb 500 male chickens were randomly assigned to 5 treatments with 10 replicates of 12 birds. Treatments were: an unchallenged control (UC), a challenged (CC) control (0% DTB), and 3 challenged groups with 0.125, 0.25, or 0.5% DTB. At d 14, birds in the CC and DTB groups were orally gavaged with mixed Eimeria spp., while the UC received water. Growth performance was evaluated during prechallenge, challenge, and postchallenge periods (0-14 d; 14-20 d; and 20-26 d, respectively). Gastrointestinal permeability was measured at 5 days postinfection (dpi). Intestinal histology and nutrient digestibility of dry matter (DM), crude protein (CP), and ileal digestible energy (IDE) were measured at 6 dpi. Liver activity of glutathione peroxidase (GSH-Px) was determined at 6 dpi, and concentrations of reduced (GSH) and oxidized glutathione (GSSG) were analyzed at 6 and 12 dpi. Data were analyzed using a linear mixed model analysis and Tukey's test (P ≤ 0.05). From 0 to 14 d, similar average daily gain (ADG) and average daily feed intake (ADFI, P > 0.05) were observed. Gain:feed ratio (GF) was higher in 0.125, 0.25, and 0.5% of DTB than the CC and UC (P < 0.001). From 14 to 20 d, the UC had the highest ADG, ADFI, and GF (P < 0.001). At 5 dpi, intestinal permeability was higher in the challenged groups than the UC. Additionally, the UC showed the highest apparent ileal digestibility of CP, whereas 0.125% DTB had higher CP digestibility than the CC and 0.5% DTB (P < 0.001). At 6 dpi, 0.125% DTB increased GSH-Px activity compared to the CC, 0.5% DTB, and UC (P < 0.001). At 12 dpi, 0.125% DTB showed increased GSH concentration compared to the CC, 0.25% DTB, and 0.5% DTB (P < 0.01). The mild coccidia infection negatively impacted growth performance, apparent ileal nutrient digestibility, intestinal histology, and gastrointestinal integrity in broilers. The use of 0.125% DTB exhibited potential in improving antioxidant responses, apparent ileal digestibility of CP, and growth performance.


A case of paraneoplastic myelopathy associated with the neuromyelitis optica antibody.
A 63-year-old woman with a history of metastatic breast cancer presented to the emergency department with chest pain in a band-like distribution. Within 1 day of presentation the patient developed bilateral lower-extremity weakness and urinary retention. The emergence of these symptoms coincided with the recurrence of her metastatic breast cancer. Fifteen months before presentation the patient had experienced a similar episode of myelopathy in the setting of recurrence of her breast cancer, from which she recovered completely following treatment with steroids. General and neurological examination, routine laboratory testing, MRI of the brain and spine, tests for serum autoimmune antibodies, infectious serology testing, lumbar puncture, paraneoplastic panel, neuromyelitis optica antibody testing, evaluation for celiac disease, CT scans of the chest, abdomen and pelvis, whole-body [(18)F]fluoro-2-deoxyglucose PET scan, lymph node biopsy, electroencephalography observing visual and brainstem auditory evoked potentials, and neuro-ophthalmological examination. Myelopathy, possibly paraneoplastic, associated with the neuromyelitis optica antibody in the setting of metastatic breast cancer. Corticosteroids to treat the myelopathy and chemotherapy for the breast cancer.


The interaction between noradrenaline and 5-hydroxytryptamine in the isolated perfused rat hindlimb.
The vascular response to bolus injections of 5-hydroxytryptamine (5HT) over the range 0.01-10.0 microgram was measured in isolated perfused rat hindlimbs. The hindlimb vasculature displayed a vasoconstrictor response to 5HT, which was potentiated by the addition of 0.01 microgram/ml noradrenaline (NA) to the perfusate at all doses tested. The response to 5HT was also enhanced by the monoamine oxidase (MAO) inhibitor, tranylcypromine (0.05 mg/ml), suggesting that MAO located in the vascular wall is involved in the termination of the response to 5HT in the peripheral circulation. MAO inhibition abolishes the potentiation of 5HT by NA, indicating that this potentiation results from competition for MAO by both amines, leaving more amine intact to activate membrane receptors. Corticosterone (0.01 mg/ml), catecholamine extraneuronal uptake inhibitor, did not alter the response to 5HT, nor the increase of this response by NA, it thus appears that 5HT and NA have different membrane transport systems in the peripheral vasculature.


