No Evidence of Coronaviruses or Other Potentially Zoonotic Viruses in Sunda pangolins (Manis javanica) Entering the Wildlife Trade via Malaysia.
The legal and illegal trade in wildlife for food, medicine and other products is a globally significant threat to biodiversity that is also responsible for the emergence of pathogens that threaten human and livestock health and our global economy. Trade in wildlife likely played a role in the origin of COVID-19, and viruses closely related to SARS-CoV-2 have been identified in bats and pangolins, both traded widely. To investigate the possible role of pangolins as a source of potential zoonoses, we collected throat and rectal swabs from 334 Sunda pangolins (Manis javanica) confiscated in Peninsular Malaysia and Sabah between August 2009 and March 2019. Total nucleic acid was extracted for viral molecular screening using conventional PCR protocols used to routinely identify known and novel viruses in extensive prior sampling (> 50,000 mammals). No sample yielded a positive PCR result for any of the targeted viral families-Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae and Paramyxoviridae. In the light of recent reports of coronaviruses including a SARS-CoV-2-related virus in Sunda pangolins in China, the lack of any coronavirus detection in our 'upstream' market chain samples suggests that these detections in 'downstream' animals more plausibly reflect exposure to infected humans, wildlife or other animals within the wildlife trade network. While confirmatory serologic studies are needed, it is likely that Sunda pangolins are incidental hosts of coronaviruses. Our findings further support the importance of ending the trade in wildlife globally.


Somatomedin-C and zinc status in rats as affected by Zn, protein and food intake.
1. The objective of the present experiment was to study the level of plasma somatomedin-C (SM-C) and the status of zinc in rats as affected by three levels of Zn given in combinations with two levels of protein. 2. Six groups of rats were fed, for 21 d, on six different diets based on combinations of two levels of dietary protein (low protein, 75 g/kg; high protein, 200 g/kg) and three levels of zinc (low Zn, 0.9 microgram/kg; moderate Zn, 55 micrograms/kg; high Zn, 110 micrograms/kg). All groups were pair-fed with the group receiving the low-Zn-low protein diet. An additional group of six rats served as an ad lib.-fed control group and was fed on a diet that contained 55 micrograms Zn/kg and 200 g protein/kg ad lib. 3. Body-weight gain and food intake were recorded daily. Rats were killed at the end of the experimental period (21 d). Zn was assayed in plasma, tibia and liver by atomic absorption technique. Plasma SM-C was assayed by radioimmunoassay. 4. In rats given the low-Zn-low-protein diet, the level of plasma SM-C increased in response to the increase in the amount of Zn or Zn and protein in the diet. However, no change was observed when the level of protein alone was increased. 5. Among all groups tested, ad lib.-fed rats showed the highest level of plasma SM-C. Thus it may be concluded that a balanced diet combined with adequate food intake is necessary to maintain an optimal level of plasma SM-C.


Origin of wavelets in the visual evoked potential.
Low amplitude high frequency wavelets have been demonstrated to be ubiquitous in the visual system of animals and are observed in the ERG of man. Wavelets have also been observed superimposed upon large slow waves obtained from electrodes on occipital scalp. Presently, the rather stereotypic wavelet repetition rate permitted the use of active analog filters tuned to 100 Hz, with a 60-200 Hz bandpass which produced no measurable distortion at 100 Hz. With this method we recorded a series of wavelets in 15 of 16 subjects that usually began from 35 to 40 msec following the onset of a 10(4) troland, 25 degrees visual angle 100 msec flash. We then sought to determine the origin of these wavelets. Wavelets recorded between occiput (Oz) and vertex (Cz) had photopic spectral sensitivity that differed from that of ERG wavelets simultaneously recorded. Moreover, in a topographical study, wavelets recorded between Cz and various lateral positions reached a maximum at Oz; and when adjacent bipolar electrode pairs were used, wavelet polarities inverted as pairs were moved across the occipital region. Thus wavelets recorded between 35 and 70 msec were likely generated from occipital cortex rather than retinal, sub cortical, or diffuse cortical sites. In addition, the topographical distribution of slow wave ('P100') and wavelets differed. Wavelet latencies had a different relation to retinal illuminance than P100 latencies, suggesting that P100 and wavelets have different neurogeneses. Wavelets recorded between Oz and Cz thus reflect the earliest cortical visual processing recorded in man.


Photon-counting spectral basis component material decomposition for musculoskeletal radiographs.
As a very fast and non-invasive examination, conventional X-ray radiography is well established as the first line diagnostic imaging method of the human bone system. While major bone injuries such as fractures and dislocations are usually easily detectable on conventional X-ray images, more subtle injuries such as microfractures are often missed, leading to mistreatment and potential long-term consequences. The technology of Photon-Counting Dual-Energy Radiography (PCDER) yields the possibility to decompose conventional X-ray images into basis material images such as bone- and soft-tissue-equivalence images. The obtained basis material images offer significant advantages in terms of image contrast and image details over the raw attenuation image which shows an overlap of bone and soft tissue. Whereas the advantages of bone- and soft-tissue-equivalence images have been broadly discussed referring to bone subtraction images in the detection of pulmonary diseases, this method has not been considered for the analysis of musculoskeletal images until present. In this study we show that basis component equivalence images have high potential to improve the diagnostic accuracy of the detection of minor bone lesions during clinical trauma imaging. A reader study performed by three experienced radiologists compares the image quality of basis material images to a standard radiograph image of a non-fractured cadaveric hand.


Ultrasound-mediated gene transfer (sonoporation) in fibrin-based matrices: potential for use in tissue regeneration.
It has been suggested that gene transfer into donor cells is an efficient and practical means of locally supplying requisite growth factors for applications in tissue regeneration. Here we describe, for the first time, an ultrasound-mediated system that can non-invasively facilitate gene transfer into cells entrapped within fibrin-based matrices. Since ultrasound-mediated gene transfer is enhanced using microbubbles, we compared the efficacy of neutral and cationic forms of these reagents on the ultrasound-stimulated gene transfer process in gel matrices. In doing so we demonstrated the beneficial effects associated with the use of cationic microbubble preparations that interact directly with cells and nucleic acid within matrices. In some cases, gene expression was increased two-fold in gel matrices when cationic microbubbles were compared with neutral microbubbles. In addition, incorporating collagen into fibrin gels yielded a 25-fold increase in gene expression after application of ultrasound to microbubble-containing matrices. We suggest that this novel system may facilitate non-invasive temporal and spatial control of gene transfer in gel-based matrices for the purposes of tissue regeneration.


Deficiency of replication-independent DNA mismatch repair drives a 5-methylcytosine deamination mutational signature in cancer.
Multiple mutational signatures have been associated with DNA mismatch repair (MMR)–deficient cancers, but the mechanisms underlying their origin remain unclear. Here, using mutation data from cancer genomes, we identify a previously unknown function of MMR that is able to protect genomes from 5-methylcytosine (5mC) deamination–induced somatic mutations in a replication-independent manner. Cancers with deficiency of MMR proteins MSH2/MSH6 (MutSα) exhibit mutational signature contributions distinct from those that are deficient in MLH1/PMS2 (MutLα). This disparity arises from unrepaired 5mC deamination–induced mismatches rather than replicative DNA polymerase errors. In cancers with biallelic loss of MBD4 DNA glycosylase, repair of 5mC deamination damage is strongly associated with H3K36me3 chromatin, implicating MutSα as the essential factor in its repair. We thus uncover a noncanonical role of MMR in the protection against 5mC deamination–induced mutation in human cancers.


[Reversion the multidrug resistance of human breast carcinoma cells by RNA interference targeting HIF-1 alpha gene].
To reverse the multidrug resistant (MDR) phenotype of human breast carcinoma cells by small hairpin RNA (shRNA) technique targeting hypoxia-inducible factor (HIF)-1alpha gene. Small hairpin RNA (shRNA) eukaryotic expression vector targeting HIF-1alpha gene, named pSilencer-HIF, was constructed and transfected into MCF-7/ADR human breast cancer cells by liposome technique. Tumor cell livability (TCL) and Rhodamine 123 efflux assay were used to monitor the biological changes of the transfected cells. The mRNA and protein expression of HIF-1alpha and mdr-1 were investigated by RT-PCR and Western blot. The successful construction of pSilencer-HIF plasmid was confirmed by DNA sequencing. HIF-1alpha mRNA and protein levels were significantly decreased in MCF-7/ADR cells after the transfection and there was a direct correlation between HIF-1alpha and mdr-1 expression. By comparing the cells transfected with control vector and the MCF-7/ADR cells transfected with pSilencer-HIF, a reduced TCL from 76% to 43%, and an increased Rhodamine 123 fluorescence intensity from 22.0% to 86.6% were observed. pSilencer-HIF-1alpha has been successfully constructed. The inhibition of HIF-1alpha expression through shRNA technique can significantly reverse the multidrug resistance phenotype of MCF-7/ADR cells.


Spathoside, a cerebroside and other antibacterial constituents of the stem bark of Spathodea campanulata.
Spathoside, a new cerebroside was isolated from the stem bark of Spathodea campanulata, besides known compounds (n-alkanes, linear aliphatic alcohols, sitosterol and their esters, beta-sitosterol-3-O-beta-D-glucopyranoside, oleanolic acid, pomolic acid, p-hydroxybenzoic acid and phenylethanol esters). The structures of the isolated compounds were established by spectroscopic studies. The antibacterial activity of the isolated compounds against a wide range of microorganisms was examined. They inhibited significantly the growth of some gram-positive and -negative bacteria.


PedBotHome: A Video Game-Based Robotic Ankle Device Created for Home Exercise in Children With Neurological Impairments.
This pilot study assesses the feasibility of using PedBotHome to promote adherence to a home exercise program, the ability of the device to withstand frequent use, and changes in participant ankle mobility.PedBotHome is a robotic ankle device with integrated video game software designed to improve ankle mobility in children with cerebral palsy. Eight participants enrolled in a 28-day trial of PedBotHome. Ankle strength, range of motion, and plantar flexor spasticity were measured pre- and posttrial. Performance was monitored remotely, and game settings were modified weekly by physical therapists. Four participants met the study goal of 20 days of use. There were statistically significant improvements in ankle strength, spasticity, and range of motion. PedBotHome is a feasible device to engage children with static neurological injuries in ankle home exercise. This pilot study expands the paradigm for future innovative home-based robotic rehabilitation.


