Use of CAM among cancer patients : Results of a regional survey in Sweden.
The use of complementary and alternative medicine (CAM) by patients is widespread. However, there is a lack of knowledge regarding the extent and details of patient CAM use in Sweden, especially in rural Sweden. The aim of this study was to estimate the extent and characteristics of CAM use among cancer patients in Region Gävleborg. A total of 631 questionnaires were distributed to which 376 responses were registered, yielding a response rate of 59.6%. Questionnaires were distributed to oncology patients at their first visit for curative treatment at the Department of Oncology, Gävle Hospital. Palliative patients were recruited at their first visit and during enrollment in palliative outpatient care in their own homes. The characteristics of the respondents were presented with standard descriptive statistics. A multivariable logistic model was fitted to calculate odds ratios (ORs) and identify potential predictors (Age, Gender, Education, Diagnosis) of CAM use post-cancer diagnosis. 54% of all participants reported lifetime CAM use, 34% reported CAM use post-diagnosis. The most common CAM methods used after diagnosis are vitamins, health food preparations, herbal teas, prayer and dietary methods. The most common source of information reported is family and friends. Almost 70% of those who used CAM after their diagnosis stated that they did not discuss their use with healthcare professionals. Most patients reported that they would like some CAM modalities to be offered within conventional care regardless of their own CAM use. The use of CAM is common among patients with cancer in the region of Gävleborg, and previous studies show a similar use in Sweden in general. Based on the widespread use of CAM and patient interest in discussing CAM use with healthcare professionals, greater attention and focus should be placed on creating a basis for this dialogue. If we, as healthcare professionals, are to emphasise our commitment to providing patient-centred care, we must acknowledge that patients use CAM and are seeking a dialogue about CAM use in their care.


Genome-wide analysis of the aquaporin genes in melon (Cucumis melo L.).
Melon (Cucumis melo L.) is a very important crop throughout the world and has great economic importance, in part due to its nutritional properties. It prefers well-drained soil with low acidity and has a strong demand for water during fruit set. Therefore, a correct water balance-involving aquaporins-is necessary to maintain the plants in optimal condition. This manuscript describes the identification and comparative analysis of the complete set of aquaporins in melon. 31 aquaporin genes were identified, classified and analysed according to the evolutionary relationship of melon with related plant species. The individual role of each aquaporin in the transport of water, ions and small molecules was discussed. Finally, qPCR revealed that almost all melon aquaporins in roots and leaves were constitutively expressed. However, the high variations in expression among them point to different roles in water and solute transport, providing important features as that CmPIP1;1 is the predominant isoform and CmTIP1;1 is revealed as the most important osmoregulator in the tonoplast under optimal conditions. The results of this work pointing to the physiological importance of each individual aquaporin of melon opening a field of knowledge that deserves to be investigated.


Ion channels as enzymes: analogy or homology?
Ion channels render nerve and muscle excitable. A typical channel protein can mediate the passive transfer of millions of ions per second across the membrane. Thus, channels catalyse the transmembrane flux of ions, fulfilling criteria traditionally associated with enzymes. Is this a semantic coincidence, or do channels and enzymes in fact rely upon similar structural principles? A general answer remains elusive given the paucity of crystallographic data on channels. Nevertheless, emerging evidence points to fundamental similarities between the pores of channels and the active sites of enzymes of resolved structure. Shared features include narrow clefts lined by protein loops, and specific binding of transition intermediates during catalysis. The often cited analogies between channels and enzymes might therefore reflect basic design homologies.


Vitamin D deficiency as a risk factor for endometriosis in Iranian women.
Vitamin D (Vit D), as an immunomodulator, has been hypothesized to play a critical role in the pathogenesis of endometriosis. Thus, in this study, we evaluated whether there is an association between 25-hydroxyvitamin D [25(OH)D] and susceptibility to endometriosis in Iranian women. Women at reproductive age, including 56 healthy women and 54 patients with endometriosis, were enrolled in the study. Serum levels of 25(OH)D, calcium, parathyroid hormone (PTH), and peritoneal fluid (PF) levels of 25(OH)D were assessed. The serum and PF levels of 25(OH)D in the patients with endometriosis were significantly lower than the control group (P = 0.001 and P = 0.03, respectively). Subjects with serum levels of 25(OH)D lower than 20 ng/mL had a 2.7 times higher risk of endometriosis than people with 25(OH)D serum levels higher than 20 ng/mL (non-deficient) (OR = 2.7, 95 % confidence interval: 1.24-5.80, P = 0.01). The serum levels of calcium and PTH were significantly lower and higher in patients with endometriosis compared with controls, respectively (P < 0.001, P = 0.02, respectively). Also, the serum levels of 25(OH)D were lower in stages I-II endometriosis than stage III-IV; however, no significant difference was observed. Our findings showed that people with Vit D deficiency are at higher risk of endometriosis.


Bacterial studies of Clindamycin-associated colitis. A preliminary report.
The cause of pseudomembraneous colitis is not known but has been attributed to an alteration in the microbial flora of the colon. To test this hypothesis, a blind, prospective study was undertaken in which fecal samples were cultured quantitatively for aerobic and anaerobic organisms. The patients from which these samples were taken were all receiving clindamycin and had diarrhea secondary to the use of the drug. We were able to show definite differences in the colonic microflora which correlated with the presence of pseudomembranes on biopsy. Those patients who had diarrhea and pseudomembranous colitis showed a striking decrease, both quantitatively and qualitatively, in the number of anaerobes present. Those patients who had diarrhea but no pseudomembranes had large numbers of anaerobes which qualitatively approximated normal fecal cultures but quantitatively were fewer in number. A third group of patients, which had resolving pseudomembranous colitis, and were no longer symptomatic, had large numbers of anaerobic organisms which approximated those found in normal fecal cultures. There were no differences among the three groups with regard to facultative anaerobic microflora. Thus, the presence of pseudomembranous colitis correlated directly with a striking quantitative and qualitative decrease in the anaerobic microflora of the colon. The symptom of diarrhea alone appeared to have no meaning with regard to changes in the bacterial flora. Resolution of pseudomembranous colitis was associated with a return of the anaerobic microflora.


Origination of the modern-style diversity gradient 15 million years ago.
The latitudinal diversity gradient (LDG) is a prevalent feature of modern ecosystems across diverse clades1-4. Recognized for well over a century, the causal mechanisms for LDGs remain disputed, in part because numerous putative drivers simultaneously covary with latitude1,3,5. The past provides the opportunity to disentangle LDG mechanisms because the relationships among biodiversity, latitude and possible causal factors have varied over time6-9. Here we quantify the emergence of the LDG in planktonic foraminifera at high spatiotemporal resolution over the past 40 million years, finding that a modern-style gradient arose only 15 million years ago. Spatial and temporal models suggest that LDGs for planktonic foraminifera may be controlled by the physical structure of the water column. Steepening of the latitudinal temperature gradient over 15 million years ago, associated with an increased vertical temperature gradient at low latitudes, may have enhanced niche partitioning and provided more opportunities for speciation at low latitudes. Supporting this hypothesis, we find that higher rates of low-latitude speciation steepened the diversity gradient, consistent with spatiotemporal patterns of depth partitioning by planktonic foraminifera. Extirpation of species from high latitudes also strengthened the LDG, but this effect tended to be weaker than speciation. Our results provide a step change in understanding the evolution of marine LDGs over long timescales.