Disordered hypothalamus-pituitary-ovary axis in heterotopic extraovarian sex cord-stromal proliferation: a case report of fallopian tube serous adenofibroma.
Fallopian tube serous adenofibromas are uncommon tumors of the female genital tract, only dozens of cases have ever been reported. Earlier study indicated that they might be derived from embryonic remnants of the Müllerian duct. Clinical presentation of these tumors is usually asymptomatic. Small cysts of 0.5-3 cm in diameter are mostly incidentally found at the fimbriae end, with coarse papillary excrescences lined by epithelial cells and connective tissue stroma without nuclear pleomorphism or mitosis. A 23-year-old woman with normal secondary sexual characters and 46, XX karyotype, presented to the gynecology clinic complaining of irregular menstrual cycles. Laboratory studies reported unique discrepancy of hormone levels; anti-Müllerian hormone (AMH): 6.05 ng/mL (The normal range of AMH is 1.70-5.63 ng/mL in women aged under 35 years old), follicle stimulating hormone (FSH): 31.9 mIU/mL (reference range: 3.85-8.78, follicular phase; 4.54-22.51, ovulatory phase; 1.79-5.12, luteal phase; 16.74-113.59, menopause), and luteinizing hormone (LH): 52.0 mIU/mL (reference range: 2.12-10.89, follicular phase; 19.18-103.03, ovulatory phase; 1.20-12.86, luteal phase; 10.87-58.64, menopause), mimicking gonadotropin-resistant ovary syndrome. The ultrasound reported a right adnexal cyst of 10.4 × 7.87 × 6.7 cm. Laparoscopic evaluation was performed; pathology revealed serous adenofibroma of the fallopian tube with ovarian stroma contents. Heterotopic extraovarian sex cord-stromal proliferations was most probable. The patient's hormone levels returned to the reproductive status two weeks after surgery; FSH: 7.9 mIU/mL, LH: 3.59 mIU/mL,and AMH: 4.32 ng/mL. The patient's menstrual cycles have resumed to normal for over two years after removal of the fallopian tube cyst. This case of fallopian tube serous adenofibromas presented a discrepancy of serum AMH and FSH mimicking gonadotropin-resistant ovary syndrome. The clinical picture derived from heterotopic extraovarian sex cord-stromal proliferation indicated a disordered hypothalamus-pituitary-ovary axis.


Synthesis and antinociceptive activity of four 1H-isoindolo-1,3(2H)-diones.
The present study aimed to design and synthesize a series of 2-hydroxy-3-(4-aryl-1-piperazinyl)propyl phthalimide derivatives, which are analogs of 1H-pyrrolo[3,4-c]pyridine-1,3(2H)-dione derivatives with proven analgesic effect. In accordance with the basic principle proposed by Lipinski's rule, the probable bioavailabilities of the F1-F4 phthalimides were assessed. The obtained values indicate good absorption after oral administration and the ability to cross the blood-brain barrier. The four compounds F1-F4 differing in the type of pharmacophore in the phenyl group of the 2-hydroxy-3-(4-aryl-1-piperazinyl)propyl on the imide nitrogen atom (R, F1-F3) and the 4-benzhydryl analog (F4) were selected for in vitro and in vivo studies. Based on the in vitro studies, the effects of compounds F1-F4 on cell viability/proliferation and COX-2 levels were evaluated. Moreover, using in vivo methods, the compounds were tested for antinociceptive activity in models of acute pain (the writhing and the hot-plate tests) in mice. Their influence on the motor coordination effect and locomotor activity was also tested. The obtained results revealed that the compounds F1-F4 strongly suppress the pain of peripheral origin and to a lesser extent (F1-F3) pain of central/supraspinal origin. In the in vitro studies, F1-F4 reduced the COX-2 level in lipopolysaccharide-activated RAW 264.7 cells, which suggests their anti-inflammatory activity.


Mesoporous Materials for Drug Delivery and Theranostics.
Mesoporous materials, especially those made of silica or silicon, are capturing great interest in the field of nanomedicine [...].