Immune abnormalities in the diabetic New Zealand obese (NZO) mouse: insulin treatment partially suppresses splenic hyperactivity measured by flow cytometric analysis.
Immune abnormalities in both the humoral and cell-mediated immune systems were found in New Zealand obese (NZO) mice, a model of diabetes associated with autoimmune disease. Both the formation of anti-sheep red blood cell plaques and mitogen stimulation of NZO spleen cells were significantly decreased compared to normal strains of mice. In addition to perturbations of splenic lymphocyte function, the enlarged spleens of NZO mice demonstrated increased cycling cells as measured by flow cytometric analysis of the DNA content of individual cells. These abnormalities are similar but less pronounced than those found in another autoimmune model, the New Zealand black (NZB) strain. The pancreases of diabetic NZO mice contained a higher fraction of nuclei with greater than 2c amount of DNA. Chronic insulin administration decreased the percentages of splenic proliferating cells and polyploid pancreas cells in NZO mice. In addition, insulin treatment of NZO mice decreased spleen weights and serum glucose levels. Chronic insulin treatment did not alter these parameters in either nondiabetic Balb/c or autoimmune NZB mice. Thus, the features of the NZO strain which serve as both an autoimmunity model and a diabetes model can be dissociated. Insulin treatment had a unique effect on NZO traits but not on NZB traits even through many of these traits were present in both strains. In conclusion, although autoimmunity may underlie the diseases of both the NZO and the NZB strains, the amelioration of some of the features of the NZO strain by insulin may represent the beneficial effects of insulin on the metabolic control of cellular function in NZO mice.


Slab gel electrophoresis of oligomeric proteins under high hydrostatic pressure. I. Description of the system and demonstration of the pressure dissociation of a dimer.
A high-pressure bomb was constructed to study the gel electrophoretic behavior of oligomeric proteins under pressure. The apparatus designed by us allows the use of a polyacrylamide slab gel with a capacity of up to 12 wells, therefore permitting the study of several samples in one experiment. The electrophoresis mobility of different single-chain proteins under pressure decreased in the same proportion and the elution pattern was similar to that of the control run at atmospheric pressure. Densitometric analysis of the gel did not show peak spread or asymmetric boundaries, indicating that their conformations were not drastically affected. On the other hand, high-pressure electrophoresis of a dimer, the tryptophan synthase beta 2 subunit, revealed the appearance of a second peak not present at atmospheric pressure. The mobility of the second peak was higher and its fraction increased by decreasing the protein concentration, indicating that the extra peak was the dissociated monomer. The separation under pressure occurs without drastic effects on the tertiary structure of the protein, which seems to furnish a method to study dissociation processes and to separate the constituent polypeptides of oligomeric complexes.


Sodium metabolism.
This brief review attempts to summarize important basic concepts of sodium metabolism including sodium ion distribution, sodium balance and the renal regulation of sodium excretion. Finally, an attempt has been made to relate these basic concepts to the mechanisms and management of common clinical situations of abnormal salt balance.


Transient response of nonlinear polymer networks: A kinetic theory.
Dynamic networks are found in a majority of natural materials, but also in engineering materials, such as entangled polymers and physically cross-linked gels. Owing to their transient bond dynamics, these networks display a rich class of behaviors, from elasticity, rheology, self-healing, or growth. Although classical theories in rheology and mechanics have enabled us to characterize these materials, there is still a gap in our understanding on how individuals (i.e., the mechanics of each building blocks and its connection with others) affect the emerging response of the network. In this work, we introduce an alternative way to think about these networks from a statistical point of view. More specifically, a network is seen as a collection of individual polymer chains connected by weak bonds that can associate and dissociate over time. From the knowledge of these individual chains (elasticity, transient attachment, and detachment events), we construct a statistical description of the population and derive an evolution equation of their distribution based on applied deformation and their local interactions. We specifically concentrate on nonlinear elastic response that follows from the strain stiffening response of individual chains of finite size. Upon appropriate averaging operations and using a mean field approximation, we show that the distribution can be replaced by a so-called chain distribution tensor that is used to determine important macroscopic measures such as stress, energy storage and dissipation in the network. Prediction of the kinetic theory are then explored against known experimental measurement of polymer responses under uniaxial loading. It is found that even under the simplest assumptions of force-independent chain kinetics, the model is able to reproduce complex time-dependent behaviors of rubber and self-healing supramolecular polymers.


Substantia nigra-mediated anticonvulsant actions: role of nigral output pathways.
Bilateral ablation of the superior colliculus in rats abolished the anticonvulsant effect of muscimol, a gamma-aminobutyric acid (GABA) agonist, infused into the substantia nigra. Our data indicate that the ability of intranigral muscimol to protect against maximal electroshock convulsions requires the integrity of the nigrotectal pathway. We present evidence that the nigrotegmental, nigrothalamic, and nigrostriatal projections do not appear to contribute to the nigral-evoked attenuation of electroshock convulsions. Inasmuch as the nigrotectal pathway utilizes the inhibitory neurotransmitter GABA, we hypothesize that the anticonvulsant effect of nigral manipulations in the electroshock test is a result of the disinhibition of neurons in the superior colliculus, the firing of which must therefore be capable of suppressing or disrupting electroshock-induced convulsions.


The digestion of fresh perennial ryegrass (Lolium perenne L. cv. Melle) and white clover (Trifolium repens L. cv. Blanca) by growing cattle fed indoors.
1. Pure swards of perennial ryegrass (Lolium perenne L. cv. Melle) or white clover (Trifolium repens L. cv. Blanca) were harvested daily at three and two stages of growth respectively, and offered to housed cattle. The grass diets comprised primary growth (May) and two later regrowths of contrasting morphology (i.e. leaf: stem values of 1.54 and 2.84 respectively), and were characterized by high contents of water-soluble carbohydrate and neutral-detergent fibre and comparable in vitro dry matter (DM) digestibilities (mean 0.80). Total nitrogen content was higher on primary growth grass (34 g/kg DM) than on regrowths (23 g/kg DM) but lower than values obtained for the two clover diets (38 and 43 g/kg DM, respectively). The clover diets had lower water-soluble carbohydrate contents than the grasses, comparable cellulose, but lower neutral-detergent fibre contents and in vitro DM digestibilities of 0.70 and 0.77 respectively. 2. The experiment lasted from May until August, during which time a total of twenty-one young Friesian steers (initial average live weight 130 kg) were used to determine both nutrient supply to the small intestine (twelve animals) and apparent digestibility (nine animals). Each diet was offered at three levels of DM intake (i.e. 18, 22 and 26 g/kg live weight). A further six steers, all fed at the rate of 22 g DM/kg live weight, were used to determine the metabolizable energy contents of the five diets by means of open-circuit calorimetry. 3. The three grass diets and the later-cut clover had, as intended, quite similar in vivo organic matter digestibilities, but that of the earlier-cut clover was lower, and this was associated with a large number of flower heads in this crop at the time of feeding. 4. On the clover diets, proportionately less of the ingested organic matter appeared to be digested in the rumen (0.40) compared with the grass diets (0.58) (P less than 0.001). On the high-N primary grass and the clover diets, substantial rumen losses of N were detected (P less than 0.01) compared with regrowth grasses. 5. The metabolizable energy content of the primary growth of grass was 12.2 MJ/kg DM, whilst the values for the other two grass diets were lower (11.6 MJ/kg DM), despite no marked decline in overall energy digestibility. Values for the two clover diets (mean 10.5 MJ/kg DM) were considerably lower than all values noted for the grasses.(ABSTRACT TRUNCATED AT 400 WORDS)


Using home monitoring technology to study the effects of traumatic brain injury in older multimorbid adults.
Internet of things (IOT) based in-home monitoring systems can passively collect high temporal resolution data in the community, offering valuable insight into the impact of health conditions on patients' day-to-day lives. We used this technology to monitor activity and sleep patterns in older adults recently discharged after traumatic brain injury (TBI). The demographics of TBI are changing, and it is now a leading cause of hospitalisation in older adults. However, research in this population is minimal. We present three cases, showcasing the potential of in-home monitoring systems in understanding and managing early recovery in older adults following TBI.


Predicting violent reconvictions using the HCR-20.
Risk assessment of future violent acts is of great importance for both public protection and care planning. Structured clinical assessments offer a method by which accurate assessments could be achieved. To test the efficacy of the Historical, Clinical and Risk Management Scales (HCR-20) structured risk assessment scheme on a large sample of male forensic psychiatric patients discharged from medium secure units in the UK. In a pseudo-prospective study, 887 male patients were followed for at least 2 years. The HCR-20 was completed using only pre-discharge information, and violent and other offending behaviour post-discharge was obtained from official records. The HCR-20 total score was a good predictor of both violent and other offences following discharge. The historical and risk sub-scales were both able to predict offences, but the clinical sub-scale did not produce significant predictions. The predictive efficacy was highest for short periods (under 1 year) and showed a modest fall in efficacy over longer periods (5 years). The results provide a strong evidence base that the HCR-20 is a good predictor of both violent and non-violent offending following release from medium secure units for male forensic psychiatric patients in the UK.


Preventing intra-urethral migration of a guidewire during antegrade placement of a JJ stent: a technical modification.
A JJ stent is usually inserted in antegrade fashion after percutaneous renal surgery. We describe a new technical modification for antegrade stent insertion that prevents intraoperative intra-urethral migration of the guidewire and saves operative time and cost.


Tracheation of abdominal ganglia and cerci in the house cricket Acheta domesticus (Orthoptera, Gryllidae).
Patterns of tracheation in the abdominal central nervous system and the cerci of Acheta domesticus are described from whole mounts, and light and electron microscopy. The tracheal supply of the ganglia is derived from ventral longitudinal tracheal trunks which have segmental connections to the spiracels. Each abdominal ganglion is served by a single pair of tracheal trunks, except the terminal ganglion, which has two pairs. Within the ganglia, tracheoles occur principally in association with glia-rich areas of the neuropile. We suggest that the respiratory exchange may be concentrated in the cell bodies of neurons and glia. Each cercus has a tracheal supply in paralle with a large air sac which, it is suggested, serves to lighten the cercus, functions as a resonator for sound reception, or facilitates tidal flow of hemolymph and postecdysial expansion of the cercus. No tracheae run continuously between ganglia or between the terminal ganglion and the cerci, and they do not appear to have a potential role as a contact guidance pathway for cercal nerve growth.


