[Application of Midline Catheter Placed Under Ultrasound Guidance in Intravenous Therapy for Oral and Maxillofacial Tumor].
To examine the application effect of ultrasound-guided placement of midline catheter and to select the appropriate placement method of intravenous catheter for patients with oral and maxillofacial tumors. We retrospectively analyzed the general data and venous catheter-related information of 143 oral and maxillofacial tumor patients who received treatment between June 2019 and December 2021. There were two patient groups, a control group of patients with inserted peripheral venous catheters (PVC) and an observation group of patients with midline catheters placed under ultrasound guidance. We made a comparative analysis of the incidence of catheter-related complications, including bleeding at the insertion site, phlebitis, catheter blockage, extravasation, etc., in the two groups. When the baseline data from the two groups were not balanced, we used propensity score matching (PSM) to match the general data before comparing the complication incidence between the two groups. There were 71 patients who underwent 215 times of PVC placement in the control group and 72 patients who underwent 72 times of midline catheter placement in the observation group. There was no significant difference between the patients in the two groups in terms of age, sex, diagnosis, or the use of anticoagulant medication ( P>0.05) . The observation group had longer average length-of-stay than the control group did ( P<0.01). The cost of catheter placement in the observation group was 1080 yuan per set, with the average daily cost being about (56.27±20.23) yuan. Patients in the control group had PVC placement for an average of (3.03±0.93) times. The cost for PVC placement was 96 yuan per time and the average daily cost was about (19.94±7.50) yuan. There was significant difference in the average daily cost between the observation group and the control group ( P<0.01). PSM was performed for the two groups. Before PSM, the incidence of catheter-related complications in the observation group (8.3%, 6/72) was lower than that of the control group (30.2%, 65/215) and the difference was statistically significant ( P<0.01). After PSM, 72 times of catheter placement from each group were included in comparative analysis. The incidence of catheter-related complications in the observation group (8.3%, 6/72) was lower than that of the control group (54.2%, 39/72) and the difference was statistically significant ( P<0.01). Patients have low incidence of catheter-related complications when they have midline catheter placed under ultrasound guidance, which helps reduce the pain of repeated venous insertion that patients incur and the workload of clinical nurses. The use of midline catheters is appropriate for and should be popularized among patients with oral and maxillofacial malignant tumors, especially patients who have poor peripheral venous conditions and those who are undergoing repair and reconstruction surgeries.


Development of amyloid burden in African Green monkeys.
The vervet is an old world monkey increasingly being used as a model for human diseases. In addition to plaques and tangles, an additional hallmark of Alzheimer's disease is damage to neurons that synthesize noradrenaline (NA). We characterized amyloid burden in the posterior temporal lobe of young and aged vervets, and compared that with changes in NA levels and astrocyte activation. Total amyloid beta (Aβ)40 and Aβ42 levels were increased in the aged group, as were numbers of amyloid plaques detected using antibody 6E10. Low levels of Aβ42 were detected in 1 of 5 younger animals, although diffusely stained plaques were observed in 4 of these. Increased glial fibrillary acidic protein staining and messenger RNA levels were significantly correlated with increased age, as were cortical NA levels. Levels of Aβ42 and Aβ40, and the number of 6E10-positive plaques, were correlated with NA levels. Interestingly messenger RNA levels of glial derived neurotrophic factor, important for noradrenergic neuronal survival, were reduced with age. These findings suggest that amyloid pathology in aged vervets is associated with astrocyte activation and higher NA levels.


Ligand-mediated dimerization of a carbohydrate-binding molecule reveals a novel mechanism for protein-carbohydrate recognition.
The structural and thermodynamic basis for carbohydrate-protein recognition is of considerable importance. NCP-1, which is a component of the Piromyces equi cellulase/hemicellulase complex, presents a provocative model for analyzing how structural and mutational changes can influence the ligand specificity of carbohydrate-binding proteins. NCP-1 contains two "family 29" carbohydrate-binding modules designated CBM29-1 and CBM29-2, respectively, that display unusually broad specificity; the proteins interact weakly with xylan, exhibit moderate affinity for cellulose and mannan, and bind tightly to the beta-1,4-linked glucose-mannose heteropolymer glucomannan. The crystal structure of CBM29-2 in complex with cellohexaose and mannohexaose identified key residues involved in ligand recognition. By exploiting this structural information and the broad specificity of CBM29-2, we have used this protein as a template to explore the evolutionary mechanisms that can lead to significant changes in ligand specificity. Here, we report the properties of the E78R mutant of CBM29-2, which displays ligand specificity that is different from that of wild-type CBM29-2; the protein retains significant affinity for cellulose but does not bind to mannan or glucomannan. Significantly, E78R exhibits a stoichiometry of 0.5 when binding to cellohexaose, and both calorimetry and ultracentrifugation show that the mutant protein displays ligand-mediated dimerization in solution. The three-dimensional structure of E78R in complex with cellohexaose reveals the intriguing molecular basis for this "dimeric" binding mode that involves the lamination of the oligosaccharide between two CBM molecules. The 2-fold screw axis of the ligand is mirrored in the orientation of the two protein domains with adjacent sugar rings stacking against the equivalent aromatic residues in the binding site of each protein molecule of the molecular sandwich. The sandwiching of an oligosaccharide chain between two protein modules, leading to ligand-induced formation of the binding site, represents a completely novel mechanism for protein-carbohydrate recognition that may mimic that displayed by naturally dimeric protein-carbohydrate interactions.


Tropical saltmarshes are important to juvenile fiddler crabs but not as refuges from large predators or high temperatures.
Tropical saltmarshes' role as a refuge for macrofauna is poorly known. We tested the hypotheses that: i) there is an increase in abundance of early life-stages of fiddler crabs associated with an increase in vegetation density (thermal and/or predation refuge) and ii) predation are lower within saltmarsh vegetation. The abundance of early life-stages increased with both vegetation density and temperature. Megalopa and juveniles might be adapted or benefit from high temperatures found on tropical saltmarshes and thus do not need protection from it. Predation was higher in saltmarshes than in nearby non-vegetated areas, thus tropical saltmarshes can not be considered a refuge from relatively large predators for juveniles of fiddler crabs. Although not offering refuge against temperature and predation, tropical saltmarshes are important habitats for the recruitment of early life-stages of fiddler crabs. Future studies should consider the evaluation of tropical saltmarsh hydrodynamics in the settlement and permanence of juveniles.


A gene homologous to topoisomerase II in African swine fever virus.
A putative topoisomerase II gene of African swine fever virus was mapped using a degenerate oligonucleotide probe derived from a region highly conserved in type II topoisomerases. The gene is located within EcoRI fragments P and H of the African swine fever virus genome. Sequencing of this region has revealed a long open reading frame, designated P1192R, encoding a protein of 1192 amino acids, with a predicted molecular weight of 135,543. Open reading frame P1192R is transcribed late after infection into a 4.6-kb RNA. The deduced amino acid sequence of this open reading frame shares significant similarity with topoisomerase II sequences from different sources, with percentages of identity between 23 and 29%. The evolutionary relationships among the topoisomerase II sequences of ASF virus, eukaryotes and prokaryotes were analyzed and a phylogenetic tree was established. The tree indicates that the ASF virus topoisomerase II gene was present in the virus genome before protozoa, yeasts, and metazoa diverged.


[Rosacea fulminans, pyostomatitis and pyovulvitis in Crohn's disease: dapsone as key factor in combination therapy].
Rosacea fulminans (also known as pyoderma faciale) has been reported to occur in association with Crohn's disease. It is still unclear whether the papulopustules and confluent nodules of rosacea fulminans represent a manifestation of mucocutaneous Crohn's disease or whether this association is a mere coincidence. A 46-year-old woman presented with the spontaneous outbreak of rosacea fulminans and pyostomatitis/pyovulvitis. Complete remission of the mucocutaneous symptoms was achieved with 2 months combination therapy with methylprednisolone, isotretinoin and dapsone. The patient's Crohn's disease, already diagnosed for 3 years, did not flare during this period.


Long-Term Outcomes of Pediatric Meningioma Surgery: Single Center Experience with 23 Patients.
To evaluate the long-term outcomes and prognostic variables in a surgical cohort of pediatric meningiomas treated in a single institution. Medical records and follow-up notes of 23 pediatric patients aged < 18 years (12 male and 11 female; mean age on presentation, 13.1 ± 4.4 years) harboring 27 meningiomas operated between 1994 and 01/2019 at Hacettepe University Ihsan Dogramaci Children's Hospital were evaluated. One patient had neurofibromatosis (NF) type 1, and five patients had NF2. Tumors were most commonly located in the convexity (n=6) and parasagittal or falcine (n=6). Gross total resection was performed in 70.4% of cases. WHO grade I tumors accounted for 56% of all cases, whereas high-grade meningiomas accounted for 44% (33% grade II, 11% grade III). The mean follow-up duration was 10.3 ± 7.7 years. Three patients (13%) died during follow-up, and 76.2% of the patients had favorable outcome (Glasgow Outcome Scale > 3) during the last follow-up assessment. Ten patients (43.5%) had relapse. In univariate analysis, low histological grade (p=0.030) and gross total resection (p=0.024) were associated with favorable outcome. The 10-year overall survival rate was 86%. Meningiomas in the pediatric age group are surgically treatable tumors with fairly good outcomes. However, relapses are common even for low-grade tumors; therefore, long-term surveillance and aggressive treatment are needed.


Methylmercury chloride induces learning deficits in prenatally treated rats.
Methylmercury chloride (MMC) was given to pregnant rats on the 6th, 7th, 8th, and 9th day after conception in doses of 0.05 and 2.0 mg/kg/day. The female offspring of these animals were tested 90 days after birth for learning ability using operant conditioning procedures. The rats were kept at 90% of their normal body weight and trained in a lever-box to press a bar in order to obtain a food pellet. Significant differences in the acquisition speed became apparent when the ratio of bar presses to reward was increased in a classical contingency of differential reinforcement of high rates even at MMC-doses of 4 X 0.05 mg/kg. These differences were not found in the general motility level nor in motor coordination.