SWI processing using a local phase difference modulated venous enhancement filter with noise compensation.
Susceptibility weighted imaging (SWI) involves post-processing of gradient echo images which are sensitive to the spatial variations in magnetic susceptibility. The aim of this study is to develop an automated filtering scheme to enhance the contrast-to-noise ratio (CNR) and blooming on SWI. Here, the high-pass filtering for SWI processing is designed by applying a weighting function to the neighboring phase differences to enhance the susceptibility-related (SuR) contrast. This is accomplished by summing the neighboring phase differences, weighted with a scaled and shifted error function of the phase difference. Besides using the filter weights of this weighted high-pass (WHP) filter to minimize the filtering artefacts using a filter scale parameter, the CNR is further increased by introduction of the neighborhood-based noise compensation weights into the filtering process. These weights are deduced from the channel phase distribution, conditioned on the channel magnitude and noise variance. Using in vivo SWI data acquired at 1.5 T (16 nos.) and 3.0 T (30 nos.), the magnitude SWI processed using the noise compensated WHP (WHPC) filter is shown to provide an average CNR improvement of 68.40% over that of a homodyne high-pass (HHP) filter. Two tailed t-tests performed separately for different field strengths, show significant differences (p < 0.001) between mean separations of phase masks generated from the WHPC and HHP filtered phase images. In conclusion, the WHPC filter, tuned by the mean separation of the phase mask, enhances the SuR contrast of magnitude SWI for evaluation of mild cognitive impairments, brain tumor and hemorrhagic stroke.


Brain Imaging in Idiopathic Intracranial Hypertension.
The primary role of brain imaging in idiopathic intracranial hypertension (IIH) is to exclude other pathologies causing intracranial hypertension. However, subtle radiologic findings suggestive of IIH have emerged with modern neuroimaging. This review provides a detailed description of the imaging findings reported in IIH and discusses their possible roles in the pathophysiology and the diagnosis of IIH. References were identified by searches of PubMed from 1955 to January 2015, with the terms "idiopathic intracranial hypertension," "pseudotumor cerebri," "intracranial hypertension," "benign intracranial hypertension," "magnetic resonance imaging," "magnetic resonance venography," "computed tomography (CT)," "CT venography," "imaging," and "cerebrospinal fluid (CSF) leak." Additional references were identified by hand search of relevant articles. When possible, we extracted the number of patients and control subjects from each study for each radiological finding. When at least 2 studies used the same criteria to define a radiological finding, all patients from these studies were pooled to obtain a mean sensitivity and specificity with 95% confidence interval. Specific neuroimaging findings may suggest long-standing IIH, including empty sella, flattening of the posterior globes, optic nerve head protrusion, distention of the optic nerve sheaths, tortuosity of the optic nerve, cerebellar tonsillar herniation, meningoceles, CSF leaks, and transverse venous sinus stenosis. Although IIH remains a diagnosis of exclusion, the most recently proposed diagnostic criteria have included neuroimaging findings to suggest IIH when major diagnostic criteria are not fulfilled. However, these findings are not diagnostic of IIH, and their presence is not required for the diagnosis of definite IIH. Their incidental discovery on brain imaging should not prompt invasive procedures, unless other signs of IIH, such as papilledema, are present.


An aggregation-induced emission fluorescent probe for highly sensitive and selective detection and imaging of Hg2+ in living cells.
Mercury ions (Hg2+), as one of heavy transition metals (HTM), is a highly toxic metal that is hazardous to human health. Here an aggregation-induced emission (AIE) fluorescent probe is designed for the highly sensitive and selective detection of Hg2+. The probe is engineered with a tetraphenylethene (TPE) derivative as the fluorophore and thiopropionic acid as the site of recognition for Hg2+. Due to the different solubilities of the probe AIE-COOH and its corresponding product after reaction with Hg2+. The probe demonstrates a maximum detection limit of 22 nM and a fast response time of ∼100 s. Simultaneously, AIE-COOH exhibits outstanding detectivity and hypersensitivity for the detection of Hg2+ in aqueous solutions. These characteristics demonstrate that AIE-COOH hold a great potential in environmental, food and biological systems. Moreover, we have also successfully applied it to Hg2+ fluorescence imaging in in living cells.