Toxic elements in the stream sediments of an urbanized basin, Eastern China: urbanization greatly elevates their adverse biological effects.
The concentration of toxic elements (Hg, Cd, Cr, Cu, Pb, Zn, Ni and As) was measured in the sediments of the Qinhuai River in Eastern China along a rural to urban gradient. Multiple approaches were undertaken to evaluate the degree of enrichment and adverse biological effects of these elements. The results showed that the concentration of Hg, Cd, Zn, Cu and Pb increased exponentially from the agricultural headwater to the urbanized downstream, which reflects a severe anthropogenic influence. In addition, area-specific references, such as the local soil background (LSB) and upper continental crust (UCC) derived from the Yangtze craton, were more applicable for evaluating the enrichment of toxic elements in the Qinhuai River than was global UCC. In addition, Cd and Hg had the highest enrichment factor values (EF, with averages of 9.18 and 7.14, respectively); Zn, Pb and Cu had moderate EFs (averages from 1.52 to 2.40), while the average EFs of Ni, Cr and As were approximately equal to 1. Based on consensus-based sediment quality guidelines (SQGs), the contamination characteristics of all of the samples studied were associated with low to moderate priority of adverse biological effects (ABEs) in the rural upstream area, while it was associated with a high to moderate priority of ABEs in the urban sections of the Qinhuai River. Our results suggest that the adverse biological effects of elevated levels of toxic elements were strongly related to the degree of anthropogenic pollution.


Human papillomavirus type 45 propagation, infection, and neutralization.
The organotypic (raft) culture system has allowed the study of the entire differentiation-dependent life cycle of human papillomaviruses (HPVs), including virion morphogenesis. We introduced linearized HPV45 genomic DNA into primary keratinocytes, where it recircularized and maintained episomally at a range of 10-50 copies of HPV genomic DNA. Following epithelial stratification and differentiation in organotypic culture, virion morphogenesis occurred. HPV45 virions were purified from raft cultures and were able to infect keratinocytes in vitro. By testing a panel of HPV VLP antisera, we were able to demonstrate that the infection was neutralized not only with human HPV45 VLP-specific antiserum, but also with human HPV18 VLP-specific antiserum, demonstrating serological cross-reactivity between HPV18 and HPV45.


Tourist hepatitis, antibodies to hepatitis A virus and immune serum globulin prophylaxis.
Immune serum globulin prophylaxis for foreign travellers should be reserved for those at high risk having no immunity against hepatitis A. In this study from Sweden the incidence of tourist hepatitis in different age groups was correlated to the prevalence of antibodies to hepatitis A virus (anti-HAV) in the population. 58% of individuals over 50 years had anti-HAV and travellers in these ages seldom experienced "tourist hepatitis". In younger age groups a low prevalence of anti-HAV (11%) was combined with a higher incidence of tourist hepatitis.


Manipulating single excess electrons in monolayer transition metal dihalide.
Polarons are entities of excess electrons dressed with local response of lattices, whose atomic-scale characterization is essential for understanding the many body physics arising from the electron-lattice entanglement, yet difficult to achieve. Here, using scanning tunneling microscopy and spectroscopy (STM/STS), we show the visualization and manipulation of single polarons in monolayer CoCl2, that are grown on HOPG substrate via molecular beam epitaxy. Two types of polarons are identified, both inducing upward local band bending, but exhibiting distinct appearances, lattice occupations and polaronic states. First principles calculations unveil origin of polarons that are stabilized by cooperative electron-electron and electron-phonon interactions. Both types of polarons can be created, moved, erased, and moreover interconverted individually by the STM tip, as driven by tip electric field and inelastic electron tunneling effect. This finding identifies the rich category of polarons in CoCl2 and their feasibility of precise control unprecedently, which can be generalized to other transition metal halides.


Environmental implications of stored cattle slurry treatment with sulphuric acid and biochar: A life cycle assessment approach.
With the increase of animal slurry produced from livestock production, the monitoring and mitigation of greenhouse gas (GHG) and ammonia (NH3) emissions represent a major issue. Life cycle assessment (LCA) has been used to evaluate the long-term environmental effects of applied strategies and technologies on cattle slurry management for mitigation of environmental harmful gases. This study was carried on two main aims: first, the effect of the addition of sulphuric acid (SA), biochar (SBi) or A + Bi to liquid cattle-slurry (treated systems) on gas emissions during storage compared to the untreated system (S) was investigated in a laboratory-controlled experiment; second, the environmental implications of each treated or untreated system were assessed through a LCA approach according to ISO 14040/44. Five CML 2001 impact categories were used: eutrophication potential (EP), acidification potential (AP), global warming potential (GWP), human toxicity potential (HTP) and Ozone Layer Depletion Potential (ODP). Comparisons were based on 1 ton fresh dairy cattle slurry. The environmental profile of untreated system showed lower efficiency in mitigation of total GHG and NH3 emissions (0.0312 and 0.0001 kg CO2-eq respectively), during storage period and greater impact on GWP and HTP categories. The electricity consumption in mechanical separation dominated the environmental impacts. From the three proposed treated systems, SA showed the highest efficiency on mitigation of gas emissions compared to the other treatments, reducing NH3, CH4 and CO2 emissions respectively in 61%, 98% and 15%, when compared to the SBi system. In all categories, acidified slurry also showed the lowest environmental impact relative to other treated systems and the benefit was more evident when the impacts were expressed per kilogram of nitrogen in the slurry. Therefore, LCA methodology was of great importance to assess the environmental implications of the treatments and acidification can be considered as an effective technique on the mitigation of environmental implications of livestock production and cattle-effluent valorization. Optimization and uniformity of performed studies are essential to validate new strategies to improve the sustainability of this sector in the management of animal wastewater.


[Primary intestinal lymphomas. Review of the literature apropos of a clinical case].
A rare case of primary lymphoma of the bowel in a 26 year old woman is reported and the complex problems of diagnosis and treatment are examined. The importance of establishing the primary or secondary nature of this tumour of the small bowel is emphasised. This is because primary intestinal tumours require the most radical treatment possible even in advanced stages of the disease in order to avoid complications and to identify the areas involved in the proliferative process. Finally the importance of continuing surgery with drug and radiation treatment in order to improve prognosis is emphasised.


Imaging Misdiagnosis Analysis of a Rare Case of Renal Subcapsular Hematoma Located in the Renal Hilum and Collecting Area.
We report a rare case of renal subcapsular hematoma, which was located in the renal hilum and collecting area. Preoperative ultrasonography, retrograde urethrography, and computed tomographic examinations misdiagnosed the patient with simple hydronephrosis, without finding a lesion causing the hydronephrosis. We retrospectively summarized the imaging features and analyzed the reasons leading to the misdiagnosis.


Therapeutic Alternatives in the Management of Late Complications of Surgery for Isolated Coarctation of the Aorta.
Despite initial technical success in the treatment of coarctation of aorta, late recurrence and/or development of aneurysms and pseudoaneurysms frequently prompt reintervention. The authors hereby present such a patient whose management required more than a single intervention to treat his complex anatomy, and they discuss the therapeutic alternatives under similar circumstances.


Intensity modulated radiotherapy with simultaneous integrated boost vs. conventional radiotherapy with sequential boost for breast cancer - A preliminary result.
This study was aimed to assess the acute dermatological adverse effect from two distinct RT techniques for breast cancer patients. We compared intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) and conventional radiotherapy followed by sequential boost (CRT-SB). The study population was composed of 126 consecutive female breast cancer patients treated with breast conserving surgery. Sixty-six patients received IMRT-SIB to 2 dose levels simultaneously. They received 50.4 Gy at 1.8 Gy per fraction to the whole breast and 60.2 Gy at 2.15 Gy per fraction to the tumor bed by integral boost. Sixty patients in the CRT-SB group received 50 Gy in 25 fractions to the whole breast followed by a boost irradiation to tumor bed in 5-7 fractions to a total dose of 60-64 Gy. Acute skin toxicities were documented in agreement with the Common Terminology Criteria for Adverse Events version 3 (CTCAE v.3.0). Ninety-eight patients had grade 1 radiation dermatitis while 14 patients had grade 2. Among those with grade 2, there were 3 patients in IMRT-SIB group (4.5%) while 11 in CRT-SB group (18.3%). (P = 0.048) There was no patient with higher than grade 2 toxicity. Three year local control was 99.2%, 3-year disease free survival was 97.5% and 3-year overall survival was 99.2%. A significant reduction in the severity of acute radiation dermatitis from IMRT-SIB comparing with CRT-SB is demonstrated.


In silico analysis of a novel protein in CAR T- cell therapy for the treatment of hematologic cancer through molecular modelling, docking, and dynamics approach.
Cellular therapy has emerged as a key tool in the treatment of hematological malignancies. An advanced cell therapy known as chimeric antigen receptor T cell therapy (CAR T-cell therapy) has been approved by the United States Food and Drug Administration (FDA) as KYMRIAH by Novartis and YESCARTA by Gilead/Kite pharma in the year 2017. A chimeric receptor is composed of an extracellular antigen recognition site along with some co-stimulating and signalling domains. On the whole, it turns out to be one of the most potent receptors on T cells targeting a specific type of cancer cell based on its antigenic marker. CD19 CAR T-cell therapy is the first clinically approved therapy for lymphoma with remarkable results in complete remission of B cell lymphoblastic leukemia up to 90%. The high rate of effectiveness of the CAR T-cell therapy against B-ALL justifies the investigation and application of this therapy for fatal diseases like all types of hematological malignancies. The most critical aspect of chimeric receptor therapy is designing and building an artificial receptor that is specific to a given type of cancer. For this reason, the in silico technique is an appropriate model to investigate the integrity and effectiveness of the engineered chimeric receptor prior to commencing in vitro experiments followed by clinical trials. This computerized experimental study aids in predicting the molecular mechanism of chimeric protein and how it interacts with both ligands. We have anticipated various features of the chimeric protein in terms of qualitative analysis (structure, protein modelling, physiological properties) and functional analysis (antigenicity, allergenicity, its receptor-ligand binding ability, involving signalling pathways). Furthermore, the reliability and validation of the binding mode of the chimeric protein against receptors were performed through a complex molecular dynamics simulation for a 100 ns timeframe in an aqueous environment. The obtained simulation study showed that CD30 was a better approachable marker as compared to CD20 due to its better binding energy score and also binding conformations stability.


