Molecular detection of tick-borne protozoan parasites in sika deer (Cervus nippon) from western regions of Japan.
The sika deer (Cervus nippon) is one of the most common species of wildlife in Japan. This study aimed to reveal the prevalence of tick-borne protozoan parasites in wild sika deer living in western Japan. We used nested polymerase chain reaction (PCR) to detect the 18S rRNA gene of tick-borne apicomplexan parasites (Babesia, Theileria, and Hepatozoon spp.) from 276 blood and liver samples from sika deer captured in the Yamaguchi, Oita, Kagoshima, Okayama, Ehime, Kochi, and Tokushima Prefectures. In total, 259 samples (259/276; 93.8%) tested positive in the nested PCR screening. Gene sequencing revealed that 99.6% (258/259) of positive samples contained Theileria sp. (sika 1), while Theileria sp. (sika 2), another Theileria species, was detected in only 3 samples. We also found that one sample from a sika deer captured in Kagoshima contained the gene of an unidentified Babesia sp. related to Babesia sp. Kh-Hj42, which was previously collected from tick in western Siberia. In conclusion, we found a high prevalence of piroplasms in sika deer from western Japan, and DNA analysis revealed that Theileria sp. (sika 1) had the highest infection rate.


Iatrogenic displacement of lower third molar roots into the sublingual space: report of 6 cases.
To describe the clinical characteristics of patients who have had sublingual displacement of a mandibular third molar root, to identify potential risk factors, and to provide the clinician with information on how to prevent and treat this complication. A retrospective analysis was performed of a series of 6 patients who underwent third molar removal with accidental displacement of a root into the sublingual space. All patients were attended at the Department of Oral Surgery, Faculty of Dentistry, University of Barcelona (Spain) from 2000 through 2010. Four patients were men, and the mean age was 38.2 ± 11.3 years. In 1 case, the fragment was removed immediately after the complication, in the same surgical procedure. In 4 cases (66.7%), the displaced root remained asymptomatic (mean follow-up, 25.5 mo), and only 1 patient presented symptoms (swelling and pain in the sublingual region). A second surgical procedure using an intraoral approach was used to extract the displaced fragment in 2 patients. These 2 cases presented transitory nerve impairment of the lingual and inferior alveolar nerves, respectively. Accidental displacement of a lower third molar root into the sublingual space is an uncommon complication. When the fragments are small, surgical removal of the displaced roots seems to be unnecessary, because patients usually remain symptom free. When surgery is needed, a considerable incidence of complications should be expected.


Oleic acid as potential immunostimulant in metabolism pathways of hybrid grouper fingerlings (Epinephelus fuscoguttatus × Epinephelus lanceolatus) infected with Vibrio vulnificus.
Grouper culture has been expanding in Malaysia due to the huge demand locally and globally. However, due to infectious diseases such as vibriosis, the fish mortality rate increased, which has affected the production of grouper. Therefore, this study focuses on the metabolic profiling of surviving infected grouper fed with different formulations of fatty acid diets that acted as immunostimulants for the fish to achieve desirable growth and health performance. After a six-week feeding trial and one-week post-bacterial challenge, the surviving infected grouper was sampled for GC-MS analysis. For metabolite extraction, a methanol/chloroform/water (2:2:1.8) extraction method was applied to the immune organs (spleen and liver) of surviving infected grouper. The distribution patterns of metabolites between experimental groups were then analyzed using a metabolomics platform. A total of 50 and 81 metabolites were putatively identified from the spleen and liver samples, respectively. Our further analysis identified glycine, serine, and threonine metabolism, and alanine, aspartate and glutamate metabolism had the most impacted pathways, respectively, in spleen and liver samples from surviving infected grouper. The metabolites that were highly abundant in the spleen found in these pathways were glycine (20.9%), l-threonine (1.0%) and l-serine (0.8%). Meanwhile, in the liver l-glutamine (1.8%) and aspartic acid (0.6%) were found to be highly abundant. Interestingly, among the fish diet groups, grouper fed with oleic acid diet produced more metabolites with a higher percent area compared to the control diets. The results obtained from this study elucidate the use of oleic acid as an immunostimulant in fish feed formulation affects more various immune-related metabolites than other formulated feed diets for vibriosis infected grouper.


Association of transcatheter direct mitral annuloplasty with acute anatomic, haemodynamic, and clinical outcomes in severe mitral valve regurgitation.
Several approaches for transcatheter mitral valve repair for functional mitral valve regurgitation are established. Interventional direct annuloplasty is a novel trans-venous, trans-septal approach. While feasibility was proven recently, knowledge on its influence on cardiac dimensions, pressures, biomarkers, and clinical outcomes is sparse. Patients consecutively treated with direct annuloplasty-only procedures between December 2015 and April 2018 were included in this monocentric analysis. Echocardiographic measurements, biomarker levels, clinical status [New York Heart Association (NYHA) class and 6 min walk test] were assessed at baseline, at discharge, and at a 30 day follow-up. Overall, 18 patients (in mean 77.0 ± 7.4 years, 44.4% women) with initially all high-grade mitral valve regurgitation (MR) were included in this study. Procedural success rate was high (94.4%) without severe complications. Direct annuloplasty resulted in MR-reduction (post-procedural-MR mild or no/trace: 72.2%) and the proportion of patients with severe dyspnoea (NYHA III/IV) was reduced (88.9% vs. 50%, P = 0.008). Clinical results were associated with a relevant diminution of left atrial volumes (-16.5%, P < 0.001) and cardiac pressures [left atrial pressure (-32.3%, P = 0.019) and systolic pulmonary arterial pressure (PAP, -15.8%, P = 0.025)]. Patients with lower baseline levels of PAP (P = 0.022) as well as elevated highly sensitive troponin (P = 0.034) were more likely to archive clinical benefit (improvement in NYHA class ≥1 grade) after 1 month, which could not be correlated with the grade of MR-reduction. Transcatheter mitral valve repair by direct annuloplasty results in a relevant reduction of intracardiac pressures, left atrial volumes, dyspnoea, and MR. Lower PAP and higher troponin values at baseline could be associated to dyspnoea reduction.


Porcine coronary arteries: immunohistochemical profile of TNF-alpha, IL-1beta, TGF-beta1 and ICAM-1.
In our study we used immunohistochemical technique to demonstrate the presence of the cytokines tumour necrosis factor alpha (TNF-α), interleukin 1beta (IL-1β), transforming growth factor beta1 (TGF-β1) and intercellular adhesion molecule-1 (ICAM-1) in porcine coronaries even in physiological conditions. Inflammatory cytokines are polypeptide mediators which act as a communication signal between immune system cells and other types of cellsin different organs and tissues, both in human and pig coronary circulation. Our results show that pro-inflammatory cytokines TNF-α, IL-1β, TGF-β1 and ICAM-1 are also present in the medium tunica of the coronary arteries under physiological conditions. These results may be compared with those found in coronary atherosclerosis, where the increase in TNF-α has a dramatic effect on the function of the left ventricle, and the high value of IL-1 correlates directly with the extent of myocardial necrosis. In our study we observe the damage and activation of endothelial cells; this induces endothelial dysfunction by accumulation and oxidation of low density lipoproteins (LDL). The formation of oxidized LDL could play a central role in the amplification of the inflammatory response causing an increased expression of pro-inflammatory cytokines which promotes leukocyte recruitment in the intimal layer. These leukocytes, after the adhesion to the endothelium, penetrate the intimate tunic. Therefore inflammatory processes promote the onset and evolution of atheroma and the development of thrombotic complications.


Gonadotropin receptors and the control of gonadal steroidogenesis: physiology and pathology.
Over the past few years, knowledge of the structure of gonadotropin receptors and their mode of action has rapidly advanced. The cDNA corresponding to the luteinizeng hormone (LH) receptor (LHR) has been cloned, leading to the identification of a novel family of G-protein-coupled receptors. The follicle stimulating hormone (FSH) receptor (FSHR) was thereafter cloned by cross-hybridization with the LHR. Structure-function relationships have been studied by mutagenesis experiments in several laboratories. The cloning and chromosomal localization to chromosome 2p21 of the two human gonadotropin receptor genes has provided insights into their evolutionary relationships. The LHR and FSHR genes are very large and contain 10 and 11 exons respectively. The obtention of monoclonal antibodies against the receptors resulted in the characterization of the receptor proteins. These antibodies also allowed the study of receptor expression in target cells in physiological and pathological conditions. The internalization of the LHR has been studied by electron microscopy. A mechanism of receptor-mediated transcytosis through the endothelial cells of the testes has been described for the LHR. The polarized expression of receptors has been studied. The cloning of gonadotropin receptor genes has opened the field of genetic study of the receptors. Inactivating mutations of the LHR have been described in Leydig cell agenesis or hypoplasia. Different phenotypes, including complete pseudohermaphroditism, ambiguous genitalia and male phenotype, have been described. In the case of the FSHR, only one mutation has been reported in familial ovarian dysgenesis with primary amenorrhea. Related males have variable alterations of spermatogenesis and fertility. Constitutive mutations of the LHR have been reported in familial testotoxicosis. One similar mutation has also been described for the FSHR. Such mutations may lead to the development of a model of receptor activation.


Complex microsatellite dynamics in the myostatin gene within ruminants.
A microsatellite has previously been identified in myostatin in cattle. Sequencing of this region from other artiodactyls coupled with phylogenetic analysis has been used to uncover the potential origins of the microsatellite event, which appears either to have been born twice or to have been gained and lost within ruminants. While caprids and ovids share the ancestral state with pigs and other mammals, microsatellite activity (length polymorphism) is uncovered in both deer and bovids. The dynamic process of microsatellite evolution, including birth, is discussed here in light of several models. Finally, these models are evaluated in the context of patterns of microsatellite conservation between closely related mammalian genomes.


Prevalence and distribution of Human Papillomavirus (HPV) genotypes among HIV infected women in Lomé, Togo.
This study showed the diversity of circulating HPV genotypes in Togo. Programs of HPV vaccination and early detection of benign or precancerous lesions should be implemented to reduce cancer-related comorbidities.