Lynch syndrome; towards more personalized management?
Lynch syndrome is the most common inherited cause of colorectal (lifetime risk up to 70%) and endometrial cancer. The diagnosis of Lynch syndrome facilitates preventive measures aimed at reducing the incidence and mortality of cancer. Colonoscopic surveillance for colorectal cancer, aspirin, and prophylactic hysterectomy and bilateral salpo-oopherectomy for endometrial and/or ovarian cancer have demonstrated to effectively reduce cancer mortality in this population. However, the lifetime risk of each cancer in people with Lynch syndrome is gene-specific and may be modified by environmental factors. Furthermore, the benefits of surveillance strategies need to be balanced against the risk of over-diagnosis and be supported by evidence of improved outcomes from cancer diagnosis in surveillance. Therefore, people with Lynch syndrome may benefit from a personalized management approach.


Curve walking is not better than straight walking in estimating ambulation-related domains after incomplete spinal cord injury.
To investigate whether a figure-of-8-shaped walking test can estimate various domains of walking in subjects with incomplete spinal cord injury (iSCI) better than the 10-meter walk test (10MWT), and to explore similarities and differences between the 2 tests and between subjects with iSCI and age-matched, healthy controls. Case-control study. Spinal cord injury center of a university hospital. A convenience sample of subjects with iSCI (n=15; mean age, 50y; 40% women; neurologic level from C3 to L5; median time since injury, 5mo) was compared with an age-matched control group (47% women). Not applicable. The figure-of-8 test (FET) included 6 conditions to test the subjects' ability to adapt their gait to several circumstances. These conditions covered normal and maximal walking speed, constrained vision, obstacles, foamed soles, and a dual task. Additionally, subjects were tested for lower extremity muscle strength, gait capacity (10MWT) and balance, independence, and fear of falling. (1) Preferred straight-walking speed correlated with the different FET conditions in both groups; (2) if normalized to preferred straight-walking speed, FET conditions showed significant differences between both groups; (3) if normalized to preferred curve-walking speed, these differences seemed to disappear; and (4) the 10MWT appeared superior to the different conditions of the FET in estimating various walking-related functions. Subjects with iSCI seem to have difficulties with curve walking compared with straight walking. We therefore recommend the implementation of curve walking into rehabilitation training programs. However, the FET did not provide a better estimate of functional ambulation performance after an iSCI compared with the 10MWT.


Characterization of the Immune Cell Infiltration Landscape in Head and Neck Squamous Cell Carcinoma to Aid Immunotherapy.
The tumor microenvironment (TME) chiefly consists of tumor cells and tumor-infiltrating immune cells admixed with the stromal component. A recent clinical trial has shown that the tumor immune cell infiltration (ICI) is correlated with the sensitivity to immunotherapy and the head and neck squamous cell carcinoma (HNSC) prognosis. However, to date, the immune infiltrative landscape of HNSC has not yet been elucidated. Herein, we proposed two computational algorithms to unravel the ICI landscape of 1,029 HNSC patients. Three ICI patterns were defined, and the ICI scores were determined by using principal-component analysis. A high ICI score was characterized by an increased tumor mutation burden (TMB) and the immune-activating signaling pathways. Activation of transforming growth factor-β (TGF-β) and WNT signaling pathways were observed in low ICI score subtypes, indicating T cell suppression, and may be responsible for poor prognosis. Two immunotherapy cohorts confirmed patients with higher ICI scores demonstrated significant therapeutic advantages and clinical benefits. This study demonstrated that the ICI scores serve as an effective prognostic biomarker and predictive indicator for immunotherapy. Evaluating the ICI patterns of a larger cohort of samples will extend our understanding of TME, and it may provide directions to the current research investigations on immunotherapeutic strategies for HNSC.


Is it just a cure? Re-evaluating the effects of prenatal exposure to the Great Chinese Famine on the risk of infectious diseases in adulthood.
Very limited studies focused on the early-life adversities on infectious diseases. Taking the Great Chinese famine as a natural experiment, this study re-evaluated the long-term effect of prenatal famine exposure on infectious diseases by using nationally representative data. Using difference-in-difference (DID) models, we analyzed 215,216 adults who participated in the Second National Sample Survey on Disability in 2006 across 734 counties of China to detect the effects of prenatal exposure to the Great Chinese Famine on the risk of infectious diseases in adulthood. Infectious diseases were ascertained by using the combination of self-reports or family members' reports and on-site medical diagnosis by experienced specialists, and the severity of famine was measured by the cohort size shrinkage index (CSSI) at the county level. All DID estimates of the effects of famine on the probability of infectious diseases were insignificant, with a coefficient of 0.0007 (-0.0024, 0.0026) for all participants and coefficients of 0.0001 (-0.0041, 0.0043) and -0.0002 (-0.0036, 0.0033) for males and females, respectively. That is, the famine cohort dwelling in regions with a greater intensity of famine had similar levels of infectious disease risks than the cohorts with post-famine prenatal exposure experience in less affected famine regions. Furthermore, there were no significant famine and post-famine cohort differences in the DID estimates by examining the variations in subgroups with different types of infectious diseases (trachoma, poliomyelitis, tuberculosis, maternal infections and other infectious diseases). No significant impact of prenatal exposure to the Chinese famine was observed on the risk of infectious diseases in adulthood. Famine survivors may be "cured" by the famine and were resilient to adverse environments in their life course because selective mortality may weaken the association between adverse prenatal exposure and later health.