Impact of phosphate additive on organic carbon component degradation during pig manure composting.
Phosphate, as an additive to composting, could significantly reduce ammonia emission and nitrogen loss but may also cause adverse effects on the degradation of organic matter. However, there is little information about the influence of pH change, salt content, and phosphate on different organic fraction degradation during composting with the addition of phosphate at a higher level. In this study, the equimolar phosphoric acid (H3PO4), sulfuric acid (H2SO4), and dipotassium phosphate (K2HPO4) were added into pig manure composting with 0.25 mol mass per kilogram of dry matter basis addition amount to evaluate the effect of H+, PO43-, and salinity on carbon component transformation and organic matter degradation. The results showed that both H3PO4 and K2HPO4 additives could lead to shorter duration in the thermophilic phase, lower degradation of lignocellulose, and lesser carbon loss compared to CK, even though had different pH, i.e., acidic and alkaline conditions, respectively. Besides, the addition of H3PO4, H2SO4, and K2HPO4 could increase the degradation of soluble protein and lipid during composting. Redundancy analysis demonstrated that the variation in different organic carbon fractions was significantly correlated with the changes of pH and the presence of PO43-, but not with SO42- and electrical conductivity, suggesting that pH and phosphate were the more predominant factors than salinity for the inhibition of organic matter degradation. Taken together, as acidic phosphate addition produces a true advantage of controlling nitrogen loss and lower inhibition of organics transformation during composting, the expected effects may result in more efficient composting products.


NPM1-mutation-based measurable residual disease assessment after completion of two courses of post-remission therapy is a valuable clinical predictor of the prognosis of acute myeloid leukemia.
Recent studies have reported that measurable residual disease (MRD) analysis using NPM1 mutations helps determine whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) is indicated in acute myeloid leukemia (AML) patients. However, the optimal timing and cutoff value for measuring MRD using genomic DNA remain undetermined. This study aimed to investigate the optimal timing and cutoff value to ascertain the value of NPM1 mutation in MRD assessment. NPM1-mutated MRD was quantified by real-time polymerase chain reaction of bone marrow samples from 56 patients with NPM1-positive AML who achieved hematological remission. The area under the receiver-operating characteristic curve was greatest when MRD was assessed after two courses of post-remission therapy with a cutoff value of 0.010% (specificity, 68.4%; sensitivity, 87.0%). Patients whose MRD was below the cutoff value throughout the course of treatment had significantly better overall survival and relapse-free survival rates. Of the 33 patients who did not undergo transplantation during the first remission, all of the 11 who were never MRD-negative at any point experienced a relapse. Evaluating MRD with a cutoff value of 0.010% after two courses of post-remission therapy helps predict prognosis and determine the indication for allo-HSCT.


ntEdit+Sealer: Efficient Targeted Error Resolution and Automated Finishing of Long-Read Genome Assemblies.
High-quality genome assemblies are crucial to many biological studies, and utilizing long sequencing reads can help achieve higher assembly contiguity. While long reads can resolve complex and repetitive regions of a genome, their relatively high associated error rates are still a major limitation. Long reads generally produce draft genome assemblies with lower base quality, which must be corrected with a genome polishing step. Hybrid genome polishing solutions can greatly improve the quality of long-read genome assemblies by utilizing more accurate short reads to validate bases and correct errors. Currently available hybrid polishing methods rely on read alignments, and are therefore memory-intensive and do not scale well to large genomes. Here we describe ntEdit+Sealer, an alignment-free, k-mer-based genome finishing protocol that employs memory-efficient Bloom filters. The protocol includes ntEdit for correcting base errors and small indels, and for marking potentially problematic regions, then Sealer for filling both assembly gaps and problematic regions flagged by ntEdit. ntEdit+Sealer produces highly accurate, error-corrected genome assemblies, and is available as a Makefile pipeline from https://github.com/bcgsc/ntedit_sealer_protocol. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Automated long-read genome finishing with short reads Support Protocol: Selecting optimal values for k-mer lengths (k) and Bloom filter size (b).


Hispanic ethnicity and the rs4880 variant in SOD2 are associated with elevated liver enzymes and bilirubin levels in children receiving asparaginase-containing chemotherapy for acute lymphoblastic leukemia.
Asparaginase is an integral component of acute lymphoblastic leukemia (ALL)3 treatment. Hepatotoxicity related to asparaginase is one of the most common treatment-related toxicities in ALL therapy. Hispanic children are at higher risk of developing ALL, and toxicities from ALL therapy. The rs4880 variant in the superoxide dismutase 2 (SOD2)4 gene, a critical mitochondrial enzyme that protects cells against oxidative stress, was found to be associated with increased incidence of asparaginase-related hepatotoxicity in adult cohort of largely White non-Hispanics patients with ALL. The risk genotype (rs4880-CC) is more frequent among adult Hispanic patients with ALL. To assess the prevalence of hepatotoxicity and risk genotype among pediatric patients with ALL, particularly of Hispanic ethnicity, we conducted a prospective study of 143 pediatric patients with ALL (62.2% Hispanic). Bilirubin and hepatic transaminase levels were collected at different times during multiagent therapy including asparaginase treatment. Germline DNA blood samples were genotyped for the SOD2 rs4880. We found that the frequency of hepatotoxicity and the rs4880-CC risk genotype are higher in Hispanic patients than non-Hispanic. Patients with the CC genotype exhibit higher bilirubin and hepatic transaminase levels compared with patients with the TT and CT genotypes. In a multivariate Cox analysis, Hispanic ethnicity was identified as a strong predictor of hepatotoxicity (hazard ratio [HR] = 1.9, 95% confidence interval [95% CI] 1.0-3.5, p = 0.05). Altogether, these findings demonstrate that hepatotoxicity is highly prevalent among Hispanic pediatric patients with ALL, and those with rs4880-CC genotype.


Closing the gaps in pediatric laboratory reference intervals: a CALIPER database of 40 biochemical markers in a healthy and multiethnic population of children.
Pediatric healthcare is critically dependent on the availability of accurate and precise laboratory biomarkers of pediatric disease, and on the availability of reference intervals to allow appropriate clinical interpretation. The development and growth of children profoundly influence normal circulating concentrations of biochemical markers and thus the respective reference intervals. There are currently substantial gaps in our knowledge of the influences of age, sex, and ethnicity on reference intervals. We report a comprehensive covariate-stratified reference interval database established from a healthy, nonhospitalized, and multiethnic pediatric population. Healthy children and adolescents (n = 2188, newborn to 18 years of age) were recruited from a multiethnic population with informed parental consent and were assessed from completed questionnaires and according to defined exclusion criteria. Whole-blood samples were collected for establishing age- and sex-stratified reference intervals for 40 serum biochemical markers (serum chemistry, enzymes, lipids, proteins) on the Abbott ARCHITECT c8000 analyzer. Reference intervals were generated according to CLSI C28-A3 statistical guidelines. Caucasians, East Asians, and South Asian participants were evaluated with respect to the influence of ethnicity, and statistically significant differences were observed for 7 specific biomarkers. The establishment of a new comprehensive database of pediatric reference intervals is part of the Canadian Laboratory Initiative in Pediatric Reference Intervals (CALIPER). It should assist laboratorians and pediatricians in interpreting test results more accurately and thereby lead to improved diagnosis of childhood diseases and reduced patient risk. The database will also be of global benefit once reference intervals are validated in transference studies with other analytical platforms and local populations, as recommended by the CLSI.


Intra-arterial fibrinolytic therapy in central retinal artery occlusion.
We have treated 23 patients with central retinal artery occlusion by intra-arterial fibrinolysis, a method already in use for treatment of thromboembolic occlusion of the cerebral arteries. Fibrinolysis was carried out through a microcatheter placed in the origin of the ophthalmic artery. When ophthalmic artery cannot be catheterised, treatment can be carried out indirectly via the maxillary-ophthalmic anastomoses. In 18 cases urokinase was used in doses of 200,000-1,200,000 units; in 5 patients recombinant tissue plasminogen activator was used. Six patients showed marked improvement or total recovery, and six partial recovery, with improvement of visual acuity or a field defect. The worst results were obtained in six patients where the mean delay between the appearance of symptoms and initiation of treatment was more than 20 h. Intra-arterial thrombolysis led to a better outcome in acute occlusion of the central retinal artery than might have been expected with conservative treatment. A good prognosis is to be expected when treatment starts within the first 6-8 h, when some vision remains and when there is less retinal oedema.


Mimicking the photosynthetic system with strong hydrogen bonds to promote proton electron concerted reactions.
A Copper(2+) complex with a Cu(II)-C bond containing sp(3) configuration was used to investigate the role of strong hydrogen bonds in proton coupled electron transfer (PCET) reactions. The only example of a Cu(II)-C system realized so far is that using tris-(pyridylthio)methyl (tptm) as a tetradentate tripodal ligand. Using this ligand, [CuF(tptm)] and [Cu(tptm)(OH)] have been prepared. The former complex forms supra-molecular arrays of layers of the complex between which hydroquinone is intercalated in the crystalline phase. This hydroquinone intercalation crystal was prepared via the photochemical conversion of quinone during the crystallization process. This conversion reaction probably involves a proton coupled electron transfer process. The nuclear magnetic resonance spectroscopic analysis of the reaction mixture shows the presence of Cu(III) during the conversion reaction. These results strongly suggest the presence of the molecular aggregate of the [CuF(tptm)] complex, water and quinone in the solution phase during the quinone to hydroquinone conversion. The presence of this type of aggregate requires a strong hydrogen bond between the [CuF(tptm)] complex and water. The presence of this particular hydrogen bond is a unique character of such a complex that has the Cu(II)-C bond. This complex is used as a model for photosynthetic water splitting since the photoconversion of quinone to hydroquinone also involves the production of oxygen from water.


Orthorexia nervosa tendency among students of the department of nutrition and dietetics at a university in Istanbul.
The aim of this study was to determine an orthorexia nervosa scale score for and evaluate orthorexic tendency among students of nutrition and dietetics according to various sociodemographic characteristics. This cross-sectional study was carried out in May and June of 2016 among 208 students in the nutrition and dietetics department at a university in Istanbul. After receiving the approval of the university ethics committee, of a total of 300 students, 208 agreed to join the study. Participants completed a questionnaire related to individual characteristics and the ORTO-11 scale during a face-to-face interview. The ORTO-11 scale is a verified Turkish scoring system in which a low score indicates orthorexic tendency. The Mann-Whitney U test, independent samples t-test, Kruskal-Wallis test, and analysis of variance were used to assess the data. P<0.05 was accepted as statistically significant. Orthorexic tendency was significantly higher in males (p=0.050) and students who lived with their family (p=0.002). Mean ORTHO-11 scale score did not differ significantly between groups when the participants were grouped by parameters of smoking, alcohol consumption, chronic disease status, body mass index, diet observance, or use of nutritional supplement products. The orthorexic tendency was higher in men and in students who lived with their family. Additional assessment of individual eating habits, eating behavior, and personality characteristics would shed light on the reasons for the difference between gender groups. Qualitative studies should be carried out and possible confounding factors should be determined.


