The potential role of pneumococcal conjugate vaccine in reducing acute respiratory inflammation in community-acquired pneumococcal pneumonia.
Pneumococcal conjugate vaccine (PCV) reduces both invasive pneumococcal disease (IPD) and other pneumococcal infections worldwide. We investigated the impact of stepwise implementation of childhood PCV programs on the prevalence of pneumococcal pneumonia, severity of acute inflammation, and associations between breakthrough pneumonia and pneumococcal serotypes in Taiwan. In total, 983 children diagnosed with community-acquired pneumococcal pneumonia were enrolled between January 2010 and December 2015. Proportions of pneumococcal vaccinations increased each year in age-stratified groups with PCV7 (32.2%) as the majority, followed by PCV13 (12.2%). The proportion of pneumococcal pneumonia decreased each year in age-stratified groups, especially in 2-5 year group. Serotype 19A is the leading serotype either in vaccinated (6.4%) or unvaccinated patients (5.2%). In particular, vaccinated patients had significantly higher lowest WBC, lower neutrophils, lower lymphocytes and lower CRP values than non-vaccinated patients (p < 0.05). After stratifying patients by breakthrough infection, those with breakthrough pneumococcal infection with vaccine coverage serotypes had more severe pneumonia disease (p < 0.05). Systematic childhood pneumococcal vaccination reduced the prevalence of community-acquired pneumococcal pneumonia, especially in 2-5 year group. Serotype 19A was the major serotype for all vaccine types in patients with pneumococcal pneumonia and severity of acute inflammatory response was reduced in vaccinated patients.


Characterizing Viscoelastic Polyvinyl Alcohol Phantoms for Ultrasound Elastography.
Ultrasound phantoms mimic the acoustic and mechanical properties of native tissues. Polyvinyl alcohol (PVA) phantoms are used extensively as models for validating ultrasound elastography approaches. However, the viscous properties of PVA phantoms have not been investigated adequately. Glycerol is a viscous liquid that has been reported to increase the speed of sound of phantoms. This study aims to assess the acoustic and viscoelastic properties of PVA phantoms and PVA mixed with glycerol at varying concentrations. The phantoms were fabricated with 10% w/v PVA in water with varying concentrations of glycerol (10%, 15% and 20% v/v) and 2% w/v silicon carbide particles as acoustic scatterers. The phantoms were subjected to either one, two, or three 24-h freeze-thaw cycles. The longitudinal sound speeds of all PVA phantoms were measured, and ranged from 1529 to 1660 m/s. Attenuation spectroscopy was performed in the range of 5 to 20 MHz. The measured attenuation followed a power-law relationship with frequency, wherein the power-law fit constants and exponents ranged from 0.02 to 0.1 dB/cm/MHzn and from 1.6 to 1.9, respectively. These results were in agreement with previous reports for soft tissues. Viscoelasticity of PVA phantoms was assessed using rheometry. The estimated values of shear modulus and viscosity using the Kelvin-Voigt and Kelvin-Voigt fractional derivative models were within the range of previously-reported tissue-mimicking phantoms and soft tissues. The number of freeze-thaw cycles were shown to alter the viscosity of PVA phantoms, even in the absence of glycerol. Scanning electron microscopy images of PVA phantoms without glycerol showed a porous hydrogel network, in contrast to those of PVA-glycerol phantoms with non-porous structure. Phantoms fabricated in this study possess tunable acoustic and viscoelastic properties within the range reported for healthy and diseased soft tissues. This study demonstrates that PVA phantoms can be manufactured with glycerol for applications in ultrasound elastography.


GnRH agonist versus GnRH antagonist in assisted reproduction cycles: oocyte morphology.
The selection of developmentally competent human gametes may increase the efficiency of assisted reproduction. Spermatozoa and oocytes are usually assessed according to morphological criteria. Oocyte morphology can be affected by the age, genetic characteristics, and factors related to controlled ovarian stimulation. However, there is a lack of evidence in the literature concerning the effect of gonadotropin-releasing hormone (GnRH) analogues, either agonists or antagonists, on oocyte morphology. The aim of this randomized study was to investigate whether the prevalence of oocyte dysmorphism is influenced by the type of pituitary suppression used in ovarian stimulation. A total of 64 patients in the first intracytoplasmic sperm injection (ICSI) cycle were prospectively randomized to receive treatment with either a GnRH agonist with a long-term protocol (n: 32) or a GnRH antagonist with a multi-dose protocol (n: 32). Before being subjected to ICSI, the oocytes at metaphase II from both groups were morphologically analyzed under an inverted light microscope at 400x magnification. The oocytes were classified as follows: normal or with cytoplasmic dysmorphism, extracytoplasmic dysmorphism, or both. The number of dysmorphic oocytes per total number of oocytes was analyzed. Out of a total of 681 oocytes, 189 (27.8%) were morphologically normal, 220 (32.3%) showed cytoplasmic dysmorphism, 124 (18.2%) showed extracytoplasmic alterations, and 148 (21.7%) exhibited both types of dysmorphism. No significant difference in oocyte dysmorphism was observed between the agonist- and antagonist-treated groups (P>0.05). Analysis for each dysmorphism revealed that the most common conditions were alterations in polar body shape (31.3%) and the presence of diffuse cytoplasmic granulations (22.8%), refractile bodies (18.5%) and central cytoplasmic granulations (13.6%). There was no significant difference among individual oocyte dysmorphisms in the agonist- and antagonist-treated groups (P>0.05). Our randomized data indicate that in terms of the quality of oocyte morphology, there is no difference between the antagonist multi-dose protocol and the long-term agonist protocol. If a GnRH analogue used for pituitary suppression in IVF cycles influences the prevalence of oocyte dysmorphisms, there does not appear to be a difference between the use of an agonist as opposed to an antagonist.


The Gut Ecosystem: A Critical Player in Stroke.
The intestinal microbiome is emerging as a critical factor in health and disease. The microbes, although spatially restricted to the gut, are communicating and modulating the function of distant organs such as the brain. Stroke and other neurological disorders are associated with a disrupted microbiota. In turn, stroke-induced dysbiosis has a major impact on the disease outcome by modulating the immune response. In this review, we present current knowledge on the role of the gut microbiome in stroke, one of the most devastating brain disorders worldwide with very limited therapeutic options, and we discuss novel insights into the gut-immune-brain axis after an ischemic insult. Understanding the nature of the gut bacteria-brain crosstalk may lead to microbiome-based therapeutic approaches that can improve patient recovery.


Zinc ferrite nanoparticles from industrial waste for Se (IV) elimination from wastewater.
The presence of high concentrations of selenium ions in wastewater is considered an environmental problem. However, the mechanism of selenium ions (Se (IV)) removal by the adsorption process has not been investigated in-depth so far. Also, the recovery and conversion of the industrial waste materials into valuable materials is a vital issue. Therefore, in this study, zinc ferrite nanopowders are economically synthesized from steel-making wastes by co-precipitation method for investigating as adsorbents of selenium species. The produced nanopowders were annealed at 150, 300, 500, and 850 °C for 5 h to scrutinize the impact of annealing temperature on their crystallite size. The compositional, optical, and magnetic features of the nanopowders were defined by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM), UV-Vis. spectrophotometer along with vibrating sample magnetometer (VSM). Optical absorbance spectra were found characteristic due to the electronic structure of Fe3+ (3d5) considering the C3v local symmetry of Fe3+ ions. The prepared nanopowders demonstrated good adsorption capacity toward selenium ions (43.67 mg/g at pH 2.5) from an aqueous medium. Adsorption data were found fitting to Freundlich isotherm model. Thus, ZnFe2O4 can be recommended to effectively eliminate selenium ions from aqueous solutions.


Systemic and local granzyme B levels are associated with disease activity, kidney damage and interferon signature in systemic lupus erythematosus.
Granzymes (Grs) are serine proteases that eliminate virally infected or tumour cells by inducing apoptosis. GrB has been shown to be associated to the pathophysiology of SLE, whereas the role of the other Grs in SLE remain unknown. Gr levels were determined in the serum of SLE patients and controls and linked to SLE activity parameters, including the IFN signature. In addition, GrB expression was investigated in LN biopsies and correlated to kidney function parameters and disease severity. Serum GrK and GrM levels were not elevated in SLE and did not correlate with disease activity. In contrast, GrB was increased in SLE serum, which correlated to both the SLEDAI and IFN signature. GrB expression was detected in LN tissue biopsies. The number of GrB-positive cells in tissue correlated to several kidney function parameters (e.g. serum creatinine, proteinuria) and to the LN chronicity index. GrB, but not GrK and GrM, is increased in the serum and kidney of patients with SLE and correlates with measures of poor prognosis in LN. These data suggest that GrB may contribute to the pathogenesis of SLE/LN, which indicates the possibility that GrB might be used as a biomarker and/or a therapeutic target.


Covalent incorporation of 3'-O-(4-benzoyl)benzoyl-ATP into a P2 purinoceptor in transformed mouse fibroblasts.
ATP, 3'-O-(4-benzoyl)benzoyl-ATP (BzATP), a photoaffinity analog of ATP, and several other ATP analogs induced an increase in plasma membrane permeability to monovalent ions and normally impermeant metabolites, including nucleotides, in transformed 3T6 mouse fibroblasts. The rank order of agonist potency for induction of nucleotide channels was BzATP (EC50 = 15 microM) greater than ATP (EC50 = 50 microM) approximately adenosine 5'-O-(1-thiotriphosphate) (ATP alpha S) greater than 2-methylthio-ATP (EC50 = 75 microM) approximately 3'-amino-3'-deoxy-ATP greater than adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) (EC50 = 175 microM). Long wavelength UV illumination of 3T6 cells in the presence of greater than or equal to 20 microM BzATP at 4 degrees C, a nonpermeabilizing temperature, followed by removal of unbound BzATP, resulted in the efflux of 86Rb+ and the release of a prelabeled pool of cytoplasmic nucleotides when the temperature was shifted to 37 degrees C. Photoincorporation of BzATP was inhibited by ATP, ATP alpha S, ATP gamma S, and other ATP analogs that induced an increase in plasma membrane permeability to nucleotides in 3T6 cells under nonphotoactivating conditions. GTP, ITP, UTP, adenosine, and ATP analogs that did not alter plasma membrane permeability to nucleotides under nonphotoactivating conditions also had no effect on BzATP photoincorporation. Photoincorporation of BzATP occurred optimally between pH 6.6 and pH 8.2 but was inhibited at pH 6.0. Photoincorporation of BzATP was also modulated by the osmolarity and the divalent cation concentration of the assay medium. The increase in plasma membrane permeability to nucleotides induced by photoincorporated BzATP occurred at the same rate and had the same temperature, pH, ionic strength, and divalent cation requirements as the increase in plasma membrane permeability to nucleotides induced by ATP and BzATP under nonphotoactivating conditions. These findings support the hypothesis that BzATP can be covalently incorporated into a P2 purinoceptor in 3T6 cells that is coupled to plasma membrane channels for ions and other metabolites.


