IGA nephropathy in HLA-identical siblings.
This report describes a patient with end stage IgA nephropathy who received a renal transplant from his asymptomatic HLA-identical brother. A biopsy of the donor kidney performed at the time of transplantation showed evidence of widespread electron-dense mesangial deposits. On immunofluorescence these deposits stained with IgA, documenting clinically occult IgA nephropathy in this otherwise healthy donor. These findings are of particular interest in view of the association of IgA nephropathy with the HLA-Bw35 alloantigen, and raise the possibility that asymptomatic disease, already present in a donor kidney, may have accounted for what has previously been called "recurrence" of this disease in renal allograft recipients.


[Study of phlebotomines sand fly wildlife suburban location of Bamako (Mali) presence of Phlebotomus (Phlebotomus) duboscqi].
During three months of sampling, one thousand nine hundred and thirty five sand flies belonging to thirteen species of Phlebotomine sandflies were collected in suburban location of Bamako. Phlebotomus duboscqi, which is the common vector of cutaneous leishmaniasis in Mali, was found for the first time in Bamako mostly within human houses, which can confirm the possibility of a local transmission of Leishmania major. Sergentomyia freetownensis was found for the first time in Mali, which raises to 15 the number of sand flies species identified in Mali.


Independent component analysis as a preprocessing step for data compression of neonatal EEG.
We propose a novel approach for compressive sampling of the neonatal electro-encefalogram (EEG) data. The method assumes that the set of EEG data is generated by linearly mixing a fewer number of source signals. Another assumption is that the sources are nearly-sparse in Gabor dictionary. The presented method, instead of compressing original EEG channels, first performs a data-reduction, and then compresses the obtained sources. With this approach we showed that the gain in reconstruction speed is 33%-50%, whereas the compression rate is enhanced by 33%.


Tight junction proteins related to blood-brain barrier and their regulatory signaling pathways in ischemic stroke.
Tight junctions (TJs) are crucial for intercellular connections. The abnormal expression of proteins related to TJs can result in TJ destruction, structural damage, and endothelial and epithelial cell dysfunction. These factors are associated with the occurrence and progression of several diseases. Studies have shown that blood-brain barrier (BBB) damage and dysfunction are the prominent pathological features of stroke. TJs are directly associated with the BBB integrity. In this article, we first discuss the structure and function of BBB TJ-related proteins before focusing on the crucial events that cause TJ dysfunction and BBB damage, as well as the regulatory mechanisms that affect the qualitative and quantitative expression of TJ proteins during ischemic stroke. Multiple regulatory mechanisms, including phosphorylation, matrix metalloproteinases (MMPs), and microRNAs, regulate TJ-related proteins and affect BBB permeability. Some signaling pathways and mechanisms have been demonstrated to have dual functions. Hopefully, our understanding of the regulation of BBB TJs in ischemic stroke will be applied to the development of targeted medications and therapeutic therapies.


Occult brain tumour presenting with burns.
An elderly male patient sustained mixed depth burns of 5% total body surface area. The incident was associated with inappropriate behaviour and subsequent clinical examination confirmed the presence of confusion and a hemiparesis. A CT scan revealed an intracranial tumour. Despite early suspicions that tumour excision would be delayed, wound healing was achieved quickly following tangential burn wound excision and skin grafting, and prompt transfer to a neurosurgical unit was expedited. Cases of burns and concomitant intracranial tumours with deteriorating neurological signs may present clinicians with a dilemma in deciding whether or not to await burn wound healing before carrying out tumour excision.


Mutagenesis strategies in zebrafish for identifying genes involved in development and disease.
It has been nearly a decade since the completion of two large-scale chemical mutagenesis screens in zebrafish, and two years since the completion of a large-scale insertional mutagenesis. In this article, we use the accumulated data from these screens to compare the efficiency of each mutagen to isolate mutants and to identify mutated genes, and argue that the two mutagens target the same set of genes. We then review how both forward genetic screens and reverse genetic techniques, such as morpholinos and TILLING, and transgenics are being used to develop models of human disease.


Fatigue in fibromyalgia: a conceptual model informed by patient interviews.
Fatigue is increasingly recognized as an important symptom in fibromyalgia (FM). Unknown however is how fatigue is experienced by individuals in the context of FM. We conducted qualitative research in order to better understand aspects of fatigue that might be unique to FM as well as the impact it has on patients' lives. The data obtained informed the development of a conceptual model of fatigue in FM. Open-ended interviews were conducted with 40 individuals with FM (US [n = 20], Germany [n = 10] and France [n = 10]). Transcripts were analyzed using qualitative methods based upon grounded theory to identify key themes and concepts. Participants were mostly female (70%) with a mean age of 48.7 years (range: 25-79). Thirty-one individuals (i.e., 77.5%) spontaneously described experiencing tiredness/lack of energy/fatigue due to FM. Participants discussed FM fatigue as being more severe, constant/persistent and unpredictable than normal tiredness. The conceptual model depicts the key elements of fatigue in FM from a patient perspective. This includes: an overwhelming feeling of tiredness (n = 17, 42.5%), not relieved by resting/sleeping (n = 15, 37.5%), not proportional to effort exerted (n = 25, 62.5%), associated with a feeling of weakness/heaviness (n = 20, 50%), interferes with motivation (n = 22, 55%), interferes with desired activities (n = 27, 67.5%), prolongs tasks (n = 15, 37.5%), and makes it difficult to concentrate (n = 21, 52.5%), think clearly (n = 12, 30%) or remember things (n = 9, 22.5%). The majority of individuals with FM who participated in this study experience fatigue and describe it as more severe than normal tiredness.


The fine structure of the hypostome and mouth of hydra. I. Scanning electron microscopy.
The hypostome and mouth of fresh-water Hydra were examined by scanning electron microscopy. The external surface of the hypostome possesses cnidocils, possibly sensory hairs, and small spiny protrusions surrounding the mouth; the internal surface has cylindrical microvilli, free flagella and adherent flagella. The adherent flagella are most numerous close to the mouth where they cause the cell surface to appear smooth when viewed at low magnifications. Free flagella and leaf-like microvilli increase in prominence towards the tentacles and enter on proper. The edge of the mouth has an abrupt boundary marking the apposition of epidermal and gastrodermal cells. A transitional groove occurs at the boundary and the cells underlying the groove are smaller than those on other regions of the hypostome. The transition groove may represent a site of cell loss in normal cell turnover. Some of the small underlying cells may represent nervous elements involved in regulating hypostome activity during the feeding reation.


Massive obesity and hyperphagia in posterior bilateral periventricular heterotopias: case report.
Bilateral posterior periventricular nodular heterotopia PNH is a complex malformation of cortical development with imaging features distinguishing it from classic bilateral PNH associated with filamin (FLNA) mutations. It distinctively consists of variably sized nodules of neurons along the trigones and temporal or occipital horns of the lateral ventricles and spectrum of developmental disorders of the mid-/hindbrain. This association suggests that pPNH is part of a more diffuse process of posterior or infrasylvian brain developmental abnormalities other than just a disorder of neuronal migration. This report describes the first case of an Italian young girl featuring pPNH and severe hyperphagic obesity. At the time of our first examination at age 3 years of age she was severely obese (body mass index, BMI 45.9 Kg/m(2)) and food-seeking behavior in the free-living situation was reported by the relatives. She showed normal linear growth and cognition, but mildly dysmorphic facial traits including deeply-set eyes, prominent zygomatic bones, downturned mouth corners and low-set ears. Over the years, the patient progressively developed further massive weight gain (at age 9 years, her BMI was 60.4 Kg/m(2)) and hyperphagia was confirmed by an ad libitum test meal. During follow-up, she presented limitations in walking capacity and in physical functioning due to the disabling obesity. On the basis of distinctive neuro-radiological findings pPNH was diagnosed, in absence of history of seizures. The present case may contribute to the expansion of the phenotypic expressions of this distinctive complex malformation.


Melatonin enhanced the heavy metal-stress tolerance of pepper by mitigating the oxidative damage and reducing the heavy metal accumulation.
Heavy metals (HMs), like vanadium (V), chromium (Cr), cadmium (Cd), and nickel (Ni) toxicity due to anthropogenic, impair plant growth and yield, which is a challenging issue for agricultural production. Melatonin (ME) is a stress mitigating molecule, which alleviates HM-induced phytotoxicity, but the possible underlying mechanism of ME functions under HMs' phytotoxicity is still unclear. Current study uncovered key mechanisms for ME-mediated HMs-stress tolerance in pepper. HMs toxicity greatly reduced growth by impeding leaf photosynthesis, root architecture system, and nutrient uptake. Conversely, ME supplementation markedly enhanced growth attributes, mineral nutrient uptake, photosynthetic efficiency, as measured by chlorophyll content, gas exchange elements, chlorophyll photosynthesis genes' upregulation, and reduced HMs accumulation. ME treatment showed a significant decline in the leaf/root V, Cr, Ni, and Cd concentration which was about 38.1/33.2%, 38.5/25.9%, 34.8/24.9%, and 26.6/25.1%, respectively, when compared with respective HM treatment. Furthermore, ME remarkably reduced the ROS (reactive oxygen species) accumulation, and reinstated the integrity of cellular membrane via activating antioxidant enzymes (SOD, superoxide dismutase; CAT, catalase; APX, ascorbate peroxidase; GR, glutathione reductase; POD, peroxidase; GST, glutathione S-transferase; DHAR, dehydroascorbate reductase; MDHAR, monodehydroascorbate reductase) and as well as regulating ascorbate-glutathione (AsA-GSH) cycle. Importantly, oxidative damage showed efficient alleviations through upregulating the genes related to key defense such as SOD, CAT, POD, GR, GST, APX, GPX, DHAR, and MDHAR; along with the genes related to ME biosynthesis. ME supplementation also enhanced the level of proline and secondary metabolites, and their encoding genes expression, which may control excessive H2O2 (hydrogen peroxide) production. Finally, ME supplementation enhanced the HM stress tolerance of pepper seedlings.


Identification of aggressive driving from naturalistic data in car-following situations.
Aggressive driving has been associated as one of the causes for crashes, sometimes with very serious consequences. The objective of this study is to investigate the possibility of identifying aggressive driving in car-following situations on motorways by simple jerk metrics derived from naturalistic data. We investigate two jerk metrics, one for large positive jerk and the other for large negative jerk, when drivers are operating the gas and brake pedal, respectively. The results obtained from naturalistic data from five countries in Europe show that the drivers from different countries have a significantly different number of large positive and large negative jerks. Male drivers operate the vehicle with significantly larger number of negative jerks compared to female drivers. The validation of the jerk metrics in identifying aggressive driving is performed by tailgating (following a leading vehicle in a close proximity) and by a violator/non-violator categorization derived from self-reported questionnaires. Our study shows that the identification of aggressive driving could be reinforced by the number of large negative jerks, given that the drivers are tailgating, or by the number of large positive jerks, given that the drivers are categorized as violators. Practical applications: The possibility of understanding, classifying, and quantifying aggressive driving behavior and driving styles with higher risk for accidents can be used for the development of driver support and coaching programs that promote driver safety and are enabled by the vast collection of driving data from modern in-vehicle monitoring and smartphone technology.