Effect of sewage sludge hydrochar on soil properties and Cd immobilization in a contaminated soil.
To investigate hydrochar as a soil amendment for the immobilization of Cd, the characteristics of hydrochars (HCs) under three temperatures and residence times, were studied, with a particular interest in soil properties, as well as the speciation, availability and plant uptake of Cd. HCs were obtained by a hydrothermal carbonization (HTC) reaction of sewage sludge (SS). Based on the study of HC properties, we found that HCs present weak acidity with relatively high ash content and low electrical conductivity (EC) values. The addition of HCs to soil decreased soil pH and EC values but increased the abundance of soil microorganism. HCs also promoted the transformation of Cd from unstable to stable speciation and can decrease the content of phyto-available Cd (optimum condition and efficiency: A13,2 15.38%), which restrained cabbage from assimilating Cd from soil both the aboveground (optimum condition and efficiency: A35, 52.29%) and underground (optimum condition and efficiency: C15, 57.53%) parts of it.


Prepaid group using prevention focus to lure back employers.
Prepaid medical groups like Grand Valley Health Plan, Grand Rapids, MI, are facing declining membership as employers shift to lower-priced PPOs. But some employers are starting to look more closely again at the value of managed care networks.


Chronic ethanol consumption increases plasma leptin levels and alters leptin receptors in the hypothalamus and the perigonadal fat of C57BL/6 mice.
Leptin, a protein secreted from adipocytes, and leptin receptors, expressed in the hypothalamus and fat tissue, regulate energy balance and adiposity. Leptin receptors exist as several forms that are delineated by the length of their cytoplasmic domains. Only the longest form is physiologically active through stimulation of the signal transducers and activators of transcription (STAT) second messenger system. Previous studies demonstrated that chronic ethanol consumption increases body adiposity and circulating leptin levels. This study examined the effect of chronic alcohol intake on the expression of leptin receptors and associated STAT second messengers in the hypothalamus and fat tissue. Female C57BL/6 mice were given water or 20% w/v ethanol and Purina 5001 laboratory chow ad libitum for 2 or 5 weeks. Plasma leptin levels were determined by radioimmunoassay and body adiposity was evaluated by measuring the amount of perigonadal fat. Expression of leptin receptors as well as STAT molecules in whole-cell lysates of the hypothalamus and the perigonadal fat were assayed by Western blot analysis. Plasma leptin and perigonadal fat were increased after 5 weeks. The overall expression of leptin receptors was increased while the expression of the physiologically active long form of leptin receptor was decreased in the hypothalamus and the perigonadal fat of ethanol-consuming mice. Ethanol consumption also decreased hypothalamic expression of STAT3, a protein associated with leptin receptor activation in this region of the brain. In contrast, STAT1, a protein associated with leptin receptor activation in adipose tissue, was significantly elevated in the perigonadal fat of ethanol-consuming mice. Chronic ethanol consumption increases the circulating level of leptin, and this is accompanied by altered expression of leptin-sensing molecules in the hypothalamus and peripheral adipose tissue. These results suggest that chronic ethanol intake affects metabolism by altering the leptin system that regulates energy balance.


Root system architecture, physiological analysis and dynamic transcriptomics unravel the drought-responsive traits in rice genotypes.
Drought is the major abiotic factors that limit crop productivity worldwide. To withstand stress conditions, plants alter numerous mechanisms for adaption and tolerance. Therefore, in the present study, 106 rice varieties were screened for drought tolerance phenotype via exposing different concentrations of polyethylene glycol 6000 (PEG) in the hydroponic nutrient medium at the time interval of 1, 3, and 7 days to evaluate the changes in their root system architecture. Further, based on root phenotype obtained after PEG-induced drought, two contrasting varieties drought-tolerant Heena and -sensitive Kiran were selected to study transcriptional and physiological alterations at the same stress durations. Physiological parameters (photosynthesis rate, stomatal conductance, transpiration), and non-enzymatic antioxidants (carotenoids, anthocyanins, total phenol content) production indicated better performance of Heena than Kiran. Comparatively higher accumulation of carotenoid and anthocyanin content and the increased photosynthetic rate was also observed in Heena. Root morphology (length, numbers of root hairs, seminal roots and adventitious roots) and anatomical data (lignin deposition, xylem area) enable tolerant variety Heena to better maintain membrane integrity and relative water content, which also contribute to comparatively higher biomass accumulation in Heena under drought. In transcriptome profiling, significant drought stress-associated differentially expressed genes (DEGs) were identified in both the varieties. A total of 1033 and 936 uniquely upregulated DEGs were found in Heena and Kiran respectively. The significant modulation of DEGs that were mainly associated with phytohormone signaling, stress-responsive genes (LEA, DREB), transcription factors (TFs) (AP2/ERF, MYB, WRKY, bHLH), and genes involved in photosynthesis and antioxidative mechanisms indicate better adaptive nature of Heena in stress tolerance. Additionally, the QTL-mapping analysis showed a very high number of DEGs associated with drought stress at AQHP069 QTL in Heena in comparison to Kiran which further distinguishes the drought-responsive traits at the chromosomal level in both the contrasting varieties. Overall, results support the higher capability of Heena over Kiran variety to induce numerous genes along with the development of better root architecture to endure drought stress.


Negative adsorption due to electrostatic exclusion of micelles.
Interactions of surfactants with solid substrates are important in the controlling of processes such as flotation, coating, flocculation and sedimentation. These interactions usually lead to adsorption on solids, but can also result in an exclusion of the reagents with dire consequences. In this work electrostatic exclusion of negatively charged dodecylbenzene sulfonate micelles from quartz/water, Bio-Sil/water and alumina/water interfaces has been investigated as a function of pH and ionic strength. Measurable negative adsorption of these surfactants from similarly charged solid/liquid interface was observed in the micellar region. In the case of porous samples with large surface area, comparison of pore size with the micelle size is necessary to avoid any erroneous conclusions regarding the role of electrostatic exclusion in a given system. A theoretical model for the electrostatic exclusion of micelles is developed and used to calculate the adsorption of negatively charged dodecylbenzene sulfonate on negatively charged quartz (pH 7), silica (Bio-Sil A, pH 3) and alumina (pH 11) in the micellar concentration region. The micellar exclusion values calculated using the model are in excellent agreement with the experimental results.


The gene for the dihydropyridine-sensitive calcium channel alpha 2 subunit (CCHL2A) maps to the proximal region of mouse chromosome 5.
A rat brain cDNA probe for the gene encoding the alpha 2 subunit of the dihydropyridine-sensitive L-type calcium channel was used as a hybridization probe for the Southern blot analysis of Chinese hamster x mouse somatic cell hybrids and the progeny of an intersubspecies backcross. This gene, termed Cchl2a, was mapped near the centromeric end of the Chromosome 5 linkage group with gene order: centromere-Pgy-1-Cchl2a-Il-6-Pgm-1.


Dietary salt, bone strength, and mineral content in unloaded rat femurs.
Reduced bone mineral and ultimate strength are regular consequences of unloading bone. The aim of this study was to determine if high dietary salt intake would reduce the bone density and strength to a greater extent in rats with unloaded bones compared to ambulatory control rats fed the same dietary calcium and phosphorus. Mature male Sprague-Dawley rats were divided into four groups: two exposed to a spaceflight model that unloaded the hind limbs (HU) and two controls (C) with normal ambulation. Half the HU and C rats were fed normal dietary salt (0.26%, NNa) and half high dietary salt (8%, HNa). The calcium (Ca) and phosphorus (P) content of the diets was normal (Ca 0.5% and P 0.6%) in all four groups. After 4 wk of hind limb unloading, the bone mineral content (BMC) of excised femurs was measured by the ash weight and the ultimate torsional strength was determined by a torsional strength test device. Femoral BMC (mg) was lower in HUNNa than C rats fed normal salt diets. Femurs from HU rats fed normal salt diets showed lower (20-26%) torsional strength (Nmm), compared to all other groups. It appears that high salt diets with normal amounts of calcium and phosphorus may prevent the decrease in bone torsional strength and BMC induced by unloading the femurs in 6-mo-old rats.


Vascular endothelial function and hypertension: insights and directions.
Hypertension contributes significantly to worldwide cardiovascular morbidity and mortality. Hypertension appears to have a complex association with endothelial dysfunction, a phenotypical alteration of the vascular endothelium that precedes the development of adverse cardiovascular events and portends future cardiovascular risk. This review concentrates on recent findings with respect to the mechanisms of hypertension-associated endothelial dysfunction, the interrelationship between these two entities, and the relationship of the efficacy of antihypertensive therapies to improvements in vascular homeostasis beyond blood pressure reduction. Current evidence suggests that hypertension and endothelial dysfunction are integrally related with respect to pathophysiologic mechanisms. Future studies will need to identify the key connections between hypertension and endothelial dysfunction to allow novel interventions to be designed and promulgated.


Myocardial ischaemia in a case of a solitary coronary ostium in the right aortic sinus with retroaortic course of the left coronary artery: documentation of the underlying pathophysiological mechanisms of ischaemia by intracoronary Doppler and pressure measurements.
Only a few cases of a single coronary ostium and retroaortic course of the coronary artery have been described. Almost all cases reported so far had additional coronary artery or valvar disease. However, myocardial ischaemia may be caused by the coronary malformation alone. A 40 year old woman with severe myocardial ischaemia in the absence of clinically relevant coronary atherosclerosis is described. To clarify the origin and mechanisms of ischaemia, intracoronary Doppler, pressure and ultrasound studies were performed using microtransducers. In its outer portion along the course behind the ascending aorta, coronary blood flow velocities were increased, there was an external elliptical compression, and distal coronary flow reserve was reduced. Furthermore, an overshoot in diastolic pressure above aortic pressure was detectable within this portion. Dobutamine stimulation exaggerated the observed intracoronary haemodynamics and induced myocardial ischaemia. The intracoronary diagnostic procedures performed were helpful in clarifying the pathophysiological mechanisms of functional coronary obstruction and ischaemia in this malformation. Bypass surgery was successfully performed with symptomatic improvement.