MRI to X-ray mammography intensity-based registration with simultaneous optimisation of pose and biomechanical transformation parameters.
Determining corresponding regions between an MRI and an X-ray mammogram is a clinically useful task that is challenging for radiologists due to the large deformation that the breast undergoes between the two image acquisitions. In this work we propose an intensity-based image registration framework, where the biomechanical transformation model parameters and the rigid-body transformation parameters are optimised simultaneously. Patient-specific biomechanical modelling of the breast derived from diagnostic, prone MRI has been previously used for this task. However, the high computational time associated with breast compression simulation using commercial packages, did not allow the optimisation of both pose and FEM parameters in the same framework. We use a fast explicit Finite Element (FE) solver that runs on a graphics card, enabling the FEM-based transformation model to be fully integrated into the optimisation scheme. The transformation model has seven degrees of freedom, which include parameters for both the initial rigid-body pose of the breast prior to mammographic compression, and those of the biomechanical model. The framework was tested on ten clinical cases and the results were compared against an affine transformation model, previously proposed for the same task. The mean registration error was 11.6±3.8mm for the CC and 11±5.4mm for the MLO view registrations, indicating that this could be a useful clinical tool.


Effect of exercise on the serum level and urinary excretion of tetracycline, doxycycline and sulphamethizole.
The serum level and urinary excretion of sulphamethizole, tetracycline and doxycycline were studied in healthy volunteers subjected to intensive exercise and bed rest in a cross-over trial. Each group consisted of 7--8 subjects. The exercise or bed rest began 15 min before oral administration of the drug and was continued for the following 4 hours. During exercise serum drug concentration and the area under the serum concentration-time curve for each agent was significantly higher (p less than 0.05) than the corresponding values at rest. Exercise greatly suppressed the renal excretion of tetracycline and doxycycline, but the decrease alone appeared insufficient to account for the pronounced increase in serum drug concentration. Total drug excretion in urine was unchanged. Thus, it seemed most unlikely that overall absorption from the gastrointestinal tract had been altered by exercise. However, the rate of absorption appeared to be more rapid in the exercise than in the rest period. Marked haemoconcentration was not produced by the exercise. In addition to changes in absorption and elimination rates, alteration in the volume of distribution might contribute to the higher serum drug concentration during exercise. Therefore, the level of physical activity should be considered in the interpretation of pharmacokinetic data both in clinical practice and in pharmacokinetic studies.


Prevalence of periodontal pathogens in subgingival lesions, atherosclerotic plaques and healthy blood vessels: a preliminary study.
Previous studies have reported different periodontal bacteria in atherosclerotic lesions, but their involvement in plaque formation remains unclear. The aim of the present study was to investigate the presence of 20 periodontal bacteria in atherosclerotic samples and healthy blood vessels (used as controls) and to clarify their relationship in regard to clinical and bacteriological periodontal status. The day before vascular surgery the patients had a thorough periodontal examination and bacteriological samples were taken from periodontally diseased sites. Atheromatous plaques, internal mammary arteries and saphenous veins were harvested during surgery. A DNA-DNA hybridization procedure was used to screen periodontal and vascular samples for the 20 selected bacterial species. Periodontal samples from the severe periodontitis group were found to have a higher prevalence and biomass of bacterial species than the moderate periodontitis group. In vessel samples, the prevalence of the same 20 bacterial species analyzed together was similar in the two groups, except for saphenous veins. The presence of periodontal pathogens in atherosclerotic plaques and in apparently healthy vessels appeared to reflect a higher level of bacteremia rather than infection of endothelial cells.


Clinical and molecular profile of a Brazilian cohort of patients with classical BCR-ABL1-negative myeloproliferative neoplasms.
The classical BCR-ABL1-negative myeloproliferative neoplasms (MPNs) are Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF). In developing countries, there are few reports that truly reveal the clinical setting of these patients. Therefore, we aimed to characterize a single center MPN population with a special focus on the correct diagnosis based on the recent review of the WHO criteria for the diagnosis of myeloid neoplasms. This retrospective study analyzed data from medical records of patients with classical BCR-ABL1-negative MPNs diagnosed from January 1997 to October 2017 and followed at the University Hospital of Ribeirão Preto Medical School. A total of 162 patients were assessed, 61 with PV, 50 with ET, and 51 with PMF. The mutational status analysis revealed that 113 (69.3%) harbored the JAK2V617F mutation, 23 (14.1%), the CALR mutation, and 12 (7.4%) had a triple-negative status. None of the patients were found to have mutations on the thrombopoietin receptor gene (MPL), including some ET and PMF patients who were not tested. Among the PV patients, 57 (93.5%) were positive for the JAK2V617F mutation, one (1.6%) presented an in-frame deletion JAK2 exon 12 mutation and one (1.6%) presented a missense JAK2 exon 9 mutation, not previously described. The overall survival was lower in the triple-negative patients with PMF, when compared to the JAK2V617F or CALR-mutated (p = 0.002). The frequency of somatic mutations and survival in our cohort, stratified according to the respective disease, was consistent with the literature data, despite some limitations. Further prospective epidemiological studies of MPN cohorts are encouraged in developing countries.


Ultrasound-assisted percutaneous liver biopsy: superiority of the Tru-Cut over the Menghini needle for diagnosis of cirrhosis.
A total of 1192 consecutive patients with diffuse liver disease were randomized to have percutaneous liver biopsy specimens taken with the Menghini or the Tru-Cut needle, to compare tissue yield, safety, and accuracy of the two needles for diagnosing cirrhosis. The sites of puncture were determined by prebiopsy ultrasound scans. Adequate samples were obtained from 94% with the Tru-Cut needle and from 79.2% with the Menghini needle (p less than 0.001). Accuracy in diagnosing cirrhosis was 89.5% for the Tru-Cut needle and 65.5% for the Menghini needle (p less than 0.05). Complication rates were very low and similar for both needles. Under these conditions, the Tru-Cut needle is superior to the Menghini needle for diagnosing cirrhosis.


Effect of Periodic Arrays of Defects on Lattice Energy Minimizers.
We consider interaction energies E f [ L ] between a point O ∈ R d , d ≥ 2 , and a lattice L containing O, where the interaction potential f is assumed to be radially symmetric and decaying sufficiently fast at infinity. We investigate the conservation of optimality results for E f when integer sublattices kL are removed (periodic arrays of vacancies) or substituted (periodic arrays of substitutional defects). We consider separately the non-shifted ( O ∈ k L ) and shifted ( O ∉ k L ) cases and we derive several general conditions ensuring the (non-)optimality of a universal optimizer among lattices for the new energy including defects. Furthermore, in the case of inverse power laws and Lennard-Jones-type potentials, we give necessary and sufficient conditions on non-shifted periodic vacancies or substitutional defects for the conservation of minimality results at fixed density. Different examples of applications are presented, including optimality results for the Kagome lattice and energy comparisons of certain ionic-like structures.


Molecular dynamics simulations of halide glasses.
Halide glasses have been extensively studied in recent years because of their potential application as infrared transmitting fibre optic materials. They are believed to be more ionic than glasses based on silica and should therefore be more amenable to molecular dynamics simulation using simple two-body potentials. Here the main features of structural models derived using such techniques are described and compared with available structural data. Possible future applications of this approach are outlined.


Assessment of mycotoxins (deoxynivalenol, zearalenone, aflatoxin B1 and fumonisin B1) in hen's eggs in Jordan.
The present study was carried out to evaluate the prevalence of mycotoxins (Deoxynivalenol (DON), Zearalenone (ZEA), Aflatoxin B1 (AFB1) and Fumonisin B1 (FB1)) in local hen's table eggs (white and yolk) as well as their stability upon refrigeration. Two hundred and fifty of fresh table eggs samples collected from Jordan governorates were analyzed using Liquid Chromatography- Mass Spectrophotometry (LC- MS/MS) More than half (67%) of the tested samples were positive for mycotoxins. The mean concentration of AFB1, FB1 and ZEA was 0.5 ± 0.4, 0.5 ± 0.2 and 3.2 ± 1.5 μg/kg, respectively. The overall prevalence of AFB1, ZEA, FB1 was 56.8, 16.0 and 7.6%, respectively. DON was not found in any of the samples. The highest prevalence was observed in Amman (85.7%) followed by Mafraq (78.6%), Karak (75.0%) and Zarqa'a (66.6%). None of the investigated mycotoxins were detected in egg whites. However, the prevalence of AFB1, ZEA, FB1 in egg yolk was 21.3, 16 and 7.6%, respectively. Refrigeration up to 4 weeks did not decrease the mycotoxin concentration significantly. Mycotoxin concentration in all investigated samples in this study were well below both the International and Jordanian acceptable limits. However, continuous exposure may lead to bioaccumulation over a long term and pose a threat to health.


Maternal exercise modifies body composition and energy substrates handling in male offspring fed a high-fat/high-sucrose diet.
Maternal training during gestation enhances offspring body composition and energy substrates handling in early adulthood. Offspring nutrition also plays a role as some beneficial effects of maternal training during gestation disappear after consumption of a high-fat diet. Maternal exercise during gestation has been reported to modify offspring metabolism and health. Whether these effects are exacerbated when offspring are receiving a high-fat diet remains unclear. Our purpose was to evaluate the effect of maternal exercise before and during gestation on the offspring fed a high-fat/high-sucrose diet (HF) by assessing its body composition, pancreatic function and energy substrates handling by two major glucose-utilizing tissues: liver and muscle. Fifteen-week-old nulliparous female Wistar rats exercised 4 weeks before as well as during gestation at a constant submaximal intensity (TR) or remained sedentary (CT). At weaning, pups from each group were fed either a standard diet (TRCD or CTCD) or a high-fat/high-sucrose diet (TRHF or CTHF) for 10 weeks. Offspring from TR dams gained less weight compared to those from CT dams. Selected fat depots were larger with the HF diet compared to control diet (CD) but significantly smaller in TRHF compared to CTHF. Surprisingly, the insulin secretion index was higher in islets from HF offspring compared to CD. TR offspring showed a higher muscle insulin sensitivity estimated by the ratio of phosphorylated protein kinase B to total protein kinase B compared with CT offspring (+48%, P < 0.05). With CD, permeabilized isolated muscle fibres from TR rats displayed a lower apparent affinity constant (Km ) for pyruvate and palmitoyl coenzyme A as substrates compared to the CT group (-46% and -58%, respectively, P < 0.05). These results suggest that maternal exercise has positive effects on young adult offspring body composition and on muscle carbohydrate and lipid metabolism depending on the nutritional status.


Periorbital Rejuvenation for Asians.
A primary concern in facial aesthetics is the rejuvenation of periorbital areas through soft tissue recontouring, skin texture improvement, and harmoniousness with souring anatomic tissues. Currently, the ease of harvesting, abundance in volume, and lack of immune rejection make autologous fat transplantation a disruptive strategy in aesthetic medicine. The evolution and improvements made by myriad surgeons have contributed to the popularity of periorbital rejuvenation and have highlighted its indispensability in Asian patients. Lin and colleagues have advocated the technique of microautologous fat transplantation since 2007 for facial recontouring and rejuvenation. This article illustrates more in-depth technical details and innovative concepts for the improvement of the periorbita.