The absence of a functional relationship between ATM and BLM, the components of BASC, in DT40 cells.
Bloom syndrome (BS) and ataxia-telangiectasia (A-T) are rare autosomal recessive diseases associated with chromosomal instability. The genes responsible for BS and A-T have been identified as BLM and ATM, respectively, whose products were recently found to be components of BRCA1-associated genome surveillance complex (BASC), a supercomplex possibly involved in the recognition and repair of aberrant DNA structures. Based on experiments using BLM(-/-) DT40 cells and BLM(-/-)/RAD54(-/-) DT40 cells, we previously suggested that BLM functions to reduce the formation of double-strand breaks (DSBs) during DNA replication. To examine whether ATM is involved in the recognition and/or repair of DSBs generated in BLM(-/-) DT40 cells and to address the functional relationship between the two BASC components, we generated BLM(-/-)/ATM(-/-) DT40 cells and characterized their properties as well as those of ATM(-/-) and BLM(-/-) DT40 cells. BLM(-/-)/ATM(-/-) cells proliferated slightly more slowly than either BLM(-/-) or ATM(-/-) cells. The sensitivity of BLM(-/-)/ATM(-/-) cells to gamma-irradiation was similar to that of ATM(-/-) cells, while BLM(-/-) cells were slightly resistant to gamma-irradiation compared with wild-type cells. BLM(-/-) cells showed sensitivity to methyl methanesulfonate (MMS) and UV irradiation while ATM(-/-) cells did not show sensitivity to either agent. The sensitivity of BLM(-/-)/ATM(-/-) cells to MMS and UV was similar to that of BLM(-/-) cells. Disrupting the function of ATM reduced the targeted integration frequency in BLM(-/-) DT40 cells. However, a defect in ATM only slightly reduced the increased sister chromatid exchanges (SCEs) in BLM(-/-) DT40 cells.


Dermatologists and antibiotic prophylaxis: a survey.
Antibiotic prophylaxis is frequently used for the prevention of infection at a distant site such as the heart valve or prosthetic joint. However, there are no published data describing how dermatologists manage patients "at risk". The purpose of this study is to document prophylactic antibiotic use by dermatologists. A total of 211 randomly selected community dermatologists and 69 academic dermatologic surgeons were surveyed by questionnaire to determine whether they would provide antibiotic prophylaxis in 20 different clinical situations. This survey showed that under certain circumstances, almost all dermatologists provide antibiotic prophylaxis to prevent infection at a distant site. However, many dermatologists use antibiotics in settings with relatively little or no indication and confuse a prophylactic regimen with treatment of a superficial infection. This survey underscores the need for education and research into the prophylactic management of patients "at risk" who undergo dermatologic surgical procedures.


The excessive use of inhaled corticosteroids in chronic obstructive pulmonary disease.
Despite the fact that the recommendations of the main clinical guidelines have restricted the indications for inhaled corticosteroids in chronic obstructive pulmonary disease (COPD), currently more than 80% of patients are receiving this treatment in Spain, mostly with high doses. A detailed review of the literature does not justify the use of these high doses, a position that agrees with the recommendations of the FDA. A re-evaluation of their safety, the consistency of the data on their efficacy showing similar results with moderate doses and a better patient selection require the use of this treatment in COPD patients to be reconsidered.


OPLC and AMD, recent techniques of planar chromatography: their interest for separation and characterization of extractive and synthetic compounds.
It is always important for the chemist to have good methods of separation, characterization and quantitative evaluation for one or several compounds resulting from a chemical reaction or an extraction procedure. In this domain the chromatographic techniques are choice methods, in particular Over Pressured Layer Chromatography (OPLC) and Automated Multiple Development (AMD). They are relatively recent methods whose use is unfortunately not yet generalized although they give very clean separation. In this paper we present numerous examples of the use of these two new types of planar chromatographies and especially the results we have obtained in the field of natural products on a wide variety of different structures: coumarins, flavonoids, anthocyanins, alkaloids and essential oils.


Spontaneous tumors in NMRI mice from carcinogenicity studies.
Twelve carcinogenicity experiments in NMRI mice from two different breeders were started at three different locations between 1974 and 1979. Tumors occurring in untreated control mice were compiled on the basis of histopathological reports. Of the 629 male and 627 female mice at the beginning of the studies, 614 males and 591 females were evaluated. The remaining animals were unavailable due to autolysis. The histopathologic diagnoses were performed by a team of 5 pathologists. A total of 1,220 tumors was seen (585 in males and 635 in females), of which 527 were classified as malignant (218 in males and 309 in females). About 56% of all tumors were located in the lungs and lymphoreticular system (LRS). Average frequencies of primary tumors: lungs 28.7%, LRS 28.2%, ovaries 21.3%, uterus 4.6%, vascular tissue 4.5%, mammary glands 3.9%, liver 3.2%, Harderian glands 3.2%, testes 3.1%, adrenals 3.1%, stomach 2.9%, pituitary 2.2%, endocrine pancreas 1.2%, thyroid 1.0%, Cowper's glands 1.0% and various other organs having tumor frequencies of less than 1%. This wide spectrum of spontaneous tumors with comparatively low frequencies renders NMRI mice a suitable strain for carcinogenicity studies. Male animals exhibited strikingly more tumors of the lungs, liver, Harderian glands, adrenals, endocrine pancreas and intestine, while LRS and pituitary tumors were predominant in females. Some tumor frequencies seem to be influenced by different husbandry conditions and different stocks. However, even under nearly identical husbandry conditions, the general frequency of benign and/or malignant tumors and of particular tumors varied markedly from one study to the next. Differences in mortality among studies had no pronounced effect on the range of tumor frequencies. Due to this biological variability in animal material, an interpretation of tumor frequencies in carcinogenicity studies necessitates an in-depth knowledge of the variability of tumor data for this mouse strain under similar husbandry conditions.


[Percutaneous biliary and gallbladder interventions].
Percutaneous transhepatic biliary and gall bladder interventions play an important role in the diagnosis and therapy of biliary tract diseases. With technical success rates up to 99% as well as complications rates up to a maximum of 26% they showed good results. Indications were opacification of the biliary tree as well as treatment of biliary system pathologies, such as drainage and stents. Interventions were used if endoscopic approaches are not possible or exploited. We describe the current state of knowledge and the range for percutaneous biliary/gall bladder interventions and give an overview of technical approaches for fundamental interventional procedures, including percutaneous transhepatic biliary drainage. Percutaneous transhepatic biliary and gall bladder interventions are safe and effective treatments for benign and malignant stenosis, postoperative complications and risk patients with cholecystitis.


[Radiogenic amyotrophy. Cauda equina lesion as a late radiation sequela].
Course and pathophysiology of a typical syndrome after irradiation of the cauda equina were studied. 7 patients with irradiation damage of the cauda equina were examined clinically and neurophysiologically. After a mean delay of 5 years and 6 months all patients developed an ascending lower motor neuron weakness of the legs without pain, in part accompanied with mild sensory and sphincter symptoms. Electromyography, evoked potentials and neurography were important for the differential diagnosis to tumor infiltration. The course was progredient. For a long time, the underlaying damage was thought to be in the anterior horn cell body. The course of the studied patients with additional sensory and vegetative symptoms implies for a direct bilateral damage of the cauda equina. A better term for the syndrome is "post-irradiation cauda-equina-syndrome".


[T lymphocytes from patients with Hodgkin's disease suppress erythroid progenitor growth from autologous marrow].
The effect of peripheral blood T lymphocytes from 42 patients with advanced Hodgkin's disease (grade III and IV) on the autologous marrow erythroid colony formation was studied in diffusion chamber culture. It was found, that unfractionated T lymphocytes suppress the BFU-E--(burst forming unit erythroid) and CFU-E--(colony forming unit erythroid)--derived colony formation by releasing an inhibitory activity. The suppression of colony formation was noted already at 0.25 x 10(5) cell concentration. In experiments with 0.5 x 10(5) and 1.0 x 10(5) T cells the inhibitory effect was increased. Subsequently it was shown, that this inhibition was generated by radioresistant, CD8+ and HLA-DR- subset of T cells. In control experiments, T lymphocytes from healthy subjects had no influence on the erythroid colony formation.


Leek-derived codoped carbon dots as efficient fluorescent probes for dichlorvos sensitive detection and cell multicolor imaging.
A biomass nitrogen and sulfur codoped carbon dots (NS-Cdots) was prepared by a simple and clean hydrothermal method using leek, and was employed as efficient fluorescent probes for sensitive detection of organophosphorus pesticides (OPs). The leek-derived NS-Cdots emitted blue fluorescence, but was quenched by H2O2. Due to acetylcholinesterase/choline oxidase-based cascade enzymatic reaction that produces H2O2 and the inhibition effect of OPs on acetylcholinesterase activity, a NS-Cdots-based fluorescence "off-on" method to detect OPs-dichlorvos (DDVP) was developed. More sensitivity and wider linear detection range were achieved from 1.0 × 10-9 to 1.0 × 10-3 M (limit of detection = 5.0 × 10-10 M). This developed method was applied to the detection of DDVP in Chinese cabbage successfully. The average recoveries were in the range of 96.0~104.0% with a relative standard deviation of less than 3.3%. In addition, the NS-Cdots fluorescent probes were also employed successfully in multicolor imaging of living cells, manifesting that the NS-Cdots fluorescent probes have great application potential in agricultural and biomedical fields. Graphical Abstract.


Convergence angles and margin widths of tooth preparations by New Zealand dental students.
Fundamental crown preparation principles are taught and are highly regarded in dental education. Whether tooth preparations made by dental students match these principles is unclear. The purpose of this retrospective study was to report the total occlusal convergence (TOC) and margin widths of crown preparations clinically prepared by New Zealand predoctoral dental students between 2013 and mid-2015. A total of 371 stereolithography files of tooth preparations for metal ceramic crowns prepared by predoctoral dental students were extracted from the Technical Services Laboratory database at the University of Otago. The files were put through the preparation measuring software Preppr, with outputs being TOC angles in faciolingual and mesiodistal cross sections and margin widths in facial, lingual, distal, and mesial aspects. Means, standard deviations, 95% confidence intervals, and distributions using box and whisker graphs were calculated and presented. The majority of TOC angles fell within an acceptable range of 10 to 20 degrees; however, the angles ranged from undercuts (<0 degrees) to >60 degrees. The majority of margin widths were between 0.5 and 1 mm, while the maximum was approximately 2 mm and the minimum was 0 mm. Predoctoral dental students in New Zealand are able to produce literature-recommended TOC angles and margin widths for metal ceramic crowns; however, further attention and training are needed for excessive tooth preparations, mainly in the form of large TOC angles.


Immunohistochemical demonstration of the small GTPase RhoA on epoxy-resin embedded sections.
The purpose of the present study was to establish a method for light microscopical immunohistochemical localization of the small G protein RhoA on specimens treated and embedded for routine transmission electron microscopy. There are advantages in antigen immunolocalization on resin semi-thin sections compared to cryostat or paraffin sections: the preservation of morphological details, the well-defined immunoprecipitate localization and the possibility to correlate the immunohistochemical results with those obtained by electron microscope on neighbouring sections. These advantages are particularly useful for the subcellular localization of low molecular weight proteins such as RhoA, a small G protein able to cycle from the inactive cytoplasmic form to the plasma membrane-bound active form.