Neonatal and child health crises due to recent floods in Pakistan.
Neonates and children are more vulnerable to the negative impact of flood-related changes and may have a variety of detrimental negative impacts on their health. They are more prone to get various infectious diseases. They are also more vulnerable to malnutrition during floods. Flooding limits access to clean water as sewage overflows and contaminates nearby water sources. The polluted setting in the flood-affected area makes it difficult to ensure the hygiene of feeding equipment used to prepare infant formula. Breastfeeding may also become less effective due to the lack of privacy for women to breastfeed their kids while living in temporary shelters with other flood victims. In addition, milk production decreases and might even cease due to mothers' reduced food intake and increased stress levels. Flooding may also cause supplemental feeding to deteriorate. The mothers and other primary caregivers usually lack the resources in affected areas to prepare supplemental diets for their kids, which further harm the babies. There is mounting evidence that children are more likely to develop clogged noses, itchy eyes, hoarseness, skin complications, and sneezing while living in humid areas.


Spontaneous Macular Hole Closure after Valsalva Retinopathy and Nd:YAG Laser Treatment.
The purpose of this report is to present a case who had spontaneous macular hole closure after Nd:YAG laser membranotomy applied to premacular haemorrhage associated with Valsalva retinopathy. Case report. A 19-year-old young male patient presented to our clinic with sudden vision loss in his right eye, which had occurred 2 weeks before, following push-up and sit-up exercise. The patient was found to have premacular haemorrhage associated with Valsalva retinopathy. Nd:YAG laser membranotomy was performed. During his follow-up at week 1, full-thickness MH was observed and he was put under observation. At month 6, his vision acuity improved, laser coagulation sites in the fundus disappeared, and macular hole closed spontaneously. Macular hole that develops after Nd:YAG laser treatment of Valsalva retinopathy may spontaneously be closed like in our case. However, there is a need for further research to understand the mechanism of closure.


Melatonin supports alendronate in preserving bone matrix and prevents gastric inflammation in ovariectomized rats.
The anti-catabolic bisphosphonate alendronate is considered as the first-line medical treatment in post-menopausal osteoporosis; but several side effects, including gastric mucosal injury, are associated with its use. The aim was to elucidate whether combined treatment with melatonin plus alendronate would be more advantageous in the maintenance of bone and the prevention of gastric side effects. Under anaesthesia, female Sprague-Dawley rats underwent bilateral ovariectomy (OVX), while control group had sham surgery. Four weeks after the surgery, OVX rats were treated with saline, melatonin (25 μg/mL/d), alendronate (70 μg/kg/wk), melatonin + alendronate, melatonin + melatonin receptor antagonist (luzindole, 10 μg/kg/d) or alendronate + melatonin + luzindole for 8 weeks. Rats were euthanized at the end of 12th week. Runx2 expression, apoptotic cells, and trabecular thickness were evaluated in tibiae, while gastric tissues were analysed for oxidative injury parameters. In all OVX groups, Runx2 expression was depressed. Saline-treated OVX group presented an extreme decrease in calcified area in opposition to melatonin- or alendronate-treated groups, while the bones in alendronate + melatonin-treated group were similar to those of the sham-operated group. Concomitant with the improvements examined histologically in bone tissues, quantitative TUNEL (+) cells were similarly lower in alendronate- or melatonin-treated groups. Oxidative gastric damage was increased in saline- or alendronate-treated groups, which were depressed in the presence of melatonin. Although melatonin and alendronate exerted similar supportive effects on the maintenance of bone mass, melatonin may have a more advantageous impact by protecting against OVX-induced gastric injury, which was aggravated by alendronate use. HIGHLIGHTS: Our results demonstrate that alendronate and melatonin had similar supportive effects on the maintenance of bone mass, while melatonin prevented the gastric side effects of alendronate, making this combination an advisable therapeutic approach in the treatment of menopausal osteoporosis.


The localization of transport properties in the frog lens.
The selectivity of fiber-cell membranes and surface-cell membranes in the frog lens is examined using a combination of ion substitutions and impedance studies. We replace bath sodium and chloride, one at a time, with less permeant substitute ions and we increase bath potassium at the expense of sodium. We then record the time course and steady-state value of the intracellular potential. Once a new steady state has been reached, we perform a small signal-frequency-domain impedance study. The impedance study allows us to separately determine the values of inner fiber-cell membrane conductance and surface-cell membrane conductance. If a membrane is permeable to a particular ion, we presume that the conductance of that membrane will change with the concentration of the permeant ion. Thus, the impedance studies allow us to localize the site of permeability to inner or surface membranes. Similarly, the time course of the change in intracellular potential will be rapid if surface membranes are the site of permeation whereas it will be slow if the new solution has to diffuse into the intercellular space to cause voltage changes. Lastly, the value of steady-state voltage change provides an estimate of the lens' permeability, at least for chloride and potassium. The results for sodium are complex and not well understood. From the above studies we conclude: (a) surface membranes are dominated by potassium permeability; (b) inner fiber-cell membranes are permeable to sodium and chloride, in approximately equal amounts; and (c) inner fiber-cell membranes have a rather small permeability to potassium.


A two-site monoclonal antibody ELISA for the quantification of group V allergens in grass extracts.
A two-site solid-phase enzymimmunoassay was used for the quantification of group V allergen in grass pollen extracts in mass units. The assay is based on the monoclonal antibodies (MoAbs), 1D11 and 3B2 which recognize different epitopes on the standard Phl p V. The MoAb-ELISA is very sensitive (15-100 ng/ml Phl p V) and highly specific for group V allergens. Six pollen extracts of different grasses demonstrated parallel binding curves. The group V content ranged between 73 and 673 micrograms/ml in the extracts. The International Standard of Phleum pratense (IS 82/520) contains 400 micrograms/ml Phl p V. A good correlation was observed between the group V content and RAST inhibition, with the exception of Poa pratensis.


Is heart failure with mid range ejection fraction (HFmrEF) a distinct clinical entity or an overlap group?
The new category of heart failure (HF), Heart Failure with mid range Ejection Fraction (HFmrEF) has recently been proposed with recent publications reporting that HFmrEF represents a transitional phase. The aim of this study was to determine the prevalence and clinical characteristics of patients with HFmrEF and to establish what proportion of patients transitioned to other types of HF, and how this affected clinical outcomes. Patients were diagnosed with HF according to the 2016 ESC guidelines. Clinical outcomes and variables were recorded for all consecutive in-patients referred to the heart failure service. In total, 677 patients with new HF were identified; 25.6% with HFpEF, 21% with HFmrEF and 53.5% with HFrEF. While clinical characteristics and prognostic factors of HFmrEF were intermediate between HFrEF and HFpEF, HFmrEF patients had the best outcome, with higher mortality in the HFrEF population (p 0.02) and higher HF rehospitalisation rates in the HFpEF population (p < 0.01).38.7% of the HFmrEF patients transitioned (56.4% to HFpEF and 43.6% to HFrEF) with fewest deaths in the patients that transitioned to HFpEF (p 0.04), and fewest HF readmissions in the patients that remained as HFmrEF (<0.01). HFmrEF patients had the best outcomes, compared to high rates of mortality seen in patients with HFrEF and high rates of HF readmissions seen in patients with HFpEF. Only 1/3 of HFmrEF patients transitioned during follow up, with the lowest mortality seen in patients transitioning to HFpEF.


A novel technique of ab interno glaucoma surgery: follow-up results after 24 months.
It was the aim of this study to investigate the efficacy, longevity, and safety of a new ab interno intervention for the treatment of primary open-angle glaucoma (POAG). The previously described method of radiofrequency-mediated "sclerothalamotomy ab interno" was applied in 53 eyes of consecutive patients with POAG between April 2002 and July 2002. Average preoperative intraocular pressure (IOP) was 25.6+/-2.3 mmHg (range 18-48 mmHg). Sclerothalamotomies were carried out with a custom-made high-frequency dissection 19 G probe (tip 0.3 x 1 mm) applying bipolar current with a frequency of 500 kHz (tip temperature 130 degrees C). After a follow-up period of 24 months, the average IOP was 15.0+/-1.6 mmHg (range 11-20 mmHg) (p<0.005). The average number of topical agents was 2.6+/-1.0 (range 1-5) preoperatively. Twenty-four months after surgery such agents were used in only five (9.6%) eyes and the average was 0.21+/-0.53 (range 0-2). Transient IOP elevation was observed in 12 of 53 eyes (22.6%) postoperatively. In all cases elevated IOP could efficiently be controlled with topical medication. In general, IOP dropped continuously over the course of the 6 months following surgery and then remained constant. This study indicates that sclerothalamotomy ab interno is a safe and efficient surgical method for the treatment of POAG. Long-term results clearly demonstrate the longevity of IOP reduction.


Three-dimensional dynamics of fluctuations appearing during pellet ablation process around a pellet in a fusion plasma experiment.
Understanding pellet ablation physics is crucial to realizing efficient fueling into a high temperature plasma for the steady state operation of ITER and future fusion reactors. Here we report the first observation of the formation of fluctuation structures in the pellet plasmoid during the pellet ablation process by a fast camera in a medium-sized fusion device, Heliotron J. The fluctuation has a normalized fluctuation level of ~ 15% and propagates around the moving pellet across the magnetic field. By comparing the fluctuation structures with the shape of magnetic field lines calculated with the field line tracing code, we successfully reconstruct the spatio-temporal structure of the fluctuations during the pellet ablation process. The fluctuations are located at the locations displaced toroidally from the pellet and propagate in the cross-field direction around the pellet axis along the field line, indicating a three-dimensional behavior and structure of fluctuations. The fluctuation would be driven by a strong inhomogeneity formed around the pellet and invoke the relaxation of the gradient through a cross-field transport induced by the fluctuations, which could affect the pellet ablation and pellet fueling processes. Such fluctuations can be ubiquitously present at the inhomogeneity formed around a pellet in the pellet ablation process in fusion devices.