Osmoregulation and expression of ion transport proteins and putative claudins in the gill of southern flounder (Paralichthys lethostigma).
The southern flounder is a euryhaline teleost that inhabits ocean, estuarine, and riverine environments. We investigated the osmoregulatory strategy of juvenile flounder by examining the time-course of homeostatic responses, hormone levels, and gill Na(+),K(+)-ATPase and Na(+),K(+),2Cl(-) cotransporter protein expression after salinity challenge. Transfer of freshwater (FW)-acclimated flounder to sea water (SW) induced an increase in plasma osmolality and cortisol and a decrease in muscle water content, plasma insulin-like growth factor I (IGF-I) and hepatic IGF-I mRNA, all returning to control levels after 4 days. Gill Na(+),K(+)-ATPase and Na(+),K(+),2Cl(-) cotransporter protein levels were elevated in response to SW after 4 days. Transfer of SW-acclimated flounder to FW reduced gill Na(+),K(+)-ATPase and Na(+),K(+),2Cl(-) cotransporter protein, increased plasma IGF-I, but did not alter hepatic IGF-I mRNA or plasma cortisol levels. Gill claudin-3 and claudin-4 immunoreactive proteins were elevated in FW versus SW acclimated flounder. The study demonstrates that successful acclimation of southern flounder to SW or FW occurs after an initial crisis period and that the salinity adaptation process is associated with changes in branchial expression of ion transport and putative tight junction claudin proteins known to regulate epithelial permeability in mammalian vertebrates.


Changes in the Treatment of Decompensated Advanced Heart Failure During Hospitalization and at Discharge.
In advanced heart failure (HF), each hospitalization for decompensation is a vulnerable moment, and it requires optimizing pharmacologic treatment. This study aimed to analyze changes in the pharmacologic treatment of HF before admission (P), during hospitalization (H), and at discharge (D) of patients with decompensated advanced HF. We performed an ambispective, cross-sectional, noninterventional study conducted from January 2020 to June 2020. There were 252 consecutive patients admitted for decompensated advanced HF. The following were excluded: de novo HF cases, deceased patients, and scheduled admissions. Finally, 134 patients were analyzed, compared in 3 subgroups: pulmonary congestion (n = 90), systemic congestion (n = 31), and low output (n = 13). In the global analysis, an increase was detected in angiotensin receptor and neprilysin inhibitors (P: 9.7%, H: 16.4, D: 22.4%; P < .02), beta blockers (P: 67.2%, H: 77.6%, D: 84.3%; P < .004), mineralocorticoid receptor antagonists (P: 29.9%, H: 44.4%, D: 46.3%; P < .01), loop diuretics (P: 70.1%, H: 99.3%, D: 95.5%; P < .001), and nitrates (P: 6.0%, H: 22.4%, D: 9.7%; P < .001). Pulmonary congestion was predominant with a significant increase in beta blockers (P: 61.1%, H: 77.8%, D: 88.9%; P < .001) and loop diuretics (P: 64.4%, H: 100%, D: 100%; P < .001); diuretics were increased in the systemic congestion group (P: 80.6%, H: 100%, D: 100%; P < .002), and 22.6% required 3% hypertonic saline solution. In patients with low output, beta blockers and diuretics were withdrawn (P: 84.6%, H: 76.9%, D: 46.1%; P < .08 and P: 84.6%, H: 92.3%, D: 61.5%; P < .1 respectively), without variation in the other pharmacologic groups. In daily clinical practice, HF drugs are increased and optimized in decompensated HF with a pulmonary or systemic congestion profile. When the profile is low output, beta blockers and diuretics are reduced.


The CYP/20-HETE/GPR75 axis in hypertension.
20-Hydroxyeicosatetraenoic acid (20-HETE) is a bioactive lipid generated from the ω-hydroxylation of arachidonic acid (AA) by enzymes of the cytochrome P450 (CYP) family, primarily the CYP4A and CYP4F subfamilies. 20-HETE is most notably identified as a modulator of vascular tone, regulator of renal function, and a contributor to the onset and development of hypertension and cardiovascular disease. 20-HETE-mediated signaling promotes hypertension by sensitizing the vasculature to constrictor stimuli, inducing endothelial dysfunction, and potentiating vascular inflammation. These bioactions are driven by the activation of the G-protein coupled receptor 75 (GPR75), a 20-HETE receptor (20HR). Given the capacity of 20-HETE signaling to drive pro-hypertensive mechanisms, the CYP/20-HETE/GPR75 axis has the potential to be a significant therapeutic target for the treatment of hypertension and cardiovascular diseases associated with increases in blood pressure. In this chapter, we review 20-HETE-mediated cellular mechanisms that promote hypertension, highlight important data in humans such as genetic variants in the CYP genes that potentiate 20-HETE production and describe recent findings in humans with 20HR/GPR75 mutations. Special emphasis is given to the 20HR and respective receptor blockers that have the potential to pave a path to translational and clinical studies for the treatment of 20-HETE-driven hypertension, and obesity/metabolic syndrome.


A central regulation of PTH secretion and function.
PTH orchestrates calcium homeostasis and doubles as a potent, clinically important regulator of bone mass. Adding to the known peripheral regulation of PTH secretion and function, a study by Zhang et al.1 in this issue of Neuron identifies centrally mediated pathways regulating these processes.


Brine shrimp (Artemia salina) nauplii as a teratogen test system.
Brine shrimp increase in length rapidly after hatching. A teratogen test system is based on disruption of elongation between 24 and 48 hr after wetting of the cysts. Teratogenicity of substances dissolved in the medium is assayed by comparison of average lengths of animals raised for the test period in suspect solution with average lengths of controls. The system is fast, inexpensive, and requires little skill. Brine shrimp are suited to testing industrial wastes, chemical formulations, drugs, and food additives that can be dissolved in water at 25 degrees C. The method appears unsuited to testing the teratogenicity of gases, particulates, very dilute wastes, or natural waters. Cadmium, mercury, lead, zinc, bromoform, n-butylphthalate, 1,2-dichloroethane, nitrobenzene, tetrachloroethylene, toluene, 1,2,4-trichlorobenzene, and 1,1,3-trichloroethane were found teratogenic. Chromium (III), chromium (VI), copper, chlorobenzene, chloroform, dimethyl sulfoxide (DMSO), and phenol were found not teratogenic. Other aquatic organism teratogen test systems are surveyed.


Multi-peril pathogen risks to global wheat production: A probabilistic loss and investment assessment.
Crop diseases cause significant food and economic losses. We examined the joint, probabilistic, long-term, bio-economic impact of five major fungal pathogens of wheat on global wheat production by combining spatialized estimates of their climate suitability with global wheat production and modeled distributions of potential crop losses. We determined that almost 90% of the global wheat area is at risk from at least one of these fungal diseases, and that the recurring losses attributable to this set of fungal diseases are upwards of 62 million tons of wheat production per year. Our high-loss regime translates to around 8.5% of the world's wheat production on average-representing calories sufficient to feed up to 173 million people each year. We estimate that a worldwide research expenditure of $350-$974 million (2018 prices) annually on these five fungal diseases of wheat, let alone other pathogens, can be economically justified, equivalent to 2 to 5 times more than the amount we estimate is currently spent on all wheat disease-related public R&D.


Dissolved oxygen in the rehabilitation phase of an estuary: influence of sewage pollution abatement and hydro-climatic factors.
Seasonal and inter-annual variations of dissolved oxygen (DO) along the estuary of Bilbao were investigated from 1998 to 2008, during its rehabilitation phase from pollution, to determine whether anthropogenic or natural forcings or both govern DO dynamics and hypoxia. Both seasonal and inter-annual variations of DO were best explained by hydro-climatic factors, sewage pollution and phytoplankton dynamics in the inner, intermediate and outer estuary respectively. The most remarkable intra-decadal improvement in DO occurred in the halocline layer of the intermediate estuary, where the factor that best explained these changes was sewage pollution abatement. However, in the estuarine hotspot for hypoxia, i.e. inner estuary bottom waters, no parallel response to sewage pollution abatement was observed and hydro-climatic factors were the main drivers of inter-annual DO variations. Differences in the degree of stratification and flushing accounted for this differential response of DO to anthropogenic and climate-related forcings at both axial and vertical scales.


Bovine fetal fluid cells in vitro: fate and fetal sex prediction accuracy.
The in vitro fate of bovine fetal fluid cells and the efficiency of fetal sex predication from cultures of these cells are studied using aspirates from live animals and pregnant uteri collected from the slaughterhouse. Over 70 percent of bovine amniotic fluid samples aspirated from pregnant uteri at the time of slaughter yielded cultures adequate for chromosome analysis whereas only 10 percent of allantoic fluid samples produced growth of cells satisfactory for chromosome analysis. Fetal sexing accuracy was 100 percent in all samples studied. Seven readily recognizable cell types were noted in cultures of fetal fluid cells obtained at various stages of gestation. In a majority of cases, the in vitro morphology of cells from both fetal cavities was similar to that observed in primary human amniotic fluid cell cultures.


Accumulation and Depuration Kinetics of Rotavirus in Mussels Experimentally Contaminated.
Bivalve mollusks as filter-feeders concentrate in their digestive tissue microorganisms likely present in the harvesting water, thus becoming risky food especially if consumed raw or poorly cooked. To eliminate bacteria and viruses eventually accumulated, they must undergo a depuration process which efficacy on viruses is on debate. To better clarify the worth of the depuration process on virus elimination from mussels, in this study we investigated rotavirus kinetics of accumulation and depuration in Mytilus galloprovincialis experimentally contaminated. Depuration process was monitored for 9 days and virus residual presence and infectivity were evaluated by real time quantitative polymerase chain reaction, cell culture and electron microscopy at days 1, 2, 3, 5, 7, 9 of depuration. Variables like presence of ozone and of microalgae feeding were also analyzed as possible depuration enhancers. Results showed a two-phase virus removal kinetic with a high decrease in the first 24 h of depuration and 5 days necessary to completely remove rotavirus.