Association of socio-economic status and ethnicity with mortality and morbidity of premature infants admitted to neonatal intensive care in South Auckland, New Zealand.
Socio-economic status (SES) and ethnicity have been associated with worse maternal and fetal outcomes. Counties Manukau is a region of New Zealand which has a high portion of the population living in areas of low SES and has a higher population of ethnic minorities (Pacific Islander, Asian and Maaori). To determine whether SES and ethnicity are associated with worse mortality and morbidity in preterm infants in Counties Manukau Hospital, New Zealand. This retrospective cohort study compared the infants of mothers who live in the most deprived neighbourhoods to the infants of mothers who live in the least deprived neighbourhoods. Infants born between 2000 and 2019 were included if <30 weeks gestation or <1500 g and born in hospital. Primary outcome was combined mortality/morbidity. Univariate analysis showed demographic differences between the SES and ethnic groups, for example maternal age and maternal smoking. Using logistic regression, SES was not associated with worse neonatal outcomes for the most deprived SES (n = 624) compared to least deprived SES (n = 164). Ethnicity (n = 1326) was not associated with worse neonatal outcomes. Gestational age and maternal smoking were associated with neonatal mortality/morbidity; gestational age and antenatal steroids were associated with neonatal mortality. It was notable that the proportion of the study population in the less deprived groups used for the comparisons was relatively low. For preterm, in-hospital births in Counties Manukau over a 20-year period, neonatal outcomes were the same regardless of SES or ethnicity.


Activity and action pattern of Bacillus licheniformis alpha-amylase in aqueous ethanol.
A purified B. licheniformis alpha-amylase in a mixture of ethanol-aqueous buffer (1:1, v/v) retains half the activity shown in water alone. In ethanol-aqueous buffer (7:3, v/v) about 20% of the activity is retained. The pattern of oligosaccharides produced from amylose changed with ethanol concentration; in aqueous buffer the products are: DP 1 and 2, 33.7%; DP 3, 28.5%; DP 4, 4.4% and DP 5, 33.4%. Whereas in ethanol-aqueous buffer (7:3, v/v) the products are DP 1 and 2, 66.8%; DP 3, 17.3%; DP 4, 4.1% and DP 5, 11.8%. These results suggest that a change in substrate affinity at the active centre subsites is induced in the ethanol-aqueous buffer medium.


DNA damage induces reactive oxygen species generation through the H2AX-Nox1/Rac1 pathway.
The DNA damage response (DDR) cascade and ROS (reactive oxygen species) signaling are both involved in the induction of cell death after DNA damage, but a mechanistic link between these two pathways has not been clearly elucidated. This study demonstrates that ROS induction after treatment of cells with neocarzinostatin (NCS), an ionizing radiation mimetic, is at least partly mediated by increasing histone H2AX. Increased levels of ROS and cell death induced by H2AX overexpression alone or DNA damage leading to H2AX accumulation are reduced by treating cells with the antioxidant N-Acetyl-L-Cysteine (NAC), the NADP(H) oxidase (Nox) inhibitor DPI, expression of Rac1N17, and knockdown of Nox1, but not Nox4, indicating that induction of ROS by H2AX is mediated through Nox1 and Rac1 GTPase. H2AX increases Nox1 activity partly by reducing the interaction between a Nox1 activator NOXA1 and its inhibitor 14-3-3zeta. These results point to a novel role of histone H2AX that regulates Nox1-mediated ROS generation after DNA damage.


Effect of protein intake and urea on sodium excretion during inappropriate antidiuresis in rats.
Administration of urea to patients with the syndrome of inappropriate antidiuresis (SIAD) is thought to ameliorate hyponatremia by both producing an osmotic diuresis and diminishing ongoing natriuresis. The present study evaluated these effects in a rat model of SIAD utilizing dilutional hyponatremia induced by continuous infusion of 1-deamino-[8-D-arginine] vasopressin. Following 48 hours of sustained hyponatremia, separate groups of rats were then refed with either: (1) 5% dextrose alone, (2) a 20% protein chow, (3) an isocaloric protein deficient (0%) chow, or (4) the isocaloric protein-deficient chow supplemented with oral urea. Our results demonstrate that rats refed a 20% protein diet significantly improved their plasma [Na+] as compared to rats refed protein deficient diets, and this improvement was accompanied by decreases in natriuresis despite an increased glomerular filtration rate and an unchanged negative free water clearance. Identical effects were observed in rats refed a protein deficient diet but supplemented with oral urea, suggesting that urea generation from catabolism of dietary protein is responsible for the effect of protein refeeding to decrease urinary sodium excretion. Both the protein and urea refed rats had significantly higher inner medullary urea contents and concentrations compared to rats refed protein-deficient diets and also to rats studied immediately before protein refeeding, supporting the hypothesis that urea and dietary protein decrease natriuresis in patients with SIAD in association with increased inner medullary urea concentrations.


Artificial intelligence (AI) vs. human in hip fracture detection.
This study aimed to assess the diagnostic accuracy and sensitivity of a YOLOv4-tiny AI model for detecting and classifying hip fractures types. In this retrospective study, a dataset of 1000 hip and pelvic radiographs was divided into a training set consisting of 450 fracture and 450 normal images (900 images total) and a testing set consisting of 50 fracture and 50 normal images (100 images total). The training set images were each manually augmented with a bounding box drawn around each hip, and each bounding box was manually labeled either (1) normal, (2) femoral neck fracture, (3) intertrochanteric fracture, or (4) subtrochanteric fracture. Next, a deep convolutional neural network YOLOv4-tiny AI model was trained using the augmented training set images, and then model performance was evaluated with the testing set images. Human doctors then evaluated the same testing set images, and the performances of the model and doctors were compared. The testing set contained no crossover data. The resulting output images revealed that the AI model produced bounding boxes around each hip region and classified the fracture and normal hip regions with a sensitivity of 96.2%, specificity of 94.6%, and an accuracy of 95%. The human doctors performed with a sensitivity ranging from 69.2 to 96.2%. Compared with human doctors, the detection rate sensitivity of the model was significantly better than a general practitioner and first-year residents and equivalent to specialist doctors. This model showed hip fracture detection sensitivity comparable to well-trained radiologists and orthopedists and classified hip fractures highly accurately.


Myocardial contractile reserve predicts left ventricular reverse remodeling and cardiac events in dilated cardiomyopathy.
Catecholamine sensitivity estimated using a dobutamine stress test (DST) is recognized as a measure of the beta-adrenergic myocardial contractile reserve, which is involved with left ventricular reverse remodeling (LV-RR). We investigated whether the prognostic ability of the DST for LV-RR could predict cardiac events. There was a total of 192 enrolled patients with dilated cardiomyopathy (DCM). DCM was defined as a LV ejection fraction (LV-EF) ≤45% and LV end-diastolic dimension (LVDd) ≥55mm. One hundred patients were subjected to micromanometer-based measurement of the maximal first derivative of LV pressure (LVdP/dtmax), an index of LV contractility, at baseline and following the infusion of dobutamine (10μg/kg/min) via a pigtail catheter. Percentage changes in LVdP/dtmax from the baseline to peak values under dobutamine stress (ΔLVdP/dtmax) were also calculated. After excluding 17 patients who received cardiac resynchronization therapy within 3 months of undergoing DST (n=15) and who did not receive follow-up echocardiography (n=2), 83 patients were enrolled (52.5±12.3 years). During the follow-up period (4.7±2.6 years), LV-RR was recognized in 49 of 83 patients (59.0%). A multivariate logistic regression analysis revealed that ΔLVdP/dtmax (hazard ratio: 1.024, p=0.007) and the symptom duration (hazard ratio: 0.977, p=0.003) were independent predictors of LV-RR. A receiver operating characteristic curve analysis revealed a ΔLVdP/dtmax cut-off value of 75.1% for LV-RR and a significantly lower cardiac event rate in the ΔLVdP/dtmax≥75.1% group (p=0.045). ΔLVdP/dtmax estimated using DST was a useful predictor of LV-RR and cardiac events in patients with DCM.


Probing conformational landscapes of binding and allostery in the SARS-CoV-2 omicron variant complexes using microsecond atomistic simulations and perturbation-based profiling approaches: hidden role of omicron mutations as modulators of allosteric signaling and epistatic relationships.
In this study, we systematically examine the conformational dynamics, binding and allosteric communications in the Omicron BA.1, BA.2, BA.3 and BA.4/BA.5 spike protein complexes with the ACE2 host receptor using molecular dynamics simulations and perturbation-based network profiling approaches. Microsecond atomistic simulations provided a detailed characterization of the conformational landscapes and revealed the increased thermodynamic stabilization of the BA.2 variant which can be contrasted with the BA.4/BA.5 variants inducing a significant mobility of the complexes. Using the dynamics-based mutational scanning of spike residues, we identified structural stability and binding affinity hotspots in the Omicron complexes. Perturbation response scanning and network-based mutational profiling approaches probed the effect of the Omicron mutations on allosteric interactions and communications in the complexes. The results of this analysis revealed specific roles of Omicron mutations as conformationally plastic and evolutionary adaptable modulators of binding and allostery which are coupled to the major regulatory positions through interaction networks. Through perturbation network scanning of allosteric residue potentials in the Omicron variant complexes performed in the background of the original strain, we characterized regions of epistatic couplings that are centered around the binding affinity hotspots N501Y and Q498R. Our results dissected the vital role of these epistatic centers in regulating protein stability, efficient ACE2 binding and allostery which allows for accumulation of multiple Omicron immune escape mutations at other sites. Through integrative computational approaches, this study provides a systematic analysis of the effects of Omicron mutations on thermodynamics, binding and allosteric signaling in the complexes with ACE2 receptor.