Amikacin treatment of pulmonary infections involving gentamicin-resistant gram-negative bacilli.
Twelve patients with pulmonary infections presumably involving gentamicin-resistant gram-negative bacilli were evaluated for their response to amikacin therapy. All patients had hospital-acquired infections for which they had been previously treated and were considered therapeutic failures with gentamicin or tobramycin. Assessment of response to amikacin therapy showed objective evidence of clinical improvement in 11. The gentamicin-resistant organism was eradicated in nine patients although, in the majority, other gram-negative bacilli persisted in respiratory tract secretions both during and after treatment. There was one clinical failure.


A confined variable region confers ligand specificity on fibroblast growth factor receptors: implications for the origin of the immunoglobulin fold.
Binding of cellular growth factors to their receptors constitutes a highly specific interaction and the basis for cell and tissue-type specific growth and differentiation. A unique feature of fibroblast growth factor (FGF) receptors is the multitude of structural variants and an unprecedented degree of cross-reactivity between receptors and their various ligands. To examine receptor-ligand specificity within these families of growth factors and receptors, we used genetic engineering to substitute discrete regions between Bek/FGFR2 and the closely related keratinocyte growth factor receptor (KGFR). We demonstrate that a confined, 50 amino acid, variable region within the third immunoglobulin-like domain of Bek and KGFR exclusively determines their ligand binding specificities. Replacing the variable region of Bek/FGFR2 with the corresponding sequence of KGFR resulted in a chimeric receptor which bound KGF and had lost the capacity to bind basic FGF. We present evidence that the two variable sequences are encoded by two distinct exons that map close together in the mouse genome and follow a constant exon, suggesting that the two receptors were derived from a common gene by mutually exclusive alternative mRNA splicing. These results identify the C-terminal half of the third immunoglobulin-like domain of FGF receptors as a major determinant for ligand binding and present a novel genetic mechanism for altering receptor-ligand specificity and generating receptor diversity.


Sleep-Disordered Breathing in Pregnancy.
Sleep-disordered breathing (SDB) is a spectrum of abnormal respiratory events including habitual snoring and increased upper airway resistance and obstructive episodes. The uncertainties concerning the incidence and recognition of SDB during pregnancy and the importance of the issue for fetal and maternal health prompted us to screen pregnant women for SDB. The study included 312 women in the third trimester of pregnancy aged 17-46 of whom 51 were preselected, based on the results of SDB questionnaires, for a nighttime home screening using a portable ApneaLink Air device. We found that single or multiple episodes of apnea were present in 35 (69%) women. The mean apnea/hypopnea index (AHI) was 1.8 ± 1.8 episodes/h of sleep, which did not exceed the prevalence in the general young-adult female population. However, we noticed a substantial number of inspiratory airflow limitation (IFL) episodes most often accompanied by snoring and more frequent in pregnant women with a greater weight gain. IFLs, although not fulfilling the quantifiable criteria of hypopnea, raise the possibility of hardly recognizable oxygenation and cardiovascular disturbances in pregnancy, reflected in an increased risk index for SDB. We conclude that pregnancy encompasses the risk of revealing or intensifying pre-existing SDB which can jeopardize maternal and fetal health. The risk particularly applies to overweight women. We submit that women in late pregnancy should be carefully screened for possible SDB.