Cladribine (2-CDA) given as subcutaneous bolus injections is active in pretreated Waldenström's macroglobulinaemia. Swiss Group for Clinical Cancer Research (SAKK).
Clinical trials with intravenous cladribine infusions in pretreated patients with Waldenström's macroglobulinaemia have shown a response rate of 40%. Our pharmacokinetic studies revealed that the bioavailability of subcutaneous cladribine is complete but that the concentration-time profile is very different from intravenous administration. We designed this phase II multi-institutional trial to study the activity and toxicity of cladribine given as s.c. bolus injections in patients with symptomatic Waldenström's macroglobulinaemia. Between May 1993 and October 1995, 25 patients were accrued: male/female 18/7, median age 65 years (range 44-85). All except one patient had been pretreated with more than one regimen (median 2, range 0-10). 18 patients had progressed under previous therapy and six were in relapse. All patients received cladribine for a total dose of 0.5 mg/kg per cycle as s.c. bolus injections divided over 5 d at > or = 4 week intervals, for a maximum of six cycles. All 25 patients were evaluable for toxicity and response. A total of 67 cycles were administered (median 3 cycles, range 1-6). Overall response rate including disease stabilization which had been progressive under previous therapy was 68%. 10 patients (40%, 95% CI 21-61%) achieved a partial remission. Seven responders had been progressive under previous therapy. Maximum responses were reached no later than the third cycle. Median time to treatment failure and remission duration were 4.4 (range 0.5-33) and 8 months (5-29), respectively. Four patients (16%) suffered from infections W.H.O. grade > or = 2 (pneumonia grade 2, Staphylococcus septicaemia grade 3, viral encephalitis and pneumonia, both grade 4 with complete resolution). No other severe adverse events were observed. Cladribine given as s.c. 5 d bolus injections was found to be active in pretreated Waldenström's macroglobulinaemia and resulted in durable remissions.


Production of succinate from glucose, cellobiose, and various cellulosic materials by the ruminal anaerobic bacteria Fibrobacter succinogenes and Ruminococcus flavefaciens.
The production of organic acids by two anaerobic ruminal bacteria Fibrobacter succinogenes S85 and Ruminococcus flavefaciens FD-1, was compared with glucose, cellobiose, microcrystalline cellulose, Walseth cellulose (acid swollen cellulose), pulped paper, and steam-exploded yellow poplar as substrates. The major end product produced by F. succinogenes from each of these substrates was succinate (69.5-83%), the principal secondary product was acetate (16-30.5%). Maximum succinate productivity ranged from 14.1 mg/L.h for steam-exploded yellow Poplar to 59.7 mg/L.h for pulped paper. For R. flavefaciens, the major end product from cellobiose, microcrystalline cellulose, and acid-swollen Walseth cellulose was acetate (39-46%), pulped paper and steam-exploded yellow poplar yielded succinate (42-54%) as the major product. Maximum succinate productivity by R. flavefaciens ranged from 9.21 mg/L.h for cellobiose to 43.1 mg/L.h for pulped paper. In general, much less succinate was produced at a lower maximum productivity by R. flavefaciens than by F. succinogenes under similar fermentation conditions. The maximum succinate productivities by these two organisms are comparable to the previously reported value of 59 mg/L.h for Anderobiospirillum succiniciproducens grown on glucose and corn steep liquor.


Surface-enhanced Raman scattering for protein detection.
Proteins are essential components of organisms and they participate in every process within cells. The key characteristic of proteins that allows their diverse functions is their ability to bind other molecules specifically and tightly. With the development of proteomics, exploring high-efficiency detection methods for large-scale proteins is increasingly important. In recent years, rapid development of surface-enhanced Raman scattering (SERS)-based biosensors leads to the SERS realm of applications from chemical analysis to nanostructure characterization and biomedical applications. For proteins, early studies focused on investigating SERS spectra of individual proteins, and the successful design of nanoparticle probes has promoted great progress of SERS-based immunoassays. In this review we outline the development of SERS-based methods for proteins with particular focus on our proposed protein-mediated SERS-active substrates and their applications in label-free and Raman dye-labeled protein detection.


Age-related activity of Poly (ADP-Ribose) Polymerase (PARP) in men with localized prostate cancer.
Mutations in DNA repair genes have been connected with familial prostate cancer and sensitivity to targeted drugs like PARP-inhibitors. Clinical use of this information is limited by the small fraction of prostate cancer risk gene carriers, variants of unknown pathogenicity and the focus on monogenic disease mechanisms. Functional assays capturing mono- and polygenic defects were shown to detect breast and ovarian cancer risk in blood-derived cells. Here, we comparatively analyzed lymphocytes from prostate cancer patients and controls applying a sensitive DNA double-strand break (DSB) repair assay and a flow cytometrybased assay measuring the activity of Poly(ADP-Ribose)-Polymerase, a target in treatment of metastatic prostate cancer. Contrary to breast and ovarian cancer patients, error-prone DNA double-strand break repair was not activated in prostate cancer patients. Yet, the activity of PARP discriminated between prostate cancer cases and controls. PARylation also correlated with the age of male probands, suggesting male-specific links between mutation-based and aging-associated DNA damage accumulation and PARP. Our work identifies prostate cancer-specific DNA repair phenotypes characterized by increased PARP activities and carboplatin-sensitivities, detected by functional testing of lymphocytes. This provides new insights for further investigation of PARP and carboplatin sensitivity as biomarkers in peripheral cells of men and prostate cancer patients.


Nuclear export and centrosome targeting of the protein phosphatase 2A subunit B56alpha: role of B56alpha in nuclear export of the catalytic subunit.
Protein phosphatase (PP) 2A is a heterotrimeric enzyme regulated by specific subunits. The B56 (or B'/PR61/PPP2R5) class of B-subunits direct PP2A or its substrates to different cellular locations, and the B56alpha, -beta, and -epsilon isoforms are known to localize primarily in the cytoplasm. Here we studied the pathways that regulate B56alpha subcellular localization. We detected B56alpha in the cytoplasm and nucleus, and at the nuclear envelope and centrosomes, and show that cytoplasmic localization is dependent on CRM1-mediated nuclear export. The inactivation of CRM1 by leptomycin B or by siRNA knockdown caused nuclear accumulation of ectopic and endogenous B56alpha. Conversely, CRM1 overexpression shifted B56alpha to the cytoplasm. We identified a functional nuclear export signal at the C terminus (NES; amino acids 451-469), and site-directed mutagenesis of the NES (L461A) caused nuclear retention of full-length B56alpha. Active NESs were identified at similar positions in the cytoplasmic B56-beta and epsilon isoforms, but not in the nuclear-localized B56-delta or gamma isoforms. The transient expression of B56alpha induced nuclear export of the PP2A catalytic (C) subunit, and this was blocked by the L461A NES mutation. In addition, B56alpha co-located with the PP2A active (A) subunit at centrosomes, and its centrosome targeting involved sequences that bind to the A-subunit. Fluorescence Recovery after Photobleaching (FRAP) assays revealed dynamic and immobile pools of B56alpha-GFP, which was rapidly exported from the nucleus and subject to retention at centrosomes. We propose that B56alpha can act as a PP2A C-subunit chaperone and regulates PP2A activity at diverse subcellular locations.