Cotransplantation of ex vivo expanded and unexpanded cord blood units in immunodeficient mice using insulin growth factor binding protein-2-augmented mesenchymal cell cocultures.
Ex vivo expansion of cord blood (CB) hematopoietic stem cells and cotransplantation of 2 CB units (CBUs) could enhance the applicability of CB transplantation in adult patients. We report an immunodeficient mouse model for cotransplantation of ex vivo expanded and unexpanded human CB, showing enhanced CB engraftment and provide proof of concept for this transplantation strategy as a means of overcoming the limiting cell numbers in each CBU. CBUs were expanded in serum-free medium supplemented with stem cell factor, Flt-3 ligand, thrombopoietin, and insulin growth factor binding protein-2 together with mesenchymal stromal cell coculture. Unexpanded and expanded CB cells were cotransplanted by tail vein injection into 45 sublethally irradiated nonobese diabetic SCID-IL2γ(-/-) (NSG) mice. Submandibular bleeding was performed monthly, and mice were sacrificed 4 months after transplantation to analyze for human hematopoietic engraftment. Expansion of non-CD34(+) selected CB cells yielded 40-fold expansion of CD34(+) cells and 3.1-fold expansion of hematopoietic stem cells based on limiting dilution analysis of NSG engraftment. Mice receiving expanded grafts exhibited 4.30% human cell repopulation, compared with 0.92% in mice receiving only unexpanded grafts at equivalent starting cell doses, even though the unexpanded graft predominated in long-term hematopoiesis (P = .07). Ex vivo expanded grafts with lower initiating cell doses also showed equivalent engraftment to unexpanded grafts with higher cell dose (8.0% versus 7.9%; P = .93). In conclusion, ex vivo expansion resulted in enhanced CB engraftment despite eventual rejection by the unexpanded CBU.


Urolithin A augments angiogenic pathways in skeletal muscle by bolstering NAD+ and SIRT1.
Urolithin A (UA) is a natural compound that is known to improve muscle function. In this work we sought to evaluate the effect of UA on muscle angiogenesis and identify the underlying molecular mechanisms. C57BL/6 mice were administered with UA (10 mg/body weight) for 12-16 weeks. ATP levels and NAD+ levels were measured using in vivo 31P NMR and HPLC, respectively. UA significantly increased ATP and NAD+ levels in mice skeletal muscle. Unbiased transcriptomics analysis followed by Ingenuity Pathway Analysis (IPA) revealed upregulation of angiogenic pathways upon UA supplementation in murine muscle. The expression of the differentially regulated genes were validated using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Angiogenic markers such as VEGFA and CDH5 which were blunted in skeletal muscles of 28 week old mice were found to be upregulated upon UA supplementation. Such augmentation of skeletal muscle vascularization was found to be bolstered via Silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor-gamma coactivator-1-alpha (PGC-1α) pathway. Inhibition of SIRT1 by selisistat EX527 blunted UA-induced angiogenic markers in C2C12 cells. Thus this work provides maiden evidence demonstrating that UA supplementation bolsters skeletal muscle ATP and NAD+ levels causing upregulated angiogenic pathways via a SIRT1-PGC-1α pathway.


Effect of the stop-signal modality on brain electrical activity associated with suppression of ongoing actions.
To clarify how the modality of stop signals affects the ability to suppress ongoing actions, we compared behavioural indices and event-related potentials (ERPs) recorded in healthy volunteers performing visual and auditory stop-signal tasks. Auditory stop signals were associated with faster reaction times and shorter stop-N2 and stop-P3 latencies. Given that the tasks did not differ in attentional/arousal processes (go-P3 or stop-P3 amplitudes) or motor preparation (LRP amplitude, onset or latency), our results suggest that stop signal modality mainly affects bottom-up sensory processes (faster auditory processing). The ERP waveform obtained by subtracting successfully stopped from unsuccessfully stopped trials showed similar amplitude and topography in both tasks, indicating that the strength of top-down processes related to inhibition was independent of modality. The findings contribute further knowledge about the variables associated with efficient inhibition and have practical implications for the design of settings or interventions to improve reactive inhibition.


Tailoring the EHR for quality.
Shifting to ICD-10 is more important than ever before. Further delay will hinder how rapidly health care organizations can respond to the changing environment.


Oculo-auriculo-vertebral syndrome (Goldenhar's syndrome).
Oculo-auriculo-vertebral syndrome (Goldenhar's syndrome) was found in a 10-month-old boy who had epibulbar dermoids, colobomata, pre-auricular skin tags, and hypomandibulosis.


The codon-optimized Δ(6)-desaturase gene of Pythium sp. as an empowering tool for engineering n3/n6 polyunsaturated fatty acid biosynthesis.
The ∆(6)-desaturase gene, encoding a key enzyme in the biosynthesis of polyunsaturated fatty acids, has potential in pharmaceutical and nutraceutical applications. The ∆(6)-desaturase gene has been isolated from a selected strain of Oomycetes, Pythium sp. BCC53698. The cloned gene (PyDes6) contained an open reading frame (ORF) of 1401 bp encoding 466 amino acid residues. The deduced amino acid sequence shared a high similarity to those of other ∆(6)-desaturases that contained the signature features of a membrane-bound ∆(6)-desaturase, including a cytochrome b 5 and three histidine-rich motifs and membrane-spanning regions. Heterologous expression in Saccharomyces cerevisiae showed that monoene, diene and triene fatty acids having ∆(9)-double bond were substrates for PyDes6. No distinct preference between the n-3 and n-6 polyunsaturated fatty acyl substrates was found. The ∆(6)-desaturated products were markedly increased by codon optimization of PyDes6. The codon-optimized ∆(6)-desaturase gene generated in this study is a promising tool for further reconstitution of the fatty acid profile, in a host system of choice, for the production of economically important fatty acids, particularly the n-3 and n-6 polyunsaturated fatty acids.


Does the first hour of continuous electroencephalography predict neonatal seizures?
Prolonged continuous video-electroencephalography (cEEG) is recommended for neonates at risk of seizures. The cost and expertise required to provide a real-time response to detected seizures often limits its utility. We hypothesised that the first hour of cEEG could predict subsequent seizures. Retrospective multicentre diagnostic accuracy study. 266 term neonates at risk of seizure or with suspected seizures. The first hour of cEEG was graded by expert and novice interpreters as normal, mildly, moderately or severely abnormal; seizures were identified. Association between abnormalities in the first hour of cEEG and the presence of seizures during total cEEG monitoring. 50/98 (51%) of neonates who developed seizures had their first seizure in the first hour of cEEG monitoring. The 'time-to-event' risk of seizure from 0 to 96 hours was 0.38 (95% CI 0.32 to 0.44) while the risk in the first hour was 0.19 (95% CI 0.15 to 0.24). cEEG background was normal in 48% of neonates, mildly abnormal in 30%, moderately abnormal in 13% and severely abnormal in 9%. Inter-rater agreement for determination of background was very good (weighted kappa=0.81, 95% CI 0.72 to 0.91). When neonates with seizures during the first hour were excluded, an abnormal background resulted in 2.4 times increased risk of seizures during the subsequent monitoring period (95% CI 1.3 to 4.4, p<0.003) while a severely abnormal background resulted in a sevenfold increased risk (95% CI 3.4 to 14.3, p<0.0001). The first hour of cEEG in at-risk neonates is useful in identifying and predicting whether seizures occur during cEEG monitoring up to 96 hours. This finding enables identification of high-risk neonates who require closer observation.


Reversal of itraconazole resistance in Sporothrix brasiliensis and Sporothrix schenckii by nonsteroidal anti-inflammatory drugs.
The emergence of resistant isolates has brought challenges to the treatment of sporotrichosis, prompting the search for new therapeutic strategies. Previous studies reported that nonsteroidal anti-inflammatory drugs (NSAIDs) show in vitro activity against several pathogenic fungi, including species of Candida, Cryptococcus, and Trichosporon. This study aimed to investigate the in vitro efficacy of three NSAIDs (acetylsalicylic acid, diclofenac sodium, and ibuprofen), alone and in combination with itraconazole, against eleven clinical isolates of Sporothrix brasiliensis and Sporothrix schenckii. Minimal inhibitory concentrations were determined by the broth microdilution method. Drug interactions and the fractional inhibitory concentration index of NSAIDs and itraconazole were assessed by the checkerboard method. When used alone, ibuprofen was the most active NSAID, followed by acetylsalicylic acid. Combinations of NSAIDs with itraconazole showed synergistic antifungal activity against nine isolates. It was also found that itraconazole combined with acetylsalicylic acid, diclofenac sodium, or ibuprofen, led to resistance reversal in two, three, and five of the six drug-resistant isolates, respectively. The results indicate that the combination of itraconazole and the evaluated NSAIDs are a promising strategy for the treatment of sporotrichosis.


The T-ACE questions: practical prenatal detection of risk-drinking.
Heavy maternal alcohol intake is a major perinatal risk but, unfortunately, is difficult for obstetricians and gynecologists to detect. To develop a brief questionnaire appropriate for office detection of "risk-drinking," that is, alcohol intake potentially sufficient to damage the fetus, defined here as greater than or equal to 1 ounce of absolute alcohol per day, we obtained a quantitative drinking history at the first prenatal visit from 971 consecutive gravid women who admitted ever having drunk alcohol. In addition, we administered the 25-question Michigan Alcoholism Screening Test and the four CAGE questions (C = cut down, A = annoyed, G = guilt, E = eye opener), a screening test previously unstudied in pregnancy, and sought evidence of tolerance to the inebriating effect of alcohol, a question which does not appear to trigger psychologic denial. The patient was considered tolerant if it took greater than 2 drinks to make her feel "high." Among 42 (4.3%) risk-drinkers and 929 women who did not report drinking at risk levels, four questions were found to contribute to reliably differentiating risk-drinkers from non-risk-drinkers (R2 = 14.6%, p less than 0.0001). The probability of risk-drinking increased from 1.5% for those responding negatively to 62.7% for those responding positively to all four questions (T = tolerance, A = annoyed, C = cut down, E = eye-opener; odds ratio = 109X). A simple scoring scheme (2 points for T and 1 each for A, C, or E, with a total score of greater than or equal to 2 considered positive) correctly identified 69% of the risk-drinkers (sensitivity) with a positive predictive value of 23%). The T-ACE questions take about 1 minute to ask and represent the first validated sensitive screen for risk-drinking appropriate for routine use in obstetric-gynecologic practice. If validated in further samples, broad application might contribute to better risk identification, secondary prevention efforts, and improved pregnancy outcomes for offspring at risk from heavy prenatal alcohol exposure.