Suppression of mucosal mastocytosis by Nematospiroides dubius results from an adult worm-mediated effect upon host lymphocytes.
Infections with the nematode Nematospiroides dubius fail to elicit mucosal mast cell (MMC) responses in the intestines of host mice, and suppress MMC responses generated by heterologous infection. Larval N. dubius have the capacity to prime for mastocytosis, and to elicit this response in primed mice during a challenge, but only if adult worms are prevented from developing, either by anthelmintic treatment or by irradiation of the larvae themselves. The suppressive effect of the adult stage was confirmed in experiments where such worms were implanted directly into the intestines of mice primed by exposure to irradiated N. dubius larvae or concurrently infected with Trichinella spiralis. Data on the mechanisms underlying this suppressive effect were obtained from experiments involving the adoptive transfer of mastocytosis by mesenteric lymph node cells (MLNC) from T. spiralis infected mice. When MLNC were taken from mice infected concurrently with both T. spiralis and N. dubius no enhanced mastocytosis was seen in recipients after challenge with T. spiralis. Exposure of MLNC from T. spiralis infected donors to the presence of adult N. dubius after transfer did not reduce the adoptively transferred response. The response was also unaffected when MLNC from adult N. dubius infected mice were simultaneously transferred with MLNC from T. spiralis donors. It is concluded that the suppressive effect of adult N. dubius upon the expression of mucosal mastocytosis acts upon the generation of lymphocytes capable of promoting the development of MMC from precursor cells.


Fas-induced apoptosis is a feature of progressive diabetic nephropathy in transgenic (mRen-2)27 rats: attenuation with renin-angiotensin blockade.
Tubular atrophy is a major feature of most renal diseases and is closely associated with the loss of renal function. The present study sought to investigate whether Fas/FasL-induced tubular epithelial cell apoptosis was a feature of experimental diabetic nephropathy. The effects of renoprotective therapy with blockade of the renin-angiotensin (RAS) system were also examined. Six-week-old female Ren-2 rats were injected with streptozotocin and maintained diabetic for 12 weeks. Further groups of diabetic rats were treated with the angiotensin-converting enzyme inhibitor, perindopril, for 12 weeks. Widespread apoptosis, identified by using mediated Terminal dUTP nick-end labelling (TUNEL) staining was noted in the tubules of diabetic Ren-2 rats. These changes were associated with an increase in both Fas mRNA and Fas L (ligand) within the tubules (P < 0.01). Treatment of diabetic Ren-2 rats with perindopril (6 mg/kg per day) reduced the apoptosis to control levels and was associated with a reduction in Fas mRNA and Fas L protein (P < 0.05). In conclusion, Fas/Fas L-induced tubular apoptosis is a feature of diabetic Ren-2 rats and is attenuated by the blockade of the RAS.


A history of severe nausea and vomiting during pregnancy predicts a higher incidence of postoperative nausea and vomiting after breast cancer surgery without breast reconstruction.
Postoperative nausea and vomiting (PONV) occur in up to 30 percent of patients after breast cancer surgery despite routine administration of antiemetic prophylaxis. A history of nausea and vomiting during pregnancy (NVP) has been reported as a risk factor of intraoperative nausea and vomiting in caesarean delivery. Nevertheless, whether a history of severe nausea and vomiting during pregnancy (SNVP) is associated with a higher occurrence of PONV remains unclear. In this study, 121 sequential female patients who were scheduled to undergo breast cancer surgery were assigned to study group (30 cases, with SNVP) or control group (91 cases, with mild NVP (MNVP)). The incidence of PONV and the need for rescue antiemetic were recorded in post-anesthesia care unit (PACU), at 6 h, 12 h, 24 h, and 36 h after operation. Moreover, postoperative pain, level of satisfaction, and the relationship of ER/PR status in breast cancer tissue with SNVP and PONV were also investigated. Data from 115 patients were analyzed. The incidence of PONV in the SNVP group was significantly higher than that in the MNVP group at 6 h (P < 0.005), 12 h (P < 0.05), and 24 h after the operation (P < 0.05). The incidence of PONV in the MNVP group was approximately 30% lower than in the SNVP group. Besides, more severe PONV, a larger number of demands for rescue antiemetic, fewer patient satisfaction scores, and more dizziness were observed in the SNVP group. Yet, no relationship was found between ER/PR status of breast cancer tissue and SNVP or PONV. Compared to patients with MNVP, those with a history of SNVP experienced a higher incidence of PONV and severe PONV, presented with a larger number of requirements for postoperative antiemetic and a lower level of satisfaction.


What is new in MS spasticity research? Poster session highlights.
Each year at the Experts Summit, recent relevant research in the field of multiple sclerosis spasticity is featured in the poster sessions. Highlights of the 2015 poster session are presented.