Molecular characterization of the porcine GBP1 and GBP2 genes.
Experimental evidence indicated that interferon-inducible guanylate-binding proteins (GBPs) are similar with genes in the myxovirus (Mx) resistance protein subfamily of the large GTPases protein family and play important roles in the resistance to intracellular pathogens. As more diseases exert significant influence on pig industry, it is anticipated that more candidate disease-resistance genes could be found in future strategies aimed at improving genetic resistance to infectious diseases. In this study, we cloned cDNA sequences and analyzed the genomic structure of porcine GBP1 (poGBP1) and GBP2 (poGBP2). The two genes were mapped to SSC4q21-q23 and SSC4q24 by the SCHP panel respectively, further IMpRH panel analysis showed both genes were most closely linked to the marker SWR153. The deduced amino acid sequences of these two genes share the same three classical GTP-binding motifs at the amino terminus and are less conserved at the carboxyl termini except for a CaaX motif, compared with human and mouse counterparts. The reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that poGBP1 and poGBP2 were both widely expressed in many tissues, and transient transfection indicated that poGBP1 and poGBP2 proteins were both located in cytoplasms within Pig Kidney Epithelial cells (PK15). Quantitative real-time PCR (Q-RT-PCR) analyses showed poGBP1 and poGBP2 had very similar expression patterns in PK15 cells at different time points after poly I:C stimulation, suggesting that ISRE (interferon-stimulated response element) plays a crucial role in the transcriptional regulation of these two genes. Four single nucleotide polymorphisms (SNPs) and three SNPs were detected in the cDNA sequences of poGBP1 and poGBP2, respectively. Association analyses revealed that the poGBP1 Eco81I and poGBP2 SspI polymorphisms both had significant associations (p<0.05) with red blood cell count (RBC), haemoglobin concentration (HGB) and hematocrit (HCT) of 17-day-old pigs.


New pathways and metabolic engineering strategies for microbial synthesis of diols.
Diols are important bulk chemicals that are widely used in polymer, cosmetics, fuel, food, and pharmaceutical industries. The development of bioprocess to produce diols from renewable feedstocks has gained much interest in recent years and is contributing to reducing the carbon footprint of the chemical industry. Although bioproduction of some natural diols such as 1,3-propanediol and 2,3-butanediol has been commercialized, microbial production of most other diols is still challenging due to the lack of natural biosynthetic pathways. This review describes the recent efforts in the development of novel synthetic pathways and metabolic engineering strategies for the biological production of C2∼C5 diols. We also discussed the main challenges and future perspectives for the microbial processes toward industrial application.


Secondary rhinoplasty using flying-bird and vestibular tornado incisions for unilateral cleft lip patients.
To correct the nasal deformity in cleft lip patients, a new procedure of open rhinoplasty using a "flying-bird" incision in the nostril tip with a vestibule "tornado"-shaped incision in the cleft side is presented. The newly designed vestibular incision produces effective vestibular advancement with the freed lower lateral cartilage. The flying-bird incision makes it possible to produce a suitable nostril tip appearance with symmetrical external nostril vestibules. If the vestibular defect after flap advancement is wide, a full-thickness skin graft is used to give priority for making a good external nostril shape. This procedure is useful for most cleft lip noses, particularly in cases of moderate to severe deformity.


Recent advances in HER2-targeted delivery for cancer therapy.
Human epidermal growth factor receptor 2 (HER2), a tyrosine kinase receptor with a molecular mass of 185kDa, is overexpressed in several cancers, such as breast, gastric, ovary, prostate, and lung. HER2 is a promising target in cancer therapy because of its crucial role in cell migration, proliferation, survival, angiogenesis, and metastasis through various intracellular signaling cascades. This receptor is an ideal target for the delivery of chemotherapeutic agents because of its accessibility to the extracellular domain. In this review, we highlight different HER2-targeting strategies and various approaches for HER2-targeted delivery systems to improve outcomes for cancer therapy.


Background levels of OCPs, PCBs, and PAHs in soils from the eastern Pamirs, China, an alpine region influenced by westerly atmospheric transport.
Long-range atmospheric transport (LRAT) plays a crucial role in the occurrence of persistent organic pollutants (POPs) in remote regions. When studying the LRAT of POPs on the Tibetan Plateau, westerly-controlled regions have received insufficient attention compared with regions influenced by the Indian monsoon or air flow from East Asia. We investigated the residual levels of POPs in soils from the eastern Pamirs and used air backward trajectory analysis to elucidate the influence of potential source regions via LRAT. Organochlorine pesticides (OCPs, mainly comprising DDTs, HCHs, and HCB), polychlorinated biphenyls (PCBs, mainly comprising penta- and hexa-CBs), and polycyclic aromatic hydrocarbons (PAHs, mainly comprising three- and four-ring) were detected at low concentrations of 40-1000, <MDL-88, and 2100-34,000 pg/g, respectively. We elucidated three major geographical distribution patterns of POPs, which were influenced by (1) the distribution of total organic carbon and black carbon in soil, (2) historical use of pesticides in the Tarim Basin, and (3) continuous emissions. Central Asia and the Tarim Basin were major potential source regions of POPs reaching the eastern Pamirs via LRAT. Historical use of technical HCH or lindane and technical DDT in potential source regions may contribute to the accumulation of HCHs and DDTs in the eastern Pamirs, respectively. Local sources seem to play a more important role in the occurrence of PAHs in the study area. By being under the control of less contaminated westerly air flow, the eastern Pamirs are more pristine than the core of the Tibetan Plateau where the Indian and East Asia monsoons deliver contaminants from highly industrialized areas in East China and India.


Visual pathways evaluation in Kearns Sayre syndrome: a diffusion tensor imaging study.
Kearns Sayre syndrome (KSS) is a mitochondrial disorder characterized by development of visual impairment. Electroretinogram (ERG) and visual evoked potentials are not able to provide topographical information of optic damage. The purpose of this study was to explore retrochiasmatic optic pathway alteration in KSS with diffusion tractographic analysis and to compare it with different tracts. DTI from 8 KSS subjects (14.7 years) and 10 healthy controls (HC) were acquired on a 3T scanner. Optic radiations (OR), optic tracts (OT), inferior frontooccipital fasciculus (IFOF) and corticospinal tract (CST) were reconstructed with probabilistic tractography. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial (RD), and axial diffusivity (AD) were calculated, evaluating group differences. T test on diffusion parameters identified significantly different track portions among cohorts. All patients had optic pathway alterations at electrophysiological examination. Significant lower FA were found in OT, IFOF, and CST of KSS group. RD was significantly higher in bilateral OR, IFOF, CST, and right OT, while ADC was higher in bilateral OR and CST. RD values were higher in the proximal and distal portion of OR bilaterally and in the distal portion of right OT, while widespread differences were found in IFOF and CST. No significant differences were found for AD. FA profiles analysis demonstrated significant differences between groups in several regions of OT, IFOF, and CST, while ADC assessment revealed spread differences in OR and CST. DTI evaluation of retrochiasmatic tracks may represent a useful tool to topographically investigate retrochiasmatic visual impairment in KSS.


Quantitative in vivo micro-computed tomography for assessment of age-dependent changes in murine whole-body composition.
Micro-computed tomography (micro-CT) is used routinely to quantify skeletal tissue mass in small animal models. Our goal was to evaluate repeated in vivo micro-CT imaging for monitoring whole-body composition in studies of growth and aging in mice. Male mice from 2 to 52 weeks of age were anesthetized and imaged using an eXplore Locus Ultra and/or eXplore speCZT scanner. Images were reconstructed into 3D volumes, signal-intensity thresholds were used to classify each voxel as adipose, lean or skeletal tissue, and tissue masses were calculated from known density values. Images revealed specific changes in tissue distribution with growth and aging. Quantification showed biphasic increases in total CT-derived body mass, lean and skeletal tissue masses, consisting of rapid increases to 8 weeks of age, followed by slow linear increases to 52 weeks. In contrast, bone mineral density increased rapidly to a stable plateau at ~ 14 weeks of age. On the other hand, adipose tissue mass increased continuously with age. A micro-CT-derived total mass was calculated for each mouse and compared with gravimetrically measured mass, which differed on average by < 3%. Parameters were highly reproducible for mice of the same age, but variability increased slightly with age. There was also good agreement in parameters for the same group of mice scanned on the eXplore Locus Ultra and eXplore speCZT systems. This study provides reference values for normative comparisons; as well, it demonstrates the usefulness of in vivo single-energy micro-CT scans to quantify whole-body composition in high-throughput studies of growth and aging in mice.


Arsenic speciation in multiple metal environments II. Micro-spectroscopic investigation of a CCA contaminated soil.
The speciation of arsenic (As) in a copper-chromated-arsenate (CCA) contaminated soil was investigated using micro-focused X-ray fluorescence (microXRF) and micro-focused X-ray absorption fine structure (microXAFS) spectroscopies to determine if and how the co-contaminating metal cations (Cu, Zn, Cr) influenced the speciation of As. 15 microXRF images were collected on 30-mum polished thin sections and powder-on-tape samples from which Pearson correlation coefficients (rho) between As and various metal species were determined based on the fluorescence intensity of each element in each image pixel. 29 microXAFS and two bulk-XAFS spectra were collected from depths of 0-20 cm (LM-A) and 20-40 cm (LM-B) to determine the chemical speciation of As in the soil by target analyses of principal components with circa 52 reference spectra and linear least-square combination fitting of individual experimental spectra with a refined reference phase list (32) of likely As species. Arsenic and metal cations (Cr, Mn, Fe, Cu, Zn) accumulated in distinct, isolated areas often not larger than 50 x 50 microm in which the Pearson correlation between the elements was strongly positive (rho>0.75). The correlation of As to Zn and Cr decreased from >0.9 to <0.8 and increased to Cu from approximately 0.6 to >0.8 with depth. Arsenic occurred predominantly in the +5 oxidation state. Abstract factor analysis and linear least square combination fit analysis suggested that As occurred as a continuum of fully and poorly-ordered copper-arsenate precipitates with additional components being characterized by surface adsorption complexes on goethite and gibbsite in the presence and absence of Zn. Precipitates other than copper-based ones, e.g., scorodite, adamite and ojuelaite were also identified. The significant co-localization and chemical speciation of As with Cu suggest that the speciation of As in a contaminated soils is not solely controlled by surface adsorption reactions, but significantly influenced by the co-contaminating metal cation fraction. Future studies into As contaminated soil therefore need to focus on identifying the speciation of As and the co-localizing metal cations.