Clinical and Laboratory Features of PCR-Confirmed and Clinically Suspected COVID-19 Pediatric Patients: A Single Hospital-Based Experience During the First COVID-19 Wave in the United Arab Emirates.
This study investigated clinical and laboratory differences between confirmed (RT-PCR-positive) and clinically suspected (RT-PCR-negative) COVID-19 pediatric patients, and explored factors associated with disease severity at presentation and duration of hospitalization. Medical charts of COVID-19-confirmed and clinically suspected pediatric patients admitted to a tertiary hospital in Abu Dhabi were reviewed. Sociodemographic information and clinical and laboratory outcomes were retrieved and analyzed. Between 1 April to 30 June, 2020, 173 patients (mean age: 3.6 ± SD 3.2 years) presented with respiratory symptoms. Of them, 18.0% had confirmed contact with COVID-19 cases, 66.5% had symptoms for ≤3 days, and 86.7% were with moderate to severe disease. Twenty-eight (16.1%) patients tested positive while the rest (83.8%) tested negative in RT-PCR. COVID-19-confirmed and clinically suspected patients were statistically similar (p > 0.05) in all sociodemographic data, disease severity, and vital signs except residence status (89.3% vs. 58.6% were residents, respectively, p = 0.002) and contact with confirmed COVID-19 cases (82.1% vs. 5.5%, respectively, p < 0.001). Fever (100 and 91.0%) and cough (100 and 95.9%) were the most common symptoms in both confirmed and clinically suspected COVID-19 patients. All patients were statistically comparable in mean white blood cell and platelet counts and hemoglobin concentration, except in mean concentration of neutrophils (higher in clinically suspected, p = 0.019). C-reactive protein was two times higher in clinically suspected compared to confirmed patients (p = 0.043). Lymphocyte (OR: 1.31, p < 0.001), LDH (OR: 1.01, p = 0.001), D-dimer (OR: 1.92, p < 0.001), and ferritin levels after 24-36 h (OR: 9.25, p < 0.05), and SGPT (OR: 1.04, p < 0.05) were all associated with disease severity. Elevated ferritin (>300 μg/L) after 24-36 h was the only correlated factor with disease severity (aOR: 17.38, p < 0.05). Confirmed compared with clinically suspected patients (aOR: 4.00, 95% CI: 2.92-5.10) and children with moderate compared with mild disease (aOR: 5.87, 95% CI: 1.08-32.06) had longer hospitalization. In pediatric patients with negative RT-PCR, COVID-19 is still suspected based on clinical symptoms and epidemiological data. A tentative diagnosis can be made based on a thorough examination, and proper medical management can be initiated promptly.


Animal models of multiple system atrophy.
Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative disorder clinically characterized by a variable combination of dysautonomia, levodopa-unresponsive parkinsonian and cerebellar symptoms. Neurodegeneration in MSA occurs in the substantia nigra, putamen, inferior olive, pontine and brainstem nuclei, as well as intermediolateral cell column of the spinal cord. MSA is recognized as a synucleinopathy due to the accumulation of insoluble alpha-synuclein in oligodendroglial cytoplasmic inclusions. Several animal models have been developed in order to reproduce various clinical and pathological features of MSA. Using "double toxin-double lesion" or "single toxin-double lesion", neurotoxin-based models were designed in rats, mice and non-human primates to reproduce the neuropathology of MSA in the nigrostriatal system while gene-based models were developed in mice to reproduce the accumulation of insoluble alpha-synuclein in oligodendrocytes. Both approaches have then been merged to create optimized, dual-hit models. This review describes the different animal models of MSA, their respective advantages and limitations and their usefulness to decipher the pathophysiology of MSA then to define efficient symptomatic and disease-modifying therapies. This article is part of a Special Issue entitled: Neuroscience Disease Models.


Machine learning - based q-RASAR modeling to predict acute contact toxicity of binary organic pesticide mixtures in honey bees.
We have reported here a quantitative read-across structure-activity relationship (q-RASAR) model for the prediction of binary mixture toxicity (acute contact toxicity) in honey bees. Both the quantitative structure-activity relationship (QSAR) and the similarity-based read-across algorithms are used simultaneously for enhancing the predictability of the model. Several similarity and error-based parameters, obtained from the read-across prediction tool, have been put together with the structural and physicochemical descriptors to develop the final q-RASAR model. The calculated statistical and validation metrics indicate the goodness-of-fit, robustness, and good predictability of the partial least squares (PLS) regression model. Machine learning algorithms like ridge regression, linear support vector machine (SVM), and non-linear SVM have been used to further enhance the predictability of the q-RASAR model. The prediction quality of the q-RASAR models outperforms the previously reported quasi-SMILEs-based QSAR model in terms of external correlation coefficient (Q2F1 SVM q-RASAR: 0.935 vs. Q2VLD QSAR: 0.89). In this research, the toxicity values of several new untested binary mixtures have been predicted with the new models, and the reliability of the PLS predictions has been validated by the prediction reliability indicator tool. The q-RASAR approach can be used as reliable, complementary, and integrative to the conventional experimental approaches of pesticide mixture risk assessment.


Is quantitative determination of fibrin(ogen) degradation products and thrombin-antithrombin III complexes useful to diagnose deep venous thrombosis in outpatients?
We studied the diagnostic value of recently introduced ELISA's for the determination of thrombin-antithrombin III (TAT) complexes, fibrin degradation products (FbDP), fibrinogen degradation products (FgDP) and total degradation products (TDP) for deep venous thrombosis (DVT) in plasma of 239 consecutive outpatients, suspected for DVT by their family doctor. DVT was confirmed by impedance plethysmography in 60 patients. Using the 95th percentile range of 42 healthy volunteers the sensitivity for the detection of DVT was: 37% for TAT, 95% for TDP, 92% for FbDP and 90% for FgDP. Specificity was: 88% for TAT, 16% for TDP, 20% for FbDP and 25% for FgDP. We conclude that these assays are of little value in the diagnosis of DVT in outpatients.


Robotic thyroidectomy. Recommendations of the AFCE (Association francophone de chirurgie endocrinienne) with the SFE (Société française d'endocrinologie) and the SFMN (Société française de médecine nucléaire).
Transaxillary robotic thyroidectomy is hardly the approach of reference. It is occasionally proposed for carefully selected patients with a small-sized (2cm maximum), exclusively cervical unilateral nodule without lymph node involvement, in a small thyroid lobe (6cm maximum) in a thin individual wishing to avoid a cervical scar. Potential candidates must be informed on the risks specific to this technique and about the scarceness of evidence of its equivalence to cervicotomy in terms of quality of life and patient satisfaction. Shall be excluded from robotic surgery: malignant nodules (or nodules suspected of malignancy>2cm), cancers with microscopic nodal metastases, plunging goiter, patients with previous cervical surgery or overactive thyroid. Robotic thyroidectomy must be performed in centers with expertise in both thyroid surgery and robotic surgery.


Evaluating Endotracheal Tube Depth in Infants Weighing Less Than 1 Kilogram.
Endotracheal tube (ETT) depth in premature infants is of critical importance because potentially life-threatening adverse events can occur if the tube is malpositioned. Analysis of current data indicates that the accuracy of current resuscitation guidelines for infants <1 kg is poor. We hypothesized that a weight-based formula that is used clinically in our institution would accurately predict appropriate ETT placement in infants weighing < 1 kg. The medical records, from July 2013 to November 2016, of all infants < 1 kg who were intubated were retrospectively reviewed and included. The 2 formulas utilized were the Duke formulas 5.5 cm + 1 cm/kg for infants 500-999 g or 5.0 + 1 cm/kg for infants <500 g. The appropriate ETT position was defined as the tip of the ETT below the thoracic inlet and above the carina, at approximately thoracic vertebrae 2 or 3 on an initial chest radiograph. The formula was defined as being accurate if the documented ETT depth was within 0.2 cm of the predicted depth. Post hoc analysis of current resuscitation guidelines (6 cm plus the weight of the infant in kg) was performed after the Duke formula performed worse than expected. A total of 131 subjects (mean ± gestational age, 26 ± 1.8 wk; mean ± weight, 729 ± 140 g) were included. The documented depth was accurately predicted by the Duke formula for 47% of the subjects, with 69% of the ETTs appropriately positioned as seen on a chest radiograph. Sensitivity was 46.6%, specificity was 53.6%, positive predictive value was 68.8% and negative predictive value was 31.4% for the Duke formula. Post hoc analysis current resuscitation guidelines found that the documented depth was accurately predicted for 23% infants, with 70% of these appropriately positioned ETTs. Our weight-based, institutional formula had a low sensitivity for predicting proper ETT depth. Weight-based formulas may have clinical utility; however, analysis of current data did not support use in infants < 1 kg. Rapid radiologic assessment of ETT placement is required for this patient population.


Tylosin sorption to silty clay loam soils, swine manure, and sand.
The objectives of this study were to assess sorption and desorption of tylosin, a macrolide antimicrobial chemical used in swine, cattle, and poultry production, in three silty clay loam soils of South Dakota and compare soil sorption to sand and manure sorption. The silty clay loam soils, from a toposequence in eastern South Dakota, standardized sand samples, and swine manure were used in 24-h batch sorption studies with tylosin concentrations ranging from 25 to 232 micro mole/L. Desorption from soil was conducted over a four-day period. Partition coefficients, based on the Freundlich isotherm (K(f)) or K(d) values, were calculated. K(f) values for the silty clay loams were similar, not influenced by landscape position, and averaged 1,350 with isotherm slopes ranging from 0.85 to 0.93. K(f) values for sand were dependent on solution/sand ratios and pH, ranging from 1.4 to 25.1. K(d) values of manure were dependent on the solution type and ranged from 840 L/kg with urine to about 175 L/kg when sorbed from water. Desorption of tylosin from each soil over the four-day period was < 0.2% of the amount added. The soils' high K(f) values and low desorption amounts suggest that once tylosin is in these soils, leaching to lower depths may not occur. However, this does not preclude runoff with soil eroded particles. If tylosin reaches a sand aquifer, through bypass flow or other mechanism(s), movement in the aquifer most likely would occur.


Hypothyroidism, Raynaud's phenomenon, and acute myocardial infarction in a young woman.
We describe an acute inferior myocardial infarction in a 29-year-old woman with normal coronary arteries. She has suffered from Raynaud's phenomenon in the fingers for several years. Manifest thyroid deficiency was discovered during hospitalization. A functional-type link between hypothyroidism and myocardial infarction via vasospasm manifested as Raynaud's phenomenon is proposed as one possible etiology for the syndrome of myocardial infarction in young women.