Landscape genetics of the tropical willow Salix humboldtiana: influence of climate, salinity, and orography in an altitudinal gradient.
Gene flow in riparian ecosystems is influenced by landscape features such as orography, climate, and salinity. The downstream increase in genetic diversity (DIGD) hypothesis states that the unidirectionality of the watercourse causes an accumulation of genetic diversity toward downstream populations, while upstream populations are more structured and less diverse, especially in water-dispersed organisms. We used chloroplast and nuclear microsatellites to characterize genetic diversity, structure, and gene flow patterns among populations of Salix humboldtiana across an elevation and salinity gradient on three rivers (Actopan, Antigua, and Blanco) in Mexico. We used optimization of resistance surface methods to determine whether genetic distances between populations are correlated with landscape features. Positive FIS values evidenced biparental inbreeding in some populations, particularly at higher elevations where lower niche availability constrains colonization and persistence. Four genetic groups were distinguished, corresponding to populations on the Actopan and Antigua rivers and upstream and downstream on the Blanco, but with high admixture between populations on the Actopan and Antigua rivers. Higher gene flow rates were found among proximate populations on the same river than among different rivers. Genetic diversity increased toward the river mouths, in support of the DIGD hypothesis, probably due to greater niche availability and larger population size. Differences among rivers in precipitation patterns and salinity, as well as geographic distance, were significant predictors of gene flow. Our results depict that the DIGD and gene flow patterns in S. humboldtiana result from the complex interaction among physiography, climate, river salinity, and life-history traits of the species.


COVID-19-related refractory status epilepticus with the presence of SARS-CoV-2 (RNA) in the CSF: a case report.
Amongst the neurologic complications of COVID-19 disease, very few reports have shown the presence of the virus in the cerebrospinal fluid (CSF). Seizure and rarely status epilepticus can be associated with COVID-19 disease. Here we present a 73-year-old male with prior history of stroke who has never experienced seizure before. He had no systemic presentation of COVID-19 disease. The presenting symptoms were two consecutive generalized tonic-clonic seizures that after initial resolution turned into a nonconvulsive status epilepticus despite antiepileptic treatment (a presentation similar to NORSE (new-onset refractory status epilepticus)). There was no new lesion in the brain magnetic resonance imaging (MRI). The CSF analysis only showed an increased protein levels and positive reverse transcription polymerase chain reaction (RT-PCR) of 2019-nCoV. Patient recovered partially after anesthetic, IVIG, steroid, and remdesivir. To our knowledge, this is the first report of a refractory status epilepticus with the presence of SARS-CoV-2 ribonucleic acid (RNA) in the CSF.


Cyclic adenosine monophosphate-stimulated anion transport in rabbit cortical collecting duct. Kinetics, stoichiometry, and conductive pathways.
Cyclic AMP stimulates HCO3 secretion and Cl self-exchange in rabbit cortical collecting tubule. We found that varying peritubular [Cl] changed the Cl self-exchange rate with saturation kinetics (Km, 3-4 mM). HCO3 secretion also showed saturation kinetics as a function of mean luminal [Cl] (Km, 4-11 mM). Both Cl self-exchange and Cl-HCO3 exchange thus appear to be carrier-mediated. Addition/removal of basolateral HCO3 qualitatively changed Cl and HCO3 transport as expected for Cl-HCO3 exchange, but quantitatively changed Cl absorption more than HCO3 secretion. The diffusive Cl permeability and the transepithelial conductance in the presence of HCO3/CO2 and cAMP were higher than in their absence suggesting that HCO3/CO2 and cAMP together increase a conductive Cl pathway parallel to a 1:1 Cl-HCO3 exchanger. Thus, cAMP not only stimulates the overall process of anion exchange (probably by increasing an electroneutral exchanger and/or a series Cl conductance), but also stimulates a Cl conductance parallel to the exchange process.


A crop type dataset for consistent land cover classification in Central Asia.
Land cover is a key variable in the context of climate change. In particular, crop type information is essential to understand the spatial distribution of water usage and anticipate the risk of water scarcity and the consequent danger of food insecurity. This applies to arid regions such as the Aral Sea Basin (ASB), Central Asia, where agriculture relies heavily on irrigation. Here, remote sensing is valuable to map crop types, but its quality depends on consistent ground-truth data. Yet, in the ASB, such data are missing. Addressing this issue, we collected thousands of polygons on crop types, 97.7% of which in Uzbekistan and the remaining in Tajikistan. We collected 8,196 samples between 2015 and 2018, 213 in 2011 and 26 in 2008. Our data compile samples for 40 crop types and is dominated by "cotton" (40%) and "wheat", (25%). These data were meticulously validated using expert knowledge and remote sensing data and relied on transferable, open-source workflows that will assure the consistency of future sampling campaigns.


Two macrocyclic pentaaza compounds containing pyridine evaluated as novel chelating agents in copper(II) and nickel(II) overload.
Two pentaaza macrocycles containing pyridine in the backbone, namely 3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),14,16-triene ([15]pyN(5)), and 3,6,10,13,19-pentaazabicyclo[13.3.1]nonadeca-1(19),15,17-triene ([16]pyN(5)), were synthesized in good yields. The acid-base behaviour of these compounds was studied by potentiometry at 298.2K in aqueous solution and ionic strength 0.10 M in KNO(3). The protonation sequence of [15]pyN(5) was investigated by (1)H NMR titration that also allowed the determination of protonation constants in D(2)O. Binding studies of the two ligands with Ca(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), and Pb(2+) metal ions were performed under the same experimental conditions. The results showed that all the complexes formed with the 15-membered ligand, particularly those of Cu(2+) and especially Ni(2+), are thermodynamically more stable than with the larger macrocycle. Cyclic voltammetric data showed that the copper(II) complexes of the two macrocycles exhibited analogous behaviour, with a single quasi-reversible one-electron transfer reduction process assigned to the Cu(II)/Cu(I) couple. The UV-visible-near IR spectroscopic and magnetic moment data of the nickel(II) complexes in solution indicated a tetragonal distorted coordination geometry for the metal centre. X-band EPR spectra of the copper(II) complexes are consistent with distorted square pyramidal geometries. The crystal structure of [Cu([15]pyN(5))](2+) determined by X-ray diffraction showed the copper(II) centre coordinated to all five macrocyclic nitrogen donors in a distorted square pyramidal environment.


Stimulation of glyceraldehyde-3-phosphate dehydrogenase by oxyhemoglobin.
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key glycolytic enzyme regulated by many diverse mechanisms. In this study we present evidence that GAPDH activity is stimulated in the presence of oxyhemoglobin (2.3-fold, P < 0.005). No stimulation was seen by myoglobin, and only slight stimulation (1.2-fold, not significant) by methemoglobin was observed. Such stimulation may have physiological significance as 1,3-bis-phosphoglycerate, the product of GAPDH, isomerises to 2,3-bis-phosphoglycerate, an allosteric effector that decreases the oxygen affinity of hemoglobin, thus providing a feedback loop. The results suggest that when assaying GAPDH activity in biological samples, hemoglobin content should be taken into account.