Exploring the functional and metabolic effects of adding garra fish meal to a plant-based broiler chicken diet.
The present study evaluated the metabolic and functional effects of adding garra meal to a broiler chicken diet. Three hundred twenty Sasso-breed day-old chicks were randomly assigned to four dietary treatments with either 0, 10, 20 or 30% garra meal added on top of formulated starter and grower basal diets. The experiment lasted for 42 days. Feed intake and body weight gain increased at the starter and grower phases of broilers with garra meal addition (P < 0.05). Broiler chickens fed 30% garra meal were more efficient in converting feed to body weight and yielded the highest carcass weight (P < 0.05). Crude protein ileal digestibility coefficient was higher with 20% (76.2%), and crude fat with 20 (92.1) and 30% (92.6%) garra meal receiving groups (P < 0.05). The increase in individual and total esterified carnitine concentrations in dried blood spots demonstrated the elevated metabolic rate with garra meal addition (P < 0.05). A better supply of glucogenic substrate to the citric acid cycle was seen with garra meal addition due to the increase of propionylcarnitine to acetylcarnitine ratio (P < 0.05) without any apparent effect on ketogenesis in terms of serum 3-hydroxybutyrylcarnitine to acetylcarnitine ratio. Yet, it likely showed that part of the amino acids from garra meal were used as glucogenic substrate (P < 0.05). Histomorphometry data showed 20% garra meal addition elevated villus height, crypt depth and their ratio in the proximal parts of the small intestine (duodenum and jejunum) with the opposite results observed in the more distal part (ileum) with the highest for the control group (P < 0.05). It can be concluded that garra meal improved broiler performance when added to a plant-based diet and only few parameters warranted for caution when using more up to 30% garra meal addition. Beyond growth performance, garra meal generated a shift to a more efficient digestion, absorption and nutrient metabolism.


Ion chromatographic method for the simultaneous determination of nitrite and nitrate by post-column indirect fluorescence detection.
This short paper highlights the suitability of ion chromatography with post-column indirect fluorescence detection to determine simultaneously nitrite and nitrate based on the quenching of tryptophan native fluorescence. The method uses an enhanced fluorescence mobile phase containing tryptophan and detects the suppression of fluorescence of the mobile phase due to the elution of the target ions. The phenomenon of fluorescence quenching of tryptophan is highly induced by the presence of phosphate ions. The quenched fluorescence intensity exhibits concentration dependence in the range 1-25 mg/l and 3-65 mg/l for nitrite and nitrate, respectively. The relative standard deviation for five replicates of a standard solution containing a mixture of 5 mg/l of nitrite and 10 mg/l of nitrate lies around 2.8%. This simple coupling technique results in a relatively sensitive, fast, and accurate method, allowing for both qualitative and quantitative analysis of nitrite and nitrate. The method can easily be implemented to real samples such as foodstuffs, fertilizers and soils and is proven to be precise and accurate when compared with reference methods.


New Approaches toward Building Csp -P bond: A Two-Decade Overview.
Since the review of Savignac, the past 20 years have seen significant progresses on the synthesis of alkynylphosphorus compounds considerably expanding the original and rather limited organic toolbox. This comprehensive review explores the latest and potentially greener methodologies using sustainable catalysis or direct metal-free couplings from stable and easy to handle precursors. Recent progress and mechanistic insights for metal-catalyzed reactions with a particular emphasis on copper, palladium, nickel and silver catalytic systems, photocatalytic and metal-free reactions are detailed covering most of the publications related to this field since 2000 until March 2022.


Maternal obesity during pregnancy and cardiovascular development and disease in the offspring.
Maternal obesity during pregnancy is an important public health problem in Western countries. Currently, obesity prevalence rates in pregnant women are estimated to be as high as 30%. In addition, approximately 40% of women gain an excessive amount of weight during pregnancy in Western countries. An accumulating body of evidence suggests a long-term impact of maternal obesity and excessive weight gain during pregnancy on adiposity, cardiovascular and metabolic related health outcomes in the offspring in fetal life, childhood and adulthood. In this review, we discuss results from recent studies, potential underlying mechanisms and challenges for future epidemiological studies.


Multilayer dextran derivative based capsules fighting bacteria resistant to Antibiotic: Case of Kanamycin-Resistant Escherichia coli.
Bacteria resistance to antibiotics has emerged as a major health problem. Developing new antibacterial systems is then of major interest. In this sense, we present biocapsules presenting inherent antibacterial capacity. The self-assembly of charged biopolymer, namely diethylaminoethyl-dextran hydrochloride (dex+) and dextran sulfate (dex-), were done on calcium carbonate microparticles, used as a template. Zeta potential measurements have shown the successful alternate adsorption of these biopolymers and related charge reversal upon the multilayer film construction onto the particles surface. The shape of the capsules was characterized by scanning electron microscopy (SEM). These particles were tested against bacteria resistant to antibiotics, namely kanamycin-resistant Escherichia coli. An inhibitory effect of the particles was observed during bacterial growth in liquid medium, i.e. in the range of 10 % for (dex+/dex-)n coated CaCO3 materials and of 50% for (dex+/dex-)n capsules. These findings evidence the high potential of capsules to act as antimicrobial agents in future and in treatments against infections.


Risk of Brain Herniation After Craniotomy With Preoperative Lumbar Spinal Drainage: A Single-Surgeon Experience of 365 Patients Among 3000 Major Cranial Cases.
Lumbar spinal drainage (LSD) can significantly facilitate brain relaxation and improve ease of surgical goals for a variety of neurosurgical indications. Although rapid drainage of large volumes of spinal fluid can theoretically produce shifts in brain compartments and herniation syndromes, the clinical significance of this phenomenon when LSD is used immediately before craniotomy is unclear. To report a large single-surgeon consecutive experience with symptomatic brain herniation after lumbar drainage before craniotomy. Included were 365 patients who underwent LSD with either lumbar drain or lumbar puncture for a variety of different neurosurgical pathologies between 2008 and 2018 immediately before craniotomy. We reviewed the surgical indications, craniotomy location, approach, type of LSD, presence of postoperative brain herniation on imaging, type of herniation, clinical symptoms, lesion pathology, and 30-d modified Rankin Scale score for each patient. There was no patient who suffered from the development of new or worsening symptomatic or radiological brain herniation directly related to use of immediate preoperative LSD. This included 204 supratentorial and 161 infratentorial procedures. Surgical indications included 188 tumors, 5 aneurysms, 37 arteriovenous malformations, 2 revascularization procedures, 97 microvascular decompressions, 10 optic nerve decompressions requiring extradural clinoidectomy for tumor removal, and 26 "other" pathologies. Brain herniation did not occur postoperatively with the use of immediate preoperative LSD in our series, regardless of craniotomy location, pathology, extent of mass effect, or approach. Our experience suggests that LSD is a potentially safe preoperative adjunct that can be used to facilitate surgical objectives.


Role of immunohistochemistry for interobserver agreement of Peritoneal Regression Grading Score in peritoneal metastasis.
Pressurized intraperitoneal aerosol chemotherapy (PIPAC)-directed therapy is a new treatment option for peritoneal metastasis (PM). The 4-tiered Peritoneal Regression Grading Score (PRGS) has been proposed for assessment of histological treatment response. We aimed to evaluate the effect of immunohistochemistry (IHC) on interobserver agreement of the PRGS. Hematoxylin and eosin (H&E)-stained and IHC-stained slides (n = 662) from 331 peritoneal quadrant biopsies (QBs) taken prior to 99 PIPAC procedures performed on 33 patients were digitalized and uploaded to a web library. Eight raters (five consultants and three residents) assessed the PRGS, and Krippendorff's alpha coefficients (α) were calculated. Results (IHC-PRGS) were compared with data published in 2019, using H&E-stained slides only (H&E-PRGS). Overall, agreement for IHC-PRGS was substantial to almost perfect. Agreement (all raters) regarding single QBs after treatment was substantial for IHC-PRGS (α = 0.69, 95% confidence interval [CI] = 0.66-0.72) and moderate for H&E-PRGS (α = 0.60, 95% CI = 0.56-0.64). Agreement (all raters) regarding the mean PRGS per QB set after treatment was higher for IHC-PRGS (α = 0.78, 95% CI = 0.73-0.83) than for H&E-PRGS (α = 0.71, 95% CI = 0.64-0.78). Among residents, agreement was almost perfect for IHC-PRGS and substantial for H&E-PRGS. Agreement (all raters) regarding maximum PRGS per QB set after treatment was substantial for IHC-PRGS (α = 0.61, 95% CI = 0.54-0.68) and moderate for H&E-PRGS (α = 0.60, 95% CI = 0.53-0.66). Among residents, agreement was substantial for IHC-PRGS (α = 0.66, 95% CI = 0.57-0.75) and moderate for H&E-PRGS (α = 0.55, 95% CI = 0.45-0.64). Additional IHC seems to improve the interobserver agreement of PRGS, particularly between less experienced raters.


Clinical review: the hospital of the future - building intelligent environments to facilitate safe and effective acute care delivery.
The translation of knowledge into rational care is as essential and pressing a task as the development of new diagnostic or therapeutic devices, and is arguably more important. The emerging science of health care delivery has identified the central role of human factor ergonomics in the prevention of medical error, omission, and waste. Novel informatics and systems engineering strategies provide an excellent opportunity to improve the design of acute care delivery. In this article, future hospitals are envisioned as organizations built around smart environments that facilitate consistent delivery of effective, equitable, and error-free care focused on patient-centered rather than provider-centered outcomes.


Chaoborus americanus predation on various zooplankters; Functional response and behavioral observations.
Predation rates for Chaoborus americanus on different types of noncyclomorphic zooplankton prey were determined in the laboratory as a function of both prey species and density. The sequence of events leading to consumption of prey was also observed, and probabilities determined for the various components.Predation rates generally reached an upper limit as the density of prey increased to high levels. Larger prey were always less vulnerable to Chaoborus predation. Among the species of zooplankton prey examined Holopedium gibberum suffered the lowest rates of predation, while those of the other plankters (Daphnia pulex, D. rosea, Moina hutchinsoni, Diaptomus birgei, D. leptopus, Cyclops vernalis) were approximately equivalent for any given size category.Observation of the predatory sequence indicates that for all the plankters except H. gibberum there were relatively high rates of evasion of attack by C. americanus and low rates of escape after capture. For H. gibberum the situation was reversed, and escape after capture was particularly important in determining the predation rate.The gelatinous envelope of Holopedium gibberum seems to operate as an effective anti-predator device which reduces the likelyhood of retention by Chaoborus after contact has been made.