Lack of correlation after reperfusion between ventricular function and infarct size estimated by thallium single-photon emission computed tomography.
In 32 patients with acute myocardial infarction, who had undergone successful intracoronary thrombolysis, the results of regional wall motion measured from contrast cineangiograms 10 to 21 days after thrombolysis were related to the results of thallium single-photon emission computed tomography (SPECT) after intravenous dipyridamole. Wall motion was measured by means of the centerline method, and thallium defect size was estimated by comparing the patient's circumferential profile with that of 20 normals. No correlation was found between ejection fraction or regional wall motion and thallium defect size. The time from symptom onset to thrombolysis was inversely correlated with the degree of hypokinesis (r = -0.51) but not with thallium defect size. In patients treated within 3 hours, hypokinesis was significantly less than in patients treated later (-1.1 +/- 0.6 SD vs -2.2 +/- 0.8 SD, p less than 0.01) whereas thallium defect size was not significantly different in both groups. It is concluded that, in patients after thrombolysis, thallium defect size determined by SPECT does not reflect the degree of left ventricular dysfunction.


The Physiological Experimental Study on the Effect of Different Color of Safety Signs on a Virtual Subway Fire Escape-An Exploratory Case Study of Zijing Mountain Subway Station.
Safety signs play a very important role in people's evacuation during emergencies. In order to explore the appropriate color for subway safety signs, four safety signs of different color combinations are designed, and the virtual reality, eye-tracking technology, and physiological indicator measurement are used in a virtual subway fire escape experiment. A total of 96 participants with equal distribution in gender and four different color combination groups were recruited. Participants' eye-tracking and physiological data (heart rate, skin conductance) were real-time recorded through ErgoLAB V3.0 in the whole experiment. The relationship between Color_of_safety_sign and escape performance, eye-tracking indicators, and physiological indicators is discussed respectively through SPSS. The results show that "Green and black" group has the best evacuation escape performance, low cognitive load, high search efficiency on safety signs, and the highest stress level and immersion and "Green and black" can be the most appropriate color for safety sign. This research is of certain significance for improving the function of subway fire-fighting infrastructure and the resilience of the metro system. Moreover, it can provide references and advice on risk management, emergency evacuation, and so on.


A Randomized Double-Blind Placebo-Controlled Trial of Lactobacillus reuteri for Chronic Functional Abdominal Pain in Children.
Functional abdominal pain (FAP) is one of the most common diseases, and large percentages of children suffer from it. The purpose of the study was to evaluate the effect of Lactobacillus reuteri in treatment of children with functional abdominal pain. This study was a randomized double-blind placebo-controlled trial. Children aged 4 to 16 years with chronic functional abdominal pain (based on Rome III criteria) were enrolled in the study. They were randomly divided into two groups, one receiving probiotic and the other placebo. Forty children received probiotic and forty others placebo. There were no significant differences in age, weight, sex, location of pain, associated symptoms, frequency and intensity of pain between the groups. The severity and frequency of abdominal pain in the first month compared to baseline was significantly less and at the end of the second month, there was no significant difference between both groups compared to the end of the first month. This study showed that the severity of pain was significantly reduced in both groups. There was no significant difference in pain scores between them. The effect of probiotic and placebo can probably be attributed to psychological effect of the drugs.


Association of low skeletal muscle mass and systemic inflammation with surgical complications and survival after microvascular flap reconstruction in patients with head and neck cancer.
Skeletal muscle mass (SMM) and chronic inflammation are associated with postoperative complications and survival. Patients with head and neck cancer (HNC) undergoing microvascular free flap reconstruction were included. SMM and neutrophil-to-lymphocyte ratio (NLR) were measured and their association with treatment outcomes analyzed. Five hundred and fifty-four patients were included. Predictors for complications were elevated NLR in all flaps (OR 1.5), low SMM in radial forearm flap (OR 2.0), and elevated NLR combined with low SMM in fibula flap surgery (OR 4.3). Patients with solely elevated NLR were at risk for flap-related complications (OR 3.0), severe complications (OR 2.2), and when combined with low SMM for increased length of hospital stays (LOS) (+3.9 days). In early-stage HNC, low SMM (HR 2.3), and combined elevated NLR with low SMM (HR 2.6) were prognostics for decreased overall survival. SMM and NLR are predictive for poor outcomes in patients with HNC undergoing microvascular reconstruction.


Do people with anorexia nervosa use sauna baths? A reconsideration of heat-treatment in anorexia nervosa.
The paper addresses the absence of reports about the sauna use among the weight loss strategies of patients with anorexia nervosa (AN). Because AN entails a relentless pursuit of thinness, it might be expected that these patients would frequently resort to saunas. The paper sustains that the absence of reports should not be taken to mean that sauna use is irrelevant to AN. Support for this possibility is founded in the apparent progress shown by AN patients whose treatment consisted of different strategies of heat supply, which included a protocol of sauna sessions. First recommended by W. Gull, heat-treatment may be relevant to hyperactivity, a significant clinical characteristic in AN. This treatment was developed as an extrapolation from animal research model, where a simple manipulation of ambient temperature (AT) was found to impede and reverse excessive running in food-restricted rats. Sauna use may have been unreported either because it impedes the development of the syndrome, or its benefits have been attributed to conventional treatments. The elucidation of sauna experience among AN patients may have potential implications for the role of heat in the treatment of AN.


The plasticity of estrogen receptor-DNA complexes: binding affinity and specificity of estrogen receptors to estrogen response element half-sites separated by variant spacers.
The consensus estrogen response element (cERE) contains a palindromic sequence of two 6-base pair (bp) half-sites separated by a spacer size of 3bp. This study investigates the extent to which estrogen receptors, ERalpha and ERbeta can bind target sequences not considered as conventional EREs. We determined the effect of spacer size (n=0-4) on the binding affinity and conformation of ERalpha and ERbeta in these complexes and the effect of HMGB1 on the complexation. We find (1) both receptors bind similarly and with progressively reduced affinity to cEREn, as n differs from 3; (2) however, both receptors bind as strongly to the cERE with no spacer (cERE0) as to cERE3; (3) HMGB1 enhances ER binding affinity in all complexes, resulting in strong and comparable binding affinities in all complexes examined; (4) the full-length ER binding differs strikingly from similar binding studies for the ER DNA binding domain (ERDBD), with the full-length ER dimer exhibiting strong binding affinity, enormous plasticity and retaining binding cooperativity as the spacer size varies; (5) both protease digestion profiles and monoclonal antibody binding assays indicate the conformation of the receptor in the ER/ERE complex is sensitive to the spacer size; (6) the ER/cERE0 complex appears to be singularly different than the other ER/cEREn complexes in binding and conformation. This multifaceted approach reinforces the notion of the plasticity in ER binding and leads to the hypothesis that in most cases, the minimum requirement for estrogen receptor binding is the ERE half-site, in which one or more cofactors, such as HMGB1, can cooperate to decrease ER binding specificity, while increasing its binding affinity.


A novel immunocytochemical assay for the detection of serotonin in platelets.
A method for the rapid, inexpensive and easy detection of platelet serotonin (5-hydroxytryptamine, 5-HT) is not currently available. Consequently, many patients suffering from unresolved platelet-related bleeding disorders are not examined for a possible platelet 5-HT deficiency. The direct measurement of 5-HT concentration with high-performance liquid chromatography (HPLC) or serotonin enzyme-linked immunosorbent assay (ELISA) is costly and highly demanding. Indirect methods, which determine the content of ATP or calcium with lumi-aggregometry or electron microscopy, rely upon the assumption that the ATP or calcium concentration is equivalent to that of 5-HT. We have developed a fluorescence-based assay for 5-HT that can be performed within 2 h on fresh or frozen samples using a fluorescence microscope or a flow cytometer. The assay requires only 0.2 ml of platelet-rich plasma and might therefore be of particular interest for paediatric patients. Samples from control and patient donors were analysed for 5-HT with the new immunocytochemical assay in comparison with HPLC and/or 5-HT ELISA. Patients with Hermansky-Pudlak syndrome were readily identified. The new assay was also reliable in cases where the 5-HT content of dense granules was not correlated with the calcium or ATP content, such as in calcium deficiency or in the presence of selective serotonin reuptake inhibitors.


Changes in the prevalence of pathogens causing hospital-acquired bacterial pneumonia and the impact of their antimicrobial resistance patterns on clinical outcomes: A propensity-score-matched study.
This study aimed to evaluate changes in the prevalence of pathogens causing hospital-acquired bacterial pneumonia (HABP) and their antimicrobial resistance patterns in recent years, and to identify risk factors for 28-day all-cause mortality (ACM) in patients with HABP. A propensity-score-matched study was performed by randomly allocating patients with ventilator-associated and non-ventilator-associated bacterial pneumonia admitted to two university hospitals between 2011 and 2021. In total, 17,250 patients with HABP were enrolled. The annual incidence of Staphylococcus aureus HABP decreased during the study period, while that of Klebsiella pneumoniae HABP increased significantly each year. Over the same period, the resistance rate of S. aureus to methicillin decreased from 88.4% to 64.4%, while the non-susceptibility rate of K. pneumoniae to carbapenems increased from 0% to 38%. HABP caused by A. baumannii [adjusted odds ratio (aOR) 1.50, 95% confidence interval (CI) 1.25-1.79], K. pneumoniae (aOR 1.28, 95% CI 1.16-1.40) and Stenotrophomonas maltophilia (aOR 1.32, 95% CI 1.05-1.66) was a risk factor for 28-day ACM. Patients with HABP caused by methicillin-resistant S. aureus and carbapenem-non-susceptible A. baumannii or K. pneumoniae had a significantly lower probability of survival. HABP with preceding coronavirus disease 2019 (COVID-19) was associated with high 28-day ACM (aOR 5.40, 955 CI 3.03-9.64) and high incidence of bacteraemic pneumonia (aOR 40.55, 95% CI 5.26-312.79). This study showed shifting trends in HABP-causing pathogens in terms of annual incidence and resistance rates to major therapeutic antimicrobial agents. HABP-causing bacterial pathogens, their antimicrobial resistance phenotypes, and preceding COVID-19 were significantly associated with progression of HABP to bloodstream infection and 28-day ACM in infected patients.