Quantifying graduation of layered below-the-knee compression garment combinations using a model-based assessment.
Often people with lymphedema and vascular conditions will be prescribed layered compression garments to assist them in donning their garments and improve treatment compliance. However, little evidence of the interface pressures produced by these layered garments is available. In the present study, we explored the pressures produced by layering high and low class below-the-knee compression garment combinations and quantified the graduation of these combinations to understand the effect that layer order might have on the interface pressure. The present study used a mechanical test design to measure the interface pressure at four sites (B, smallest ankle dimension; B1, circumference at Achilles tendon and gastrocnemius muscle junction; C, widest calf dimension; and D, below the knee) for 30 combinations of low and high class compression garments using a PicoPress (Microlab Elettronica, Ponte San Nicolò, Italy). The results demonstrated a pattern consistent with graduation for sites B1 to D for 100% of the garment combinations. However, the graduation was reversed for sites B to B1 for 100% of the garment combinations, possibly due to limitations regarding the shape of the model limb. The results indicated no significant differences in the interface pressure when the higher class garment was applied as the bottom layer vs the top layer. A strong correlation (R > 0.95; P < .001) was between the actual pressures produced by the combinations of the garments and the expected pressure determined by summing the pressures of the individual garments. Graduation was observed from site B1 to site D, indicating that double layering of these garment combinations maintained guideline adherence. Layering the garments produced pressures that were, in general, cumulative of the pressure from each garment alone, with some variance. Because of the uncertainty of the B site results in the present study, the clinical implications in relation to the primary aim are limited. The findings from the secondary aim suggest that clinically, garment wearers can don their layered garments in any order and achieve the same interface pressure results.


Socio-economic status and survival from breast cancer for young, Australian, urban women.
To estimate the association between measures of socio-economic status (SES) and breast cancer (BC) survival for young, urban Australian women. We used a population-based sample of 1,029 women followed prospectively for a median of 7.9 years. SES was defined by education and area of residence. Hazard ratios (HRs) associated with SES measures were estimated for (i) distant recurrence (DR) and (ii) all-cause mortality as end-points. HRs for area of residence were not significantly different from unity, with or without adjustment for age at diagnosis and education level. The univariable HR estimate of DR for women with university education compared with women with incomplete high school education was 1.51 (95% CI = 1.08 - 2.13, p = 0.02), which reduced to 1.20 (95% CI = 0.85 - 1.72, p = 0.3) after adjusting for age at diagnosis and area of residence. Adjusting for prognostic factors differentially distributed across SES groups did not substantially alter the association between survival and SES. Among young, urban Australian women there is no association between SES and BC survival. This lack of estimates of association may be partly attributed to universal access to adequate breast cancer care in urban areas.


Acute Aerobic Exercise Induces Short-Term Reductions in Ambulatory Blood Pressure in Patients With Hypertension: A Systematic Review and Meta-Analysis.
[Figure: see text].


Acute epiglottitis: intubation versus tracheostomy.
Acute epiglottitis is a disease with significant mortality. The patient, usually an otherwise healthy pre-school child, develops a sore throat and muffled voice from swollen supraglottic structures, and may progress rapidly to respiratory arrest. Early diagnosis and airway maintenance can prevent these fatalities. Whether to secure an airway by tracheostomy or endotracheal intubation is the subject of much discussion. Nineteen series totalling 738 cases of epiglottitis plus 11 new cases are reviewed. These patients were treated as follows: Tracheostomy = 348 (3 deaths - 0.86%); Endotracheal intubation = 216 (2 deaths - 0.92%); medical management with no artificial airway = 214 (13 deaths - 6.1%). The difference in morbidity and mortality between tracheostomy or nasotracheal intubation is so slight that the choice should be determined by local factors. Medical management with no artificial airway should not be used in children.


Gram-positive rhizobacterium Bacillus amyloliquefaciens FZB42 colonizes three types of plants in different patterns.
The colonization of three types of different plants, Zea mays, Arabidopsis thaliana, and Lemna minor, by GFP-labeled Gram-positive rhizobacterium Bacillus amyloliquefaciens FZB42 was studied in gnotobiotic systems using confocal laser scanning microscopy and electron microscopy. It was demonstrated that FZB42 was able to colonize all the plants. On one hand, similar to some Gram-negative rhizobacteria like Pseudomonas, FZB42 favored the areas such as the concavities in root surfaces and the junctions where lateral roots occurred from the primary roots; on the other hand, we clearly demonstrated that root hairs were a popular habitat to the Gram-positive rhizobacterium. FZB42 exhibited a specific colonization pattern on each of the three types of plants. On Arabidopsis, tips of primary roots were favored by FZB42 but not so on maize. On Lemna, FZB42 accumulated preferably along the grooves between epidermal cells of roots and in the concave spaces on ventral sides of fronds. The results suggested L. minor to be a promising tool for investigations on plant-microbial interaction due to a series of advantages it has. Colonization of maize and Arabidopsis roots by FZB42 was also studied in the soil system. Comparatively, higher amount of FZB42 inoculum (∼10(8) CFU/ml) was required for detectable root colonization in the soil system, where the preference of FZB42 cells to root hairs were also observed.


Variants in interleukin family of cytokines genes influence clearance of high risk HPV in HIV-1 coinfected African-American adolescents.
Our work aimed to examine the potential influence of variants in interleukin/interleukin receptors genes on high-risk (HR-HPV) HPV clearance. Clearance of genital HR-HPV infection was evaluated for 134 HIV-1 seropositive African-American female adolescents from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort. Genotyping targeted 225 single nucleotide polymorphisms (SNPs) within the exons, 5' untranslated region (UTR) and 3' UTR sequences of 27 immune-related candidate genes encoding interleukin family of cytokines. Cox proportional hazard models were used to determine the association of type-specific HPV clearance adjusting for time-varying CD4+ T-cell count and low-risk (LR-HPV) HPV co-infections. HR-HPV clearance rates were significantly (p < 0.001) associated with five SNPs (rs228942, rs419598, rs315950, rs7737000, and rs9292618) mapped to coding and regulatory regions in three genes (IL2RB, IL1RN, and IL7R). These data suggest that the analyzed genetic variants in interleukin family of cytokines modulate HR-HPV clearance in HIV-1 seropositive African-Americans that warrants replication.


The growth performances of broiler chickens as affected by diets containing common bean (Phaseolus vulgaris) treated by different methods.
The utilization of grain legumes as a protein source for poultry is limited by the presence of antinutritional factors. Various methods have been developed to eliminate them. One hundred and sixty 3-week-old birds of 622 g were used to evaluate the effect of feeding 15% of common beans (Phaseolus vulgaris) either soaked (R1), soaked and extruded (R2) or soaked and heated (R3) and a control (R0) in a completely randomized design. The protein content of the common bean decreased with all the treatments, while the other characteristics remained similar. Feed consumption was highest (p < 0.05) for the R0 birds and lowest for the R3; however, there was no significant difference between R1 and R2 in feed consumption. Body weight gain was comparable for R0 and R2 birds and significantly higher than that of R1 and R3 birds. The control and R2 birds recorded the best feed conversion ratio, while the R1 birds had the poorest (p < 0.05) as well as the highest feed cost for 1 kg body weight. However, there was no difference among the three other groups of birds with regard to cost. All the treatment groups were comparable (p > 0.05) for carcass yield and serum creatinine level. However, the R3 birds had the lowest proportions of liver (2.26%) and heart (1.07%) to body weight.


Feeding patterns in grasshoppers (Orthoptera: Acrididae): Factors influencing diet specialization.
Diets of grasshopper species from two arid grassland communities in Trans-Pecos, Texas, were determined by gut analysis. Species-specific food plant choice and niche breadths are presented for each of these species. As a group, grasshoppers range from monophagous to polyphagous feeders although most species fall in the oligophagous to polyphagous group. Phylogenetic constraints are evident such that gomphocerinae are primarily grass feeders while melanoplinae feed predominantly on forbs; the oedipodinae show less clearcut tendencies.Feeding patterns are remarkably constant from site to site and overall, community niche breadth distributions between sites do not differ greatly. Individual species tend to eat the same plant species at various sites and maintain similar niche breadths. Species with relatively specialized diets tend to feed on predictable plant species such as grasses and long-lived perrenial forbs.Grasshopper feeding patterns present some problems to the current theory of herbivore diet specialization since forb feeding melanoplines tend to be polyphagous (contrary to predictions). Life history patterns unrelated to tracking host plants may explain some aspects of diet breadth since diet selectivities are presumably adjusted according to the probability of finding suitable food plants.


Understanding nursing students' perspectives on the grading of group work assessments.
Grading group work assessments so that students perceive the grade to be fair to all group members is sometimes challenging. This is particularly important in a higher education environment that is increasingly concerned with student perceptions of teaching quality and satisfaction. This article reports on research that compared undergraduate nursing students perceptions of two different approaches to the grading of group work assessment. A survey design was used to identify students' perspectives and preferences for different group work assessment methods. Participants were undergraduate bachelor of nursing students from a large, metropolitan university in Australia. Data analysis indicated that the perceptions of students around group work assessments changed little as they progressed across the program, although students who had experienced the calculation of individual grades for a group assessment preferred this approach. Many believed the grading of group assessments penalised good students and were less reliable than individual assessments. Students maintained the belief that teamwork skills were essential for the registered nurse role. In conclusion group work assessment should only be used when it is the best assessment method to demonstrate student learning of specific objectives. The weighted mark approach is the group work assessment grading approach of choice.


Histone Deacetylase Inhibitors: Providing New Insights and Therapeutic Avenues for Unlocking Human Birth.
The pregnant uterus remains relaxed throughout fetal gestation before transforming to a contractile phenotype at term to facilitate birth. Despite ongoing progress, the precise mechanisms that regulate this phenotypic transformation are not yet understood. This knowledge gap limits our understanding of how dysregulation of uterine smooth muscle biology contributes to life-threatening obstetric complications, including preterm birth, and hampers our ability to develop effective therapeutic intervention strategies. Protein acetylation plays a vital role in regulating protein structure, function, and subcellular localization, as well as gene transcription availability through regulating chromatin condensation. Histone deacetylase inhibitors (HDACis) are a class of compounds that block the removal of acetyl functional groups from proteins and, as such, have profound effects on important cellular events, including phenotypic transformation. A large body of data now demonstrates that HDACis have profound effects on pregnant human myometrium. Studies to date show that HDACis operate through both genomic and non-genomic mechanisms to affect myometrial function and phenotype. Interestingly, the effects of HDACis on pregnant myometrium are largely "pro-relaxation," including the direct inhibition of contractile machinery as well as repression of pro-labor genes. The "dual action" effects of HDACis make them a powerful tool for unlocking the regulatory processes that underpin myometrial phenotypic transformation and raises prospects of their therapeutic applications. Here, we review the new insights into human myometrial biology that have garnered through the application of HDACis and explore their potential therapeutic application toward the development of novel preterm birth prevention strategies.