Folded free radial forearm flap for reconstruction of full-thickness defects of the cheek.
Full thickness defects of the cheek have been conventionally reconstructed using the folded forehead flap, cervical flap, pectoralis major myocutaneous flap, or deltopectoral flap in various combinations. We report a modified technique of folding the radial forearm flap for reconstruction of full-thickness defects of the cheek. The free radial forearm flap is a type C fasciocutaneous flap based on the radial artery along with its vena commitans and superficial forearm vein. The size and shape of the flap are determined according to the dimensions of the surgical defect. The flap is then lifted off with the fascia of the forearm making it a fasciocutaneous flap, in which the radial artery lies deep to the fascia and gives numerous branches. The flap is disconnected from the donor site only after the recipient vessels have been prepared for anastomosis. Vascular anastomosis is then performed using the operating microscope. This technique was used in 13 patients with carcinoma of the buccal mucosa who underwent fill-thickness excision of the cheek. Flap edema was observed in 4 patients in the immediate post-operative period. Necrosis of the outer paddle was seen in 1 patient. Donor site morbidity was seen in 4 patients who required dressings on an outpatient basis for up to 3 weeks. Single-stage reconstruction of full-thickness defects of the cheek with the folded free radial forearm flap is reliable and produces excellent cosmesis with minimal donor site morbidity.


Horace Barlow (1921-2020).
An obituary by David Burr and Simon Laughlin of visual neuroscientist Horace Barlow, whose contributions to the understanding of brain function inspired generations of neurophysiologists, psychologists and computational neuroscientists.


Developmental responses to opioids reveals a lack of effect on stress-induced corticosterone levels in neonatal rats.
The neonate has an unusual capacity for survival and the possibility exists that mechanisms for controlling stress responses may differ in the developing animal. In adults both endogenous and exogenous opioids can modulate the corticosterone responses to stress. We have studied this effect in neonatal rats and found that opioid modulation is absent in early postnatal development. Neonatal rats of either sex were injected with morphine (5-50 mg kg-1), fentanyl (10-100 micrograms kg-1), buprenorphine (0.1-30 mg kg-1) or naloxone (0.1-10 mg kg-1) and plasma corticosterone measured fluorimetrically 15 or 20 min later. In addition naloxone reversibility studies (1 mg kg-1, co-administered) were carried out for the opioid agonists. In adult rats, elevations in plasma corticosterone caused by injection stress were potentiated by morphine, fentanyl and buprenorphine. In neonates, though injection stress-induced rises in plasma corticosterone were absent at 10 days, elevations were observed at 21 days and later. However, significant potentiation of this corticosterone response by fentanyl was absent at 21 days and at later ages (30 and 40 days) for morphine and buprenorphine. The potentiating effect of all three agonists did not become fully effective until day 45. In addition, in animals acclimatized to injection stress by 7 day injection pretreatment, fentanyl did not significantly alter corticosterone levels in 30 day old neonates. High doses of naloxone (10 mg kg-1) significantly increased the corticosterone response to injection stress in adult rats but this effect was absent in 30 day old animals. A dose of naloxone (I mg kg-') which had no significant effect on the corticosterone response inhibited the effects of morphine, fentanyl and buprenorphine in 45 day old and adult rats. 5 This late development of opioid action is unusual in comparison with the maturation of endogenous peptides, receptors and antinociceptive responses and suggests that alternative mechanisms may be involved in stress-control in the neonate.


Effects of Static Stretching and Foam Rolling on Ankle Dorsiflexion Range of Motion.
Static stretching (SS) has been used for inducing acute and long-term increases in range of motion (ROM). Foam rolling (FR) has recently gained popularity for acutely increasing ROM. However, the long-term effects of FR on ROM have not been thoroughly evaluated. Therefore, the purpose of this study was to investigate the acute and long-term changes in dorsiflexion ROM as a result of 6 wk of FR, SS, and FR followed by SS (FR + SS). Participants (n = 44) were randomly assigned to FR, SS, and FR + SS groups. The FR group foam rolled the triceps surae. The SS group performed a wall stretch for both legs. The FR + SS group performed FR immediately followed by SS. All groups completed 12 training sessions in 6 wk. Dorsiflexion ROM was assessed before and after the first training session, before the second session of week 3, before and after the last session in week 6, and at week 7. There was a 4.0% acute increase in ROM at week 6 (P = 0.004) for all three groups. ROM increased 8.4% from week 3 to week 7 for all three groups (P < 0.001). When comparing week 1 baseline to week 7, ROM increased 18.3% for all three groups (P = 0.003). SS and FR seem to be comparable in terms of increasing dorsiflexion ROM acutely as well as after 6 wk of training for healthy, university-age participants. FR combined with SS does not seem to provide a synergistic effect on improving dorsiflexion ROM.


Noninvasive Fibrosis Testing in Chronic Liver Disease Including Caveats.
Assessment of liver fibrosis is important as the range of liver disease management has expanded, rendering biopsy both imperfect and impractical in many situations. Noninvasive tests of fibrosis leverage laboratory, imaging and elastography techniques to estimate disease extent, often with the goal of identifying advanced fibrosis. This review attempts to summarize their utility across a broad range of possible clinical scenarios while considering the central tenets of health care quality: access, quality, and cost. For each test, it also discusses the caveats whereby each test may have reduced effectiveness and how to consider each in a typical clinical setting.


Activation of human eosinophils by monokines and lymphokines: source and biochemical characteristics of the eosinophil cytotoxicity-enhancing activity produced by blood mononuclear cells.
We and others have previously reported that human blood mononuclear cells release in culture certain substances that enhance the capacity of purified human blood eosinophils to kill the antibody-coated larvae of Schistosoma mansoni. The present study shows that this eosinophil cytotoxicity-enhancing activity (ECEA) is released by monocytes and T lymphocytes. Monocytes produce ECEA in resting and in LPS-stimulated cultures; T lymphocytes release such activity when stimulated by mitogens such as concanavalin A. Furthermore, the human monocytic line U-937 also releases ECEA-like activity when stimulated by LPS. The enhancing activity produced by monocytes has been partially characterized: it is sensitive to proteolysis by trypsin, relatively heat stable, and associated with molecules that have an apparent molecular weight of 14,000 to 65,000 daltons and isoelectric points of 3.8-3.9, 4.2, 4.5, 4.8-4.9. This shows that while ECEA produced by monocytes is heterogeneous in size and charge, it is probably different from interleukin 1.


Identifying the best measures of alcohol consumption to predict future HIV viral suppression trajectories.
Alcohol use is associated with poor outcomes among people living with HIV (PLWH), but it remains unclear which alcohol use measures best predict future HIV viral non-suppression over time. This study aimed to compare the ability of five alcohol use measures to predict risk of suboptimal HIV viral load trajectories over 36 months. We analyzed data from a cohort of PLWH in Florida including survey data linked to the state HIV surveillance system on prospective HIV viral loads over 36 months (n = 783; 66% male; 55% Black; Mage=46, SD = 11). Four trajectory patterns for HIV viral load were identified: consistently low (65.1%), decreasing (15.9%), increasing (10.6%), and consistently high (8.4%). Past year alcohol use frequency (OR = 2.1, CI:1.0-4.4), drinks consumed on a typical drinking day (OR = 2.2, CI:1.2-4.1), frequency of binge drinking (OR = 2.6, CI:1.3-5.2), and alcohol-related problems score (OR = 1.7, CI:1.1-2.7) were the measures predictive of the risk of future viral non-suppression above specific thresholds.


Regulation of chromatin structure via histone post-translational modification and the link to carcinogenesis.
The loss of genome integrity contributes to the development of tumors. Although genome instability is associated with virtually all tumor types including both solid and liquid tumors, the aberrant molecular origins that drive this instability are poorly understood. It is now becoming clear that epigenetics and specific histone post-translational modifications (PTMs) have essential roles in maintaining genome stability under normal conditions. A strong relationship exists between aberrant histone PTMs, genome instability, and tumorigenesis. Changes in the genomic location of specific histone PTMs or alterations in the steady-state levels of the PTM are the consequence of imbalances in the enzymes and their activities catalyzing the addition of PTMs ("writers") or removal of PTMs ("erasers"). This review focuses on the misregulation of three specific types of histone PTMs: histone H3 phosphorylation at serines 10 and 28, H4 mono-methylation at lysine 20, and H2B ubiquitination at lysine 120. We discuss the normal regulation of these PTMs by the respective "writers" and "erasers" and the impact of their misregulation on genome stability.


Models that matter: white matter stroke models.
Stroke is a devastating neurological disease with limited functional recovery. Stroke affects all cellular elements of the brain and impacts areas traditionally classified as both gray matter and white matter. In fact, stroke in subcortical white matter regions of the brain accounts for approximately 30% of all stroke subtypes, and white matter injury is a component of most classes of stroke damage. However, most basic scientific information in stroke cell death and neural repair relates principally to neuronal cell death and repair. Despite an emerging biological understanding of white matter development, adult function, and reorganization in inflammatory diseases, such as multiple sclerosis, little is known of the specific molecular and cellular events in white matter ischemia. This limitation stems in part from the difficulty in generating animal models of white matter stroke. This review will discuss recent progress in studies of animal models of white matter stroke, and the emerging principles of cell death and repair in oligodendrocytes, axons, and astrocytes in white matter ischemic injury.


Prenatal diagnosis of diastematomyelia: presentation of eight cases and review of the literature.
Diastematomyelia is a rare form of spinal dysraphism. We present eight cases of diastematomyelia diagnosed prenatally in our institution as well as a review of the literature in order to determine the prognosis of isolated cases of this very unusual condition. Records of fetuses with diastematomyelia diagnosed in our institution between January 2000 and June 2005 were collected. All liveborn fetuses were examined by a pediatric neurologist. Pre- and postnatal data were analyzed. A search was then conducted using PubMed to review previously reported cases in the literature. Eight cases of diastematomyelia were diagnosed during the study interval. The mean (range) gestational age at diagnosis was 21 (13-25) weeks. The main sonographic findings were widening of the spinal canal in the coronal view and an additional echogenic focus in the posterior part of the spinal column in the axial view. The diagnosis of associated open spina bifida was made in one fetus with elevated levels of amniotic fluid alpha-fetoprotein (AF-AFP) and acetylcholinesterase (AF-AChE) and the pregnancy was terminated. The other seven cases of diastematomyelia had normal levels of AF-AFP and AF-AChE and were considered isolated. One pregnancy miscarried spontaneously 1 week following amniocentesis and the remaining six were delivered at term. Review of the literature revealed 14 reports involving 26 cases of prenatally diagnosed diastematomyelia. Twelve cases had normal biochemistry and/or no additional abnormalities and all had a favorable outcome. When diastematomyelia is not associated with other spinal anomalies, the prognosis is favorable. Prenatal diagnosis is generally made in the second trimester but sonographic signs may be recognized as early as the first trimester. Intrauterine diagnosis of diastematomyelia should facilitate appropriate management of affected cases.