Balancing precision versus cohort transcriptomic analysis of acute and recovery phase of viral bronchiolitis.
Viral infections affecting the lower respiratory tract place enormous burdens on hospitals. As neither vaccines nor antiviral agents exist for many viruses, understanding risk factors and outcomes in each patient using minimally invasive analysis, such as blood, can lead to improved health care delivery. A cohort of PAXgene RNA sequencing of infants admitted with moderate or severe acute bronchiolitis and respiratory syncytial virus were compared with case-control statistical analysis and cohort-based outlier mapping for precision transcriptomics. Patients with severe bronchiolitis had signatures connected to the immune system, interferon signaling, and cytokine signaling, with marked sex differences in XIST, RPS4Y1, KDM5D, and LINC00278 for severity. Several patients had unique secondary infections, cytokine activation, immune responses, biological pathways, and immune cell activation, highlighting the need for defining patient-level transcriptomic signatures. Balancing relative contributions of cohort-based biomarker discoveries with patient's biological responses is needed to understand the totality of mechanisms of adverse outcomes in viral bronchiolitis.


Acute Peritoneal Dialysis System for Neonates with Acute Kidney Injury Requiring Renal Replacement Therapy: A Case Series.
Acute kidney injury (AKI) is common in critically ill neonates, and peritoneal dialysis (PD) can be a lifesaving option. In China, however, much of the equipment for PD in neonates is not available. We describe results with a novel system for PD, which has been developed locally to improve access to therapy and care for critically ill neonates requiring PD in China. The system comprises a 14-gauge single-lumen central venous catheter serving as a PD catheter, inserted by Seldinger technique, with an adapted twin bag PD system. Ten neonates with AKI were treated using the novel PD system. The 10 patients ranged in age from 1 day to 22 days, with bodyweights between 700 g and 3,300 g. Average time to renal function recovery was between 14 and 96 hours. Complications related to the novel PD system included leak (n = 1), catheter displacement (n = 1), and catheter obstruction (n = 1). There were no complications related to insertion, no cases of peritonitis or exit-site infection, and no subsequent hernias. A comparison of costs indicated that the novel PD system is less expensive than conventional systems involving open insertion of Tenckhoff catheters. Peritoneal dialysis using the novel PD system is simple, safe, and effective for suitable neonates with AKI in China.


Nickel: an essential micronutrient for legumes and possibly all higher plants.
Soybean plants deprived of nickel accumulated toxic concentrations of urea (2.5 percent) in necrotic lesions on their leaflet tips. This occurred regardless of whether the plants were supplied with inorganic nitrogen or were dependent on nitrogen fixation. Nickel deprivation resulted in delayed nodulation and in a reduction of early growth. Addition of nickel (1 microgram per liter) to the nutrient media prevented urea accumulation, necrosis, and growth reductions. This evidence suggests that nickel is essential for soybeans and possibly for higher plants in general.


Acute myeloid leukemia sensitivity to metabolic inhibitors: glycolysis showed to be a better therapeutic target.
Cancer cells alter their metabolism by switching from glycolysis to oxidative phosphorylation (OXPHOS), regardless of oxygen availability. Metabolism may be a molecular target in acute myeloid leukemia (AML), where mutations in metabolic genes have been described. This study evaluated glycolysis and OXPHOS as therapeutic targets. The sensitivity to 2-deoxy-D-glucose (2-DG; glycolysis inhibitor) and oligomycin (OXPHOS inhibitor) was tested in six AML cell lines (HEL, HL-60, K-562, KG-1, NB-4, THP-1). These cells were characterized for IDH1/2 exon 4 mutations, reactive oxygen species, and mitochondrial membrane potential. Metabolic activity was assessed by resazurin assay, whereas cell death and cell cycle were assessed by flow cytometry. Glucose uptake and metabolism-related gene expression were analyzed by 18F-FDG and RT-PCR/qPCR, respectively. No IDH1/2 exon 4 mutations were detected. HEL cells had the highest 18F-FDG uptake and peroxides/superoxide anion levels, whereas THP-1 showed the lowest. 2-DG reduced metabolic activity in all cell lines with HEL, KG-1, and NB-4 being the most sensitive cells. Oligomycin decreased metabolic activity in a cell line-dependent manner, the THP-1 resistant and HL-60 being the most sensitive. Both inhibitors induced apoptosis and cell cycle arrest in a cell line- and compound-dependent manner. 2-DG decreased 18F-FDG uptake in HEL, HL-60, KG-1, and NB-4, while oligomycin increased the uptake in K-562. Metabolism gene expression had different responses to treatments. In conclusion, HEL and KG-1 show to be more glycolytic, whereas HL-60 was more OXPHOS dependent. Results suggest that AML cells reprogram their metabolism to overcome OXPHOS inhibition suggesting that glycolysis may be a better therapeutic target.


The association between exposure to multiple toxic metals and the risk of endometriosis: Evidence from the results of blood and follicular fluid.
Endometriosis affects up to 10 % of women of reproductive age and can lead to infertility. Research investigating whether combined exposure to arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg) is related to an increased risk of endometriosis, especially using different biological samples to validate the association, is very limited. This investigation aimed to evaluate the associations between the concentrations of As, Cd, Pb and Hg in blood and follicular fluid and the risk of endometriosis. A total of 609 endometriosis cases and controls seen at the reproductive center of the First Affiliated Hospital of Anhui Medical University in Hefei, China, between April 2020 and December 2021 were included in our study. Blood (217 cases and 234 controls) and follicular fluid (182 cases and 203 controls) samples were collected from these subjects. The concentrations of Cd, Hg, As and Pb in the blood and follicular fluid were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Unconditional logistic regression models were used to assess the associations between Cd, Hg, As or Pb levels and the risk of endometriosis; Bayesian kernel machine regression (BKMR) was used to evaluate the combined effect of metals on the risk of endometriosis. We found significant associations between blood concentrations of As (highest vs. lowest tertile: aOR = 5.53, 95 % CI: 2.97, 10.30), Cd (second vs. lowest tertile: aOR = 1.96, 95 % CI: 1.07, 3.58; highest vs. lowest tertile: aOR = 3.21, 95 % CI: 1.79, 5.77), Pb (highest vs. lowest tertile: aOR = 2.73, 95 % CI: 1.56, 4.78) and Hg (high-level group vs. low-level group: aOR = 13.10, 95 % CI: 6.74, 25.44; second vs. lowest tertile: aOR = 15.27, 95 % CI: 4.96, 46.97; highest vs. lowest tertile: aOR = 35.66, 95 % CI: 11.99, 106.08) and increased risk of endometriosis adjusting for confounders. Follicular fluid As (highest vs. lowest tertile: aOR = 2.42, 95 % CI: 1.35, 4.33), Hg (highest vs. lowest tertile: aOR = 1.86, 95 % CI: 1.05, 3.29), Cd (second vs. lowest tertile: aOR = 2.45, 95 % CI: 1.29, 4.65; highest vs. lowest tertile: aOR = 3.12, 95 % CI: 1.67, 5.83), and Pb (second vs. lowest tertile: aOR = 1.97, 95 % CI: 1.11, 3.52) concentrations were positively associated with endometriosis risk. The BKMR analyses showed linear associations between the metal mixtures and the risk of endometriosis. Both in blood and in follicular fluid, As exhibited the highest contribution. The data from this study suggest that toxic metals, individually and as a mixture, play a role in the risk of endometriosis, thus providing a novel idea for endometriosis prevention.