Expression of functional Y1 receptors for neuropeptide Y in human Ewing's sarcoma cell lines.
In the human Ewing's sarcoma cell line WE-68, saturation analysis using 3H-labelled neuropeptide Y ([3H]NPY) as the radioligand disclosed a homogeneous population of binding sites with a dissociation constant (Kd) of 4.5 nM and maximal binding capacity (B(max)) of 712 fmol/mg cell protein. Besides the WE-68 cell line, ten other human Ewing's sarcoma cell lines (FM-62, HS-80, HT-78, HT-M1-78, NT-68, RM-82, RS-63, VH-64, WE-M1-68, WE-M2-68) were also found to display NPY receptors with Kd varying from 3.5 nM to 10.7 nM and B(max) = 247-3744 fmol/mg cell protein. NPY, its natural analogues and the Y1-receptor-specific peptide ligand [Leu31,Pro34]NPY inhibited [3H]NPY binding in the potency order: [Leu31,Pro34]NPY greater than or equal to human NPY greater than or equal to peptide YY (PYY) greater than salmon pancreatic polypeptide (PP) greater than human PP greater than porcine NPY13-36 much greater than NPY22-36. In the Ewing's sarcoma cell lines NPY provoked inhibition of forskolin-stimulated cyclic AMP formation by up to 98%. Pertussis toxin alleviated the cyclic-AMP-inhibitory response to NPY. In isolated Ewing's sarcoma plasma membranes pertussis toxin [32P]ADP-ribosylated a 41-kDa protein. The ability of NPY and analogues to inhibit cyclic AMP accumulation paralleled their potencies in displacing radioligand binding. By contrast, a cell line derived from an atypical form of Ewing's sarcoma did not express specific and functional NPY receptors. These results demonstrate that conventional Ewing's sarcoma cells possess Gi-protein-coupled NPY receptors of the Y1 type, which upon interaction with NPY, PYY, and PP mediate inhibition of cyclic AMP generation.


Comprehensive study on identification of water inrush sources from deep mining roadway.
To accurately identify the location of the water inrush sources, correlation analysis and factor analysis were used to discuss the similarity of hydrochemical control mechanism of different aquifers and inrush water. On this basis, Fisher and BP neural network are used to judge the probability of inrush water. Finally, it is verified by hydrological observation holes. According to the water sources mixing model, the water inrush sources of 11601 working face were mainly No. 13 stratum Carboniferous limestone water with a small amount of No. 10 stratum Carboniferous limestone water, and the mixing ratio is 11:1. Combining the results of water inrush source identification, water yield mutation, geophysical exploration results, and underground drilling, it is speculated that there are two faults in this working face. The normal fault stops at the top of No. 13 stratum Carboniferous limestone aquifer, and the reverse fault develops to No. 13 stratum Carboniferous limestone aquifer. This research is of great significance for the identification of mine water sources and guidance for the prevention and control of water inrush.


Assessing the impact of the "one-child policy" in China: A synthetic control approach.
There is great debate surrounding the demographic impact of China's population control policies, especially the one-birth restrictions, which ended only recently. We apply an objective, data-driven method to construct the total fertility rates and population size of a 'synthetic China', which is assumed to be not subjected to the two major population control policies implemented in the 1970s. We find that while the earlier, less restrictive 'later-longer-fewer' policy introduced in 1973 played a critical role in driving down the fertility rate, the role of the 'one-child policy' introduced in 1979 and its descendants was much less significant. According to our model, had China continued with the less restrictive policies that were implemented in 1973 and followed a standard development trajectory, the path of fertility transition and total population growth would have been statistically very similar to the pattern observed over the past three decades.


"They're all struggling as well": social and economic barriers and facilitators to self-managing chronic illness among marginalized people who use drugs.
Self-management is recommended for addressing chronic conditions, and self-management programmes improve health behaviours and outcomes. However, social and economic factors have been neglected in self-management research, despite their relevance for marginalized groups. Thus, we aimed to explore barriers and facilitators that influence self-management among socioeconomically marginalized people who use drugs (PWUD). Using community-based participatory methods, we developed a qualitative interview guide and conducted peer-led recruitment. Participants were admitted into the study after self-identifying as using non-prescribed drugs, having a chronic health issue, and experiencing socioeconomic marginalization. Data were analysed using reflexive thematic analysis, taking a relational autonomy lens. Participants highlighted substantial barriers to managing their health issues, mostly stemming from their social and economic environments, such as unstable housing, low income, lack of supportive social networks, and negative healthcare experiences. Participants also described how their ability to self-manage their chronic conditions benefited from specific aspects of social interactions, including close relationships, community connectedness, and engaging in peer support. Our findings suggest that structural interventions are needed to support self-management among marginalized PWUD, especially stable housing. Self-management supports for PWUD would benefit from including a range of low-barrier community-based options, peer work opportunities, and advocacy for needs.


Differential Glial Chitotriosidase 1 and Chitinase 3-like Protein 1 Expression in the Human Primary Visual Cortex and Cerebellum after Global Hypoxia-Ischemia.
Here, we studied the neuroinflammation- and ischemia-related glial markers chitotriosidase 1 (CHIT1) and chitinase-3-like protein 1 (CHI3L1, alias YKL-40) in the human striate cortex and cerebellum at different time points after global hypoxic-ischemic brain injury (HIBI). Both regions differ considerably in their glial cell population but are supplied by the posterior circulation. CHIT1 and CHI3L1 expression was compared to changes in microglial (IBA1, CD68), astrocytic (GFAP, S100β), and neuronal markers (H&E, neurofilament heavy chain, NfH; calretinin, CALR) using immunohistochemistry and multiple-label immunofluorescence. Initial striatal cortical and cerebellar Purkinje cell damage, detectable already 1/2 d after HIBI, led to delayed neuronal death, whereas loss of cerebellar NfH-positive stellate and CALR-positive granule cells was variable. During the first week post-HIBI, a transient reduction of IBA1-positive microglia was observed in both regions, and fragmented/clasmatodendritic cerebellar Bergmann glia appeared. In long-term survivors, both brain regions displayed high densities of activated IBA1-positive cells and CD68-positive macrophages, which showed CHIT1 co-localization in the striate cortex. Furthermore, enlarged GFAP- and S100β-positive astroglia emerged in both regions around 9-10 d post-HIBI, i.e., along with clearance of dead neurons from the neuropil, although GFAP-/S100β-positive gemistocytic astrocytes that co-expressed CHI3L1 were found only in the striate cortex. Thus, only GFAP-/S100β-positive astrocytes in the striate cortex, but not cerebellar Bergmann glia, differentiated into CHI3L1-positive gemistocytes. CHIT1 was co-expressed almost entirely in macrophages in the striate cortex and not cerebellum of long-term survivors, thereby indicating that CHIT1 and CHI3L1 could be valuable biomarkers for monitoring the outcome of global HIBI.


Opposite turning effects of dainic and ibotenic acid injected in the rat substantia nigra.
Unilateral intranigral administration of kainic and ibotenic acid, two putative stimulants of glutamatergic mechanisms, elicited turning behaviour starting from doses of 10 ng. While the turning produced by kainic acid was ipsilateral, that produced by ibotenic acid was contralateral to the injected side. Previous destruction of dopaminergic neurons on the side of the intranigral injection failed to reduce the turning behaviour. Peripheral treatment with picrotoxin did not reduce the turning in response to ibotenic acid. The results might suggest the existence of excitatory and inhibitory glutamate receptors which control nigral non-dopaminergic neurons mediating turning-behaviour.


Smooth Muscle Cell Foam Cell Formation, Apolipoproteins, and ABCA1 in Intracranial Aneurysms: Implications for Lipid Accumulation as a Promoter of Aneurysm Wall Rupture.
Saccular intracranial aneurysm (sIA) aneurysm causes intracranial hemorrhages that are associated with high mortality. Lipid accumulation and chronic inflammation occur in the sIA wall. A major mechanism for lipid clearance from arteries is adenosine triphosphate-binding cassette A1 (ABCA1)-mediated lipid efflux from foam cells to apolipoprotein A-I (apoA-I). We investigated the association of wall degeneration, inflammation, and lipid-related parameters in tissue samples of 16 unruptured and 20 ruptured sIAs using histology and immunohistochemistry. Intracellular lipid accumulation was associated with wall remodeling (p = 0.005) and rupture (p = 0.020). Foam cell formation was observed in smooth muscle cells, in addition to CD68- and CD163-positive macrophages. Macrophage infiltration correlated with intracellular lipid accumulation and apolipoproteins, including apoA-I. ApoA-I correlated with markers of lipid accumulation and wall degeneration (p = 0.01). ApoA-I-positive staining colocalized with ABCA1-positive cells particularly in sIAs with high number of smooth muscle cells (p = 0.003); absence of such colocalization was associated with wall degeneration (p = 0.017). Known clinical risk factors for sIA rupture correlated inversely with apoA-I. We conclude that lipid accumulation associates with sIA wall degeneration and risk of rupture, possibly via formation of foam cells and subsequent loss of mural cells. Reduced removal of lipids from the sIA wall via ABCA1-apoA-I pathway may contribute to this process.


Biliary ascariasis.
Biliary ascariasis is a less frequent, but important complication of ascaris infestation, because it may cause biliary colic, pyogenic cholangitis, and septicemia. Early diagnosis and treatment is important to prevent these complications. We present here a five-year-old girl with biliary ascariasis, whose main complaint was abdominal pain. After giving piperazin salt, multiple ascaris worms were seen in the stool within 10 days. She is at the follow-up without any complication.


Explainable analytics: understanding causes, correcting errors, and achieving increasingly perfect accuracy from the nature of distinguishable patterns.
In addition to pursuing accurate analytics, it is invaluable to clarify how and why inaccuracy exists. We propose a transparent classification (TC) method. In training, data consist of positive and negative observations. To obtain positive patterns, we find the intersection between each of the two positive observations. The negative patterns are obtained in the same manner. Next, pure positive and pure negative patterns are established by selecting patterns that appear in only one type. In testing, such pure positive and pure negative patterns are used for scoring observations. Next, an observation is classified as positive if its positive score is not zero or if both its positive and negative scores are zero; otherwise, it is classified as negative. By experiment, TC can identify all positive (e.g., malignant) observations at low ratios of training to testing data, e.g., 1:9 using the Breast Cancer Wisconsin (Original) and 3:7 using the Contraceptive Method Choice. Without fine-tuned parameters and random selection, the uncertainty of the methodology is eliminated when using TC. TC can visualize causes, and therefore, prediction errors in a network are traceable and can be corrected. Furthermore, TC shows potential in identifying whether the ground truth is incorrect (e.g., identifying diagnostic errors).