[Diagnosis and treatment of duodenal injury].
To increase the value of early diagnosis and decrease postoperative complications of duodenal injury. 16 patients with duodenal injury were treated and 5 patients were treated successfully with Modified Cogbill's techniques. We emphasized the importance of early diagnosis and treatment of duodenal injury. The simplified techniques produce less complications and considered to be used clinically application.


Subpallial amygdala and nucleus taeniae in birds resemble extended amygdala and medial amygdala in mammals in their expression of markers of regional identity.
Two regions were recently recognized as subpallial amygdaloid nuclei in birds, the nucleus taeniae of the amygdala (TnA) and the newly identified subpallial amygdala (SpA). Here we further confirm these nuclei to be subpallial and amygdaloid and show similarity to specific mammalian subpallial amygdaloid nuclei. By its topological, connectional and neurochemical traits, avian TnA has been suggested to be comparable to mammalian medial amygdala (MeA) and SpA to be comparable to the sublenticular part of mammalian extended amygdala (ExA). We examined molecular traits of these areas using immunohistochemistry for limbic system-associated membrane protein (LAMP) and in situ hybridization for glutamic acid decarboxylase-65 (GAD65) and chicken ovalbumin upstream promoter-transcription factor II (COUP-TF II). Mammalian GAD65 is a subpallial marker and was enriched in ExA and MeA. Chick GAD65 was enriched in SpA and TnA, indicating that they are subpallial. LAMP, which is enriched in limbic regions such as mammalian ExA and MeA, was enriched in avian SpA and TnA. COUP-TF II was enriched in mammalian amygdala including MeA and ExA to a lesser extent. In birds, COUP-TF II was enriched in TnA and moderate in SpA. Overlap of these markers confirms avian TnA resembles mammalian MeA and SpA resembles ExA.


Non-spanning external fixation of the distal radius.
Non-spanning external fixation of the distal radius is a simple, reliable, and noninvasive technique to restore the anatomy in unstable extra-articular or minimal articular fractures of the distal radius. Rehabilitation is faster and more complete than with other comparable techniques. It is also a successful technique for stabilization of corrective osteotomy of the distal radius formal union.


Main types of insoles described in the literature and their applicability for musculoskeletal disorders of the lower limbs: A systematic review of clinical studies.
The objective of this review was to identify the main types of insoles described in the literature that are used to treat musculoskeletal alterations of lower limbs and to analyze the existence of previous evaluation for the prescription of these insoles. To this end, two researchers, independently and blindly, searched the PubMed, SciELO, Bireme, MEDLINE, Lilacs, PEDro, Cochrane Library and Web of Science databases between June and July of 2018, from the free combination of the following descriptors: insoles, foot orthoses, foot, orthoses, musculoskeletal diseases and clinical trial. We included randomized or non-randomized clinical trials in which at least one intervention group used insoles and individuals with some type of musculoskeletal disorder had been sampled. Of the 227 documents identified in date bases, 20 were included in this review. In general, it is suggested to carry out more studies with more precise methods and that include evaluation before the prescription. This is a systematic review of clinical trials registered in PROSPERO (International Prospective Register of Systematic Reviews) under the protocol no. CRD42018099534e.


Investigation of the anti-glioma activity of Oviductus ranae protein hydrolysate.
Oviductus Ranae is the dry oviducts of Rana temporaria chensinensis, and it has been reported to have a range of biological activities. This study aimed to investigate the effects of Oviductus Ranae protein hydrolysate (ORPH) on human glioma C6 cell proliferation and apoptosis in vitro and in vivo. Following in vitro treatment, cell viability and colony formation assays showed that ORPH inhibited C6 cell proliferation. In addition, the results of western blotting also demonstrated that ORPH effectively regulated the expression of the apoptosis related proteins, cleaved caspase-3, Bax and Bcl-2, DNA staining and flow cytometry analysis demonstrated that ORPH significantly promoted apoptosis in this cell line, a finding that was confirmed in vivo using terminal deoxynucleotidyl transferase dUTP nick end labeling. Further investigation demonstrated that ORPH increased apoptosis by modulating the release of inflammatory cytokines and the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway; this was demonstrated using a PI3K/AKT inhibitor (NVP-BEZ235). In summary, the present study suggested that ORPH promoted apoptosis and inhibited glioma cell proliferation by influencing the PI3K/AKT signaling pathway.


The effect of kinetic positioning on lung function and pulmonary haemodynamics in posttraumatic ARDS: a clinical study.
In the treatment of adult respiratory distress syndrome (ARDS) no breakthrough has been achieved so far. In several cases of severe ARDS in multiply injured patients we have seen improvements of lung function by means of continuous body positioning. We therefore compared the effect of kinetic positioning (KIN) on lung function and haemodynamics in ARDS patients with conventional (CON) supine positioning. Pulmonary and systemic haemodynamics were determined on the basis of pulmonary artery catheter measurements. On a daily basis oxygenation ratio (PaO2/FiO2) and pulmonary shunt (Os/Ot. per cent) were calculated. Extravascular lung water (EVLW, ml/kg BW) was determined by the double indicator thermodilution technique. Twenty-two patients were included: KIN, N = 11, CON, N = 11. Mortality from ARDS in KIN patients was 18.2 per cent (N = 2): in CON patients it was 63.6 per cent (N = 7). The oxygenation ratio (PaO2/FiO2) increased significantly in KIN patients from 140 + 45 (day 0) to 237 + 40 (P < 0.05) (day 5); in CON patients no improvement was seen (143 + 48 (day 0). 133 + 44 (day 5); n.s. between groups at day 0: P < 0.05 between groups at day 5). Pulmonary shunt decreased significantly from 26.6 + 4 per cent (day 0) to 12.5 + 2 per cent (day 5) (P < 0.05) in KIN patients and was 36.6 + 6 per cent at day 0 and 31.4 + 2 per cent at day 5 in CON patients (P < 0.05 between groups at day 5).(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of angiotensin-converting-enzyme (ACE) inhibitor trandolapril on human diabetic neuropathy: randomised double-blind controlled trial.
Diabetes is a common cause of polyneuropathy. The development and progression of nephropathy, retinopathy, and neuropathy are closely related. Angiotensin-converting enzyme (ACE) inhibitors delay progression of both nephropathy and retinopathy. We investigated the effect of ACE inhibition on diabetic neuropathy. We recruited 41 normotensive patients with type I or type II diabetes and mild neuropathy into a randomised double-blind placebo-controlled trial. Changes in the neuropathy symptom and deficit scores, vibration-perception threshold, peripheral-nerve electrophysiology, and cardiovascular autonomic function, were assessed at 6 and 12 months. The primary endpoint was the change in peroneal nerve motor conduction velocity. We found no significant difference at baseline for age, HbA1c, blood pressure, or severity of neuropathy between two groups. There was no change in HbA1c over the treatment period. Peroneal motor nerve conduction velocity (p=0.03) and M-wave amplitude (p=0.03) increased, and the F-wave latency (p=0.03) decreased and sural nerve action potential amplitude increased (p=0.04) significantly after 12 months of treatment with trandolapril compared with placebo. Vibration-perception threshold, autonomic function, and the neuropathy symptom and deficit score showed no improvement in either group. The ACE inhibitor trandolapril may improve peripheral neuropathy in normotensive patients with diabetes. Larger clinical trials are needed to confirm these data before changes to clinical practice can be advocated.


Neutron reflectometry study of the conformation of HIV Nef bound to lipid membranes.
Nef is an HIV-1 accessory protein that directly contributes to AIDS progression. Nef is myristoylated on the N-terminus, associates with membranes, and may undergo a transition from a solution conformation to a membrane-associated conformation. It has been hypothesized that conformational rearrangement enables membrane-associated Nef to interact with cellular proteins. Despite its medical relevance, to our knowledge there is no direct information about the conformation of membrane-bound Nef. In this work, we used neutron reflection to reveal what we believe are the first details of the conformation of membrane-bound Nef. The conformation of Nef was probed upon binding to Langmuir monolayers through the interaction of an N-terminal His tag with a synthetic metal-chelating lipid, which models one of the possible limiting cases for myr-Nef. The data indicate that residues are inserted into the lipid headgroups during interaction, and that the core domain lies directly against the lipid headgroups, with a thickness of ∼40 A. Binding of Nef through the N-terminal His tag apparently facilitates insertion of residues, as no insertion occurred upon binding of Nef through weak electrostatic interactions in the absence of the specific interaction through the His tag.


Positive feedback regulation of type I IFN genes by the IFN-inducible transcription factor IRF-7.
The interferon regulatory factor (IRF) family of transcription factors regulate the interferon (IFN) system, among which IRF-3 is involved in the virus-induced IFN-beta gene expression. Here we show that another member IRF-7 is critical for the IFN-alpha gene induction. Unlike the IRF-3 gene, the IRF-7 gene is induced by IFNs through activation of the ISGF3 transcription factor, and IRF-7 undergoes virus-induced nuclear translocation. In cells lacking p48, an essential component of IFN stimulated gene factor 3 (ISGF3), ectopic expression of IRF-7 but not IRF-3 can rescue the deficiency to induce IFN-alpha genes. These results indicate that IRF-7 is a key factor in the positive feedback regulation of IFN-alpha/beta production.


Jmjd3-Mediated H3K27me3 Dynamics Orchestrate Brown Fat Development and Regulate White Fat Plasticity.
Progression from brown preadipocytes to adipocytes engages two transcriptional programs: the expression of adipogenic genes common to both brown fat (BAT) and white fat (WAT), and the expression of BAT-selective genes. However, the dynamics of chromatin states and epigenetic enzymes involved remain poorly understood. Here we show that BAT development is selectively marked and guided by repressive H3K27me3 and is executed by its demethylase Jmjd3. We find that a significant subset of BAT-selective genes, but not common fat genes or WAT-selective genes, are demarcated by H3K27me3 in both brown and white preadipocytes. Jmjd3-catalyzed removal of H3K27me3, in part through Rreb1-mediated recruitment, is required for expression of BAT-selective genes and for development of beige adipocytes both in vitro and in vivo. Moreover, gain- and loss-of-function Jmjd3 transgenic mice show age-dependent body weight reduction and cold intolerance, respectively. Together, we identify an epigenetic mechanism governing BAT fate determination and WAT plasticity.