Leadership Training and Undergraduate Medical Education: a Scoping Review.
The purpose of this scoping review is to fill the gap in understanding the current status of intervention-based studies regarding leadership training in undergraduate medical education. As of late, there is an increased focus on the role of physicians as leaders in their fields, and communities. In order to evaluate these studies, both the PubMed and ERIC databases were searched, and an ultimate total of 35 articles methodologies were evaluated for their general methodology, curricular content, specific teaching methods, and evaluation methodologies. There were a number of trends identified, as well as remaining gaps. The online version contains supplementary material available at 10.1007/s40670-021-01308-9.


Management of immune haemolytic disease in the fetus.
Although Rh alloimmunization has been successfully reduced in frequency and severity since the implementation of Rh immune globulin, cases still occur. The management of affected pregnancies requires the efforts of a team which includes obstetrics/fetal medicine, the blood transfusion service, haematological support, nursing assistance and neonatology. The aim of antenatal management is to predict whether or not the fetus is severely affected, to correct the fetal anaemia and to deliver the baby at the optimal time. The management has improved markedly with the introduction of high-resolution real-time ultrasound, fetal blood sampling, intravascular fetal blood transfusion and/or intraperitoneal transfusion and meticulous fetal surveillance. With appropriate and timely management in severely alloimmunized patient, the survival rate of affected fetuses in some centres is now about 90%. There is still a need for research into new methods of treatment such as high dose intravenous immunoglobulin, which might non-invasively diminish fetal red cell destruction. Due to the reduced frequency of severe disease, regionalized treatment centres are essential in order to maximize the experience and efficiency of the management teams.


Introduction of loop sutures in microsurgical telescoping anastomosis.
We have designed a loop suture technique for use in microsurgical telescoping (sleeve) anastomosis to prevent problems from the free floating inserted vessel stump. The patency rate of rat femoral arteries repaired with this technique was 95% and that of interpositional vein grafts, in which both the proximal and distal anastomoses were completed with the same sleeve technique, was 81.0%.


Assessing accumulated solvent near a macromolecular solute by preferential interaction coefficients.
Biological macromolecules are often studied in mixed solvents. To understand cosolvent-macromolecule interactions, the preferential interaction coefficient, Gamma(3), may help determine surface solvent compositions. Gamma(3) measures the amounts of water, B(1), and cosolvent, B(3), within the "local domain," the (possibly far-reaching) region surrounding the macromolecule where the solvent is non-bulk-like. The local domain's boundary is, however, vague and it is unclear which molecules are counted in B(i). It is useful to explore a simple model system to make B(i) more concrete and to understand which aspects of the surface solvent distribution, rho(x), are sampled by Gamma(3). We performed computer simulations on a two-dimensional (2D) system consisting of a hard-wall solute (the macromolecule) in a mixed solvent (hard disks of different radii). We simultaneously calculated Gamma(3) and rho(x). We found that 1) in practice, the local domain's boundary is demarked by the outer limit of the first cosolvent (not water) layer; B(i) mainly counts the solvent near the macromolecule; 2) assuming B(1) to count only the waters within the first water layer is a poor approximation; 3) when determining B(1) and B(3), water and cosolvent molecules must be counted from the same region of space. We speculate that these 2D results may serve as a first-order approximation for the dominant contributions to Gamma(3) even in three dimensions, so long as the cosolvent is not strongly excluded from the macromolecular surface and there is no significant long-ranged solvent structure.


Amphotericin B is cytotoxic at locally delivered concentrations.
Orthopaedic fungal infections are commonly treated with systemic amphotericin, which has a narrow therapeutic index and is associated with systemic toxicities. Local delivery of amphotericin has been described yet is poorly understood. As with bacterial infections, fungal infections are associated with biofilm. However, it is unclear whether experience with local delivery of antibacterials can be applied to local antifungal delivery. We asked whether (1) 100 to 1000 μg amphotericin/mL caused osteoblast cell death; (2) 1 to 10 μg amphotericin/mL caused sublethal toxicity to osteoblasts and fibroblasts; and (3) sublethal amphotericin toxicity could be reversed. Mouse osteoblasts and fibroblasts were exposed in vitro to amphotericin concentrations of 0, 1, 10, 100, and 1000 μg/mL for 5 hours or 0, 1, 5, and 10 μg/mL for 7 days and then 3 days with no amphotericin. Cell morphology on light microscopy and proliferation assays (alamarBlue(®) and MTT) were used as measures of toxicity. Amphotericin concentrations of 100 μg/mL and above caused cell death; 5 to 10 μg/mL caused abnormal cell morphology and decreased proliferation. Cells regained normal morphology and resumed cell proliferation within 3 days after removal of amphotericin. In this in vitro study, amphotericin was cytotoxic to osteoblasts and fibroblasts at concentrations achievable by local delivery. If local concentrations of 100 to 1000 times the minimum inhibitory concentration are necessary to treat biofilm-associated fungal infections as they are for bacterial infection, cell toxicity at the local depot site should be considered.


Influence of land use and topography on distribution and bioaccumulation of potentially toxic metals in soil and plant leaves: A case study from Sekhukhuneland, South Africa.
Potentially toxic metal (PTM) enrichment of the soil-plant system in ultramafic and mining regions is a global concern as it affects the food chain. With expanding mining industry, it is important to assess if anthropogenic factors (i.e., land use practices) have a greater influence in this regard compared to natural factors (i.e., topography). Localities in Sekhukhuneland, South Africa, were selected along an altitudinal gradient (i.e., topography: upper slope, footslope, valley and valley bottom) and a land use profile (i.e., rangelands, gardens, tailings and wastelands) to investigate the distribution of Co, Cr, Cu, Fe, Mg, Mn, Mo, Ni, Sr and Zn of natural (i.e., ultramafic geology) and anthropogenic (i.e., mining) origin in surface soil and plant leaf tissue. Plant life form was considered as an additional factor to evaluate PTM accumulation in leaves. Findings revealed a wider distribution range for Cr and Ni in the surface soil. Co, Cu, Mg, Mo, Sr and Zn were accumulated (bioaccumulation factor, BAF > 1) in leaf tissue of 74% of the evaluated plants of which 83% were indigenous. Grasses, forbs, dwarf shrubs and shrubs showed the highest accumulation levels. Despite an observed trend in the distribution of PTMs in soils and plant leaves along the altitudinal gradient, no significant differences were determined among the topographic positions. Land use practices, however, differed significantly indicating anthropogenic interference as a predominant determinant of PTM enrichment of soil-plant systems. Metal tolerant dominant plants in Sekhukhuneland could be classified as metallophytes. Indigenous species, accumulators and excluders, showed prospects for phytoremediation and rehabilitation of metal contaminated sites, respectively. Concentrations of Cr and Co in food and medicinal plant leaves exceeded the international permissible limits, which highlighted the necessity to estimate human health risks for PTMs in metalliferous sites.