Blogging through dementia: Reworking mainstream discourse through metaphor in online early-onset dementia narratives.
The depiction of dementia in public discourse tends to operate on two levels: the tragedy discourse or the living well with dementia discourse, where metaphors play a decisive role in the characterization of the condition and the voice of those living with the condition is usually underrepresented. This article analyzes whether and how mainstream discourse on dementia is reworked in first-person accounts of the disease online and explores the attitudes and assumptions about dementia that illness blogs reflect and defy. Drawing on Conceptual Metaphor Theory, the article analyzes a corpus of 10 blogs (622 posts) written by individuals living with early-onset dementia to identify the metaphors used to depict dementia, its impact on the self and its social and relational aspects. Metaphor identification was based on the PRAGGLEJAZ metaphor identification procedure. The study demonstrates that across blogs no single metaphor alone is capable of capturing the complexity of the dementia experience; instead multiple metaphors are deployed to provide a characterization of the multiple faces of this condition. In this way blogs transcend and reshape the reductionist view of dementia that emerges from the either/or dichotomy of the tragedy versus living well with dementia discourses that dominate in media representations. By reshaping some of the metaphors used in mainstream discourse and introducing new ones, blog narratives draw attention to the complex nature of the experience of dementia, acknowledging both the suffering and social and functional losses that the condition brings, while also claiming recognition for personhood, agency, validation, and the aspiration to grow beyond the diagnosis and live a valued life as part of a family and community. Overall, this study demonstrates that metaphor is a useful tool for providing insights into people's experience of dementia and that blogs are a platform where stereotypes may be defied and mainstream representations of dementia reworked offering a more holistic view of the condition and granting narrative agency to those who live with dementia.


Repurposing drugs as COVID-19 therapies: A toxicity evaluation.
Drug repurposing is an appealing method to address the Coronavirus 2019 (COVID-19) pandemic because of the low cost and efficiency. We analyzed our in-house database of approved drug screens and compared their activity profiles with results from a severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) cytopathic effect (CPE) assay. The activity profiles of the human ether-à-go-go-related gene (hERG), phospholipidosis (PLD), and many cytotoxicity screens were found significantly correlated with anti-SARS-CoV-2 activity. hERG inhibition is a nonspecific off-target effect that has contributed to promiscuous drug interactions, whereas drug-induced PLD is an undesirable effect linked to hERG blockers. Thus, this study identifies preferred drug candidates as well as chemical structures that should be avoided because of their potential to induce toxicity. Lastly, we highlight the hERG liability of anti-SARS-CoV-2 drugs currently enrolled in clinical trials.


The reversible behavior of locally invasive endometrial carcinoma in a chromosomally mosaic (45,X/46,Xr(X)) young woman treated with Clomid.
A 22 year-old phenotypic female with a 45,x/46,x, r(x) mosaic complement had anovulatory cycles, histologically normal ovaries, and atypical endometrial hyperplasia which, when clinically followed by repeated biopsies, was found to progress to locally invasive endometrial carcinoma. This was successfully managed by the induction of ovulation with Clomid, which resulted in conversion of the endometrium to a normal secretory pattern for two subsequent years.


A 10-year follow-up study on endoscopic total extraperitoneal repair of primary and recurrent inguinal hernia.
To determine whether endoscopic repair is favorable in the long term, follow-up recurrence rates after 10 years need to be assessed. Between January 1995 and January 1996, 306 consecutive patients underwent total extraperitoneal (TEP) inguinal hernia repair. Long-term follow-up assessment occurred from January 2006 to May 2006. After a 10-year follow-up period, six (4%) recurrences were found in the primary inguinal hernia group and three recurrences (11%) in the recurrent inguinal hernia group. Age, experience, hospital stay, and operating time were not significantly correlated with recurrences. The long-term results of TEP primary inguinal hernia repair demonstrate it to be an effective and safe procedure with an acceptable recurrence rate. Recurrence rates may be underestimated because the findings show that recurrences continue to occur for as long as 10 years.


Predictors for clinical and functional outcomes in stroke patients with first-pass complete recanalization after thrombectomy.
The aim was to identify baseline clinical and radiological/procedural predictors and 24-h radiological predictors for clinical and functional outcomes in stroke patients obtaining complete recanalization in one pass of mechanical thrombectomy (MT) in an optimal baseline and procedural setting. A retrospective analysis was conducted of prospectively collected data from 924 stroke patients with anterior large vessel occlusion, Alberta Stroke Program Early Computed Tomography (ASPECT) score ≥6 and pre-stroke modified Rankin Scale score 0, who started MT ≤6 h from symptom onset and obtained first-pass complete recanalization. A first logistic regression model was performed to identify baseline clinical predictors and a second model to identify baseline radiological/procedural predictors. A third model including baseline clinical and radiological/procedural predictors was performed, and a fourth model including independent baseline predictors from the third model plus 24-h radiological variables (hemorrhagic transformation [HT] and cerebral edema [CED]). In the fourth model, higher National Institutes of Health Stroke Scale (NIHSS) score (odds ratio [OR] 1.089) and higher ASPECT score (OR 1.292) were predictors of early neurological improvement (ENI) (NIHSS score ≤4 points from baseline or NIHSS score of 0 at 24 h), whereas older age (OR 0.973), longer procedure time (OR 0.990), HT (OR 0.272) and CED (OR 0.569) were inversely associated with ENI. Older age (OR 0.970), diabetes mellitus (OR 0.456), higher NIHSS score (OR 0.886), general anesthesia (OR 0.454), longer onset-to-groin time (OR 0.996), HT (OR 0.340) and CED (OR 0.361) were inversely associated with 3-month excellent functional outcome (mRS score 0-1), whereas higher ASPECT score (OR 1.294) was a predictor of excellent outcome. Higher NIHSS score was a predictor of ENI but inversely associated with 3-month excellent outcome. Older age, HT and CED were inversely associated with both good outcomes.


Vocal fold scars: current concepts and future directions. Consensus report of the Phonosurgery Committee of the European Laryngological Society.
Scarring of the vocal folds leads to a deterioration of the highly complex micro-structure with consecutively impaired vibratory pattern and glottic insufficiency. The resulting dysphonia is predominantly characterized by a reduced vocal capacity. Despite the considerable progress in understanding of the underlying pathophysiology, the treatment of scarred vocal folds is still an unresolved chapter in laryngology and phonosurgery. Essential for a successful treatment is an individual, multi-dimensional concept that comprises the whole armamentarium of surgical and non-surgical (i.p. voice therapy) modalities. An ideal approach would be to soften the scar, because the reduced pliability and consequently the increased vibratory rigidity impede the easiness of vibration. The chosen phonosurgical method is determined by the main clinical feature: Medialization techniques for the treatment of glottic gap, or epithelium freeing techniques for improvement of vibration characteristics often combined with injection augmentation or implantation. In severe cases, buccal mucosa grafting can be an option. New developments, include treatment with anxiolytic lasers, laser technology with ultrafine excision/ablation properties avoiding coagulation (Picosecond infrared laser, PIRL), or techniques of tissue engineering. However, despite the promising results by in vitro experiments, animal studies and first clinical trials, the step into clinical routine application has yet to be taken.


Student vet nurse to practice manager - shaped by skills learnt in life and work.
Although Claire Mariner has been a practice manager for less than two years, she recognises that her experiences have helped her identify how to be a supportive and understanding member of the team.


Deletion of the sigB gene in Bacillus cereus ATCC 14579 leads to hydrogen peroxide hyperresistance.
The sigB gene of Bacillus cereus ATCC 14579 encodes the alternative sigma factor sigma(B). Deletion of sigB in B. cereus leads to hyperresistance to hydrogen peroxide. The expression of katA, which encodes one of the catalases of B. cereus, is upregulated in the sigB deletion mutant, and this may contribute to the hydrogen peroxide-resistant phenotype.


Landscape-level variability and insect herbivore outbreak captured within modern forests provides a framework for interpreting the fossil record.
Temporal patterns of plant-insect interactions are readily observed within fossil datasets but spatial variability is harder to disentangle without comparable modern methods due to limitations in preservation. This is problematic as spatial variability influences community structure and interactions. To address this we replicated paleobotanical methods within three modern forests, creating an analogous dataset that rigorously tested inter- and intra-forest plant-insect variability. Random mixed effects models, non-metric multidimensional scaling (NMDS) ordinations, and bipartite network- and node-level metrics were used. Total damage frequency and diversity did not differ across forests but differences in functional feeding groups (FFGs) were observed across forests, correlating with plant diversity, evenness, and latitude. Overall, we found higher generalized herbivory within the temperate forests than the wet-tropical, a finding also supported by co-occurrence and network analyses at multiple spatial scales. Intra-forest analyses captured consistent damage type communities, supporting paleobotanical efforts. Bipartite networks captured the feeding outbreak of Lymantria dispar caterpillars; an exciting result as insect outbreaks have long been unidentifiable within fossil datasets. These results support paleobotanical assumptions about fossil insect herbivore communities, provide a comparative framework between paleobotanical and modern communities, and suggest a new analytical framework for targeting modern and fossil outbreaks of insect feeding.


Relationships between chemical structure and inhibition of epinephrine-induced human blood platelet aggregation.
The effect of structural features in a series of carbamoylpiperidine and nipecotoylpiperazine congeners on epinephrine-induced aggregation of human blood platelets is examined. Epinephrine-induced primary aggregation is effectively inhibited by the nipecotoylpiperazine derivatives (culminating at an IPA50 of 11.9 microM). While among nipecotoylpiperazine as well as carbamoylpiperidine congeners there are potent inhibitors of ADP-stimulated platelet function (cresting at an IA50 of 12.4 and 11.4 microM, respectively), the carbamoylpiperidine analogs are much less active (e.g., IPA50 of 298.1), or practically inactive, in impeding epinephrine-induced primary aggregation (PA).


Elimination of stress factors by continuous embryo culture and its influence on in vitro fertilization outcomes.
Recently, infertility has become one of the most important endemic conditions, affecting approximately 15-20 % of couples worldwide. Among others, the careerist lifestyle, the increasing maternal age and the parallel increment in the aneuploidy rate of embryos play a crucial role in this phenomenon. In this study, embryological parameters and pregnancy outcomes were investigated in IVF cycles using either sequential embryo culture or a single step culture system. By sequential media, oocytes/embryos are needlessly exposed to the potentially negative effects of light exposure, temperature decrement and altered oxygen tension. In comparison with sequential media, single step media induced 1.28, 1.21 and 1.21-fold increments in implantation, biochemical pregnancy and clinical pregnancy rates, respectively. Pregnancy outcomes showed strong maternal age-dependency, so the difference between the two investigated culture systems was equalized by the increasing maternal ages (35-44 years) and the supposed incidence of embryo aneuploidy. Nevertheless, the significant enlargements in the outcomes of the younger ages (25-34) induced by the single step cultures suggest that, beside the resultant maternal aneuploidy, aneuploidy (reduced pregnancy rates) may evolve from exposure to the mentioned environmental stress factors.