Derivation and Validation of Clinical Prediction Rules for COVID-19 Mortality in Ontario, Canada.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently causing a high-mortality global pandemic. The clinical spectrum of disease caused by this virus is broad, ranging from asymptomatic infection to organ failure and death. Risk stratification of individuals with coronavirus disease 2019 (COVID-19) is desirable for management, and prioritization for trial enrollment. We developed a prediction rule for COVID-19 mortality in a population-based cohort in Ontario, Canada. Data from Ontario's provincial iPHIS system were extracted for the period from January 23 to May 15, 2020. Logistic regression-based prediction rules and a rule derived using a Cox proportional hazards model were developed and validated using split-halves validation. Sensitivity analyses were performed, with varying approaches to missing data. Of 21 922 COVID-19 cases, 1734 with complete data were included in the derivation set; 1796 were included in the validation set. Age and comorbidities (notably diabetes, renal disease, and immune compromise) were strong predictors of mortality. Four point-based prediction rules were derived (base case, smoking excluded, long-term care excluded, and Cox model-based). All displayed excellent discrimination (area under the curve for all rules > 0.92) and calibration (P > .50 by Hosmer-Lemeshow test) in the derivation set. All performed well in the validation set and were robust to varying approaches to replacement of missing variables. We used a public health case management data system to build and validate 4 accurate, well-calibrated, robust clinical prediction rules for COVID-19 mortality in Ontario, Canada. While these rules need external validation, they may be useful tools for management, risk stratification, and clinical trials.


Allocentric lock in anorexia nervosa: new evidences from neuroimaging studies.
Individuals with anorexia nervosa (AN) have a disturbance in the way in which their body is experienced and tend to evaluate negatively their own body and body parts. It is controversial whether these symptoms are secondary to dysfunctions in the neuronal processes related to appetite and emotional regulation or reflect a primary disturbance in the way the body is experienced and remembered. According to the "Allocentric Lock Hypothesis--ALH" (http://dx.doi.org/10.1016/j.mehy.2011.10.039) individuals with AN may be locked to an allocentric (observer view) negative memory of the body that is no more updated by contrasting egocentric representations driven by perception. Recent neuroimaging studies are showing several structural and functional alterations in frame- and memory-related body-image-processing brain circuits that may support ALH.


Role of smoking in global and regional cardiovascular mortality.
Smoking is a major cause of cardiovascular disease mortality. There is little information on how it contributes to global and regional cause-specific mortality from cardiovascular diseases for which background risk varies because of other risks. We used data from the American Cancer Society's Cancer Prevention Study II (CPS II) and the World Health Organization Global Burden of Disease mortality database to estimate smoking-attributable deaths from ischemic heart disease, cerebrovascular disease, and a cluster of other cardiovascular diseases for 14 epidemiological subregions of the world by age and sex. We used lung cancer mortality as an indirect marker for accumulated smoking hazard. CPS-II hazards were adjusted for important covariates. In the year 2000, an estimated 1.62 (95% CI, 1.27 to 2.04) million cardiovascular deaths in the world, 11% of total global cardiovascular deaths, were due to smoking. Of these, 1.17 million deaths were among men and 450,000 among women. There were 670,000 (95% CI, 440,000 to 920,000) smoking-attributable cardiovascular deaths in the developing world and 960,000 (95% CI, 770,000 to 1,200,000) in industrialized regions. Ischemic heart disease accounted for 54% of smoking-attributable cardiovascular mortality, followed by cerebrovascular disease (25%). There was variability across regions in the role of smoking as a cause of various cardiovascular diseases. More than 1 in every 10 cardiovascular deaths in the world in the year 2000 were attributable to smoking, demonstrating that it is an important preventable cause of cardiovascular mortality.


Embryotoxicity of 5-azacytidine in mice. Phase- and dose-specificity studies.
The agent 5-azacytidine, which directly affects nucleic acid metabolism, is a potent teratogen in NMRI mice. The establishment of general teratological data revealed clear-cut dose-response relationships after administration of this agent on either day 12 or day 14 of gestation. Inspection of skeletal abnormalities revealed a clear-cut phase specificity of this drug when administered on days 10 or 11 of pregnancy. Additional histological studies showed that central nervous system anomalies were induced mainly after administration of azacytidine on days 10, 11, 12, or 13 of pregnancy. A most conspicuous finding was the formation of anomalous glioblast islets within the ventricular zone covering the basal ganglia. The latter malformation mainly occurred after treatment on day 11 or 12 of pregnancy. Another important malformation syndrome was the appearance of capillary ectasias and hind paw hematomas, together with an intense necrotic cardiomyopathy after treatment on either day 11 or 12 of gestation.


Visualization of Carotenoid-Storage Structures in Fruits by Transmission Electron Microscopy.
Plastids are cell organelles that, beside other functions, have the capability to store carotenoids in specialized structures, which may vary among the different plant species, tissues or according to the carotenoid complement. Fruits are an important source of carotenoids, and during ripening, chloroplasts differentiate into chromoplasts that are able to accumulate large amounts of carotenoids, rendering then the characteristic fruit coloration. Whereas lycopene or β-carotene may accumulate as crystal in the chromoplasts of some fruit, other xanthophyll-accumulating fruits differentiate plastoglobuli as a preferred system to enhance carotenoids stability and storage. Visualization of plastid ultrastructure and their transformation during ripening or in fruit of contrasting coloration are fundamental objectives within carotenoids research in fruits. Therefore, in this chapter, we describe a protocol for the visualization and analysis of plastid ultrastructure by transmission electron microscopy (TEM), specially designed and adapted to fruit tissues.


Clinical significance of atypical glandular cells of undetermined significance. A follow-up study from an academic medical center.
To determine the rate of atypical glandular cells of undetermined significance (AGUS) and the incidence of subsequent clinically significant lesions. A computer-based search of our cytology laboratory files was performed for cervicovaginal smears diagnosed as AGUS from January 1996 to December 1996. In 43,456 cervicovaginal smears examined during the 12-month period, AGUS was reported in 222 (0.5%) cases, with follow-up in 191 (86.0%) (133 [59.9%] biopsies and 58 [26.1%] repeat cervicovaginal smears). Among the patients with repeat cervicovaginal smears, 1 (1.7%) had a high grade squamous intraepithelial lesion, and 10 (17.2%) had persistent AGUS/atypical squamous cells of undetermined significance; the remainder were within normal limits. Thirty-three (24.8%) patients had preneoplastic or neoplastic, squamous or glandular lesions on biopsy (8 [6.0%] cervical intraepithelial neoplasia [CIN] 1, 18 [13.5%] CIN 2/3 and 7 [5.3%] endometrial adenocarcinomas). Half the patients with CIN 2/3 also had evidence of endocervical gland involvement. Squamous lesions were seen more commonly in premenopausal women, while glandular lesions were noted predominantly in postmenopausal women. Patients with a prior abnormal gynecologic history or a concomitant diagnosis of squamous intraepithelial lesion (SIL) had a higher incidence of significant lesions on subsequent biopsy. Our incidence of AGUS was 0.5%, similar to that in other published reports. AGUS is associated with a significant number of squamous or glandular, premalignant or malignant lesions. A majority of these lesions are high grade SIL, often with endocervical gland involvement. A small but significant number of patients had a glandular malignancy. Our results justify close and persistent follow-up for patients with a diagnosis of AGUS on cervicovaginal smears.


High risk of acute kidney injury in Malawian trauma patients: a prospective observational cohort study.
Trauma is a common cause of acute kidney injury (AKI). Yet little data exist regarding trauma-related-AKI in low-resourced settings, where the majority of deaths from AKI and trauma occur. We prospectively evaluated epidemiology of AKI in hospitalized Malawian trauma patients. AKI was defined by creatinine-only Kidney Disease Improving Global Outcomes (KDIGO) criteria. Those with AKI were followed up 3-6 months later to determine persistent kidney abnormalities. We calculated univariate statistics with Wilcoxon rank sum tests, Fisher's exact, and chi-square tests to compare those with and without AKI. Multivariate log-risk regression modelling was used to determine risk ratios (RR) and 95% confidence intervals (CI) for AKI development. Of 223 participants, 14.4% (n = 32) developed AKI. Most patients were young (median age 32) males (n = 193, 86.5%) involved in road traffic injuries (n = 120, 53.8%). After adjusting for confounders, those with severe anemia during their admission were 1.4 times (RR 1.4, 95% CI 1.1-1.8) more likely to develop AKI than those without. Overall mortality was 7.6% (n = 17), and those who developed AKI were more likely to die than those who did not (18.8% vs 5.6%, p-value = 0.02). Almost half of those with AKI (n = 32) either died (n = 6) or had persistent kidney dysfunction at follow-up (n = 8). In one of the few African studies on trauma-related AKI, we found a high incidence of AKI (14.4%) in Malawian trauma patients with associated poor outcomes. Given AKI's association with increased mortality and potential ramifications on long-term morbidity, urgent attention is needed to improve AKI-related outcomes.


The effects of SCH 23390, YM 09151-2, (+)- and (-)-3-PPP and some classical neuroleptics on D-1 and D-2 receptors in rat neostriatum in vitro.
The actions in vitro of SCH 23390, YM 09151-2 and both enantiomers of 3-PPP on D-1 and D-2 dopamine receptors were investigated in superfused rat neostriatal slices. For comparison the following neuroleptics of different chemical classes were incorporated in our investigations: (+)-bulbocapnine, clozapine, chlorpromazine, cis-flupenthixol, (-)-sulpiride and haloperidol. The increase in the efflux of cyclic AMP was used as a measure for D-1 receptor stimulation. The decrease in the K+-evoked release of [3H]acetylcholine was used as measure of D-2 receptor stimulation. None of the drugs stimulated the D-1 receptor. Only (+)-3-PPP stimulated the D-2 receptor. All other drugs, including (-)-3-PPP, behaved as antagonists on the D-2 receptor, YM 09151-2 being the most potent. SCH 23390 was the most potent antagonist on the D-1 receptor. Haloperidol, cis-flupenthixol and (+)-bulbocapnine showed an appreciable D-1 receptor blocking potency in our model, whereas the other drugs were inactive. We found SCH 23390 to be the most D-1 selective antagonist although the drug still displayed considerable potency on the D-2 receptor. YM 09151-2 was the most D-2 selective antagonist.