Quantification of redox conditions in the nucleus.
Many nuclear proteins contain thiols, which undergo reversible oxidation and are critical for normal function. These proteins include enzymes, transport machinery, structural proteins, and transcription factors with conserved cysteine in zinc fingers and DNA-binding domains. Uncontrolled oxidation of these thiols causes dysfunction, and two major thiol-dependent antioxidant systems provided protection. The redox states of these systems, including the small redox active protein thioredoxin-1 (Trx1) and the abundant, low molecular weight thiol antioxidant glutathione (GSH), in nuclei provide means to quantify nuclear redox conditions. Redox measurements are obtained under conditions with excess thiol-reactive reagents. Here we describe a suite of methods to measure nuclear redox state, which include a redox Western blot technique to quantify the redox state of Trxl, a biotinylated iodoacetamide (BIAM) method for thioredoxin reductase-1 (TrxR1), GSH redox measurement using total protein S-glutathionylation, and a redox isotope-coded affinity tag (ICAT) method for measuring oxidation of specific cysteines in high-abundance nuclear proteins.


Reduction of the equilibrium binding of cardiac glycosides and related compounds to Na+,K+-ATPase as a possible mechanism for the potassium-induced reversal of their toxicity.
The influence of potassium ions on the equilibrium state of the binding of cardiac glycosides and their derivatives to partially purified dog heart and rat brain enzyme preparations was studied in vitro. The addition of potassium to the incubation mixture containing enzyme preparation, 3H-ouabain, Na+, Mg2+ and ATP, at the time when the binding reaction is close to equilibrium, caused an immediate reduction of the bound drug concentration; the concentration apparently shifting toward a lower equilibrium state. The degree of the potassium-induced reduction in bound drug concentration was dependent on the potassium concentration and on the chemical structure of the compound. The binding of aglycones, pentacetyl-gitoxin and cassaine was affected to a greater extent than that of the glycosides. These data suggest that one of the mechanisms by which potassium antagonizes the toxic actions of digitalis on the heart is to reduce the drug binding to cardiac Na+,K+-ATPase.


The ELF Honest Data Broker: informatics enabling public-private collaboration in a precompetitive arena.
New precompetitive ways of working in the pharmaceutical industry are driving the development of new informatics systems to enable their execution and management. The European Lead Factory (ELF) is a precompetitive, 30-partner collaboration between academic groups, small-medium enterprises and pharmaceutical companies created to discover small molecule hits against novel biological targets. A unique HTS screening and triage workflow has been developed to balance the intellectual property and scientific requirements of all the partners. Here, we describe the ELF Honest Data Broker, a cloud-based informatics system providing the scientific triage tools, fine-grained permissions and management tools required to implement the workflow.


Metacognitive training to reduce diagnostic errors: ready for prime time?
The accuracy of medical diagnosis is often degraded when diagnosis deviates from the principles of normative decision making. Although diagnostic errors can potentially be reduced by metacognitive training, that proposal (put forth by Croskerry in an accompanying article) needs validation and extensive exploration.


Polymeric nanoparticles for DNA vaccine-based cancer immunotherapy: a review.
Cancer is one of the leading causes of death and mortality in the world. There is an essential need to develop new drugs or therapeutic approaches to manage treatment-resistant cancers. Cancer immunotherapy is a type of cancer treatment that uses the power of the body's immune system to prevent, control, and eliminate cancer. One of the materials used as a vaccine in immunotherapy is DNA. The application of polymeric nanoparticles as carriers for DNA vaccines could be an effective therapeutic approach to activate immune responses and increase antigen presentation efficiency. Various materials have been used as polymeric nanoparticles, including: chitosan, poly (lactic-co-glycolic acid), Polyethylenimine, dendrimers, polypeptides, and polyesters. Application of these polymer nanoparticles has several advantages, including increased vaccine delivery, enhanced antigen presentation, adjuvant effects, and more sustainable induction of the immune system. Besides many clinical trials and commercial products that were developed based on polymer nanoparticles, there is still a need for more comprehensive studies to increase the DNA vaccine efficiency in cancer immunotherapy using this type of carrier.


Weight change affects serum leptin and corticosterone in the collared lemming.
The aim of this study was to determine whether photoperiod-induced changes in body and fat mass are accompanied by changes in leptin and corticosterone concentrations in collared lemmings. At weaning, eighty male lemmings were maintained in either long photoperiod (LD, n = 40 ) or short photoperiod (SD, n = 40 ). Ten weeks post-weaning lemmings were weighed and assigned to a secondary photoperiod that consisted of either remaining in the same photoperiod or being transferred to the alternate photoperiod (LD-LD, LD-SD, SD-SD, and SD-LD; n = 20 per group). Ten days post-switch, half the animals from each group were sacrificed. The remaining animals were sacrificed on day 21 post-switch. Blood was collected for determination of serum leptin and corticosterone, and carcasses were analyzed for body composition. LD-SD lemmings gained the most weight, whilst SD-LD lemmings lost weight. SD-LD lemmings had significantly lower leptin levels relative to fat mass than SD-SD lemmings. Corticosterone levels were higher in the SD-LD than SD-SD lemmings on both days 10 and 21. Levels were not significantly different between LD-LD and LD-SD lemmings; however by day 21 the levels were slightly lower in the LD-SD lemmings. Discussion. Lemmings showed seasonally appropriate body weight changes in response to the changing photoperiod. Weight loss was associated with higher corticosterone, and lower leptin levels adjusted for fat mass. Neither relative leptin levels, nor corticosterone levels changed significantly with weight gain. Our results indicate that corticosterone and leptin are associated more with seasonal weight loss than weight gain in lemmings.


Retracted: Sustainable Trend of Big Data in Enterprise Supply Chain Under the Artificial Intelligence Green Financial System.
[This retracts the article DOI: 10.1155/2022/3065435.].


Corneal ulceration associated with Nivolumab use.
To describe a case of corneal ulceration associated with Nivolumab use. An 80-year-old woman treated with Nivolumab for metastatic melanoma developed an intractable corneal ulcer in her left eye, refractory to all therapies - including surgery to cover the ulcer with a conjunctival flap - until topical prednisolone acetate was tried, which was curative. Nivolumab use may be associated with a form of steroid-responsive corneal ulceration.


ScaleS: an optical clearing palette for biological imaging.
Optical clearing methods facilitate deep biological imaging by mitigating light scattering in situ. Multi-scale high-resolution imaging requires preservation of tissue integrity for accurate signal reconstruction. However, existing clearing reagents contain chemical components that could compromise tissue structure, preventing reproducible anatomical and fluorescence signal stability. We developed ScaleS, a sorbitol-based optical clearing method that provides stable tissue preservation for immunochemical labeling and three-dimensional (3D) signal rendering. ScaleS permitted optical reconstructions of aged and diseased brain in Alzheimer's disease models, including mapping of 3D networks of amyloid plaques, neurons and microglia, and multi-scale tracking of single plaques by successive fluorescence and electron microscopy. Human clinical samples from Alzheimer's disease patients analyzed via reversible optical re-sectioning illuminated plaque pathogenesis in the z axis. Comparative benchmarking of contemporary clearing agents showed superior signal and structure preservation by ScaleS. These findings suggest that ScaleS is a simple and reproducible method for accurate visualization of biological tissue.


Prostate cancer: unmet supportive and palliative care needs: national survey of patients and family carers.
Men living with prostate cancer have supportive and palliative needs. However, few studies detail unmet needs (vs quality of life measurement) or include data from those with advanced disease. We aimed to identify unmet needs of people living with prostate cancer (men, family carers), including those with advanced disease. Mixed-methods national survey (patient Supportive Care Needs Survey; Carer Support Needs Assessment Tool) and health status (EuroQol Visual Analogue Scale). Quantitative data were explored using regression analysis. Free text data were subjected to thematic analysis. 216 men (mean age 65±8.5 years; active cancer 136 [63%]) and 97 carers (68 (70%) spouse/partner) provided data. 133 men (62%) reported moderate-to-high need which was more likely in advanced disease. Men's health status was worse with active vs remitted disease (mean difference -11; 95% CI -17 to -5; p<0.001). 85 (88%) carers reported at least one unmet need relating to 'enabling them to care' and 83 (86%) relating to 'their own well-being'. Carers with chronic illnesses had more unmet needs (p=0.01 to p=0.04) and patient receipt of palliative care independently predicted higher unmet carer needs (p=0.02).Free text data demonstrated widespread burden with: (1) poor communication/information, including about palliative care; (2) poorly managed symptoms/concerns and (3) poor care co-ordination. Incontinence, sexual dysfunction and hormone side-effects were serious problems, often left unaddressed. Many living with prostate cancer continue with wide-ranging concerns. Lack of systematic, ongoing needs assessment and poor communication compound inadequate clinical pathways. Person-centred care, interdisciplinary working and integrated palliative care should be resourced.


Indoor air quality guidelines from across the world: An appraisal considering energy saving, health, productivity, and comfort.
Buildings are constructed and operated to satisfy human needs and improve quality of life. Good indoor air quality (IAQ) and thermal comfort are prerequisites for human health and well-being. For their provision, buildings often rely on heating, ventilation, and air conditioning (HVAC) systems, which may lead to higher energy consumption. This directly impacts energy efficiency goals and the linked climate change considerations. The balance between energy use, optimum IAQ and thermal comfort calls for scientifically solid and well-established limit values for exposures experienced by building occupants in indoor spaces, including homes, schools, and offices. The present paper aims to appraise limit values for selected indoor pollutants reported in the scientific literature, and to present how they are handled in international and national guidelines and standards. The pollutants include carbon dioxide (CO2), formaldehyde (CH2O), particulate matter (PM), nitrogen dioxide (NO2), carbon monoxide (CO), and radon (Rn). Furthermore, acknowledging the particularly strong impact on energy use from HVAC, ventilation, indoor temperature (T), and relative humidity (RH) are also included, as they relate to both thermal comfort and the possibilities to avoid moisture related problems, such as mould growth and proliferation of house dust mites. Examples of national regulations for these parameters are presented, both in relation to human requirements in buildings and considering aspects related to energy saving. The work is based on the Indoor Environmental Quality (IEQ) guidelines database, which spans across countries and institutions, and aids in taking steps in the direction towards a more uniform guidance for values of indoor parameters. The database is coordinated by the Scientific and Technical Committee (STC) 34, as part of ISIAQ, the International Society of Indoor Air Quality and Climate.