Higher reliability and validity of Wavelet-ALFF of resting-state fMRI: From multicenter database and application to rTMS modulation.
Amplitude of low-frequency fluctuation (ALFF) has been widely used for localization of abnormal activity at the single-voxel level in resting-state fMRI (RS-fMRI) studies. However, previous ALFF studies were based on fast Fourier transform (FFT-ALFF). Our recent study found that ALFF based on wavelet transform (Wavelet-ALFF) showed better sensitivity and reproducibility than FFT-ALFF. The current study aimed to test the reliability and validity of Wavelet-ALFF, and apply Wavelet-ALFF to investigate the modulation effect of repetitive transcranial magnetic stimulation (rTMS). The reliability and validity were assessed on multicenter RS-fMRI datasets under eyes closed (EC) and eyes open (EO) conditions (248 healthy participants in total). We then detected the sensitivity of Wavelet-ALFF using a rTMS modulation dataset (24 healthy participants). For each dataset, Wavelet-ALFF based on five mother wavelets (i.e., db2, bior4.4, morl, meyr and sym3) and FFT-ALFF were calculated in the conventional band and five frequency sub-bands. The results showed that the reliability of both inter-scanner and intra-scanner was higher with Wavelet-ALFF than with FFT-ALFF across multiple frequency bands, especially db2-ALFF in the higher frequency band slow-2 (0.1992-0.25 Hz). In terms of validity, the multicenter ECEO datasets showed that the effect sizes of Wavelet-ALFF with all mother wavelets (especially for db2-ALFF) were larger than those of FFT-ALFF across multiple frequency bands. Furthermore, Wavelet-ALFF detected a larger modulation effect than FFT-ALFF. Collectively, Wavelet db2-ALFF showed the best reliability and validity, suggesting that db2-ALFF may offer a powerful metric for inspecting regional spontaneous brain activities in future studies.


Survival, excitability, and transfection of retinal neurons in an organotypic culture of mature zebrafish retina.
Over the last 20 years, the zebrafish has become an important model organism for research on retinal function and development. Many retinal diseases do not become apparent until the later stages of life. This means that it is important to be able to analyze (gene) function in the mature retina. To meet this need, we have established an organotypic culture system of mature wild-type zebrafish retinas in order to observe changes in retinal morphology. Furthermore, cell survival during culture has been monitored by determining apoptosis in the tissue. The viability and excitability of ganglion cells have been tested at various time points in vitro by patch-clamp recordings, and retinal functionality has been assessed by measuring light-triggered potentials at the ganglion cell site. Since neurogenesis is persistent in adult zebrafish retinas, we have also monitored proliferating cells during culture by tracking their bromodeoxyuridine uptake. Reverse genetic approaches for probing the function of adult zebrafish retinas are not yet available. We have therefore established a rapid and convenient protocol for delivering plasmid DNA or oligonucleotides by electroporation to the retinal tissue in vitro. The organotypic culture of adult zebrafish retinas presented here provides a reproducible and convenient method for investigating the function of drugs and genes in the retina under well-defined conditions in vitro.


Chaos in an enzyme reaction.
Dynamic systems are usually thought to have either monotonic or periodic behaviour. Although the possibility of other types of behaviour has been recognised for many years, the existence of non-monotonic, non-periodic behaviour in dynamic systems has been firmly established only recently. It is termed chaotic behaviour. A review on the rapidly expanding literature on chaos in discrete model systems described by difference equations has been published by May. Rössler, on the other hand, has discussed a few published works on systems of differential equations with chaotic solutions, and he has proposed a three-component chemical model system which he argues has chaotic solutions [figure see text]. The argument is based on a theorem by Li and Yorke. Here we report the finding of chaotic behaviour as an experimental result in an enzyme system (peroxidase). Like Rössler we base our identification of chaos on the theorem by Li and Yorke.


Microglia-independent peripheral neuropathic pain in male and female mice.
The dominant view in the field of pain is that peripheral neuropathic pain is driven by microglia in the somatosensory processing region of the spinal dorsal horn. Here, to the contrary, we discovered a form of neuropathic pain that is independent of microglia. Mice in which the nucleus pulposus (NP) of the intervertebral disc was apposed to the sciatic nerve developed a constellation of neuropathic pain behaviours: hypersensitivity to mechanical, cold, and heat stimuli. However, NP application caused no activation of spinal microglia nor was pain hypersensitivity reversed by microglial inhibition. Rather, NP-induced pain hypersensitivity was dependent on cells within the NP which recruited macrophages to the adjacent nerve. Eliminating macrophages systemically or locally prevented NP-induced pain hypersensitivity. Pain hypersensitivity was also prevented by genetically disrupting the neurotrophin brain-derived neurotrophic factor selectively in macrophages. Moreover, the behavioural phenotypes as well as the molecular mechanisms of NP-induced pain hypersensitivity were not different between males and females. Our findings reveal a previously unappreciated mechanism for by which a discrete peripheral nerve lesion may produce pain hypersensitivity, which may help to explain the limited success of microglial inhibitors on neuropathic pain in human clinical trials.


Comparison of EJC-enhanced and EJC-independent NMD in human cells reveals two partially redundant degradation pathways.
Nonsense-mediated mRNA decay (NMD) is a eukaryotic post-transcriptional gene regulation mechanism that eliminates mRNAs with the termination codon (TC) located in an unfavorable environment for efficient translation termination. The best-studied NMD-targeted mRNAs contain premature termination codons (PTCs); however, NMD regulates even many physiological mRNAs. An exon-junction complex (EJC) located downstream from a TC acts as an NMD-enhancing signal, but is not generally required for NMD. Here, we compared these "EJC-enhanced" and "EJC-independent" modes of NMD with regard to their requirement for seven known NMD factors in human cells using two well-characterized NMD reporter genes (immunoglobulin μ and β-Globin) with or without an intron downstream from the PTC. We show that both NMD modes depend on UPF1 and SMG1, but detected transcript-specific differences with respect to the requirement for UPF2 and UPF3b, consistent with previously reported UPF2- and UPF3-independent branches of NMD. In addition and contrary to expectation, a higher sensitivity of EJC-independent NMD to reduced UPF2 and UPF3b concentrations was observed. Our data further revealed a redundancy of the endo- and exonucleolytic mRNA degradation pathways in both modes of NMD. Moreover, the relative contributions of both decay pathways differed between the reporters, with PTC-containing immunoglobulin μ transcripts being preferentially subjected to SMG6-mediated endonucleolytic cleavage, whereas β-Globin transcripts were predominantly degraded by the SMG5/SMG7-dependent pathway. Overall, the surprising heterogeneity observed with only two NMD reporter pairs suggests the existence of several mechanistically distinct branches of NMD in human cells.


Carrageenan-induced NFkappaB activation depends on distinct pathways mediated by reactive oxygen species and Hsp27 or by Bcl10.
Carrageenans are highly sulfated polysaccharides that are widely used as food additives due to their ability to improve food texture. They are also widely recognized for their ability to induce inflammation in animal models of colitis. Recently, we reported that carrageenan (CGN) activated a pathway of innate immunity in human colonic epithelial cells mediated by Bcl10 (B-cell CLL/lymphoma 10). However, increases in phospho-IkappaBalpha and Interleukin-8 (IL-8) were not completely inhibited by silencing Bcl10, suggesting that CGN also influenced another mechanism, or mechanisms, of inflammation. In this report, we demonstrate that CGN increases production of reactive oxygen species (ROS) in human colonic epithelial cells. The combination of ROS quenching by the free radical scavenger Tempol and of Bcl10 silencing by siRNA completely inhibited the CGN-induced increases in nuclear NFkappaB (p65), phospho-IkappaBalpha, and secretion of IL-8. The CGN-induced increase in ROS was associated with declines in phosphorylation of MAPK 12 (p38gamma), MAPK 13 (p38delta), and heat-shock protein (Hsp) 27. The CGN-induced decline in phospho-Hsp27 was reversed by co-administration of Tempol (100 nM), but unaffected by silencing Bcl10. Since Hsp27 phosphorylation is inversely associated with phosphorylation of the IkappaBalpha kinase (IKK) signalosome, CGN exposure appears to affect the IKK signalosome by both the catalytic component, mediated by ROS-phospho-Hsp27, and the regulatory component, mediated by Bcl10 interaction with IKKgamma (Nemo). Hence, the CGN-activated inflammatory cascades related to innate immunity and to generation of ROS may be integrated at the level of the IKK signalosome.


Shorter acute hospital length of stay in hip fracture patients after surgery predicted by early surgery and mobilization.
Time to surgery, early mobilization, fracture type, and ASA grades independently affect acute hospital length of stay after hip fracture surgery. Modifiable factors can be audited to reduce length of stay, and non-modifiable factors can be used for consideration of a tiered bundled payment reimbursement model. As hip fracture incidence rises with our ageing global population, there will be an increase in consumption of healthcare resources. We hypothesized that hospital management and patient factors can affect healthcare burden load. Using length of stay (LOS) as a surrogate for consumption, the aim of this study is to elucidate the effect of hospital management and patient-related factors on length of stay (LOS) for patients after hip fracture surgery. We studied modifiable and non-modifiable factors influencing LOS, and identification of these modifiable factors accords opportunities for mitigating these factors. This retrospective study examines hip fracture data from a large tertiary hospital in Singapore over the period of 2017 to 2020. Data collected on the electronic medical record included age, gender, race, marital status, payer type, ASA score, TTS, type of surgery, fracture type, POD1 mobilization, discharge position, and presence of pressure sores, and they were correlated with LOS using binary logistic regression on SAS. A total of 1045 patients were included in this study with 704 females and 341 males. The mean age was 79.5 ± 8.57 years (range 60-105) with an average LOS 13.64 ± 10.0 days (range 2-114). On binary logistic regression, ASA and trochanteric fracture remains a significant non-modifiable factor for LOS with OR = 1.486 (95% CI 1.106, 1.996, p = 0.0086) and OR 1.522 (95% CI 1.149, 2.015, p = 0.0034) respectively. Significant modifiable factors were TTS > 48 h (OR = 1.819, 95% CI 1.205, 2.746, p = 0.0044) and POD1 mobilization (OR = 0.441, 95% CI 0.257, 0.756, p = 0.0029). Our analysis showed TTS and POD1 are significant modifiable factors for LOS, and resources can be diverted towards them for the management of hip fracture patients and pre-empting the increasing load on our healthcare system.