Expression of Twist gene in human hepatocellular carcinoma cell strains of different metastatic potential.
In order to investigate the role of Twist gene in the metastasis of hepatocellular carcinoma (HCC), total RNA was respectively extracted from three HCC cell strains with different metastatic potentials, HepG2, MHCC-97L and MHCC-97H. The first strand cDNA was synthesized by reverse transcription, which was then used as template to perform fluorescent quantitative polymerase chain reaction (FQ-PCR). The quantity of Twist gene expression was normalized by that of the housekeeping gene, GAPDH for each sample. ANOVA was used to estimate the relationship between Twist gene and metastasis potential of HCC. The results showed that the normalized initial cDNA concentrations of Twist gene in HepG2, MHCC-97L and MHCC-97H were (9.45+/-0.25)x10(-4), (1.82+/-0.41)x10(-3), (3.06+/-0.62)x10(-3), respectively. FQ-PCR revealed significant differences in the expression level of Twist among HCC cell strains with different metastatic potentials. It was concluded that high expression level of Twist was closely associated with more aggressive behaviors of HCC. Twist provides a novel indicator for HCC metastasis.


Coding and Legal Issues in Obstetric and Gynecologic Ultrasound.
This article addresses coding and liability related to obstetric and gynecologic ultrasound examinations. The coding section includes an overview of general concepts, highlighting the differences between coding in hospital-owned facilities and provider-owned clinics. It also addresses the importance of correct International Classification of Diseases, 10th edition, coding, emphasizing the use of the most specific applicable codes. This section discusses proper coding and applicable parameters for early pregnancy and gynecologic ultrasound examination. The liability section addresses common errors leading to litigation in obstetric and gynecologic ultrasound practice. Examples are given demonstrating how such errors lead to liability actions.


UV-activated adsorbents as novel materials for enhanced removal of malodorous gases.
The performance of UV-activated Fe2O3-containing ZSM-5 (UFZ5) and silica (UFS) as adsorbents for the removal of low concentration of volatile organic sulfur compounds (VOSCs) was investigated in ambient conditions. A ∼99.9% and ∼89.2% removal of 10 ppm DMDS was observed for UFZ5 and UFS, respectively, due to a higher proportion of iron in UFZ5. The N2 adsorption isotherm confirmed an unpredictable increase in the surface area and pore volume of adsorbents after the fifth adsorption-oxidation cycle, which made adsorbents highly reusable for multiple cycles. The spectroscopic analysis predicted an increase in the hydroxyl density along with the resistance of catalytic sites against sulfur deactivation, which favored the adsorption-oxidation process. The adsorption capacity of UFZ5 remained in the range of 0.12-0.22, 0.26-0.48, 0.40-0.75 mg g-1 for methyl mercaptan (MM), dimethyl sulfide (DMS), and dimethyl disulfide (DMDS), respectively which were significantly higher than those calculated for UFS. The analysis confirmed SO2, CO, CH3OH, H2O, and elemental S as by-products. The UFZ5 was found competent and robust for the treatment of VOSCs-contaminated indoor air.


Complete genome sequence of Streptomyces sp. strain VNUA24, a potential antifungal bacterium isolated from soil.
Streptomyces species are important resources for secondary metabolites, including antimicrobial compounds. The Streptomyces sp. strain VNUA24 was isolated from a soil sample in Vietnam. The strain was identified as having antifungal activity against numerous fungal pathogens. Whole-genome sequencing was done to explore the biocontrol capability of this strain.


Effect evaluation of a self-management programme for employees with complaints of the arm, neck or shoulder: a randomised controlled trial.
To evaluate the effectiveness of a self-management intervention (including an eHealth module), compared with usual care, in employees with chronic non-specific complaints of the arm, neck or shoulder (persisting >3 months). Participants were randomised into the self-management group (SG) or usual care group (UCG). The SG participated in 6 self-management sessions and could use an eHealth module; the UCG could use all available usual care. The primary outcome of the study was score on the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH). Secondary outcomes included: absenteeism, pain in the previous week, quality of life, pain catastrophising, self-efficacy, work style, presenteeism, fatigue, and limitations experienced during work. Data were analysed using generalised estimating equations (GEE) linear regression and Mann-Whitney U tests, and were collected at baseline, 3-month, 6-month, and 12-month follow-up. On the general module of the DASH, no significant difference between SG and the UCG was detected. On most of the other outcome measures, there were no significant between-group differences. In the DASH work module, the between-group effect was -3.82 (95% CI -7.46 to -0.19, p=0.04). For limitations experienced in job-related activities the between-group effect was -1.01 (95% CI -1.97 to -0.04, p=0.04). The mean hours of sport activities in the past 3 months, measured at 12 months, was 1.00 h (95% CI -1.90 to -0.12 h, p=0.03) less in the SG compared with the UCG. The self-management intervention improved the participants' perceived disability during work. Since no significant between-group differences were found on most outcome measures, the results of this study should be interpreted with caution. Dutch Trial Registration number NTR 3816.


The cost-effectiveness of as-needed budesonide/formoterol versus low-dose inhaled corticosteroid maintenance therapy in patients with mild asthma in the UK.
As-needed budesonide/formoterol is effective in patients with mild asthma for whom low-dose inhaled corticosteroid (ICS) maintenance therapy is appropriate. We assessed the cost-effectiveness of this regimen versus maintenance low-dose ICS plus as-needed short-acting β2-agonist (SABA). A probabilistic Markov cohort model was developed that simulated time within/outside severe asthma exacerbations, conducted from a UK NHS perspective with a 70-year time horizon. Clinical efficacy inputs were derived from the SYGMA 2 trial. Patients with mild asthma eligible for low-dose maintenance ICS therapy received as-needed budesonide/formoterol 200/6 μg or twice-daily budesonide 200 μg maintenance therapy plus as-needed terbutaline 0.5 mg. A severe exacerbation was defined as worsening asthma requiring systemic corticosteroid use alone/in combination with an emergency department visit, or hospitalisation for acute asthma. Utility values were derived from SYGMA 2 EQ-5D-5L data, and all-cause- and asthma-related mortality, reduction in utility of an exacerbation, and costs were based on published data. The base-case analysis discount rate was 3.5%. Model robustness was evaluated with one-way sensitivity, probabilistic sensitivity, and two scenario analyses. On average, as-needed budesonide/formoterol was associated with a £292.99 cost saving and quality-adjusted life year (QALY) gains of 0.001 versus ICS + SABA. At a willingness-to-pay of £20,000/QALY, as-needed budesonide/formoterol had >85% probability of being cost-effective versus ICS + SABA. Key drivers were budesonide/formoterol and budesonide maintenance annual exacerbation rates, mean daily budesonide/formoterol inhalations, and costs and outcomes discount rates. From a UK healthcare payer perspective, as-needed budesonide/formoterol is a cost-effective option for the treatment of mild asthma versus regular ICS.


ASCUS (Atypical Squamous Cells of Undetermined Significance) in the Cervical Smears of Women from Rural Population of Lucknow West.
Though Atypical squamous cells of undetermined significance (ASCUS) are not always precursors of cervical pre-malignancy but they need timely diagnosis and careful periodical follow-up. The present study was carried out to investigate the incidence of ASCUS and SIL (squamous intraepithelial lesion of cervix) in women under rural setting. Cervical cancer screening is in progress in rural population of West Lucknow, India, since May 2013 under auspices of Era's Lucknow Medical College and Hospital, Lucknow, and a total of 2478 women have been cytologically examined till October 2017. The incidence of ASCUS was found to be 8.8%, which was approximately less than half of the squamous intraepithelial lesions of cervix (SIL) rate (17.9%). The ASCUS rate was higher in the symptomatic women (9.4%) than (7.4%) seen in women without symptoms. The ASCUS incidence was higher in younger sexually active group up to 40 years after which it declined. The ASCUS rate was higher in all parity groups and was commonly associated with pain in lower abdomen and vaginal discharge. The ASCUS rate was higher with erosion cervix, while the commonly associated sexually transmitted diseases (STD) were found to be Candida albicans (2.4%). Follow-up after 18-24 months was available in 40 cases of ASCUS, and progression to low-grade SIL (LSIL) was seen in 7 (17.5%) and to high-grade SIL (HSIL) in one case (2.5%). The findings suggest that the ASCUS are not always precursors of SIL, but they need periodical follow-up after every 6 months. This will be ideal management of ASCUS under low-resource settings.


New drug development in the United States, 1963 through 1984.
This study is the fifth in a series that documents changes in the status of drug development in the United States based on a survey of the pharmaceutical industry. For example, the study shows that, although there has been a recent increase in the number of new chemical entities being tested by US firms, an increasing proportion are acquired from outside the firm. Moreover, a growing number of acquired new chemical entities are coming from sources outside the United States, particularly Japan. These and other trends suggest an overall decline in research activity in the United States. At the same time, foreign firms are becoming more active, foretelling greater competition in the United States for both market share and research resources. The analyses also show a continued increase in synthesis-to-approval time, surpassing 13 years in the early 1980s, and rising success rates, reaching about 12% by the late 1970s.


Evaluation of volatile fatty acids and ammonia recovery approach from landfill leachate using pilot-scale mechanical vapor recompression.
Treatment of landfill leachate is still a current problem due to the high treatment costs in addition to the difficulty of meeting the discharge criteria. However, there is a more important issue that should be underlined; it is also valuable compounds that leachate contains. Conventional methods used for treatment of leachate such as membrane filtration, advanced oxidation processes, biological processes and their combinations have largely focused on treatment. However, the recovery of ammonia and volatile organic acids (VFA) in leachate is a promising approach both to overcome high treatment costs and to sustainably manage leachate. In this study, leachate treatment potential was investigated by mechanical vapor recompression (MVR) process, which offers an operational opportunity to recover high value-added products from leachate while providing an effective treatment for wastewater. Optimum operating conditions for the pilot-scale MVR process have been determined by laboratory-scale studies. VFAs were recovered as organic acid salts from the pilot-scale MVR distillate, while ammonia recovery was accomplished as ammonium sulfate from a highly contaminated concentrate stream. VFA and ammonia recovery rates were 89% and 99%, respectively. The treatment cost of leachate with MVR process was calculated according to the data obtained in pilot scale MVR studies considering the operating cost, chemical cost and economical contribution of value-added products. The results showed that the integrated MVR-crystallization process, all treatment costs are covered, with a net gain of 3.8 USD/m3. Consequently, MVR integrated crystallization process offers an economical and sustainable solution for the treatment of leachate by recovering valuable products.