Improving communication of breast cancer recurrence risk.
Doctors commonly use genomic testing for breast cancer recurrence risk. We sought to assess whether the standard genomic report provided to doctors is a good approach for communicating results to patients. During 2009-2010, we interviewed 133 patients with stages I or II, node-negative, hormone receptor-positive breast cancer and eligible for the Oncotype DX genomic test. In a randomized experiment, patients viewed six vignettes that presented hypothetical recurrence risk test results. Each vignette described a low, intermediate, or high chance of breast cancer recurrence in 10 years. Vignettes used one of five risk formats of increasing complexity that we derived from the standard report that accompanies the commercial assay or a sixth format that used an icon array. Among women who received the genomic recurrence risk test, 63% said their doctors showed them the standard report. The standard report format yielded among the most errors in identification of whether a result was low, intermediate, or high risk (i.e., the gist of the results), whereas a newly developed risk continuum format yielded the fewest errors (17% vs. 5%; OR 0.23; 95% CI 0.10-0.52). For high recurrence risk results presented in the standard format, women made errors 35% of the time. Women rated the standard report as one of the least understandable and least-liked formats, but they rated the risk continuum format as among the most understandable and most liked. Results differed little by health literacy, numeracy, prior receipt of genomic test results during clinical care, and actual genomic test results. The standard genomic recurrence risk report was more difficult for women to understand and interpret than the other formats. A less complex report, potentially including the risk continuum format, would be more effective in communicating test results to patients.


Dietary protein and energy requirements in ESRD patients.
The published reports of dietary protein and energy intake and protein and energy requirements for maintenance hemodialysis (MHD) patients and chronic peritoneal dialysis (CPD) patients are reviewed. Evidence indicates that the dietary energy intake of patients undergoing MHD or continuous ambulatory peritoneal dialysis (CAPD) is less than normal. Dietary protein intake in various surveys averages approximately 1.0 g/kg/d. The energy expenditure of MHD patients appears to be normal or slightly increased during resting and normal during various other daily activities. Energy expenditure in CAPD patients appears normal. Nitrogen balance and anthropometric studies in MHD or CAPD patients ingesting controlled diets in a metabolic unit research ward also indicate that dietary energy requirements are normal and are approximately 35 to 38 kcal/kg/d in MHD patients. For CAPD patients, total energy requirements (from diet and dialysate) also appear to be 35 to 38 kcal/kg/d. These recommended energy intakes are for adult patients aged approximately 60 years or younger. Thus, the low dietary energy intakes of MHD and CPD patients are maladaptive. Nitrogen balance studies indicate that a safe dietary allowance for protein is approximately 1.2 g/kg/d for MHD patients and 1.2 to 1.3 g/kg/d for CAPD patients. Because the nutritional status of patients at the onset of chronic dialysis therapy is a strong predictor of both their nutritional status during the course of chronic dialysis treatment and their subsequent morbidity and mortality, it is important to maintain good nutritional status in patients with chronic renal failure before their development of end-stage renal disease (ESRD) and establishment on chronic dialysis. Evidence indicates that there is a reduction in dietary protein and energy intake and a gradual deterioration of nutritional status in patients with chronic renal insufficiency as the glomerular filtration rate (GFR) decreases progressively to less than 50 to 60 mL/min/1.73 m2. More studies are needed to assess dietary protein and energy requirements both for MHD and CPD patients who are clinically stable and for those who have sustained comorbid conditions that increase energy expenditure or protein nitrogen appearance.


Predictive models on COVID 19: What Africans should do?
In this study, predictive models are proposed to accurately estimate the confirmed cases and deaths due to of Corona virus 2019 (COVID-19) in Africa. The study proposed the predictive models to determine the spatial and temporal pattern of COVID 19 in Africa. The result of the study has shown that the spatial and temporal pattern of the pandemic is varying across in the study area. The result has shown that cubic model is best outperforming compared to the other six families of exponentials ( R 2 = 0.996 , F = 538.334 , D F 1 = 3 , D F 1 = 7 , b 1 = 13691.949 , b 2 = - 824.701 , b 1 = 12.956 ) . The adopted cubic algorithm is more robust in predicting the confirmed cases and deaths due to COVID 19. The cubic algorithm is more superior to the state of the art of the works based on the world health organization data. This also entails the best way to mitigate the expansion of COVID 19 is through persistent and strict self-isolation. This pandemic will sustain to grow up, and peak to the highest for which a strong care and public health interventions practically implemented. It is highly recommended for Africans must go beyond theory preparations implementations practically through the public interventions.


A closed-loop multi-scale model for intrinsic frequency-dependent regulation of axonal growth.
This article develops a closed-loop multi-scale model for axon length regulation based on a frequency-dependent negative feedback mechanism. It builds on earlier models by linking molecular motor dynamics to signaling delays that then determine signal oscillation period. The signal oscillation is treated as a front end for a signaling pathway that modulates axonal length. This model is used to demonstrate the feasibility of such a mechanism and is tested against two previously published reports in which experimental manipulations were performed that resulted in axon growth. The model captures these observations and yields an expression for equilibrium axonal length. One major prediction of the model is that increasing motor density in the body of an axon results in axonal growth-this idea has not yet been explored experimentally.


Characterization of the 5'-flanking region of the human tartrate-resistant acid phosphatase (TRAP) gene.
Tartrate-resistant acid phosphatase (TRAP) is expressed at high levels in osteoclasts and may play an important role in the bone resorptive process. However, factors regulating human TRAP gene expression have not been clearly defined. Therefore, we isolated a genomic clone (CL-9) for TRAP containing a 14-kb insert. A restriction map was generated for this insert, and a 2.6-kb ApaI fragment containing the 5'-flanking region was subcloned. Sequence analysis of this fragment revealed the presence of candidate transcription factor-binding sequences for H-APF-1, SP1, GATA2, and the c-Myc proto-oncogene. PCR analysis of RNA isolated from human osteoclastomas and pagetic bone revealed a 276-bp intron at -1 bp to -276 bp relative to the ATG and a transcript originating from this intron. Rapid amplification of the 5' end of the human TRAP mRNA by PCR indicated the presence of a 93-bp untranslated region 5' from the intron. Promoter activity was detected in the DNA fragment from +1 bp to -1903 bp relative to the ATG initiation codon, which drove the transient expression of a luciferase reporter gene when transfected into HRE H9 rabbit endometrial cells. Comparison of the human TRAP 5'-flanking region with mouse TRAP and uteroferrin revealed 41% and 47% homology, respectively. This suggests that regulation of human TRAP gene expression may differ from that for the murine TRAP gene.


Removal of retained Foley catheter in bladder with novel use of ureteral catheter: lasso technique.
Numerous and varied foreign bodies have been described in the lower urinary tract. Techniques previously used to remove these objects have included open and endoscopic removal. We present a novel endoscopic technique using a ureteral catheter as a lasso to remove a retained foreign body, in this case a retained Foley catheter.


Foraging pattern of pine siskins and its influence on winter moth survival in an apple orchard.
Foraging by migratory pine siskins in an apple orchard infested with varying densities of winter moth was observed, and winter moth mortality in the presence and absence of birds was recorded. Time spent foraging in a tree and number of birds foraging per tree was positively related to larval density but number of larvae removed per leaf cluster or per unit time was not. Level of defoliation was a better predictor of the number of clusters searched per tree than was prey density. Despite poor predictability in allocation of search effort with respect to prey density, siskins acted as a source of strong compensatory mortality on the winter moth population.


The cerebral palsies in Western Australia: trends, 1968 to 1981.
Data were analyzed from all cases of cerebral palsy in a population-based register in Western Australia. The number of cases of cerebral palsy diagnosed by age 5 years varied little among cohorts of infants born between 1960 and 1982. Trends toward more intensive perinatal care, increasing frequency of cesarean section, and the increased use of electronic fetal monitoring to detect fetal distress were associated with decreases in perinatal mortality but not in cerebral palsy. The increase in survival of low birth weight infants has resulted in an increased number of children with cerebral palsy, but this has had a minimal impact on total cerebral palsy rates. These descriptive trends raise doubts about the relationship between cerebral palsy and perinatal events, the effects of obstetric and neonatal interventions in reducing cerebral palsy, and the use of cerebral palsy data as an index of perinatal care practices.


A novel benzofuran, 4-methoxybenzofuran-5-carboxamide, from Tephrosia purpurea suppressed histamine H1 receptor gene expression through a protein kinase C-δ-dependent signaling pathway.
Histamine H1 receptor (H1R) gene is upregulated in patients with allergic rhinitis (AR), and its expression level is strongly correlated with the severity of allergic symptoms. We previously reported isolation of the putative anti-allergic compound, 4-methoxybenzofuran-5-carboxamide (MBCA) from Tephrosia purpurea and its chemical synthesis (Shill et al., Bioorg Med Chem 2015;23:6869-6874). However, the mechanism underlying its anti-allergic activity remains to be elucidated. Here, we report the mechanism of MBCA on phorbol 12-myristate-13-acetate (PMA)- or histamine-induced upregulation of H1R gene expression in HeLa cells, and in vivo effects of MBCA were also determined in toluene-2,4-diisocyanate (TDI)-sensitized rats. MBCA suppressed PMA- and histamine-induced upregulation of H1R expression at both mRNA and protein levels and inhibited PMA-induced phosphorylation of PKCδ at Tyr(311) and subsequent translocation to the Golgi. Furthermore, MBCA ameliorated allergic symptoms and suppressed the elevation of H1R and helper T cell type 2 (Th2) cytokine mRNAs in TDI-sensitized rats. Data suggest that MBCA alleviates nasal symptoms in TDI-sensitized rats through the inhibition of H1R and Th2 cytokine gene expression. The mechanism of its H1R gene suppression underlies the inhibition of PKCδ activation.


Inhibitors of the renin-angiotensin system in experimental hypertension, with a note on the measurement of angiotensin I, II and III during infusion of converting-enzyme inhibitor.
1 Prolonged infusion (11 h) of both saralasin and angiotensin-converting enzyme inhibitor (SQ20881) gradually lowered BP in two-kidney hypertensive rats to levels similar to that in normotensive rats infused with dextrose. 2 Saralasin did not lower BP in DOCA-salt hypertensive rats. 3 These observations support the notion that in chronic renal hypertension, angiotensin II may maintain hypertension by a slowly developing action. 4 Plasma angiotensin II in rats infused with SQ20881 was suppressed relative to renin, but was not eliminated. 5 Chromatography of angiotensin II extracts from dogs infused with converting enzyme inhibitor (SQ14,225) showed that the very high levels of angiotensin I achieved after treatment with SQ14,225 can lead to falsely high estimated angiotensin II levels as a result of angiotensin I cross-reacting with the angiotensin II assay.