Doxorubicin-Induced Myocardial Fibrosis Involves the Neurokinin-1 Receptor and Direct Effects on Cardiac Fibroblasts.
Cancer patients receiving anthracycline-based chemotherapy (Anth-bC) may experience early cardiac fibrosis, which could be an important contributing mechanism to the development of impaired left ventricular (LV) function. Substance P, a neuropeptide that predominantly acts via the neurokinin 1 receptor (NK-1R), contributes to adverse myocardial remodelling and fibrosis in other cardiomyopathies. We sought to determine if NK-1R blockade is effective against doxorubicin (Dox - a frequently used Anth-bC)-induced cardiac fibrosis and cardiomyocyte apoptosis. In addition, we explored the direct effects of Dox on cardiac fibroblasts. Male Sprague-Dawley rats were randomised to receive saline, six cycles of Dox (1.5mg Dox/kg/cycle) or Dox with an NK-1R antagonist (L732138, 5mg/kg/daily through Dox treatment). At 8 weeks after the initial dose of Dox, LV function and histopathological myocardial fibrosis and cell apoptosis were assessed. Collagen secretion was measured in vitro to test direct Dox activation of cardiac fibroblasts. Rats undergoing Dox treatment (9mg/kg cumulative dose) developed cardiac fibrosis and cardiomyocyte apoptosis. NK-1R blockade partially mitigated cardiac fibrosis while completely preventing cardiomyocyte apoptosis. This resulted in improved diastolic function. Furthermore, we found that Dox had direct effects on cardiac fibroblasts to cause increased collagen production and enhanced cell survival. This study demonstrates that cardiac fibrosis induced by Anth-bC can be reduced by NK-1R blockade. The residual fibrotic response is likely due to direct Dox effects on cardiac fibroblasts to produce collagen.


Radioimmunoassay of norethindrone : serum levels of norethindrone in lactating women after insertion of a single Silastic implant releasing norethindrone acetate.
A specific radioimmunoassay was developed for the estimation of norethindrone levels in the serum of lactating women. A conjugate of norethindrone-3-BSA was synthesized and antiserum raised against it in rabbits. The antiserum showed high affinity (1.5 x 10(9)M/L) and titer and was specific. The sensitivity of the assay was 125 pg/ml serum. Serum levels of norethindrone were estimated in 25 lactating women, inserted with subdermal implant releasing about 150 ug of norethindrone acetate daily. The norethindrone levels were initially high in the first two months. From there onwards the levels of norethindrone remained constant with an average value of 1.0 ng/ml up to six months. These values were comparable to those obtained in non-lactating women. Thus, lactation does not seem to alter or affect the release of norethindrone acetate from the subdermal implant or its metabolism.


SAM-T04: what is new in protein-structure prediction for CASP6.
The SAM-T04 method for predicting protein structures uses a single protocol across the entire range of targets, from comparative modeling to new folds. This protocol is similar to the SAM-T02 protocol used in CASP5, but has improvements in the iterative search for similar sequences in finding and aligning templates, in creating fragment libraries, in generating protein conformations, and in scoring the conformations. The automatic procedure made some improvements over simply selecting an alignment to the highest-scoring template, and human intervention made substantial improvements over the automatic procedure. The main improvements made by human intervention were from adding constraints to build (or retain) beta-sheets and from splitting multidomain proteins into separate domains. The uniform protocol was moderately successful across the entire range of target difficulty, but was somewhat less successful than other approaches in CASP6 on the comparative modeling targets.


Increased levels of vasoactive intestinal peptide (VIP) and oxytocin during suckling in lactating dogs.
The aim of the present study was to investigate how suckling influences the plasma levels of oxytocin and vasoactive intestinal peptide in lactating dogs. Blood-samples were drawn from ten lactating beagles during suckling, in week one and week three of the five week long lactation period and the levels of vasoactive intestinal peptide and oxytocin were determined by radioimmunoassay. The immunoreactive levels of vasoactive intestinal peptide and oxytocin (below referred to VIP and oxytocin) increased rapidly in response to the suckling stimulus. The rise of both peptides was significant at both suckling experiments. The origin and role of suckling-released oxytocin is well established. The origin of and function of the VIP released in response to suckling remains unknown.


Treatment of Imiquimod Resistant Epidermodysplasia Verruciformis With Ingenol Mebutate.
Epidermodysplasia verruciformis (EV) is a rare genetic disorder characterized by widespread human papillomavirus (HPV) associated lesions and an increase susceptibility to cutaneous malignancies. A host of medications traditionally used to treat warty lesions have been used with variable results and limited success. To our knowledge, we describe the first reported case of a patient with Imiquimod resistant EV successfully treated with topical ingenol mebutate (Picato). A patient with a 5 year history of EV failed to respond to a 6 week course of 5% imiquimod on the forehead and was subsequently treated with a 3 day course of 0.015% Picato gel which resulted in significant clinical improvement. A one month follow-up examination showed no reoccurrence of the lesions with the patient reporting continued satisfaction of the outcome. Our case provides insight into the potential use of ingenol mebutate for EV patients unresponsive to traditional medical treatments.


Initial studies of hypoxic radioprotection by deoxygenated dextran-hemoglobin.
Initial studies were performed to examine the potential of perfused dextran-hemoglobin to protect pig skin or mouse bone marrow cells against radiation damage. Some protection was indicated in both systems. In the pig skin a protection factor of 1.5 was observed for moist desquamation, and 2.0 for necrosis. These results suggest the possibility of using blood substitutes to induce tissue hypoxia for therapeutic purposes.


Immunosuppression in the elderly renal allograft recipient: a systematic review.
The Elderly are the fastest growing part of kidney transplant recipients. The best immunosuppressive strategy is unknown. We performed a systematic search of randomized controlled trials and observational studies focused on safety and efficacy of different immunosuppression strategies in elderly kidney recipients. Data extraction and risk of bias evaluation were systematically performed. Ten studies were included: 2 randomized clinical trials and 8 observational. A marginal benefit was found for early renal function with delayed tacrolimus or complete tacrolimus avoidance using mycophenolate mofetil (MMF). Observational cohort studies looked at different antibody induction strategies, calcineurin-inhibitors based maintenance immunosuppression, calcineurin-inhibitor-free sirolimus-based therapy and use of MMF versus azathioprine. Treatment with interleukin-2 receptor antibody induction, calcineurin-inhibitor minimization with MMF and steroid minimization is advisable in the low immunologic risk elderly recipient, considering the increased risk of toxicities, infection and malignancies. In the high immunologic risk elderly recipient, taking into account the morbid consequences of acute rejection in the elderly, observational studies support antibody induction with depletive antibodies, calcineurin-inhibitor, MMF and steroids; calcineurin-inhibitor-minimization is not recommended. There is very limited evidence for the benefits and harms of different immunosuppression strategies in the elderly. Most of the published literature are observational studies, and randomized controlled trials are urgently needed.


Diet heart controversies--Quality of fat matters.
There has been a lot a debate recently regarding the effect of the quality of dietary fat on the risk of atherosclerotic vascular diseases, especially coronary heart disease (CHD). Long term randomized controlled interventions are almost lacking and the body of evidence is based on epidemiological data which allows conclusions only regarding associations, instead of effects. However, a recent systematic review, which included prospective cohort studies with high or moderate quality, showed convincing evidence on the favorable effect of partially replacing saturated fatty acids by polyunsaturated fatty acids on the risk of CHD. For some reason it seems tempting even in the scientific discussion to question the evidence of the quality of dietary fat on the risk of CHD every time when a controversial scientific article is published.


A rationale for service responses to self-injury.
In this paper, reasons reported by people who self-injure to explain this behaviour are presented. Traditional service responses are examined and it is suggested that these may exacerbate the reasons why people self-injure and are likely to create vulnerability to further harm. A rationale is presented which suggests that service-providers should aim to respond to the specific feelings underlying self-injury (SI) in a therapeutic way. Guidance is provided for implementing constructive responses to SI within clinical practice. If service-providers are trained to understand and accept SI as a comprehensible act of coping, then attitudes of respect and empathy are more likely to be exhibited. In turn, these approaches are therapeutic to service-users, potentially mitigating the feelings that initially prompt SI.


Ischaemic heart disease among livestock and agricultural workers.
Agricultural workers are exposed to organic dust containing endotoxins, mites, and moulds. To compare the occurrence of ischaemic heart disease (IHD) among male and female livestock and agricultural workers with gainfully employed men and women in Sweden. Male and female livestock and agricultural workers were identified in the Swedish National Censuses of 1970 and 1990 and were followed until the end of 1995. The IHD mortality among the livestock and agricultural workers was compared with that of gainfully employed men and women. Information of smoking habits was gathered from a previous national survey. Male as well as female livestock workers had slightly higher standardised mortality ratios (SMR) regarding IHD compared with all gainfully employed men and women in Sweden. The SMR for male workers was 1.06 (95% CI 0.95 to 1.18). The SMR for female workers was 1.10 (95% CI 0.98 to 1.23). Agricultural workers had lower SMRs. Adjustments for smoking habits would further increase the SMRs by about 9% in male workers and about 5% in female workers. The present data suggest a slightly increased risk for IHD among both male and female livestock workers, which may be the result of organic dust exposure.


Allogeneic blood transfusion and postoperative duration of mechanical ventilation: effects of red cell supernatant, platelet supernatant, plasma components and total transfused fluid.
In patients undergoing open-heart surgery, allogeneic blood transfusion (ABT) may be related to an enhanced inflammatory response and impaired pulmonary function, resulting in a need for prolonged mechanical ventilation. Transfused red blood cell (RBC) supernatant, platelet supernatant or plasma components, may exercise varying effects on pulmonary function, because these fluids differ in their content of soluble biological-response modifiers. The records of 416 patients undergoing coronary artery bypass graft operations at the Massachusetts General Hospital were reviewed. Possible predictors and the number of days of postoperative ventilation, as well as the number of all transfused blood components, were recorded. The association between mechanical ventilation past the day of operation and the volume of transfused RBC supernatant, platelet supernatant, or plasma components, was calculated by logistic regression analyses. The volume of each transfused fluid differed (P < 0.0001) among patients ventilated for 0, 1, 2, 3, or > or = 4 days after the day of the operation. After adjusting for the effects of confounding factors, the volume of administered RBC supernatant was associated (P = 0.0312) with the likelihood of postoperative ventilation past the day of operation, but the volume of platelet supernatant, plasma components, or total transfused fluid was not (P = 0.1528, P = 0.1847, and P = 0.0504, respectively). These results are congruent with the hypotheses that ABT may impair postoperative pulmonary function and that any such adverse effect of ABT is probably mediated by the supernatant fluid of stored RBCs. Both hypotheses should be examined further, in future studies of the outcomes of ABT.