Atrial natriuretic peptide influence on nitric oxide system in kidney and heart.
Atrial natriuretic peptide (ANP) and nitric oxide (NO) induce diuresis, natriuresis and diminish vascular tone. Our previous studies showed NO system is involved in ANP hypotensive effect. The aim was to investigate ANP effects on renal and cardiac NO-synthase (NOS) activity. Rats were divided into two groups: group I, infused with saline (1 h, 0.05 ml/min); group II, received ANP bolus (5 microg/kg)+ANP infusion (1 h, 0.2 microg/kg x min). NADPH-diaphorase activity (NADPH-d) was determined in kidney and heart. NOS catalytic activity was determined in renal medulla and cortex and cardiac atria and ventricle by measuring the conversion of l-[U(14)C]-arginine to l-[U(14)C]-citrulline. In group I, NOS activity was determined in basal conditions and plus 1 microM ANP and in group II, NOS activity was determined in basal conditions. NADPH-d was higher in group II than in group I in glomeruli, proximal tubule, cortical and medullar collecting duct, right atria and left ventricle. NOS activity was increased by in vitro ANP addition and, in vivo, ANP infusion in all the studied tissues. ANP treatment increases renal and cardiac NO synthesis. This effect would be independent on the hemodynamic changes induced by ANP. The activation of NO pathway would be one of the mechanisms involved in diuretic, natriuretic and hypotensive effects of ANP.


Correction to: Focus on Recommendations for the Management of Non-small Cell Lung Cancer.
The authors would like to apologize for the misspelling of one of the co-authors names.


Formation of proximal and anterior limb skeleton requires early function of Irx3 and Irx5 and is negatively regulated by Shh signaling.
Limb skeletal pattern relies heavily on graded Sonic hedgehog (Shh) signaling. As a morphogen and growth cue, Shh regulates identities of posterior limb elements, including the ulna/fibula and digits 2 through 5. In contrast, proximal and anterior structures, including the humerus/femur, radius/tibia, and digit 1, are regarded as Shh independent, and mechanisms governing their specification are unclear. Here, we show that patterning of the proximal and anterior limb skeleton involves two phases. Irx3 and Irx5 (Irx3/5) are essential in the initiating limb bud to specify progenitors of the femur, tibia, and digit 1. However, these skeletal elements can be restored in Irx3/5 null mice when Shh signaling is diminished, indicating that Shh negatively regulates their formation after initiation. Our data provide genetic evidence supporting the concept of early specification and progressive determination of anterior limb pattern.


Angiomyolipoma: clinical metamorphosis and concepts for management.
In 10 years the diagnosis of renal angiomyolipoma was made in 44 patients (female-to-male ratio 8:1) at our institution; 4 cases were associated with tuberous sclerosis. Of these patients 29 underwent surgical exploration because of a renal mass; 11 patients with renal masses that were consistent with angiomyolipoma radiologically have not undergone exploration. Of the 4 patients with and the 29 patients without tuberous sclerosis 1 (25 per cent) and 2 (7 per cent), respectively, had renal cell cancer in association with angiomyolipoma. Metachronous involvement of the contralateral kidney has not been noted in any of our patients who underwent nephrectomy for unilateral involvement, nor has there been progression of the contralateral lesion in 3 patients with bilateral disease without tuberous sclerosis during a followup of about 6 years. Furthermore, we have not noted progression of lesions in the 11 patients under observation for a mean followup of almost 3 years. We recommend elective exploration and a renal preserving operation when possible, not only for patients with pain and hemorrhage but also for the complex multiple lesions occasionally seen in patients who do not have tuberous sclerosis. Lesions associated with tuberous sclerosis require surgical intervention only when they become symptomatic or enlarge silently.


A longitudinal cohort study to investigate the retention of knowledge and skills following attendance on the Newborn Life support course.
To investigate whether airway management and non-invasive ventilatory skills are retained after the Neonatal Life support (NLS) course. Candidates who attended and passed the NLS course were retested by two registered instructors using the NLS 'airway testing sheet' unannounced at 3-5 and 12-14 months after their NLS course. Prior to the test, they were also asked to complete a proforma, indicating their own assessment of their competence in being able to effectively carry out all the items used in the NLS airway test. Sixty-seven candidates were tested at 3-5 months, 26 (39%) passed first time, 34 (51%) on retest and 7 (10%) failed. At 12-14 months, 43 were tested, 19 (44%) passed on first attempt, 22 (51%) on retest and 2 (5%) failed. At 12-14 months, more candidates exposed to more than five resuscitations per month passed first time compared to those who were exposed to less than one resuscitation per month (p=0.029). More candidates who were offered resuscitation training at 6 monthly intervals compared to at yearly intervals passed the test on their first attempt at 3-5 months (p=0.022). Self-assessment of competence was not different between candidates who passed and those who failed. This study suggests that skills when tested in a simulated scenario are highly likely to have deteriorated within a few months of attending the NLS course. There is a need for research to determine whether deteriorations in skills after the NLS, as assessed by simulation, correlate with deterioration of skills in clinical practice.


[Three-dimensional parallel collagen scaffold promotes tendon extracellular matrix formation].
To investigate the effects of three-dimensional parallel collagen scaffold on the cell shape, arrangement and extracellular matrix formation of tendon stem cells. Parallel collagen scaffold was fabricated by unidirectional freezing technique, while random collagen scaffold was fabricated by freeze-drying technique. The effects of two scaffolds on cell shape and extracellular matrix formation were investigated in vitro by seeding tendon stem/progenitor cells and in vivo by ectopic implantation. Parallel and random collagen scaffolds were produced successfully. Parallel collagen scaffold was more akin to tendon than random collagen scaffold. Tendon stem/progenitor cells were spindle-shaped and unified orientated in parallel collagen scaffold, while cells on random collagen scaffold had disorder orientation. Two weeks after ectopic implantation, cells had nearly the same orientation with the collagen substance. In parallel collagen scaffold, cells had parallel arrangement, and more spindly cells were observed. By contrast, cells in random collagen scaffold were disorder. Parallel collagen scaffold can induce cells to be in spindly and parallel arrangement, and promote parallel extracellular matrix formation; while random collagen scaffold can induce cells in random arrangement. The results indicate that parallel collagen scaffold is an ideal structure to promote tendon repairing.


Dosimetry study of Nd:YAG laser damage to canine renal cortex.
A dosimetry study of factors affecting the extent of tissue damage inflicted upon the canine renal cortex by the Neodymium:Yttrium Aluminum Garnet (Nd:YAG) laser was undertaken. Laser parameters and renal tissue conditions were varied independently in duplicate in the following manner: (1) power - 5, 10, 20, 50, 75, 100 watts with a spot size of 1.2 mm; (2) exposure duration - 1, 2, and 4 seconds; (3) kidney perfusion and temperature--renal artery unclamped (perfused) without cooling; renal artery clamped (non-perfused) without cooling; and renal artery clamped with cooling. Five days following application of the laser, the animals were sacrificed and serial sections of the renal cortex were examined for maximum depth and width of tissue damage and ablation. Multiple linear regression analysis of the data indicated a direct linear relationship between the joules (watts X seconds) of energy delivered to the renal cortex and the depth and width of tissue damage and ablation (p less than 0.001 for joule regression coefficient for each variable). Seconds and/or watts alone were not major predictors of the outcome after accounting for joules. Clamping the main renal artery significantly reduced the depth and width of laser damage when compared to the perfused kidney (p less than 0.001 for each variable). The depth of damage was similar in the cooled and the non-cooled non-perfused kidney. These data suggest that increased laser energy and kidney perfusion significantly increase renal cortical laser induced damage. Adjustment of these parameters may permit controlled tumor ablation or tissue incision with minimal damage to adjacent normal tissue.


The colonoscope in cecal volvulus: report of three cases.
Colonoscopy was employed to attempt detorsion of volvulus of the right colon in four patients considered to be high-risk surgical patients. In one patient detorsion was accomplished, so that emergency laparotomy became unneccesary. The site of torsion was reached in every patient. When detorsion does not occur reasonably soon after the colonoscope enters the right colon, persistent efforts are more likely to be harmful than helpful. Abdominal symptoms in a patient who has been ill or injured for some time should suggest the possibility of volvulus of the right colon. Early diagnosis and earlier employment of colonoscopy would almost surely result in an increased rate of success in accomplishing detorsion. When detorsion is accomplished, subsequent resection of the right colon should be seriously considered as, without it, volvulus is said to recur frequently.


Subdural hemorrhage in a child with acute promyelocytic leukemia presenting as subtle headache.
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) and is rare in children (< 10% of childhood AML). It tends to bleed with disseminated intravascular coagulation (DIC) and intracranial hemorrhage complication is often fatal. We report a 12-year-old child with APL who suffered a subdural hemorrhage and initially presented with a subtle headache mistaken as the side effect of all-trans-retinoic acid (ATRA). Blood component therapy and a pediatric dosage of ATRA (25 mg/m2/day) combined with idarubicin as induction chemotherapy were administered in the first week, but the bleeding diathesis persisted and DIC profiles showed no improvement. The patient then developed photophobia, neck stiffness, and constant headache. Evidence of increased intracranial pressure (IICP) and persistent bleeding from previous venous puncture sites were also noticed clinically. DIC and life-threatening IICP were beyond control until the ATRA dosage was increased to adult levels (45 mg/m2/day). This case suggests that the ATRA dosage for pediatric APL patients must be modified according to clinical condition. Emergency brain imaging should be considered in APL patients with signs of IICP to distinguish intracranial lesions from ATRA complications.


Chromosomal aberrations and sister-chromatid exchanges in Chinese hamster cells treated in vitro with hexavalent chromium compounds.
Chinese hamster cells (CHO line) were treated in vitro for 30--39 h with hexavalent chromium compounds (K2Cr2O7 and Na2CrO7), at concentrations ranging from 0.1 to 1.0 microgram of Cr6+ per ml, in medium containing BUdr. Chromosomal aberrations and sister-chromatid exchanges were scored on BUdr-labelled 2nd division metaphases, collected at the end of treatment and stained with Giemsa. Treatment with mitomycin C 0.009--0.030 microgram/ml) was carried out as a control for the responsiveness of the cell system to chromosomal damage. Both chromium compounds induced marked mitotic delays. Chromosomal aberrations were increased about 10-fold by exposure to Cr6+ (1.0 microgram/ml). The principal aberrations observed were single chromatid gaps, breaks and interchanges, whose frequencies increased proportionally to the concentration of chromium. Dicentric chromosomes, isochromatid breaks, chromosome and chromatid rings were also induced. The frequenyc of sister-chromatid exchanges was hardly doubled 30 h after exposure to Cr6+ at 0.3 microgram/ml, whereas it was trebled 39 h after treatment, in the cells whose division cycle had been slowed down by chromium.