Duration of Hospitalization in Association with Type of Inhalation Therapy Used in the Management of Children with Nonsevere, Acute Bronchiolitis.
Acute bronchiolitis is one of the main respiratory emergencies in young children. Although supportive therapy is recommended, substantial inconsistency in the clinical usage of inhaled treatments has been reported. In the present study, we evaluated the association between different types of nebulized therapies in clinical practice and the length of stay (LOS) of young children hospitalized with nonsevere bronchiolitis. Medical records of 195 patients with bronchiolitis, without evidence of pneumonia or congenital/chronic respiratory conditions, were stratified with respect to the type of inhalation therapy received: nebulized albuterol (Group 1, n = 53), nebulized albuterol with 3% saline (Group 2, n = 38), nebulized 3% saline alone (Group 3, n = 33), or no inhaled treatment (Group 4, n = 71). Duration of hospital stay was reported with respect to the type of inhalation therapy received after controlling for variability in patient age (months), oxygen saturation, respiratory score, and use of other treatments (antibiotics, oxygen supplementation, and/or corticosteroids). LOS is presented in terms of mean and 95% confidence interval (95% CI). The groups were similar except for differences in the mean level of oxygen saturation, respiratory score, and corticosteroid use. Children in Group 4 had the lowest mean respiratory score due to a lesser prevalence of wheezing and/or retractions than in other groups. The LOS for children in Groups 1 and 4 was shorter (43.2 hours, 95% CI 34.9-51.3, and 44.1 hours, 95% CI 37.3-51.0, respectively) than in Groups 2 and 3 (72 hours, 95% CI 62.1-81.6, and 65.1 hours, 95% CI 54.7-75.6, respectively) (p < 0.02). The mean LOS in each group did not change significantly after adjustment for covariants. Prolonged hospitalization of children younger than 2 years with acute, nonsevere bronchiolitis is associated with administration of nebulized 3% saline, independent of age, clinical presentation of disease, or inclusion of other treatments in their management.


LGP2 plays a critical role in MDA5-mediated antiviral activity against duck enteritis virus.
Duck viral enteritis (DEV) is a DNA virus that leads to heavy economic losses in the commercial duck industry. As a key cytoplasmic sensor, melanoma differentiation-associated gene 5 (MDA5) can recognize viral RNA and enhance the antiviral immune response. Retinoic acid-inducible gene-I (RIG-I) and MDA5 both belong to the RIG-I-like receptors family, and RIG-I is known to be involved in the anti-DEV signaling pathway. However, the role of MDA5 in DEV infection remains unclear. In this study, we used overexpression and knockdown methods to determine if MDA5 affected DEV infection in ducks. We confirmed that DEV infection was significantly suppressed in MDA5-overexpressing DEF cells, while knockdown of MDA5 by siRNA markedly enhanced DEV growth. We demonstrated that overexpression of duck MDA5 significantly upregulated expression of interferon (IFN)-stimulated genes, including myxovirus resistance protein (Mx), IFN-induced oligodenylate synthetase-like (OASL), IFN-induced transmembrane protein 1 (IFITM1) and IFN-β. In addition, the transcriptional level of MDA5 was upregulated both in vivo and in vitro upon DEV infection. We also showed that there was an association between MDA5 and laboratory of genetics and physiology 2 (LGP2) in antiviral signaling. LGP2 functioned as a concentration-dependent switch between MDA5-specific enhancement and interference. Overall, these findings indicated that MDA5 restricted DEV replication and LGP2 plays a critical role in MDA5-mediated antiviral activity against DEV.


[Dual localisation of ischaemic fasciitis with local relapse at one site].
Ischaemic fasciitis (IF) is a rare pseudosarcomatous proliferation initially described on the pressure points of long-term bedridden patients. Healing is the rule after surgical excision. No multifocal localisations have been reported to date. Herein, we describe the case of a patient with FI affecting two sites and having recurred at one of them. A 50-year-old woman with scoliosis and mental retardation consulted for a hard skin lesion next to her right scapula. Elastofibroma was diagnosed on the basis of a surgical biopsy sample. Early local recurrence led to a second resection four months later. Histologically, central fibrinoid necrosis was observed, surrounded by collagenous tissue containing occasionally atypical fibroblasts and numerous capillaries. The diagnosis of ischaemic fasciitis was made by a national expert. Six months later, we observed a 13-cm purplish erythematous infiltrated mass with a 6-cm ulceration at the surgical site. A second 6-cm non-ulcerated indurated purplish lesion was visible next to the right greater trochanter. The scan showed deep soft-tissue infiltration with subfascial extension and contact with the greater trochanter. Superficial biopsies of both lesions showed only an appearance of granulation tissue. MRI performed after five months showed an extension of lesions at the two sites with an appearance evocative of ischaemic fasciitis. Surgical excision was refused by the patient and her family. We report a rare case of ischaemic fasciitis at two separate sites with local relapse after surgical excision.


Oestrogen reporter transgenic medaka for non-invasive evaluation of aromatase activity.
Vertebrate reproduction involves complex steroid hormone interplay and inter-conversion. A critical element in maintaining sex steroid levels is the enzyme aromatase (cytochrome P450 19A1) which converts androgens to oestrogens. In turn oestrogen signalling is targeted by numerous chemicals, from pharmaceuticals to agricultural chemicals, both frequent sources of contamination in waste waters and consequently rivers. Although many models are now available to address disruption of oestrogen signalling, there are currently no published protocols allowing discrimination between alterations in testosterone metabolism and in oestrogenic signalling. It was with this limitation in mind that we optimised this protocol. We show using a 48h protocol that pre-feeding fry of the choriogenin h-gfp (chgh-gfp) medaka line are sensitive to 0.05nM EE2 (15ng/L), within the range of the lowest published observable physiological effect concentrations for medaka. In addition, co-treatment with testosterone can reveal potential effects of test substances on aromatase enzymatic activity. As the measurements are visualised in real-time without affecting embryo viability, repeated measures are possible. We demonstrate the ability of this model to detect oestrogen receptor agonists, aromatisable androgens, P450 aromatase activity modulators and selective oestrogen response modulators. Importantly, the range of this assay is physiologically relevant.


Longitudinal GP placements - inspiring tomorrow's doctors?
General practice worldwide is facing a severe recruitment crisis, with significantly fewer medical students choosing to pursue careers in primary care than are required to meet society's growing demands. The role of GP placements and GP tutors has been highlighted as having a significantly positive influence on medical students' perceptions of general practice. However, how students perceive these experiences to have influenced their subsequent career preferences remains poorly understood.We sought to explore how a longitudinal GP placement influences medical students' preferences regarding a career in general practice, in order to gain a deeper understanding of the significance of such placements. Semi-structured interviews were undertaken with five fourth-year medical students using Interpretive Phenomenological Analysis methodology.Four overarching concepts were identified, with nine superordinate themes, to describe how a longitudinal placement had influenced medical students' preference regarding a career in general practice. There appears to have been a matching process between an expanding knowledge of the realities of being a GP and an increasing understanding of self. The GP tutor and 'authentic' experiences to consult patients themselves developed a growing sense of self-efficacy within students, all of which resulted in a significant internal desire to become future GPs.


Powder diffraction computed tomography: a combined synchrotron and neutron study.
Diffraction and imaging using x-rays and neutrons are widely utilized in different fields of engineering, biology, chemistry and/or materials science. The additional information gained from the diffraction signal by x-ray diffraction and computed tomography (XRD-CT) can give this method a distinct advantage in materials science applications compared to classical tomography. Its active development over the last decade revealed structural details in a non-destructive way with unprecedented sensitivity. In the current contribution an attempt to adopt the well-established XRD-CT technique for neutron diffraction computed tomography (ND-CT) is reported. A specially designed 'phantom', an object displaying adaptable contrast sufficient for both XRD-CT and ND-CT, was used for method validation. The feasibility of ND-CT is demonstrated, and it is also shown that the ND-CT technique is capable to provide a non-destructive view into the interior of the 'phantom' delivering structural information consistent with a reference XRD-CT experiment.


Conflict amongst chloroplast DNA sequences obscures the phylogeny of a group of Asplenium ferns.
A previous study of the relationships amongst three subgroups of the Austral Asplenium ferns found conflicting signal between the two chloroplast loci investigated. Because organelle genomes like those of chloroplasts and mitochondria are thought to be non-recombining, with a single evolutionary history, we sequenced four additional chloroplast loci with the expectation that this would resolve these relationships. Instead, the conflict was only magnified. Although tree-building analyses favoured one of the three possible trees, one of the alternative trees actually had one more supporting site (six versus five) and received greater support in spectral and neighbor-net analyses. Simulations suggested that chance alone was unlikely to produce strong support for two of the possible trees and none for the third. Likelihood permutation tests indicated that the concatenated chloroplast sequence data appeared to have experienced recombination. However, recombination between the chloroplast genomes of different species would be highly atypical, and corollary supporting observations, like chloroplast heteroplasmy, are lacking. Wider taxon sampling clarified the composition of the Austral group, but the conflicting signal meant analyses (e.g., morphological evolution, biogeographic) conditional on a well-supported phylogeny could not be performed.


Racial/ethnic differences in US drug overdose mortality, 2017-2018.
The year 2018 marked the first year since 1999 in which the number of drug overdose deaths in the United States (US) declined compared to the previous year. However, it is unclear whether this decline was observed across all racial/ethnic groups. Death certificate data from the National Center for Health Statistics were examined for drug overdoses among US residents with a race and ethnicity specified (69,764 in 2017 and 66,949 in 2018). Age-specific and age-adjusted drug overdose mortality rates for 2017 and 2018 were compared by race/ethnicity, overall, by sex, and for overdoses involving stimulants. Percentages of overdose deaths involving specific drug combinations were computed by race/ethnicity. From 2017 to 2018, the age-adjusted drug overdose mortality rate significantly decreased in Non-Hispanic (NH) Whites; among Hispanics, in contrast, a significant increase was observed. Significant increases in drug overdose mortality rates from 2017 to 2018 were observed for NH Black males, Hispanic males, and NH Blacks aged 65 and older, as well as for overdoses involving psychostimulants (in all racial/ethnic groups) and cocaine (in NH Blacks and Hispanics). In 2018, the proportion of drug overdose deaths involving opioids ranged from 43.2% among NH Asian/Pacific Islanders to 70.8% among NH Whites, and the level of opioid co-involvement in stimulant-involved overdose deaths also varied by race/ethnicity. The continually-evolving US overdose crisis necessitates an evolving response, not only to address changes in the drug combinations most involved in overdose deaths, but also to strengthen interventions targeting racial/ethnic minority groups.