Resurgence of Positive qRT-PCR Test Results in Patients Recovered from COVID-19: Case Reports.
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a newly emerging coronavirus. This virus poses a great threat to human society and has been marked as the third introduction of a highly pathogenic coronavirus into the human population. This is following severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) in the 21st-century. While China has achieved initial success in controlling the spread of COVID-19 and treating those infected with SARS-CoV-2, up to 14% of COVID-19 convalescents can still be detected with virus nucleic acid. Thus, there is an urgent need for more information to understand this new virus. Here we report the detailed clinical characteristics of three cases of COVID-19 convalescents that had repeated positive quantitative reverse transcription-polymerase chain reaction (qRT-PCR) test results for over three months. This may arouse concerns regarding the present quarantine protocol after convalescence and provide a reference for governments to consider when to reopen the community.


Endometrial receptivity after oocyte donation in recipients with a history of chemotherapy and/or radiotherapy.
Information is scarce regarding the outcome of oocyte donation (OD) in patients with a history of cancer treatment. Therefore, we conducted a matched controlled analysis on the outcome of OD in these recipients. Between January 2000 and November 2005, 33 patients with a history of chemotherapy and/or radiotherapy had an OD cycle. Matching was performed to the chronologically closest patient without a history of cancer therapy by number of days of hormonal stimulation before embryo replacement, number of replaced embryos, day of embryo transfer and origin of sperm. The primary diseases of the patients were Hodgkin's lymphoma (n = 12), non-Hodgkin's lymphoma (n = 3), leukaemia (n = 7), ovarian cancer (n = 6), Ewing's sarcoma (n = 2), breast cancer (n = 1), sympathoblastoma (n = 1) and histiocytosis X (n = 1). Twenty-three patients had undergone chemotherapy and radiotherapy, nine patients chemotherapy only and one radiotherapy only. The mean age of the recipients was 33.1 years [95% confidence interval (CI) 30.9-35.3] and 39.6 (95% CI 37.1-42.1) in the study and control groups, respectively. The average number of received oocytes and transferred embryos, was similar in both groups. Nineteen (57.6%) versus 13 (39.4%) pregnancies resulting in an ongoing pregnancy (i.e. viable at 12 weeks) in 15 (45.4%) versus 9 cycles (27.3%) (NS) were obtained in study and control groups, respectively. Implantation rate in study and control groups was 35.8 versus 17.9%, respectively (P = 0.02). The results suggest that patients with a history of cancer treatment have a pregnancy rate after OD similar to that in the general population of oocyte recipients.


The adult eosinophilic oesophagitis quality of life questionnaire: a new measure of health-related quality of life.
Eosinophilic oesophagitis (EoO) is a chronic disease characterised by significant symptoms and challenging treatment regimens. Health-related quality of life (HRQOL) is a useful way to direct patient care. EoO symptoms and treatment may impact patient HRQOL. Currently, there is no reliable and valid measure of adult EoO patient HRQOL. To validate the Adult Eosinophilic Oesophagitis Quality of Life (EoO-QOL-A) questionnaire as a measure of HRQOL in this population. The EoO patients aged 18-70 recruited via an out-patient GI clinic and two EoO advocacy groups completed the preliminary EoO-QOL-A, demographic and clinical information, and measures of general HRQOL, psychological distress and EoO symptom severity. A subset of patients completed test-retest assessments. Scale reliability, internal consistency, factor structure, concurrent and convergent validity were evaluated. A total of 201 patients have participated. The study sample was primarily Caucasian, college-educated, and evenly split by gender. The average duration of disease was 7 years with duration of symptoms of 26 months prior to diagnosis. Patients reported were using both pharmacological and dietary treatments. Factor analysis yielded a 37-item, 5-factor structure: Eating/Diet Impact, Social Impact, Emotional Impact, Disease Anxiety and Choking Anxiety. The EoO-QOL-A demonstrated excellent internal consistency, split-half and test-retest reliability. Concurrent and convergent validity were supported by moderate correlations with established HRQOL measures, psychological distress and oesophageal symptoms. The EoO-QOL-A is a valid and reliable disease-specific HRQOL measure for adult EoO patients. Developing the Adult Eosinophilic Oesophagitis Quality of Life is an important step in guiding treatment practices, improving disease education and standardising research protocols.


Pharmaceuticals, illicit drugs and their metabolites in fish from Argentina: Implications for protected areas influenced by urbanization.
Because an understanding of aquatic bioaccumulation of human pharmaceuticals in Latin America is limited, this area was recently identified as a priority environmental quality research need. We examined bioaccumulation of twenty-seven pharmaceuticals, illicit drugs and their metabolites in muscle, liver and gills of multiple fish species (Rhamdia quelen, Hypostomus commersoni, Hoplias lacerdae, Prochilodus lineatus) from an urban river receiving wastewater discharges (Paraná) and a lotic system (Acaraguá) without direct wastewater sources, which runs through a protected area. All samples were analyzed using isotope-dilution liquid chromatography-tandem mass spectrometry. Caffeine, which was detected up to 13 μg/kg, and antibiotics were consistently detected in all fish. Among antibiotics, erythromycin was ubiquitous (0.7-5.6 μg/kg) but its tissue concentrations were lower than levels of sulfamethoxazole, sulfathiazole and trimethoprim (0.9-5.5 μg/kg), which are used in human medicine, aquaculture and livestock. Erythromycin bioaccumulation in fish is reported here from Argentina for the first time, though levels of antibiotics in edible muscles of these species were lower than the maximum residue limits for human consumption. We observed norfluoxetine, the primary active metabolite of the antidepressant fluoxetine, ranging from 1.1-9.1 μg/kg in fish. We further identified benzoylecgonine, a primary metabolite of cocaine, in fish from both study systems, representing the first observation an illicit drug or associated metabolites bioaccumulation in aquatic life from Argentina. Interestingly, high pharmaceutical levels were observed in fish from the Acaraguá river suggesting their transport into the protected area, from the surrounding lands. Though fish from the Paraná river were sampled near WWTP discharges, pharmaceutical concentrations may have been reduced by hydrological and other environmental conditions, and biological differences among species. These findings, which observed bioaccumulation of select pharmaceuticals, their metabolites and illicit drugs in wild fish sampled inside a protected area, highlight the importance of developing an advanced understanding of urban influences on inland protected watersheds.


Pulcherralpin, a new diterpene ester from Caesalpinia pulcherrima.
From the stems of Caesalpinia pulcherrima, the new cassane-type diterpene ester pulcherralpin (1) has been isolated and characterized. The structure of 1 was established through spectroscopic studies, including the 1H-1H homonuclear and 1H-13C heteronuclear correlation studies.