A simulated ecological restoration of bare cut slope reveals the dosage and temporal effects of cement on ecosystem multifunctionality in a mountain ecosystem.
Cement is a critical building material used in the restorations of bare cut slopes. Yet, how cement affects ecosystem's functions and their undertakers remains elusive. Here, we revealed the dosage and temporal effects of cement on plant and soil traits, extracellular enzymes, greenhouse gas fluxes and microbiome using simulation experiments. The results showed that soil pH increased with the cement content at 1st day but relatively constant values around 7 to 7.5 were detected in the flowing days. The β-1,4-glucosidase, phenol oxidase, leucine aminopeptidase and acid phosphatase showed high activities under high cement content, and they generally increased with the cultivations except for acid phosphatase. CH4 fluxes at 16th day were less than zero, and they increased to peak around at 37th to 44th days followed by decreasing until reaching to relatively stable fluctuations around 0. Despite of decrease patterns, N2O fluxes stayed around zero across the temporal gradient except for the maximum around at 30th day in 2%, 5% and 8% cement treatment. Microbial diversity decreased with the cement content, in which there were a recovery trend for bacteria. By integrating above- and belowground ecosystem traits into a multifunctionality index, we identified a potential optimum cement content (11%). PLSPM showed that multifunctionality was affected by the shifts in soil bacterial community, enzyme activity and greenhouse gases while these components were effected by other environmental changes resulted from cement. Our results demonstrate that cement determines multifunctionality through mediating microbial community and activity, providing new insights for designing in situ experiments and ecological restoration strategies for bare cut slopes.


Anomalous kinetics of galactose-deficient IgA incurring nephropathy revealed by cross-scale optical imaging.
IgA nephropathy (IgAN) is the most common glomerulonephritis, characterized by the presence of predominant IgA deposits in the mesangium. Deposition of pathogenic IgA in kidney tissue is a fundamental initiating process that has not been fully studied. Here, we employed optical imaging to directly visualize kidney deposition of IgA with optimized spatial and temporal resolution in BALB/c nude mice. Real-time fluorescence imaging revealed that IgA isolated from patients with IgAN preferentially accumulated in the kidneys, compared with IgA purified from healthy individuals. There was no difference in the distribution of either IgA preparation by the liver. Photoacoustic computed tomography dynamically demonstrated and quantified the enhanced retention of pathological IgA in the kidney cortex. Photoacoustic microscopy tracked IgA deposition in the glomeruli with a resolution down to three microns in a mouse model. Notably, longitudinal fluorescent imaging revealed that galactose-deficient IgA (Gd-IgA), which was elevated in the circulation of patients with IgAN, persisted in the kidney for longer than two weeks, and stable deposition of Gd-IgA induced kidney impairment, including albuminuria and mesangial proliferation. Thus, our study highlights that the aberrant kidney depositional kinetics of Gd-IgA is involved in the pathogenesis of IgAN. Hence, cross-scale optical imaging has potential applications in assessing immune-mediated kidney diseases and uncovering underlying mechanisms of disease.


Clinical pharmacology of antibiotics and other drugs in cystic fibrosis.
The disposition of many drugs in cystic fibrosis is abnormal. In general, changes in pharmacokinetics include: increased volume of distribution, decreased plasma concentration, and enhanced renal and sometimes non-renal elimination of drugs. Pathophysiology of the disease important for drug disposition includes: (a) hypersecretion of gastric acid and duodenal secretions which are of small volume, viscous and low in bicarbonate; (b) increased intestinal permeability to some sugars and probe substances; (c) hypergammaglobulinaemia and sometimes hypoalbuminaemia; (d) significant elevation of free fatty palmitoleic acid level and decreased low-density and high-density serum lipoproteins; (e) an average increase by 30 to 45% in plasma volume in patients with cystic fibrosis who have moderately severe pulmonary disease, right ventricle hypertrophy and dilatation, which occurs in 15 to 35% of patients with a Shwachman score of 81 to 100; (f) abnormal bile acid metabolism and enterohepatic recirculation; and (g) enlarged kidneys and glomerulomegaly with increased glomerular filtration rate, tubular clearance and urine flow rate in some patients with cystic fibrosis. Delayed absorption from the gastrointestinal tract has been reported in patients with cystic fibrosis for cloxacillin, epicillin, clindamycin, ciprofloxacin and probably for cephalexin, para-aminobenzoic acid and chloramphenicol. A possible increased absorption was reported for cimetidine. Of 7 drugs studied only theophylline had significantly decreased plasma protein binding. An increased volume of distribution and increased renal clearance reported for several drugs is caused mainly by increases in plasma volume and urine flow rate in many of these patients. Possible increased elimination of some drugs in bile (which probably results from bile acid malabsorption) and in bronchial secretions (which are abundant in some cystic fibrosis patients with acute pulmonary infection) may explain enhanced non-renal elimination of these drugs. The metabolism of cimetidine in cystic fibrosis was reported not to be changed significantly compared to control subjects.


DNA binding and ToxR responsiveness by the wing domain of TcpP, an activator of virulence gene expression in Vibrio cholerae.
Virulence in Vibrio cholerae requires activation of toxT by two membrane-localized activators, TcpP and ToxR. We isolated 12 tcpP activation mutants that fell into two classes: class I mutants were inactive irrespective of the presence of ToxR, and class II mutants exhibited near wild-type activity when coexpressed with ToxR. Most class I mutants had lesions in the wing domain predicted by homology with the winged helix-turn-helix family of activators. Class I mutants bound promoter DNA poorly and were largely unable to interact with ToxR in a crosslinking assay, whereas class II mutants retained physical interaction with ToxR. One mutant constructed in vitro bound DNA poorly but nevertheless responded to ToxR by activating toxT and also maintained ToxR interaction. We propose that ToxR interaction, but not DNA binding, is essential for TcpP function and that the wing domain of TcpP enables contact with ToxR required for productive TcpP-RNA polymerase association.


Dysregulated flow-mediated vasodilatation in the human placenta in fetal growth restriction.
Increased vascular resistance and reduced fetoplacental blood flow are putative aetiologies in the pathogenesis of fetal growth restriction (FGR); however, the regulating sites and mechanisms remain unclear. We hypothesised that placental vessels dictate fetoplacental resistance and in FGR exhibit endothelial dysfunction and reduced flow-mediated vasodilatation (FMVD). Resistance was measured in normal pregnancies (n = 10) and FGR (n = 10) both in vivo by umbilical artery Doppler velocimetry and ex vivo by dual placental perfusion. Ex vivo FMVD is the reduction in fetal-side inflow hydrostatic pressure (FIHP) following increased flow rate. Results demonstrated a significant correlation between vascular resistance measured in vivo and ex vivo in normal pregnancy, but not in FGR. In perfused FGR placentas, vascular resistance was significantly elevated compared to normal placentas (58 ± 7.7 mmHg and 36.8 ± 4.5 mmHg, respectively; 8 ml min(-1) ; means ± SEM; P < 0.0001) and FMVD was severely reduced (3.9 ± 1.3% and 9.1 ± 1.2%, respectively). In normal pregnancies only, the highest level of ex vivo FMVD was associated with the lowest in vivo resistance. Inhibition of NO synthesis during perfusion (100 μm l-NNA) moderately elevated FIHP in the normal group, but substantially in the FGR group. Human placenta artery endothelial cells from FGR groups exhibited increased shear stress-induced NO generation, iNOS expression and eNOS expression compared with normal groups. In conclusion, fetoplacental resistance is determined by placental vessels, and is increased in FGR. The latter also exhibit reduced FMVD, but with a partial compensatory increased NO generation capacity. The data support our hypothesis, which highlights the importance of FMVD regulation in normal and dysfunctional placentation.


Information avoidance in the age of COVID-19: A meta-analysis.
Guided by three major theoretical frameworks, this meta-analysis synthesizes 17 empirical studies (15 articles with 18,297 participants, 13 of them are from non-representative samples) and quantifies the effect sizes of a list of antecedents (e.g., cognitive, affective, and social factors) on information avoidance during the COVID-19 context. Findings indicated that information-related factors including channel belief (r = -0.35, p < .01) and information overload (r = 0.23, p < .01) are more important in determining individual's avoidance behaviors toward COVID-19 information. Factors from the psychosocial aspects, however, had low correlations with information avoidance. While informational subjective norms released a negative correlation (r = -0.16, p < .1) which was approaching significant, positive and negative risk responses were not associated with information avoidance. Moderator analysis further revealed that the impacts of several antecedents varied for people with different demographic characteristics (i.e., age, gender, region of origin), and under certain sampling methods. Theoretically, this meta-analysis may help determine the most dominant factors from a larger landscape, thus providing valuable directions to refine frameworks and approaches in health information behaviors. Findings from moderator analysis have also practically inspired certain audience segmentation strategies to tackle occurrence of information avoidance during the COVID-19 pandemic.


How do new members affect the relationship between principal investigator's network position and academic output of granted funds?
The paper focuses on how to improve academic output of a granted fund when the adding of new members changes principal investigator's network position. This objective is refined by exploring how new members affect the relationship between principal investigator's network position and the academic output of granted funds, and whether this effect is similar in high-output and low-output collaboration networks. New members are divided into two groups, namely, international collaboration and inbound mobility. Using negative binomial regression on research funds supported by the National Natural Science Foundation of China, the results indicate that new members indeed have moderating effects on the relationship between principal investigator's network position and the academic output of granted funds. Moreover, we find that this moderating effect in high-output collaboration networks is larger than that in low-output collaboration networks. Our findings provide practical implications for the decision makers to design funding planning and for the principal investigators to improve academic output.