A concept of essentially secondary factors central to definitive subtype characterization of Hodgkin's disease.
Conceptually, Hodgkin's disease would appear to constitute a neoplasm that integrally incorporates responsive cellular elements in terms strictly of morphologic patterns of interaction resulting especially in a predictable scale of therapeutic and prognostic implications as related particularly to pathobiologic course and response to treatment. In this sense, Hodgkin's disease might in a real sense constitute a valid point of reference in terms of processes not only in the generation of the neoplastic process but particularly in terms of how such a neoplastic process interacts with host systems in specifically characterizing the very nature of the intrinsic neoplastic process itself. In this manner, therefore, it might be valid to consider the totality of manifestations of Hodgkin's disease as a fundamental series of processes that integrally determines the genesis and nature of the neoplastic process as a function especially of various host systems in response to that neoplasm. In terms strictly related to a viral or Epstein-Barr virus-related development of Hodgkin's disease, it might perhaps be true that transcription factor NF-kappaB might induce the signaling of a CD30 receptor pathway that is intrinsically linked with anti-apoptosis of germinal center lymphocytes. In overall terms, perhaps, the Epstein-Barr viral nuclear antigens such as Latent membrane protein 1 would activate NF-kappaB as a mechanism that induces anti-apoptotic effect by multiple pathways in the added context particularly of a concerted series of cytokines that secondarily regulate T lymphocyte response. Indeed, in simple terms, Hodgkin's disease would appear to involve a basic mechanism of induced transcription as an effective anti-apoptotic mechanism as exerted on Reed-Sternberg cells. The Epstein-Barr viral nuclear antigens might be pivotal in orchestrating a full series of cytokine and T lymphocyte responses that would perhaps contribute significantly to the effective perpetuation of such anti-apoptotic effect or effects as exerted on the Reed-Sternberg cells.


The frequency of Chlamydia trachomatis infection in women with intraepithelial neoplasia of the uterine cervix.
To evaluate the frequency of Chlamydia trachomatis (CT) infection in patients with cervical intraepithelial neoplasia (CIN) referred for conisation. 423 patients with histologically proven CIN were included in this study. Before conisation, cytological material for direct immunofluorescence analysis was obtained. The incidence of CT in cytologic smears of all three CIN groups was calculated. Among all patients with CIN, 27 (6.4%) were CT positive and 396 (93.6%) CT negative. There were 2 (8.3%) CT positive patients with CIN 1, 10 (9.3%) with CIN 2 and 15 (5.2%) with CIN 3. The difference between CT infection incidence in patients with CIN 1 and CIN 2 was not significant; neither was it significant between patients with CIN 1 and CIN 3 nor between those with CIN 2 and CIN 3. Chlamydia trachomatis infection in patients with CIN is not very common. The impact of CT infection does not seem to interfere with development or even promotion of CIN.


[Logarithmic attachment to a monochromator for recording small changes in absorption].
The paper describes a device consisting of a spectrophotometer (SP-4, SP-4A, SP-16), logarithmic amplifier, recording instrument and a flow-type cuvette that allows quantitative registration of biological substances during their separation on chromatographic columns.


Molecular characterization and tissue distribution of nine selenoprotein genes in grass carp Ctenopharyngodon idella and their mRNA expressions in response to high-fat diet and high-fat diet supplemented with selenium.
Our previous study has found that selenium (Se) can alleviate lipid accumulation caused by high-fat diet (HFD) in fish. This study aims to explore the selenoproteins (SePs) in grass carp Ctenopharyngodon idella by characterizing cDNAs of nine SeP genes (SELENOF, SELENOM, SELENOS, SELENOP1, SELENOP2, SELENOE, SELENOL, SELENOU1a and SELENOU1b) and measuring their transcriptional activity in response to HFD and HFD supplemented with 0.3 mg/Kg and 0.6 mg/Kg of Se (HSe 0.3 and HSe 0.6). Firstly, the nine SeP genes in grass carp encoded proteins with conserved functional protein regions in fish and other vertebrates. Secondly, the nine SeP genes except SELENOS showed high expression levels in the hepatopancreas, but in the adipose tissue, only SELENOS, SELENOE and SELENOU1b showed high expression levels. Further, HFD significantly up-regulated the expressions of SELENOF and SELENOS in the hepatopancreas and SELENOM in the adipose tissue of grass carp (P < 0.05), but significantly down-regulated the expressions of SELENOU1b in the hepatopancreas, SELENOP2, SELENOE, SELENOL and SELENOU1a in the adipose tissue and SELENOM in the muscle of grass carp (P < 0.05). In addition, for the hepatopancreas, the expressions of SELENOS in the HSe 0.3 group and SELENOF, SELENOM and SELENOP2 in the HSe 0.6 group significantly decreased compared with the HFD group (P < 0.05). For the adipose tissue, the expressions of SELENOF, SELENOP2, SELENOL, SELENOU1a and SELENOU1b in the HSe 0.3 group and SELENOP2, SELENOE, SELENOU1a and SELENOU1b in the HSe 0.6 group significantly increased compared with the HFD group (P < 0.05). In summary, the transcriptional activities of the nine SeP genes were regulated by the HFD and HFD supplemented with Se, indicating the potential role of these genes in the Se regulated lipid metabolism processes in grass carp, which is worthy of in-depth study.


Mammalian WDR12 is a novel member of the Pes1-Bop1 complex and is required for ribosome biogenesis and cell proliferation.
Target genes of the protooncogene c-myc are implicated in cell cycle and growth control, yet the linkage of both is still unexplored. Here, we show that the products of the nucleolar target genes Pes1 and Bop1 form a stable complex with a novel member, WDR12 (PeBoW complex). Endogenous WDR12, a WD40 repeat protein, is crucial for processing of the 32S precursor ribosomal RNA (rRNA) and cell proliferation. Further, a conditionally expressed dominant-negative mutant of WDR12 also blocks rRNA processing and induces a reversible cell cycle arrest. Mutant WDR12 triggers accumulation of p53 in a p19ARF-independent manner in proliferating cells but not in quiescent cells. Interestingly, a potential homologous complex of Pes1-Bop1-WDR12 in yeast (Nop7p-Erb1p-Ytm1p) is involved in the control of ribosome biogenesis and S phase entry. In conclusion, the integrity of the PeBoW complex is required for ribosome biogenesis and cell proliferation in mammalian cells.


Investigation of pharmaceuticals and their metabolites in Brazilian hospital wastewater by LC-QTOF MS screening combined with a preliminary exposure and in silico risk assessment.
This work evaluates the occurrence of pharmaceuticals, with special emphasis on their metabolites, in raw hospital wastewater (HWW) using wide-scope screening based on liquid chromatography coupled to high resolution mass spectrometry. The applied strategy uses an extended purpose-built database, containing >1000 pharmaceuticals and 250 metabolites. Raw HWW samples from a hospital located in south Brazil were collected over six months, with a monthly sampling frequency. Accurate-mass full-spectrum data provided by quadrupole-time of flight MS allowed the identification of 43 pharmaceuticals and up to 31 metabolites in the samples under study. Additionally, other four metabolites not included in the initial database could be identified using a complementary strategy based on the common fragmentation pathway between the parent compound and its metabolites. Nine metabolites derived from four pharmaceuticals were identified in the raw HWW samples, whereas their parent compounds were not found in these samples. The results of this work illustrate the importance of including not only parent pharmaceuticals but also their main metabolites in screening analysis. Besides, the inclusion of in silico QSAR predictions allowed assessing the environmental fate and effect of pharmaceuticals and metabolites in terms of biodegradability, as possible Persistent, Bioaccumulative and Toxic (PBT) compounds, and their potential hazard to the aquatic environment.


Coronary-to-bronchial artery anastomosis complicated with myocardial infarction.
A patient with bronchiectasis had an inferolateral myocardial infarction. Coronary arteriography revealed a large anastomosis from the left circumflex artery to the left lower lobe bronchial arteries. The relationship between the patient's myocardial infarction and possible "coronary steal" is discussed.


Prevention of medical errors and malpractice: Is creating resilience in physicians part of the answer?
In this article, we present key concepts regarding physician and resident resilience and burnout, the legal and educational context for these distinctions, and the effects of improved physician resilience through self-care on a reduction in medical errors and malpractice. Resilience here indicates the mental processes and behaviors that enable an individual to overcome the potential negative effects of stressors. In order to explore the multiple factors that contribute to physician resilience, the authors approached the topic from a variety of perspectives, including the current ways of thinking about medical malpractice in the United States, physician resilience and medical errors, and building resilience during postgraduate medical education. The authors review steps taken and in process to mitigate physician burnout and enhance physician resilience.


Estrogen stabilizes vitellogenin mRNA against cytoplasmic degradation.
We have demonstrated, by DNA excess filter hybridizations to pulse-labeled cell RNA, that estrogen selectively stabilizes Xenopus liver vitellogenin mRNA against cytoplasmic degradation. The half-life of vitellogenin mRNA is approximately 3 weeks in the presence of estrogen and 16 hr after estrogen is withdrawn from the culture medium. Total poly(A) mRNA exhibits the same half-life (16 hr) in the presence or absence of estrogen. The rapid cytoplasmic degradation of vitellogenin mRNA in the absence of estrogen is fully reversible upon restimulation with estrogen, indicating that nuclear modification of vitellogenin RNA transcripts is not responsible for their stability. Intermediate levels of vitellogenin mRNA stability and changes in the relative rate of vitellogenin gene transcription are not observed late in estrogen induction, when vitellogenin mRNA levels plateau. Instead, Xenopus liver cells achieve fine control over the level of vitellogenin mRNA through down-regulation of the overall rate of total nuclear RNA synthesis.


Gadofullerene inhibits the degradation of apolipoprotein B100 and boosts triglyceride transport for reversing hepatic steatosis.
Hepatic steatosis is a widespread metabolic disease characterized by excessive accumulation of triglyceride (TG) in liver. So far, effective approved drugs for hepatic steatosis are still in development, and removing the unnecessary TG from the hepatocytes is an enormous challenge. Here, we explore a promising anti-hepatic steatosis strategy by boosting hepatocellular TG transport using β-alanine-modified gadofullerene (GF-Ala) nanoparticles. We confirm that GF-Ala could reverse hepatic steatosis in oleic acid-induced hepatocytes, fructose-induced mice, and obesity-associated transgenic ob/ob mice. Observably, GF-Ala improves hepatomegaly and hepatic lipid accumulation, reduces lipid peroxidation, and repairs abnormal mitochondria. Of note, we demonstrate that GF-Ala markedly inhibits the posttranslational degradation of apolipoprotein B100 (ApoB100) and boosts hepatocellular TG transport based on their superior antioxidant property. Together, we conclude that GF-Ala could potently ameliorate hepatic TG transport and maintain hepatic metabolic homeostasis without apparent toxicity, being beneficial for treatments of hepatic steatosis and other fatty liver diseases.