Granulomatous colitis in a patient with metastatic melanoma under immunotherapy: a case report and literature review.
Immune checkpoint inhibitors (ICPIs) have changed the way advanced malignancies are currently confronted, improving cancer patients' outcomes but also generating distinct immune-related (ir) adverse events. ICPIs-induced colitis is a common complication showing different clinical and histological manifestations. In the literature review, 14 cases with ICPIs related colon granulomas have been reported in 5 studies with either limited or unavailable information regarding histology. Granulomatous reactions can be mistakenly perceived as disease recurrence or progression. Better understanding and identification of this infrequent histological display can help to avoid misdiagnosis and mismanagement. A 63-year-old female patient with metastatic melanoma was admitted to the hospital with symptoms of nausea, persistent diarrhea and shivering fever under consecutive treatments with ICPIs, initially pembrolizumab and subsequently ipilimumab. Sigmoidoscopy was performed revealing mucosal edema, hyperemia and erosions of the rectum and sigmoid colon. Histological evaluation of sigmoid colon mucosa biopsies revealed an unusual colitis pattern characterized by multiple intracryptal granulomas attributed to ICPIs therapy. Steroids were administered and the patient recovered. ICPIs treatment was discontinued. The patient was subsequently treated with chemotherapy but follow up radiology showed disease progression. A re-challenge with another ICPI regimen was decided and the patient is currently under immunotherapy with stable disease regarding melanoma status and without any sign of colitis recurrence. The present report provides detailed histological description of a distinctive ICPIs-induced granulomatous colitis and highlights the need for awareness of the distinct adverse events and reaction patterns in the context of immunotherapy.


Cognitive outcome and gamma noise power unrelated to neuregulin 1 and 3 variation in schizophrenia.
Neuregulins are a family of signalling proteins that orchestrate a broad range of cellular responses. Four genes encoding Neuregulins 1-4 have been identified so far in vertebrates. Among them, Neuregulin 1 and Neuregulin 3 have been reported to contribute to an increased risk for developing schizophrenia. We hypothesized that three specific variants of these genes (rs6994992 and rs3924999 for Neuregulin 1 and rs10748842 for Neuregulin 3) that have been related to this illness may modify information processing capacity in the cortex, which would be reflected in electrophysiological parameters (P3b amplitude or gamma noise power) and/or cognitive performance. We obtained DNA from 31 patients with schizophrenia and 23 healthy controls and analyzed NRG1 rs6994992, NRG1 rs3924999 and NRG3 rs10748842 promoter polymorphisms by allelic discrimination with real-time polymerase chain reaction (PCR). We compared cognitive outcome, P300 amplitude parameters and an electroencephalographic measure of noise power in the gamma band between the groups dichotomized according to genotype. Contrary to our hypothesis, we could not detect any significant influence of variation in Neuregulin 1/Neuregulin 3 polymorphisms on cognitive performance or electrophysiological parameters of patients with schizophrenia. Despite our findings, we cannot discard that other genetic variants and, more likely, interactions between those variants and with genetic variation related to different pathways may still influence cerebral processing in schizophrenia.


EpCAM: another surface-to-nucleus missile.
The epithelial-specific cell adhesion molecule (EpCAM) modulates cell adhesion and proliferation. Its overexpression correlates with tumor cell proliferation, and EpCAM is a therapeutic target. In the February issue of Nature Cell Biology, Maetzel et al. demonstrate that proliferative responses to EpCAM require regulated intramembrane proteolysis and a nucleocytoplasmic intracellular domain fragment.


Quality of life in patients with moderate to severe ulcerative colitis and the impact of treatment: A narrative review.
As a chronic inflammatory disease, ulcerative colitis has significant negative impact on the quality of life (QoL) of patients. Since the disease affects many aspects of QoL, comprising multiple domains, treatments that induce and maintain remission can provide benefits beyond hard clinical endpoints. Effective treatment of ulcerative colitis can restore QoL and return it to normal or near normal levels. Biological therapies have shown consistent improvement in the QoL of patients with ulcerative colitis during the induction phase, with benefits that are generally maintained in the long-term. Current medical treatment options broadly comprise aminosalicylates, corticosteroids, thiopurines, and calcineurin inhibitors, as well as biologic therapies. Conventional therapies do not always adequately control disease in a sizeable portion of patients, while anti-TNF antibodies are associated with several issues such as contraindications, intolerance, primary non-response, and loss of response in some patients. JAK inhibitors have been associated with clinical improvements in disease manifestations and long-term improvement in QoL outcomes. However, additional studies are needed to better understand the comparative effects of different treatments on QoL and patient preferences for therapy. Herein, the available evidence is reviewed regarding the impact of various treatments on QoL in patients with moderate to severe ulcerative colitis.


Activation of TRPM8 channel inhibits contraction of the isolated human ureter.
The transient receptor potential melastin-8 (TRPM8) channel is a "cooling" receptor expressed in primary sensory neurons and can be activated by compounds like menthol or icilin. TRPM8 is involved in the regulation of urinary bladder sensory function and contraction, but the role of TRPM8 in the ureter, particularly in the human ureter, is poorly understood. The aim of this study is to examine the effects of TRPM8 activation on human ureter contraction. Human ureters were acquired from 20 patients undergoing radical nephrectomy. Contractions of ureter strips were recorded by an isometric transducer in the organ bath. Ureteral TRPM8 expression in the human ureter was examined by immunofluorescence and western blot. The two TRPM8 agonists menthol and icilin both reduced the frequency of spontaneous, electrical field stimulation, or neurokinin A-evoked ureteral contractions in a dose-dependent manner. The inhibitory effects were decreased by 10-fold in mucosa-denuded strips. The inhibitory effects of TRPM8 agonists were mimicked by calcitonin gene-related peptide (CGRP), and were blocked by KRP2579 (a TRPM8 antagonist), tetrodotoxin (a sodium channel blocker), olcegepant (BIBN, a CGRP receptor antagonist), SQ22536 (an adenylate cyclase antagonist), or H89 (a nonspecific cAMP-dependent protein kinase A inhibitor). TRPM8 was coexpressed with CGRP on the nerves located in the suburothelial and intermuscular regions and was not expressed in the urothelium. The TRPM8 channel expressed on sensory nerve terminals of the human ureter is involved in the inhibitory sensory neurotransmission and modulate ureter contraction via the CGRP-adenylyl cyclase-protein kinase A pathway. TRPM8 may be involved in stone-induced changes in ureter contraction or pain.


Early-stage Parkinson's disease: Abnormal nigrosome 1 and 2 revealed by a voxelwise analysis of neuromelanin-sensitive MRI.
Previous pathologic studies evaluated the substantia nigra pars compacta (SNpc) of a limited number of idiopathic Parkinson's disease (IPD) patients with relatively longer disease durations. Therefore, it remains unknown which region of the SNpc is most significantly affected in early-stage IPD. We hypothesized that a voxelwise analysis of thin-section neuromelanin-sensitive MRI (NM-MRI) may help determine the significantly affected regions of the SNpc in early-stage IPD and localize these areas in each nigrosome on high-spatial-resolution susceptibility map-weighted imaging (SMwI). Ninety-six healthy subjects and 50 early-stage IPD patients underwent both a 0.8 × 0.8 × 0.8 mm3 NM-MRI and a 0.5 × 0.5 × 1.0 mm3 multi-echo gradient-recalled echo imaging for SMwI. Both NM-MRI and SMwI templates were created by using image data from the 96 healthy subjects. Permutation-based nonparametric tests were conducted to investigate spatial differences between the two groups in NM-MRI, and the results were displayed on both NM-MRI and SMwI templates. The posterolateral and anteromedial regions of the SNpc in NM-MRI were significantly different between the two groups, corresponding to the nigrosome 1 and nigrosome 2 regions, respectively, on the SMwI template. There were the areas of significant spatial difference in the hypointense SN on SMwI between early-stage IPD patients and healthy subjects. These areas on SMwI were slightly greater than those on NM-MRI, including the areas showing group difference on NM-MRI. Our voxelwise analysis of NM-MRI suggests that two regions (nigrosome 1 and nigrosome 2) of the SNpc are separately affected in early-stage IPD.