Differential transplacental binding of diazepam: causes and implications.
Diazepam plasma binding was determined in 17 matched pairs of maternal and foetal plasma, collected at delivery. Diazepam % free was higher (p less than 0.001) in maternal (mean 3.24%) than in either umbilical venous (mean 1.50%) or umbilical arterial (mean 1.24%) plasma. The data from in vitro dialysis studies were consistent with the reported higher diazepam concentrations in infants than in mothers at delivery. Plasma nonesterified fatty acids (NEFA) concentrations were higher (p less than 0.001) in maternal (mean = 643 microM) than in matched umbilical venous plasma (means = 211 microM) and there was a significant correlation (p less than 0.01) between diazepam % free and corresponding plasma NEFA concentration for pooled data (r = 0.871, n = 34). Multiple and partial regression analysis indicates that transplacental differences in albumin, bilirubin and total protein concentrations made a minimal contribution to diazepam binding differences between mother and foetus and that approximately 76% of the variability in diazepam % free was accounted for by plasma NEFA concentration. The binding of diazepam to human serum albumin (HSA) was markedly perturbed by the presence of NEFA but not by bilirubin and there was no apparent cooperativity between bilirubin and NEFA on diazepam-HSA binding. Moreover, our findings provide further evidence that substantial differences in binding affinities exist between foetal and maternal plasma albumins.


SARS-CoV-2 Infection Can Lead to an Increase in Tacrolimus Levels in Renal Transplant Patients: A Cohort Study.
The aim of this study is to evaluate the effect of SARS-CoV-2 infection on serum tacrolimus levels. Tacrolimus levels of 34 transplant patients diagnosed with SARS-CoV-2 in 2020 were compared with their pre-infection values and those of a control group with alternative infections. 20 out of 34 (59%) had high levels. At diagnosis, median tacrolimus level in the SARS-CoV-2 cohort was 9.6 μg/L (2.7-23) compared to 7.9 μg/L in the control group (p = 0.07, 95% CI for difference -0.3-5.8). The ratio of post-infection to pre-infection tacrolimus values was higher in the SARS-CoV-2 group (1.7) compared to the control group (1.25, p = 0.018, 95% CI for difference 0.08-0.89). The acute kidney injury rate was 65% (13 of 20) in SARS-CoV-2 patients with a level >8 μg/dl, compared to 29% (4 of 14) in those with lower levels (p = 0.037). Median length of stay was 10 days among SARS-CoV-2 infected patients with high tacrolimus levels compared to 0 days in the rest (p = 0.04). Four patients with high levels died compared to 2 in the control group. Clinicians should be aware of this potential effect on tacrolimus levels and take appropriate measures.


The Transcriptome and Metabolome Reveal the Potential Mechanism of Lodging Resistance in Intergeneric Hybrids between Brassica napus and Capsella bursa-pastoris.
Lodging is one of the main reasons for the reduction in seed yield and is the limitation of mechanized harvesting in B. napus. The dissection of the regulatory mechanism of lodging resistance is an important goal in B. napus. In this study, the lodging resistant B. napus line, YG689, derived from the hybridization between B. napus cv. Zhongyou 821 (ZY821) and Capsella bursa-pastoris, was used to dissect the regulation mechanism of hard stem formation by integrating anatomical structure, transcriptome and metabolome analyses. It was shown that the lignocellulose content of YG689 is higher than that of ZY821, and some differentially expressed genes (DEGs) involved in the lignocellulose synthesis pathway were revealed by transcriptome analyses. Meanwhile, GC-TOF-MS and UPLC-QTOF-MS identified 40, 54, and 31 differential metabolites in the bolting stage, first flower stage, and the final flower stage. The differential accumulation of these metabolites might be associated with the lignocellulose biosynthesis in B. napus. Finally, some important genes that regulate the metabolic pathway of lignocellulose biosynthesis, such as BnaA02g18920D, BnaA10g15590D, BnaC05g48040D, and NewGene_216 were identified in B. napus through the combination of transcriptomics and metabolomics data. The present results explored the potential regulatory mechanism of lignocellulose biosynthesis, which provided a new clue for the breeding of B. napus with lodging resistance in the future.


Genome organization and long-range regulation of gene expression by enhancers.
It is now well accepted that cell-type specific gene regulation is under the purview of enhancers. Great strides have been made recently to characterize and identify enhancers both genetically and epigenetically for multiple cell types and species, but efforts have just begun to link enhancers to their target promoters. Mapping these interactions and understanding how the 3D landscape of the genome constrains such interactions is fundamental to our understanding of mammalian gene regulation. Here, we review recent progress in mapping long-range regulatory interactions in mammalian genomes, focusing on transcriptional enhancers and chromatin organization principles.


The extent of dermatopathology education: a comparison of pathology and dermatology.
An indispensable component of all pathology and dermatology residencies is obtaining proficiency in the area of dermatopathology. The purpose of this study is to quantify dermatopathology training in pathology and dermatology residencies and the amount of continuing medical education in dermatopathology in leading journals of both fields. Dermatology residents complete more hours of dermatopathology than pathology residents. There is also more dermatopathology in the dermatology literature than in the pathology literature. Dermatopathology falls into the scope of both pathology and dermatology practice.


Identification of and Molecular Basis for SIRT6 Loss-of-Function Point Mutations in Cancer.
Chromatin factors have emerged as the most frequently dysregulated family of proteins in cancer. We have previously identified the histone deacetylase SIRT6 as a key tumor suppressor, yet whether point mutations are selected for in cancer remains unclear. In this manuscript, we characterized naturally occurring patient-derived SIRT6 mutations. Strikingly, all the mutations significantly affected either stability or catalytic activity of SIRT6, indicating that these mutations were selected for in these tumors. Further, the mutant proteins failed to rescue sirt6 knockout (SIRT6 KO) cells, as measured by the levels of histone acetylation at glycolytic genes and their inability to rescue the tumorigenic potential of these cells. Notably, the main activity affected in the mutants was histone deacetylation rather than demyristoylation, pointing to the former as the main tumor-suppressive function for SIRT6. Our results identified cancer-associated point mutations in SIRT6, cementing its function as a tumor suppressor in human cancer.


Robust glyoxalase activity of Hsp31, a ThiJ/DJ-1/PfpI family member protein, is critical for oxidative stress resistance in Saccharomyces cerevisiae.
Methylglyoxal (MG) is a reactive metabolic intermediate generated during various cellular biochemical reactions, including glycolysis. The accumulation of MG indiscriminately modifies proteins, including important cellular antioxidant machinery, leading to severe oxidative stress, which is implicated in multiple neurodegenerative disorders, aging, and cardiac disorders. Although cells possess efficient glyoxalase systems for detoxification, their functions are largely dependent on the glutathione cofactor, the availability of which is self-limiting under oxidative stress. Thus, higher organisms require alternate modes of reducing the MG-mediated toxicity and maintaining redox balance. In this report, we demonstrate that Hsp31 protein, a member of the ThiJ/DJ-1/PfpI family in Saccharomyces cerevisiae, plays an indispensable role in regulating redox homeostasis. Our results show that Hsp31 possesses robust glutathione-independent methylglyoxalase activity and suppresses MG-mediated toxicity and ROS levels as compared with another paralog, Hsp34. On the other hand, glyoxalase-defective mutants of Hsp31 were found highly compromised in regulating the ROS levels. Additionally, Hsp31 maintains cellular glutathione and NADPH levels, thus conferring protection against oxidative stress, and Hsp31 relocalizes to mitochondria to provide cytoprotection to the organelle under oxidative stress conditions. Importantly, human DJ-1, which is implicated in the familial form of Parkinson disease, complements the function of Hsp31 by suppressing methylglyoxal and oxidative stress, thus signifying the importance of these proteins in the maintenance of ROS homeostasis across phylogeny.


The impact of sarcobesity on incisional hernia after laparoscopic colorectal cancer surgery.
Incisional hernia is a common complication after abdominal surgery, especially in obese patients. The aim of the present study was to evaluate the relationship between sarcobesity and incisional hernia development after laparoscopic colorectal cancer surgery. In total, 262 patients who underwent laparoscopic colorectal cancer surgery were included in the present study. Univariate and multivariate analyses were performed to evaluate the independent risk factors for the development of incisional hernia. We then performed subgroup analyses to assess the impact of visceral obesity according to clinical variables on the development of incisional hernia in laparoscopic surgery for colorectal cancer surgery. Forty-four patients (16.8%) developed incisional hernias after laparoscopic colorectal cancer surgery. In the univariate analysis, the development of incisional hernia was significantly associated with female sex (P = 0.046), subcutaneous obesity (P = 0.002), visceral obesity (P = 0.002), sarcobesity (P < 0.001), and wound infection (P < 0.001). In the multivariate analysis, sarcobesity (P < 0.001) and wound infection (P < 0.001) were independent predictors of incisional hernia. In subgroup analysis, the odds ratio of visceral obesity was the highest (13.1; 95% confidence interval [CI], 4.51-37.8, P < 0.001) in the subgroup of sarcopenia. Sarcobesity may be a strong predictor of the development of incisional hernia after laparoscopic surgery for colorectal cancer, suggesting the importance of body composition in the development of incisional hernia.


Predictors of Discharge Destinations and Three-Month Evolution of Patients Initially Hospitalized in a Cognitive Behavioral Unit.
Previous studies showed that a third of patients living at home entered an institution after hospitalization in Cognitive and Behavioral Units (CBUs). The main objective of this study was to identify predictors of discharge destination for these patients. The secondary objective was to estimate whether institutionalization can have an impact on a patient's long-term prognosis. The study population was selected from the EVITAL study and included 140 participants living at home before hospitalization in CBUs. Factors favoring nursing-home admission were investigated and the impact of discharge destinations (i.e., home or nursing home) on patients' prognosis was examined. Institutionalized patients were more likely to be women (F = 4.7; p = 0.03), with a higher dementia severity (F = 9.82; p = 0.007), often living alone (F = 19.69; p = 0.001), with a caregiver other than spouse (F = 8.93; p = 0.003), and with a higher patient quality of life (QoL) according to the caregiver (F = 11.73; p = 0.001). When using multivariate logistic linear regressions, we showed a relationship between marital status (OR = 0.19, 95% CI: 0.08-0.43, p < 0.001), dementia severity (OR = 0.15, 95% CI: 0.03-0.79, p = 0.03), QoL (OR = 0.88, 95% CI: 0.79-0.98, p = 0.017), and institutionalization. At three months, a higher overall rate of rehospitalization (F = 12.21; p < 0.001) and rehospitalization for behavioral and psychological symptoms of dementia (F = 6.76; p = 0.006) were observed for patients staying at home after CBU discharge. Our study allows for a better understanding of the institutionalization risk factors of the patients hospitalized in CBUs. Identification of these factors could help clinicians to better support patients and to help the transition to be smoother. Moreover, our results suggest that prognosis of institutionalized patients is not unfavorable when compared with patients staying at home.