Effects of Saccharomyces cerevisiae hydrolysate on growth performance, immunity function, and intestinal health in broilers.
The current study was performed to explore the effects of dietary supplementation of Saccharomyces cerevisiae hydrolysate (SCH) on growth performance, immune function, and intestinal health in broiler chicken. A total of 300 Ross 308 male broilers (1-day-old) were randomly assigned to 2 dietary treatments including a basal diet (control group), and a basal diet supplemented with SCH feed additive (500 mg/kg in starter and grower phase, and 250 mg/kg in finisher phase). Each treatment had 6 replicates with 25 birds each. The results showed that the addition of SCH promoted growth during d 15 to 28 (P < 0.05). Although the addition of SCH had no significant effect on the intestinal relative indexes, it significantly increased the jejunum villus height (VH) and the ratio of villus height to crypt depth (VCR) of jejunum, and decreased the crypt depth (CD) of ileum (P < 0.05). Furthermore, SCH addition significantly downregulated the mRNA expression of immunomodulatory genes (TNF-α, IL-1β, and IL-6), and upregulated the tight junction genes (ZO-1 and Claudin-1) (P < 0.05). High throughput sequencing analysis of bacterial 16S rRNA revealed that dietary SCH supplementation altered cecum microbiota. Alpha diversity analysis showed that a higher bacterial richness in cecum of broilers fed with SCH. The composition of cecum microbiota regulated by SCH addition was characterized by an increased abundance of Firmicutes and a reduced abundance of Bacteroidetes. At the genus level, dietary SCH resulted in a decrease of Bacteroides and an increase of short-chain fatty acids (SCFA) -producing bacteria including Lactobacillus and Faecalibacterium. Taken together, dietary SCH supplementation can stimulate the growth of broilers by regulating the intestinal immunity and barrier function, and improving the intestinal morphology, which may be related to the enhancement of bacterial diversity and the changes of intestinal microbial composition.


Cost-effectiveness of non-vitamin K antagonist oral anticoagulants for atrial fibrillation in Portugal.
Recently, three novel non-vitamin K antagonist oral anticoagulants received approval for reimbursement in Portugal for patients with non-valvular atrial fibrillation (AF). It is therefore important to evaluate the relative cost-effectiveness of these new oral anticoagulants in Portuguese AF patients. A Markov model was used to analyze disease progression over a lifetime horizon. Relative efficacy data for stroke (ischemic and hemorrhagic), bleeding (intracranial, other major bleeding and clinically relevant non-major bleeding), myocardial infarction and treatment discontinuation were obtained by pairwise indirect comparisons between apixaban, dabigatran and rivaroxaban using warfarin as a common comparator. Data on resource use were obtained from the database of diagnosis-related groups and an expert panel. Model outputs included life years gained, quality-adjusted life years (QALYs), direct healthcare costs and incremental cost-effectiveness ratios (ICERs). Apixaban provided the most life years gained and QALYs. The ICERs of apixaban compared to warfarin and dabigatran were €5529/QALY and €9163/QALY, respectively. Apixaban was dominant over rivaroxaban (greater health gains and lower costs). The results were robust over a wide range of inputs in sensitivity analyses. Apixaban had a 70% probability of being cost-effective (at a threshold of €20 000/QALY) compared to all the other therapeutic options. Apixaban is a cost-effective alternative to warfarin and dabigatran and is dominant over rivaroxaban in AF patients from the perspective of the Portuguese national healthcare system. These conclusions are based on indirect comparisons, but despite this limitation, the information is useful for healthcare decision-makers.


COVID-19 pneumonia in kidney transplant recipients: Focus on immunosuppression management.
The coronavirus disease of 2019, also known as COVID-19, has been declared a global pandemic. Significant controversies exist regarding treatment modalities for this novel disease, especially in immunocompromised patients. Experience with management of COVID-19 in kidney transplant recipients is scarce; effects of this virus on immunosuppressed individuals are not well understood. We identified 30 renal transplant recipients with confirmed COVID-19 pneumonia who were admitted to inpatient between March 2020 and April 2020. All patients received a 5-day course of hydroxychloroquine and azithromycin; half of the patients received methylprednisolone. During hospitalization, calcineurin inhibitors and antimetabolites were held; prednisone was continued. Clinical presentation of flu-like symptoms was similar to those in the general population. Hyponatremia, lymphopenia, acute kidney injury, and elevated inflammatory markers were common. Over the course of follow-up, 23 have been discharged home with a functioning allograft and in stable condition; 4 experienced acute kidney injury requiring renal replacement therapy; 7 patients were intubated, and 6 expired. The mortality rate in our cohort was 20%. Our findings described the characteristics and outcomes of this highly fatal illness in a multi-ethnic kidney transplant cohort, with insights on immunosuppression management that could further our understanding of this unique disease in immunocompromised populations.


Concentrations of ionized and total magnesium and calcium in healthy horses: effects of age, pregnancy, lactation, pH and sample type.
Magnesium (Mg) and calcium (Ca) are the main divalent cations in the body. The free ionized fraction is the physiologically active form of both Mg and Ca. As ion-selective-electrode (ISE) analyzers are becoming widely used in veterinary practice it will be useful to establish reference intervals for horses. In the present study, reference intervals were established for ionized, total and the ratio of the ionized to total Mg and Ca concentrations in four horse groups: adults, neonatal foals, and pregnant and lactating mares, as well as in three sample types, whole blood, plasma and serum, using an ISE-analyzer. Sample pH effect was assessed. Concentration differences in both total and ionized cations were recorded for some measures between horse groups and different sample types. The most significant differences were recorded between neonatal foals and other groups. These results demonstrate the need to use specific reference intervals for horses of different physiologic status and in specific sample types.


Unemployment causes ill health: the wrong track.
It is not unemployment per se that causes ill health. It can be a very desirable state. There are no diseases specific to unemployment. Contrast this with employment. Unemployment shares with all other socio-environmental situations risk of exposure to common physical, social and psychological stressors that predispose to disease. Focus for action and research should be on reducing such stressors and not on provision of full employment. The former is likely to be possible and beneficial. The latter is likely to be impossible and carries a risk of making matters worse. As an immediate first step, that will reduce 'cratogenic' disease, people in authority should stop misleading the public into believing that unemployment is the cause of ill health.


Association of Liver Transaminase Levels and Long-Term Blood Pressure Variability in Military Young Males: The CHIEF Study.
Background: An inverse relationship of serum liver transaminases and mortality might be due to better blood pressure control in hypertensive patients. Whether it holds true regarding such an association for long-term blood pressure variability (BPV) in those without antihypertensive therapy is unclear. Methods: A population of 1112 military males without antihypertensive medications, aged 32 years, was collected from a retrospective longitudinal study in Taiwan. Serum liver aspartate and alanine transaminase (AST and ALT) levels were obtained from a 12 h-fast blood sample of each participant. BPV was assessed by standard deviation (SD) and average real variability (ARV) of systolic and diastolic blood pressure (SBP and DBP), respectively across 4 visits during the study period (2012-2014, 2014-2015, 2015-2016, and 2016-2018). Multivariable linear regression analysis was utilized to determine the association adjusting for demographics, anthropometric indexes, SBP, DBP, and lipid profiles. Results: In the unadjusted model, ALT was significantly and positively correlated with SDDBP and ARVDBP (β (standard errors) = 0.36 (0.16) and 0.24 (0.12), respectively), and so was AST (β = 0.19 (0.08) and 0.14 (0.06), respectively). All the associations were insignificant with adjustments. However, ALT was significantly and negatively correlated with SDSBP and ARVSBP (β = -0.35 (0.14) and -0.25 (0.11), respectively) and so was AST (β = -0.14 (0.07) and -0.12 (0.06), respectively) with adjustments. Conclusion: Our findings suggested that serum liver transaminases were negatively correlated with long-term systolic BPV in young male adults without antihypertensive therapy, and the clinical relevance needs further investigations.


Histologic features of the liver biopsy predict the clinical outcome for patients with graft-versus-host disease of the liver.
We reviewed liver histologic results from all allogeneic hematopoietic stem cell transplant recipients from our institution with a confirmed diagnosis of liver graft-versus-host disease (L-GVHD), no concomitant causes of liver dysfunction, and at least 1 diagnostic liver biopsy sample (n=33) to ascertain whether histologic features predicted clinical outcome. The 1-year probability of nonrelapse mortality (NRM) from the onset of liver dysfunction was 68.15%, with a median overall survival (OS) of 6.2 months for the entire group. Histologic features traditionally linked to the diagnosis of L-GVHD (eg, bile duct damage, bile duct lymphocytic infiltration, portal inflammation, and ductopenia) had no association with patient outcome. However, an extended histologic analysis showed that a high level of lobular inflammation (LI) and a low level of hepatocyte ballooning (HB) were independent favorable prognostic factors for NRM (RR, 5.14; P=.033; and relative risk (RR), 0.18; P=.018, respectively) and OS (RR, 3.99; P=.032; and RR, 0.23; P=.037, respectively). The presence and severity of LI and HB were not associated with patient- or transplant-related characteristics or L-GVHD clinical factors such as timing of the biopsy from the onset of L-GVHD, acute versus chronic presentation, or whether the patients had started immunosuppressive treatment with steroids at the time of the biopsy. In multivariate analysis that included clinical prognostic factors, the combined histologic risk posed by high LI and low HB retained independent favorable prognostic value for NRM (RR, 5.05; P=.015) and OS (RR, 3.31; P=.038). This information, if replicated in other studies, could expand current indications for liver biopsy in patients with L-GVHD, not only to exclude other causes of liver injury, but also to predict clinical outcome, and should be considered in the selection of patients and the design of future trials with new experimental therapies for this complication. Prospective validation of our findings is warranted.