Plasminogen activator inhibitor-type 1 in Lewis lung carcinoma.
Plasminogen activator inhibitor-type 1 (PAI-1) was identified in extracts of Lewis lung carcinoma, and its immunohistochemical localization was studied together with that of urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators. All primary tumors (n = 11) contained heterogeneously distributed immunoreactivity against each of the three components. Most often, areas that contained u-PA immunoreactivity also contained PAI-1 immunoreactivity. However, several areas showed a strong u-PA immunoreactivity, but no or low PAI-1 immunoreactivity. The latter staining pattern was only found in peripheral areas, and usually in areas with histological signs of tissue destruction. Lung metastases always contained u-PA immunoreactivity, while PAI-1 immunoreactivity was found in most, but not all, metastases. t-PA immunoreactivity was found in a few scattered tumor cells, in primary carcinomas as well as metastases. Controls that included absorption with highly purified antigen preparations and immunoblotting, indicated that all the immunoreactivity represented genuine PAI-1, u-PA and t-PA, respectively. The results are consistent with an assumption that the plasminogen activation system, and particularly u-PA and PAI-1, plays a role in regulation of breakdown of extracellular matrix proteins during invasive growth in this carcinoma.


MRI-guided targeted needle placement during motion using hydrostatic actuators.
Magnetic resonance imaging (MRI) has unique advantages for guiding interventions, but the narrow space is a major challenge. This study evaluates the feasibility of a remote-controlled hydrostatic actuator system for MRI-guided targeted needle placement. The effects of the hydrostatic actuator system on MR image quality were evaluated. Using a reference step-and-shoot method (SS) and the proposed actuator-assisted method (AA), two operators performed MRI-guided needle placement in targets (n = 12) in a motion phantom. The hydrostatic actuator system exhibited negligible impact on MR image quality. In dynamic targets, AA was significantly more accurate and precise than SS, with mean ± SD needle-to-target error of 1.8 ± 1.0 mm (operator 1) and 1.3 ± 0.5 mm (operator 2). AA reduced the insertion time by 50% to 80% and total procedure time by 25%, compared to SS. The proposed hydrostatic actuator system may improve accuracy and reduce procedure time for MRI-guided targeted needle placement during motion.


Sex disparities in non-small cell lung cancer: mechanistic insights from a cRaf transgenic disease model.
Women are at greater risk of developing non-small cell lung cancer (NSCLC), yet the underlying causes remain unclear. We performed whole genome scans in lung tumours of cRaf transgenic mice and identified miRNA, transcription factor and hormone receptor dependent gene regulations. We confirmed hormone receptors by immunohistochemistry and constructed regulatory gene networks by considering experimentally validated miRNA-gene and transcription factor-miRNA/gene targets. Bioinformatics, genomic foot-printing and gene enrichment analysis established sex-specific circuits of lung tumour growth. Translational research involved a large cohort of NSCLC patients. We evaluated commonalities in sex-specific NSCLC gene regulations between mice and humans and determined their prognostic value in Kaplan-Meier survival statistics and COX proportional hazard regression analysis. Overexpression of the cRaf kinase elicited an extraordinary 8-fold increase in tumour growth among females, and nearly 70% of the 112 differentially expressed genes (DEGs) were female specific. We identified oncogenes, oncomirs, tumour suppressors, cell cycle regulators and MAPK/EGFR signalling molecules, which prompted sex-based differences in NSCLC, and we deciphered a regulatory gene-network, which protected males from accelerated tumour growth. Strikingly, 41% of DEGs are targets of hormone receptors, and the majority (85%) are oestrogen receptor (ER) dependent. We confirmed the role of ER in a large cohort of NSCLC patients and validated 40% of DEGs induced by cRaf in clinical tumour samples. We report the molecular wiring that prompted sex disparities in tumour growth. This allowed us to propose the development of molecular targeted therapies by jointly blocking ER, CDK1 and arginase 2 in NSCLC. We gratefully acknowledge the financial support of the Lower Saxony Ministry of Culture and Sciences and Volkswagen Foundation, Germany to JB (25A.5-7251-99-3/00) and of the Chinese Scholarship Council to SZ (202008080022). This publication is funded by the Deutsche Forschungsgemeinschaft (DFG) as part of the "Open Access Publikationskosten" program.