Temperature-dependent phenology of Campaea margaritaria (L) (Lepidoptera: Geometridae) derived from field data.
A new phenology model, using thermal sums of triangulated daily temperatures, was applied to the derivation and validation of lower temperature threshold limit and thermal constants of bivoltine Campaea margaritaria (L) from 70 observed flight peak days in The Netherlands (period of 1986-2020) and daily ambient air temperatures of 10 weather stations. Development was assumed to be controlled directly by temperature for the summer generation. During fall a diapause of young larvae was assumed and confirmed. A lower threshold limit of TL = 6.70 ± 0.06 °C was found and a mean thermal winter and summer generation constant of K1,m = 838 ± 9 and K2,m = 848 ± 6 °C.day, respectively, for the reference period of 1993-2013. Generation differences could not be explained with temperature-size rules in ectotherm organisms. Threshold limit and thermal constants depended slightly on the period of derivation indicating short-term plasticity. Flight peak days were calculated with root mean square errors of 2.2-3.0 days for both generations. Changing temperatures of the reference period led to temperature dependences of flight peak days of -6.4 and -8.7 day/°C of the winter and summer generation, respectively. Neglecting physiological changes a complete third generation would require an increase of 3.7 °C, a single generation a decrease of 4.1 °C.


The inflammatory milieu of amniotic fluid in acute-chorioamnionitis decreases with increasing gestational age.
The inflammatory milieu decreases in the placenta and amniotic fluid (AF) with gestational age (GA). However, there is no information about whether the inflammatory milieu of AF in the setting of the same placental inflammatory condition decreases with GA. We hypothesized that the inflammatory milieu of AF in acute chorioamnionitis would decrease with increasing GA. The inflammatory milieu of AF was examined in 617 singleton preterm pregnancies (<36 weeks) delivered within 5 days of amniocentesis. Study population was divided into GA at delivery ≤30 weeks (n = 148), 30-34 weeks (n = 226), and 34-36 weeks (n = 226). Acute-chorioamnionitis was classified according to the severity (i.e., mild, total grade 1; moderate, total grade 2; and severe, total grade 3-6) or involved compartment (i.e., chorionic plate, amnion and chorio-decidua). The inflammatory milieu of AF was determined by matrix metalloproteinase-8 (MMP-8) concentration. 1) AF MMP-8 concentrations decreased in patients with acute-chorioamnionitis (P < 0.001), but not inflammation-free placenta, with increasing GA; 2) AF MMP-8 concentrations were less intense at higher GA in patients with moderate and severe (each-for P < 0.005), but not mild, acute-chorioamnionitis; 3) AF MMP-8 concentrations decreased in the context of the same involved compartment (i.e., chorionic plate inflammation, amnionitis, or chorio-deciduitis) of acute-chorioamnionitis (each-for P < 0.001) with increasing GA; 4) Moreover, there was a significant inverse relationship between GA and AF MMP-8 concentrations in patients with acute-chorioamnionitis (r = -0.453, P < 0.0000001), but not inflammation-free placenta (r = -0.071, P = 0.170). AF MMP-8 concentrations in acute-chorioamnionitis distinctly decrease throughout preterm-gestation. This finding suggests that the inflammatory milieu of AF decrease in acute-chorioamnionitis with GA.


ICA-based artifact correction improves spatial localization of adaptive spatial filters in MEG.
Beamformers are one of the most common inverse models currently used in the estimation of source activity from magnetoencephelography (MEG) data. They rely on a minimization of total power while constraining the gain in the voxel of interest, resulting in the suppression of background noise. Nonetheless, in cases where background noise is strong compared to the source of interest, or when many sources are present, the ability of the beamformer to detect and accurately localize weak sources is reduced. In visual paradigms, two main background sources can substantially impact an accurate estimation of weaker sources. Ocular artifacts are orders of magnitude higher than neural sources making it difficult for the beamformer to effectively suppress them. Primary visual activations also result in strong signals that can impede localization of weak sources. In this paper, we systematically evaluated how neural (visual) and non-neural (eye, heart) sources affect the localization accuracy of frontal and medial temporal sources in visual tasks. These sources are of tremendous interest in learning and memory studies as well as in clinical settings (Alzheimer's/epilepsy) and are typically difficult to localize robustly in MEG. Empirical data from two tasks - active learning and control - were used to evaluate our analysis techniques. Global field power calculations showed multiple time periods where active learning was significantly different from response selection with dominant sources converging to the eyes. Extensive leakage of eye activity into frontal and visual that evoked responses into parietal cortices was also observed. Contributions from ocular activity to the reconstructed time series were indiscernible from task-based recruitment of frontal sources in the original data. Removing artifacts (eye movements, cardiac, and muscular) by means of independent component analysis (ICA) led to a significant improvement in detection and localization of frontal and medial temporal sources. We verified our results by using simulations of sources placed in frontal and medial temporal regions with various types of background noise (eye, heart, and visual). We report that the detection and localization accuracy of frontal and medial temporal sources with beamformer techniques is highly dependent on the magnitude and location of background sources and that removing artifacts can substantially improve the beamformer's performance.


A new radiocarbon revolution and the dispersal of modern humans in Eurasia.
Radiocarbon dating has been fundamental to the study of human cultural and biological development over the past 50,000 yr. Two recent developments in the methodology of radiocarbon dating show that the speed of colonization of Europe by modern human populations was more rapid than previously believed, and that their period of coexistence with the preceding Neanderthal was shorter.


Seroprevalence of antibodies against SARS-CoV-2 and risk of COVID-19 in Navarre, Spain, May to July 2022.
In Navarre, Spain, in May 2022, the seroprevalence of anti-nucleocapsid (N) and anti-spike (S) antibodies of SARS-CoV-2 was 58.9% and 92.7%, respectively. The incidence of confirmed COVID-19 thereafter through July was lower in people with anti-N antibodies (adjusted odds ratio (aOR) = 0.08; 95% confidence interval (CI): 0.05-0.13) but not with anti-S antibodies (aOR = 1.06; 95% CI: 0.47-2.38). Hybrid immunity, including anti-N antibodies induced by natural exposure to SARS-CoV-2, seems essential in preventing Omicron COVID-19 cases.


Hyperlocal environmental data with a mobile platform in urban environments.
Environmental data with a high spatio-temporal resolution is vital in informing actions toward tackling urban sustainability challenges. Yet, access to hyperlocal environmental data sources is limited due to the lack of monitoring infrastructure, consistent data quality, and data availability to the public. This paper reports environmental data (PM, NO2, temperature, and relative humidity) collected from 2020 to 2022 and calibrated in four deployments in three global cities. Each data collection campaign targeted a specific urban environmental problem related to air quality, such as tree diversity, community exposure disparities, and excess fossil fuel usage. Firstly, we introduce the mobile platform design and its deployment in Boston (US), NYC (US), and Beirut (Lebanon). Secondly, we present the data cleaning and validation process, for the air quality data. Lastly, we explain the data format and how hyperlocal environmental datasets can be used standalone and with other data to assist evidence-based decision-making. Our mobile environmental sensing datasets include cities of varying scales, aiming to address data scarcity in developing regions and support evidence-based environmental policymaking.


A novel antireflux procedure: gastroplasty with restricted antrum to control emesis (GRACE).
Nissen fundoplication is the most commonly performed operation to treat gastroesophageal reflux disease and vomiting in children with neurologic impairment. However, failure rates of Nissen fundoplication in this population are higher, and alternatives to Nissen fundoplication have technical and functional disadvantages. We hypothesize that the novel gastroplasty with restricted antrum to control emesis (GRACE) would be more effective than Nissen fundoplication at reducing emetic reflux. To compare the GRACE with Nissen fundoplication, 15 canine subjects were randomized to Nissen fundoplication or GRACE. All subjects underwent gastrostomy tube placement. Baseline gastric emptying, electrogastrography, and induced vomiting studies were performed. Nissen fundoplication or GRACE was then performed. Postoperatively, gastric emptying and vomiting studies were repeated. Gastric emptying before and after antireflux procedures was not significantly different between groups. Both Nissen fundoplication (38%, P = .04) and GRACE (69%, P < .01) procedures prevented reflux compared with baseline. However, the GRACE procedure significantly reduced reflux when compared with Nissen fundoplication (P = .03). In this canine model, GRACE appears to be significantly more effective than Nissen fundoplication at reducing emetic reflux. This novel procedure preserves gastric function and is well tolerated. The GRACE procedure may provide an alternative to Nissen fundoplication as a primary or repeat antireflux procedure for children with neurologic impairment.


Coupling hydroclimate-hydraulic-sedimentation models to estimate flood inundation and sediment transport during extreme flood events under a changing climate.
Extreme flood events are disastrous and can cause serious damages to society. Flood frequency obtained based on historical flow records may also be changing under future climate conditions. The associated flood inundation and environmental transport processes will also be affected. In this study, an integrated numerical modeling framework is proposed to investigate the inundation and sedimentation during multiple flood events (2,5,10, 20, 50, 100, 200-year) under future climate change scenarios in a watershed system in northern California, USA. The proposed modeling framework couples physical models of various spatial resolution: kilometers to several hundred kilometers climatic processes, hillslope scale hydrological processes in a watershed, and centimeters to meters scale hydrodynamic and sediment transport processes in a riverine system. The modeling results show that compared to the flows during historical periods, extreme events become more extreme in the 21st century and higher flows tend to be larger and smaller flows tend to be smaller in the system. Flood inundation in the study area, especially during 200-year events, is projected to increase in the future. More sediment will be trapped as the flow increases and the deposition will also increase in the settling basin. Sediment trap efficiency values are within 37.5-65.4% for the historical conditions, within 32.4-68.8% in the first half of the 21st century, and within 34.9-69.3% in the second half of the 21st century. The results highlight the impact of climate change on extreme flood events, the resulting sedimentation, and reflected the importance of incorporating the coupling of physical models into the adaptive watershed and river system management.


Characterization of a new ScbR-like γ-butyrolactone binding regulator (SlbR) in Streptomyces coelicolor.
γ-Butyrolactones in Streptomyces are well recognized as bacterial hormones, and they affect secondary metabolism of Streptomyces. γ-Butyrolactone receptors are considered important regulatory proteins, and various γ-butyrolactone synthases and receptors have been reported in Streptomyces. Here, we characterized a new regulator, SCO0608, that interacted with SCB1 (γ-butyrolactone of Streptomyces coelicolor) and bound to the scbR/A and adpA promoters. The SCO0608 protein sequences are not similar to those of any known γ-butyrolactone binding proteins in Streptomyces such as ScbR from S. coelicolor or ArpA from Streptomyces griseus. Interestingly, SCO0608 functions as a repressor of antibiotic biosynthesis and spore formation in R5 complex media. We showed the existence of another type of γ-butyrolactone receptor in Streptomyces, and this SCO0608 was named ScbR-like γ-butyrolactone binding regulator (SlbR) in S. coelicolor.