Mycophenolate mofetil for the treatment of uveitis.
To evaluate the efficacy and tolerance of mycophenolate mofetil (MMF) for the treatment of noninfectious uveitis using the methods of analysis advocated by the Standardization of Uveitis Nomenclature (SUN) Working Group, and to compare this with other SUN-compliant reports of immunosuppression in ocular inflammation. Retrospective case series. MEDHODS: A predefined data set was retrospectively obtained from the case notes of 100 consecutive uveitis patients treated with MMF at a single academic referral center between April 1, 2000 and August 1, 2006. These data were then analyzed in accordance with SUN recommendations. The main outcome measures were: 1) rate of tapering oral prednisone to 10 mg daily, 2) requirement for alternative second-line immunosuppressive therapy, and 3) rate of MMF dose discontinuation because of side effects. In this large cohort with noninfectious persistent, chronic, or recurrent uveitis, there was an 84.6% probability of achieving a prednisone dose of < or =10 mg daily after one year of MMF treatment. Alternative second-line immunosuppressive therapy was introduced at a rate of 0.18 per patient-year (PY) and MMF was discontinued because of intolerance at a rate of 0.09/PY, predominantly because of gastrointestinal upset. This corroborates the findings of the only previous SUN-compliant study of MMF in ocular inflammation and is comparable to the rates of treatment success and intolerance we have recently reported for tacrolimus. This data generates concordant evidence with other SUN-compliant studies supporting the use of MMF in uveitis.


High performance perovskite solar cell via multi-cycle low temperature processing of lead acetate precursor solutions.
A lead acetate-based precursor, as a lead source in CH3NH3PbI3 perovskite, showed potential in rapidly (<60 seconds) forming homogeneous films with a very smooth interface and large grain growth at relatively low temperatures via multi-step coating. Cells based on this method exhibited high power conversion efficiency beyond 17% with good reproducibility.


A composite scaffold of MSC affinity peptide-modified demineralized bone matrix particles and chitosan hydrogel for cartilage regeneration.
Articular cartilage injury is still a significant challenge because of the poor intrinsic healing potential of cartilage. Stem cell-based tissue engineering is a promising technique for cartilage repair. As cartilage defects are usually irregular in clinical settings, scaffolds with moldability that can fill any shape of cartilage defects and closely integrate with the host cartilage are desirable. In this study, we constructed a composite scaffold combining mesenchymal stem cells (MSCs) E7 affinity peptide-modified demineralized bone matrix (DBM) particles and chitosan (CS) hydrogel for cartilage engineering. This solid-supported composite scaffold exhibited appropriate porosity, which provided a 3D microenvironment that supports cell adhesion and proliferation. Cell proliferation and DNA content analysis indicated that the DBM-E7/CS scaffold promoted better rat bone marrow-derived MSCs (BMMSCs) survival than the CS or DBM/CS groups. Meanwhile, the DBM-E7/CS scaffold increased matrix production and improved chondrogenic differentiation ability of BMMSCs in vitro. Furthermore, after implantation in vivo for four weeks, compared to those in control groups, the regenerated issue in the DBM-E7/CS group exhibited translucent and superior cartilage-like structures, as indicated by gross observation, histological examination, and assessment of matrix staining. Overall, the functional composite scaffold of DBM-E7/CS is a promising option for repairing irregularly shaped cartilage defects.


Running economy in long-distance runners is positively affected by running experience and negatively by aging.
The maximum oxygen uptake (V˙O2max), the maximum rate of oxygen that can be sustained before the onset of blood lactate accumulation, and the metabolic cost of locomotion are the main physiological factors associated with long-distance running performance. The latter is known as the running economy. Generally, runners reach peak performance in long races between 25 and 30 years of age, with a progressive decline occurring thereafter. However, it is not known whether the running economy is affected or how it is affected by aging. To investigate the effect of age and years of running experience on the running economy of amateur long-distance runners aged 20-80 years. Sixty-nine recreational long-distance runners, divided into five age groups according to decade of life, participated in this study: Group 1 (n= 9) 27.2 ± 1.3 years, Group 2 (n= 18) 35.9 ± 2.2 years, Group 3 (n= 17) 43.4 ± 2.8 years, Group 4 (n= 17) 53.0 ± 2.3 years, and Group 5 (n= 8) 65.5 ± 2.9 years. For running economy assessment, oxygen cost (OC) and energy cost (EC) were measured. Furthermore, the participants were interviewed on their running experience. For EC, the two independent variables composing the regression model were age (ß = 0.703, t= 5.443, p < 0.001) and running experience (ß = -0.230, t = -1.785, p= 0.07), and 34% of the energy cost variation can be explained by these two factors. EC and OC were compared among the groups. There were no significant differences between Groups 1 and 2 (p= 0.999), Groups 1 and 3 (p= 1.000), and Groups 1 and 4 (p= 0.528). However, Group 5 had a significantly higher energy cost than Group 1 (p < 0.001), Group 2 (p < 0.001), Group 3 (p < 0.001) and Group 4 (p < 0.001). The number of years of running experience has a positive effect on running economy, but it is insufficient to overcome the negative effect of the aging process. Furthermore, running economy was significantly worse in participants aged ≥60 years compared with that in younger athletes.


Antiglomerular basement membrane antibodies in human sera: detection by a modified micro-ELISA.
An enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to human glomerular basement membrane has been developed. Special emphasis has been put on the choice of microtiter plates which were coated with a collagenase digest of human glomerular basement membrane. Results differed markedly between the different microtiter plates. Best results were obtained with a flexible polyvinylchloride microtiter plate with flat wells (Dynatec). This plate exhibited the highest positive/negative ratio and the lowest intraassay standard deviation. Optimal conditions for each step in the ELISA have been determined. The assay proved to be specific, sensitive, and reproducible. Circulating antibodies in each of 11 patients with active antiglomerular basement membrane disease were detected by the ELISA, while sera from patients with various renal and nonrenal diseases were negative by the test.


Social media use, sleep, and psychopathology in psychiatrically hospitalized adolescents.
Sleep disruption among adolescents represents a major public health concern, and social media use may play an important role in affecting sleep and subsequent mental health. While prior studies of youth sleep and mental health have often focused on social media use frequency and duration, adolescents' emotional experiences related to social media have been underexplored, particularly among clinically acute populations. This study offers a preliminary investigation of associations among negative emotional experiences using social media, sleep disturbance, and clinical symptom severity in a sample of psychiatrically hospitalized youth. A sample of 243 adolescents (Mage = 15.34) completed self-report measures at a single time point. Measures assessed social media use, including frequency and duration, subjective experiences of use, and emotional responses to use, as well as sleep disturbance and clinical symptom severity, including suicidal ideation, internalizing symptoms, and attention problems. Results revealed that more frequent negative emotional responses to social media use were linked to greater sleep disturbance and higher clinical symptom severity. Furthermore, sleep disturbance mediated the relation between negative emotional responses to social media and clinical symptom severity. While gender differences were revealed in characteristics of social media use, sleep disturbance, and clinical outcomes, the associations among these constructs did not vary across gender groups. Overall, these findings highlight sleep disturbance as a potential mechanism through which negative emotional experiences on social media may impact clinical symptoms in psychiatrically vulnerable youth.


Bone marrow purging with dibutyl phthalate--experimental basis and a preliminary clinical application.
It has been found recently that di-n-butyl phthalate (DBP) possesses a new pharmacological activity in the selective elimination of tumor cells from marrow. In combination with long-term liquid culture of marrow cells in vitro, DBP purged autologous bone marrow transplantation has first been applied to a case of acute myeloid leukemia at the first complete remission with successful reconstitution of hematopoiesis.


A hierarchical three-dimensional NiCo2O4 nanowire array/carbon cloth as an air electrode for nonaqueous Li-air batteries.
A 3D NiCo2O4 nanowire array/carbon cloth (NCONW/CC) was employed as the cathode for Li-air batteries with a non-aqueous electrolyte. After its discharge, novel porous ball-like Li2O2 was found to be deposited on the tip of NiCo2O4 nanowires. The special structure of Li2O2 and active sites of catalysts are also discussed.


Antitumor activity without on-target off-tumor toxicity of GD2-chimeric antigen receptor T cells in patients with neuroblastoma.
The reprogramming of a patient's immune system through genetic modification of the T cell compartment with chimeric antigen receptors (CARs) has led to durable remissions in chemotherapy-refractory B cell cancers. Targeting of solid cancers by CAR-T cells is dependent on their infiltration and expansion within the tumor microenvironment, and thus far, fewer clinical responses have been reported. Here, we report a phase 1 study (NCT02761915) in which we treated 12 children with relapsed/refractory neuroblastoma with escalating doses of second-generation GD2-directed CAR-T cells and increasing intensity of preparative lymphodepletion. Overall, no patients had objective clinical response at the evaluation point +28 days after CAR-T cell infusion using standard radiological response criteria. However, of the six patients receiving ≥108/meter2 CAR-T cells after fludarabine/cyclophosphamide conditioning, two experienced grade 2 to 3 cytokine release syndrome, and three demonstrated regression of soft tissue and bone marrow disease. This clinical activity was achieved without on-target off-tumor toxicity. Targeting neuroblastoma with GD2 CAR-T cells appears to be a valid and safe strategy but requires further modification to promote CAR-T cell longevity.


An environmental forensic procedure to analyse anthropogenic pressures of urban origin on surface water of protected coastal agro-environmental wetlands (L'Albufera de Valencia Natural Park, Spain).
Detection and spatial distribution of 14 drugs of abuse and 17 pharmaceuticals in surface waters was investigated to determine transport hydrological connectivity between urban, agriculture and natural environments. Solid-phase extraction and liquid chromatography tandem mass spectrometry was applied to all samples. To determine spatial incidence of contaminants, analytical results of target compounds were georeferenced and integrated into a geographical information systems structure together with layers of municipal population, location of sewage water treatment plants and irrigation channels and sectors. The methodology was applied to L'Albufera Natural Park in Valencia (Spain). A total of 9 drugs of abuse were detected at 16 points (76% of the sample sites). Cocaine and its metabolite, benzoylecgonine, were the most detected substances, being found in 12 and 16 samples, respectively. Maximum concentrations were found in benzoylecgonine (78.71 ng/L) and codeine (51.60 ng/L). Thirteen pharmaceuticals were found at 16 points. The most detected compounds were carbamazepine (15 samples) and ibuprofen (11 samples). Maximum concentrations were detected in acetaminophen (17,699.4 ng/L), ibuprofen (3913.7 ng/L) and codeine (434.0 ng/L). Spatial distribution of pharmaceuticals showed a clear relationship between irrigation areas, high population densities municipalities (above 1000 h/km(2)) and sewage water treatment plants.