Simplified sample preparation method for triclosan and methyltriclosan determination in biota and foodstuff samples.
An improved method for the determination of triclosan (TCS) and methyltriclosan (MTCS) in fish and foodstuff samples is presented. Analytes were simultaneously extracted and purified using the matrix solid-phase dispersion (MSPD) technique, and then selectively determined by gas chromatography with tandem mass spectrometry (GC-MS/MS). Several combinations of dispersants, clean-up co-sorbents and extraction solvents were tested in order to obtain lipid-free extracts and quantitative recoveries for TCS and MTCS. Under optimised conditions, 0.5 g samples were dispersed using 1.5 g of neutral silica in a mortar with a pestle, and transferred to a polypropylene cartridge containing 3 g of silica impregnated with 10% of sulphuric acid (SiO2-H2SO4, 10%, w/w). Analytes were recovered with 10 mL of dichloromethane whereas lipids were oxidized in the layer of acidic silica. The extract was concentrated to dryness and re-constituted with 1 mL of ethyl acetate. Then, a fraction of 0.5 mL was mixed with 50 microL of N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA) and injected in the GC-MS/MS system. The developed method provided absolute recoveries between 77 and 120% for different samples spiked at the low ng g(-1) level, quantification limits in the range of 1-2 ng g(-1) and a considerable simplicity in comparison with previously developed sample preparation approaches. Experiments carried out placing sliced food samples in direct contact with TCS-treated kitchenware surfaces showed the capability of the biocide to migrate into foodstuffs.


Palliative Care in Heart Failure: A Public Health Emergency.
Palliative care (PC) is the holistic care of patients with life-limiting illnesses focused on relief of suffering and maximizing quality of life for patients and their families. Patients with heart failure (HF) are the largest group eligible for PC services, but only a small percentage of them receive PC. The optimal content and method of delivery of PC interventions to HF patients in resource-limited countries remain unknown. The integration of PC into existing HF disease management continues to be a challenge. PUBMED was searched to identify articles on the topic published in the last 5 years (2014-April 2019). One hundred thirty-six articles were identified-14 articles out of were included in the revision. Research concerning PC in HF is still scarce and comes predominantly from developed countries. PC in HF improves patients' and caregivers' outcomes in terms of dyspnea, sleep, depression, communication, coping, and care-giving burden. Specialized home-based PC services have a positive impact on patients' physical and emotional wellbeing while decreasing utilization of medical services. Fatigue, dyspnea, and pain are frequent symptoms. Evidence concerning use of opioids for dyspnea is increasing. Family caregivers offer a considerable amount of care during the disease trajectory. There is often incongruence between the carer's and the patient's wishes in terms of treatment decisions and preferences. Carers should be assessed for risk and supported in their roles in care management and care coordination. Because of the unpredictability of the disease and difficulty in prognostication, PC should be introduced at the point of diagnosis of HF. Basic education in PC needs to be introduced early in the training of cardiology staff, focused on concept definition, differencing PC and terminal care, symptom management, communication, and decision-making.


Predictors of shuttle walking test performance in patients with cardiovascular disease.
The incremental shuttle walking test (ISWT) is used to estimate cardiorespiratory fitness, but data from healthy individuals suggest that demographic and anthropometric measures account for much of the variance in test performance. The aim of this study was to determine whether anthropometric, demographic and selected gait measures also predict ISWT performance (i.e. distance walked) in patients with cardiovascular disease. Observational study. A community-based cardiac rehabilitation centre (Cohort 1) and a hospital outpatient cardiac rehabilitation programme (Cohort 2). Sixteen patients with clinically stable cardiovascular disease (Cohort 1) and 113 patients undergoing cardiac rehabilitation (Cohort 2). Patients in Cohort 1 performed the ISWT on two occasions. Anthropometric data and walking and turning variables were collected. Linear regression analyses were used to identify the predictors of test performance. The authors subsequently attempted to validate the equation created by comparing predicted and actual ISWT values in a larger (n=113) validation sample (Cohort 2). Distance walked during ISWT, step length and height. No gait or turning measures were significantly associated with ISWT performance. Distance walked correlated most strongly with step length (r=0.83, P<0.05) and height (r=0.74, P<0.05). Given the similarity of these correlations and the rarity of step length assessment in clinical practice, ISWT performance was predicted using patient's height; this explained 55% of the variance in ISWT performance. Height was also the best predictor in Cohort 2, explaining 17% of test variance (P<0.01). Body mass index explained an additional 3% of variance (P<0.05) in ISWT performance. Routine clinical measures, particularly patient's height, are predictive of ISWT performance. The findings of the present study are in partial agreement with similar studies performed in healthy individuals, and it remains unclear whether the ISWT performance of patients with cardiovascular disease is influenced by the same factors as the ISWT performance of healthy individuals.


Prognostic factors in advanced epithelial ovarian cancer. (Gruppo Interregionale Cooperativo di Oncologia Ginecologica (GICOG)).
The data on 914 patients enrolled in four randomised trials in advanced ovarian cancer, consecutively conducted by the same cooperative group between 1978 and 1986, were analysed with the aims of: (1) determining the impact of selected prognostic variables on survival; (2) finding, from the interaction of favourable prognostic factors and treatment, an approximate estimate of the magnitude of the survival advantage associated with the use of platinum-based combination chemotherapy. The overall 3-year survival in this series of patients is twice that reported historically (22%; 95% CL 18.7-25.4). The proportional hazard regression model was used to perform the analysis on survival. Residual tumour size, age, FIGO stage and cell type were all independent determinants of survival. Differences in survival from the various prognostic groups were impressive with 5-year survival rates ranging from 7 to 62%. However, these differences were not qualitative (i.e. the kinetics of survival were similar for the best and the worst groups) suggesting that current prognostic factors are of little use for selecting 'biologically' different sub-populations. Platinum-based regimens were associated to an overall prolonged median survival, but this benefit was not observable in the subgroup with most favourable prognosis (less than 2 cm residual tumour size). The implications of these observations for clinical research and ovarian cancer patients care are discussed.


The effects of raloxifene on endothelial function and Inflammation in Postmenopausal women: A Meta-analysis of randomized controlled trials.
Raloxifene treatment has been reported to be associated with cardiovascular benefits if prescribed to women during the postmenopausal period. However, a final conclusion regarding this hypothesis has not yet been achieved. We conducted a systematic review and meta-analysis to evaluate the effect of raloxifene on the endothelial function and inflammation in postmenopausal women. We systematically searched the following 4 databases from inception to 23 January 2021 without any language restrictions: Web of Science, PubMed/Medline, Embase and Scopus. The eligible randomized controlled trials (RCTs) reporting the effects of raloxifene on the flow-mediated dilatation (FMD), C-reactive protein (CRP), carotid intima-media thickness (CIMT), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin levels, were included in the final meta-analysis. A total of 16 RCTs were included in the final analysis. Raloxifene administration had no significant effect on ICAM-1 and E-selectin levels. However, we observed a decrease of the CIMT (WMD: -0.071 mm, 95% CI: -0.09 to -0.04, P = 0.000), CRP (WMD: -0.342 mg/L, 95% CI: -0.591, -0.094, p = 0.007), and VCAM-1 (WMD: -197.90 mg/L, 95% CI: -269.58 to -126.23, P = 0.000) levels in the intervention versus control groups following the prescription of this pharmacological agent. Moreover, raloxifene treatment resulted in a significant elevation of the FMD (WMD: 1.64%, 95% CI: 0.46 to 2.81, P = 0.006), particularly if the intervention was equal to or exceeded 12 weeks. Raloxifene might emerge as a potential therapeutic option in the management of endothelial dysfunction and inflammation in postmenopausal women.


Distinct atrophy of septal nuclei in Parkinson's disease.
Parkinson's disease (PD) mainly affects basal ganglia including septal nuclei. Septal nuclei have extensive cholinergic connections with thalamus and brain stem nuclei. We hypothesized that the degeneration of septal nuclei has an impact on dopaminergic (motor) and non-dopaminergic (cognitive) symptoms in PD. Clinical and MRI data of 80 patients with Parkinson's disease and 20 healthy controls (HC) with a structural magnetic resonance imaging (MRI) were selected from their first visit from PPMI database. Septal nuclei were manually segmented from T1W images according to previously established anatomical criteria. In addition, subcortical structures such as thalamus, amygdala, hippocampus, caudate, putamen, pallidum and accumbens were automatically segmented. Volume of septal nuclei in the patients with PD was decreased in comparison with controls. These changes were independent of volume changes in other subcortical grey structure in PD. In addition, we found a correlation between motor components of unified Parkinson's disease rating scale (UPDRS) and volume of septal nuclei in PD. Other clinical measures such as olfactory test, upper extremity function (mobility) performance, total UPDRS, lower extremity function (mobility) performance, and cognitive function were significantly more in PD group than in control. No correction was found between cognitive function and volume of septal nuclei. We concluded that septal nuclei is distinctly affected in PD and is strongly associated with motor impairment. This may be a modulatory effect of cholinergic system on dopaminergic and glutamergic system. It is suggested that volume of septal nuclei may be a useful biomarker in PD diagnosis and monitoring.


The role of IL-6 and STAT3 in inflammation and cancer.
The defense of the host from foreign pathogens is the commonly accepted function of the vertebrate immune system. A complex system consisting of many differing cells and structures communicating by both soluble and cell bound ligands, serves to protect the host from infection, and plays a role in preventing the development of certain types of tumours. Numerous signalling pathways are involved in the coordination of the immune system, serving both to activate and attenuate its responses to attack. The ability of the immune system, specifically those cells involved in acute inflammatory responses, to mediate the directed (and sometimes indirect) killing of cells and pathogens, make it a potential threat to host survival. Furthermore, the production and release of various survival factors such as the pleiotropic cytokine IL-6, a major mediator of inflammation and activator of signal transducer and activator of transcription 3, serves to block apoptosis in cells during the inflammatory process, keeping them alive in very toxic environments. Unfortunately, these same pathways serve also to maintain cells progressing towards neoplastic growth, protecting them from cellular apoptotic deletion and chemotherapeutic drugs. Here, we discuss the relationships between cancer and inflammation, and some of the molecular mechanisms involved in mediating the unintended consequences of host defense and tumour survival.


Corrigendum: Recurrent multifocal adult rhabdomyoma in an elderly woman diagnosed with Birt-Hogg-Dubé syndrome: A case report.
[This corrects the article DOI: 10.3389/fsurg.2022.1017725.].