Cwc2 and its human homologue RBM22 promote an active conformation of the spliceosome catalytic centre.
RNA-structural elements play key roles in pre-mRNA splicing catalysis; yet, the formation of catalytically competent RNA structures requires the assistance of spliceosomal proteins. We show that the S. cerevisiae Cwc2 protein functions prior to step 1 of splicing, and it is not required for the Prp2-mediated spliceosome remodelling that generates the catalytically active B complex, suggesting that Cwc2 plays a more sophisticated role in the generation of a functional catalytic centre. In active spliceosomes, Cwc2 contacts catalytically important RNA elements, including the U6 internal stem-loop (ISL), and regions of U6 and the pre-mRNA intron near the 5' splice site, placing Cwc2 at/near the spliceosome's catalytic centre. These interactions are evolutionarily conserved, as shown by studies with Cwc2's human counterpart RBM22, indicating that Cwc2/RBM22-RNA contacts are functionally important. We propose that Cwc2 induces an active conformation of the spliceosome's catalytic RNA elements. Thus, the function of RNA-RNA tertiary interactions within group II introns, namely to induce an active conformation of domain V, may be fulfilled by proteins that contact the functionally analogous U6-ISL, within the spliceosome.


Simvastatin-induced up-regulation of gap junctions composed of connexin 43 sensitize Leydig tumor cells to etoposide: an involvement of PKC pathway.
Some of lipophilic statins have been reported to enhance toxicities induced by antineoplastic agents but the underling mechanism is unclear. The authors investigated the involvement of Cx43-mediated gap junction intercellular communication (GJIC) in the effect of simvastatin on the cellular toxicity induced by etoposide in this study. The results showed that a major component of the cytotoxicity of therapeutic levels of etoposide is mediated by gap junctions composed of connexin 43(Cx43) and simvastatin at the dosage which does not induce cytotoxicity enhances etoposide toxicity by increasing gap junction coupling. The augmentative effect of simvastatin on GJIC was related to the inhibition of PKC-mediated Cx43 phosphorylation at ser368 and subsequent enhancement of Cx43 membrane location induced by the agent. The present study suggests the possibility that upregulation of gap junctions may be utilized to increase the efficacy of anticancer chemotherapies.


Subclinical Heart Dysfunction in Relation to Metabolic and Inflammatory Markers: A Community-Based Study.
Population studies investigating the contribution of immunometabolic disturbances to heart dysfunction remain scarce. We combined high-throughput biomarker profiling, multidimensional network analyses, and regression statistics to identify immunometabolic markers associated with subclinical heart dysfunction in the community. In 1,236 individuals (mean age, 51.0 years; 51.5% women), we measured 39 immunometabolic markers and assessed echocardiographic indexes of left ventricular diastolic dysfunction (LVDD) and left atrial (LA) reservoir dysfunction. We used partial least squares (PLS) to filter the most relevant biomarkers related to the echocardiographic characteristics. Subsequently, we assessed the associations between the echocardiographic features and biomarkers selected in PLS while accounting for clinical confounders. Influential biomarkers in PLS of echocardiographic characteristics included blood sugar, γ-glutamyl transferase, d-dimer, ferritin, hemoglobin, interleukin (IL)-4, IL-6, and serum insulin and uric acid. In stepwise regression incorporating clinical confounders, higher d-dimer was independently associated with higher E/e' ratio and LA volume index (P ≤ 0.05 for all). In multivariable-adjusted analyses, the risk for LVDD increased with higher blood sugar and d-dimer (P ≤ 0.048). After full adjustment, higher serum insulin and serum uric acid were independently related to worse LA reservoir strain and higher risk for LA reservoir dysfunction (P ≤ 0.039 for all). The biomarker panels detected LVDD and LA reservoir dysfunction with 87% and 79% accuracy, respectively (P < 0.0001). Biomarkers of insulin resistance, hyperuricemia, and chronic low-grade inflammation were associated with cardiac dysfunction. These biomarkers might help to unravel cardiac pathology and improve the detection and management of cardiac dysfunction in clinical practice.


The dynamic behavior of lipid droplets in the pre-metastatic niche.
The pre-metastatic niche is a favorable microenvironment for the colonization of metastatic tumor cells in specific distant organs. Lipid droplets (LDs, also known as lipid bodies or adiposomes) have increasingly been recognized as lipid-rich, functionally dynamic organelles within tumor cells, immune cells, and other stromal cells that are linked to diverse biological functions and human diseases. Moreover, in recent years, several studies have described the indispensable role of LDs in the development of pre-metastatic niches. This review discusses current evidence related to the biogenesis, composition, and functions of LDs related to the following characteristics of the pre-metastatic niche: immunosuppression, inflammation, angiogenesis/vascular permeability, lymphangiogenesis, organotropism, reprogramming. We also address the function of LDs in mediating pre-metastatic niche formation. The potential of LDs as markers and targets for novel antimetastatic therapies will be discussed.


Integrative Imaging Informatics for Cancer Research: Workflow Automation for Neuro-Oncology (I3CR-WANO).
Efforts to use growing volumes of clinical imaging data to generate tumor evaluations continue to require significant manual data wrangling, owing to data heterogeneity. Here, we propose an artificial intelligence-based solution for the aggregation and processing of multisequence neuro-oncology MRI data to extract quantitative tumor measurements. Our end-to-end framework (1) classifies MRI sequences using an ensemble classifier, (2) preprocesses the data in a reproducible manner, (3) delineates tumor tissue subtypes using convolutional neural networks, and (4) extracts diverse radiomic features. Moreover, it is robust to missing sequences and adopts an expert-in-the-loop approach in which the segmentation results may be manually refined by radiologists. After the implementation of the framework in Docker containers, it was applied to two retrospective glioma data sets collected from the Washington University School of Medicine (WUSM; n = 384) and The University of Texas MD Anderson Cancer Center (MDA; n = 30), comprising preoperative MRI scans from patients with pathologically confirmed gliomas. The scan-type classifier yielded an accuracy of >99%, correctly identifying sequences from 380 of 384 and 30 of 30 sessions from the WUSM and MDA data sets, respectively. Segmentation performance was quantified using the Dice Similarity Coefficient between the predicted and expert-refined tumor masks. The mean Dice scores were 0.882 (±0.244) and 0.977 (±0.04) for whole-tumor segmentation for WUSM and MDA, respectively. This streamlined framework automatically curated, processed, and segmented raw MRI data of patients with varying grades of gliomas, enabling the curation of large-scale neuro-oncology data sets and demonstrating high potential for integration as an assistive tool in clinical practice.


Risk of hepatitis C infection in neonates transfused with blood from donors infected with hepatitis C.
This look-back study was undertaken to identify newborn infants who had been infected with the hepatitis C virus (HCV) as a result of transfusions received before the introduction of routine screening in 1991 and to determine the transmission rates and persistence of transfusion-transmitted HCV infection acquired in the neonatal period. A total of 24 infants, transfused between 1980 and 1991, were identified as having received potentially infected blood from 11 blood donors. Ten of the donors had been administered batches of anti-D in 1977 known to have transmitted HCV genotype 1b infection. HCV RNA was detected in five of these donors when tested in 1994-95; the past donations of five of the donors, who had received anti-D immunoglobulin and had serological evidence of previous HCV infection but who were PCR negative when tested in 1994-95, were considered of lower risk. The source and time of acquisition of HCV infection for the one remaining donor in the study was not determined. Twenty-one (88%) of the 24 children were living at time of lookback. The median age at transfusion was 12 days. The median age at time of testing was 6.3 years. One child, who tested negative, was excluded from further analysis of HCV transmission, due to incomplete transfusion records. Overall, 12 of 20 (60%) children tested were positive for anti-HCV and seven (35%) were HCV RNA positive. Twelve (71%) of the 17 recipients of viraemic blood were ELISA positive and seven (41%) were PCR positive. Resolved HCV infection, as determined by ELISA pos, RIBA pos or indeterminate and PCR negativity, occurred in five of 12 (42%). In many instances there was more than one recipient per HCV infected donation. All of the reported children are clinically asymptomatic. However, the duration of HCV infection is relatively short and there is evidence of a degree of hepatitis in five of the seven children who are HCV RNA positive as judged by mildly elevated transaminase levels. The three who have undergone liver biopsy show mild hepatitis. The lower rates of persistence of HCV infection in this study may be due to the young age at exposure or to the source of infection which for all but one of the children was linked to one HCV genotype from female donors. Sharing of units of blood among multiple infants should be discouraged.


Nutrient-induced thermogenesis (NIT) following amino acid infusion.
Nutrient-induced thermogenesis (NIT) induced by parenteral infusion of amino acid (AA) mixtures of different composition and of the same AA mixtures given via different routes (parenteral or intraportal infusion) were investigated in rats using a small animal indirect calorimeter. When 8 different AA solutions of differing composition but with the same total concentration were infused parenterally, both standard NIT (each AA is assumed to generate 3.28 kcal/g) and specific NIT (heat energy of each AA is calculated assuming that it is oxidized to carbon dioxide and water, and metabolised to urea and sulphuric acid) values of the leucine (Leu)-rich and the glycine (Gly)-rich solutions were significantly greater than those of the control solution. Removal of Leu or Gly from the respective AA solutions reversed the increase of both NIT values down to control levels. When the parenteral and portal infusion routes were used in one rat, both NIT values for parenteral infusion of the Leu-rich solution were again significantly greater than those of the control. Likewise, both NIT values for intrportal infusion of the Leu-rich solution were also significantly greater than those of the control. However, no difference in NIT values was found between parenteral and portal infusion of either solution. The result of this study indicated that Leu and Gly may be thermogenic AAs, and the thermogenic effect of Leu is not dependent upon the route of infusion.


Hindfoot issues in the treatment of the cavovarus foot.
Cavovarus foot deformity is a result of a dysbalance of the extrinsic musculature about the foot. Because of the multi-articular bony structure of the foot and ankle, the slightest imbalance of muscular forces causes osteo-articular malalignment and consequent gross deformities. This article discusses hindfoot issues involved in the treatment of cavovarus foot.


Case report of probable desert black snake envenomation in 22-year-old male causing profound weakness and respiratory distress.
We describe a case of a 22-year-old male who presented to our facility 1 hour after a snake bite, which he identified as the desert black snake. He presented with severe weakness and respiratory distress. He was treated with polyvalent antivenom and observed in the Intensive Care Unit (ICU) with resolution of his respiratory symptoms. He developed paresthesias locally around his wound and later complained of diplopia. Two days later, he had total resolution of his symptoms. This is one of the only clinical reports of neurotoxic effects after Walterinnesia morgani envenomation.