The comparative performance of the single intradermal test and the single intradermal comparative tuberculin test in Irish cattle, using tuberculin PPD combinations of differing potencies.
In national bovine tuberculosis (BTB) control programmes, testing is generally conducted using a single source of bovine purified protein derivative (PPD) tuberculin. Alternative tuberculin sources should be identified as part of a broad risk management strategy as problems of supply or quality cannot be discounted. This study was conducted to compare the impact of different potencies of a single bovine PPD tuberculin on the field performance of the single intradermal comparative tuberculin test (SICTT) and single intradermal test (SIT). Three trial potencies of bovine PPD tuberculin, as assayed in naturally infected bovines, namely, low (1192IU/dose), normal (6184IU/dose) and high (12,554IU/dose) were used. Three SICTTs (using) were conducted on 2102 animals. Test results were compared based on reactor-status and changes in skin-thickness at the bovine tuberculin injection site. There was a significant difference in the number of reactors detected using the high and low potency tuberculins. In the SICTT, high and low potency tuberculin detected 40% more and 50% fewer reactors, respectively, than normal potency tuberculin. Furthermore, use of the low potency tuberculin in the SICTT failed to detect 20% of 35 animals with visible lesions, and in the SIT 11% of the visible lesion animals would have been classified as negative. Tuberculin potency is critical to the performance of both the SICTT and SIT. Tuberculin of different potencies will affect reactor disclosure rates, confounding between-year or between-country comparisons. Independent checks of tuberculin potency are an important aspect of quality control in national BTB control programmes.


Development of a system to measure color in fresh and microwave dried banana slices.
The main focus of this study was to develop and calibrate a computerized image analysis system in order to measure the color of banana (Musa Cavendish) under microwave treatment. Bananas were cut into 2 mm slice thickness and dried at two different microwave power level; 540 W and 180 W. An algorithmic was developed which converted RGB color value from a color image into CIE L*a*b* values very well (ErrorL* = 2.163%, Errora* = 4.458%, Errorb* = 5.224%). Once the calibration is completed, it was applied to measure the color change in the banana slice during drying. The value of L* decreased from 89.01 to 71.17 and from 82.60 to 72.53 for both microwave treated samples suggesting browning is taking place during the drying operation. The value of a* increased from - 0.80 to 11.50 and from - 3.90 to 5.18 for 540 and 180 W microwave treated banana slices respectively suggesting tendency of redness increased. The same type of increment was observed for b* value. It changed from 36.46 to 60.51 and 34.02 to 72.82 for 540 and 180 W microwave treated banana slices, respectively. Artificial Neural Network (ANN) modeling was used for prediction of the developed CVS's values.


Incidence and patterns of recurrence following curative resection for colorectal carcinoma.
This study was designed to determine incidence and patterns of recurrence after curative resection of colorectal carcinoma and to determine which variables are significant in predicting outcome. A retrospective review of 524 patients operated on by one surgeon from 1975 to 1992 was conducted. Variables recorded included age, gender, location, gross morphology, histology, stage of each primary and evidence of perforation and direct extension at time of original operation. Overall survival and pattern of recurrence were documented. Overall recurrence rate was 27.9 percent. Anastomotic recurrence rate was 11.7 percent. Anastomotic recurrences were higher for rectal than colon lesions (20.3 vs. 6.2 percent; P = 0.001). Distant metastases developed in 14.4 percent of patients, 13.9 percent for colon carcinoma and 15.5 percent for rectal carcinoma. Average time for anastomotic recurrence was 16.2 months vs. 22.9 months for distant disease. T1,2,N0,M0 lesions had a 17.6 percent recurrence rate, T3,N0,M0 was 23.4 percent, and T1,2,3,N1,M0 was 43.7 percent (P = .001). Patients who did not undergo any intervention after diagnosis of recurrence survived an average of 28 months. Those who received palliative treatment survived an average of 39 months. Twenty-four percent of patients had reresection for cure, and 47 percent of these patients were alive at a mean of 80 months; those who died of their disease did so at an average of 53 months. Positive predictive factors for recurrence include site of lesion (rectum vs. colon), stage, invasion of contiguous organs, and presence of perforation. Age, gender, degree of differentiation, mucin secretion, and gross morphology were not found to be predictive factors in this study. Recurrence after resection for rectal carcinoma is higher than after colon carcinoma. In those patients in whom reresection is possible, up to 50 percent may have long-term survival. Understanding patterns of recurrence and features that predispose to them may guide the physician in aggressive but more selective adjuvant therapy and recommendations for targeted surveillance in follow-up.


Prenatal care among immigrant and racial-ethnic minority women in a new immigrant destination: exploring the impact of immigrant legal status.
Despite the rising share of undocumented immigrants in the US population, research has been quite limited regarding immigrant legal status and how it may limit healthcare access, especially research involving direct identification of undocumented populations. Drawing upon the Utah Population Database, a unique, comprehensive linked system of vital, medical, and administrative records, we analyze the prenatal care utilization in a large and recent cohort of births to mothers residing in the pre-emerging immigrant gateway state of Utah. Our analyses focus on the racial-ethnic, nativity and legal status of mothers as factors that influence prenatal care utilization. State administrative records are used to assess legal status among foreign-born mothers, specifically driver privilege cards made available to undocumented migrants. Our results indicate the importance of disaggregating the expansive categories of Hispanics and the foreign born to better understand health outcomes and healthcare utilization among immigrants. In particular, we find that the legal status of immigrant mothers is one of several important factors influencing prenatal care utilization. Undocumented women are among the least likely to obtain adequate levels of prenatal care. However, undocumented women's prenatal care utilization is enhanced among those using the state's integrative driver privilege program, and among those residing in neighborhoods with high concentrations of immigrants. Results are discussed in light of theory on immigrant integration and healthcare access, and in terms of public policies, such as those extending driver privileges to unauthorized immigrants, which aim to facilitate immigrants' access to institutions within destination communities.


[Prognostic factors in COPD: the head, the legs and the breath!].
Today COPD is generally regarded as a generalised illness starting in the respiratory system. Numerous extra-pulmonary manifestations and a range of co-morbidities complicate the natural history of the disease. They aggravate the symptoms, affect the quality of life and increase the risks of hospital admission and death. Recently a new step has been taken with the recognition of prognostic factors that are independent of bronchial obstruction. The true predictive factors of survival in patients with COPD are effort intolerance, loss of independence, the level of physical activity, diminution of body mass index, loss of muscle mass or quadriceps strength, dispense, anxiety, depression and quality of life. Different tools, such as the BODE index or its modifications which integrate the predictive value of several manifestations of COPD, are now validated for the estimation of life expectancy. These new data are a further advance in the understanding of the disease and the optimisation of the diagnosis, evaluation and management of patients.


Trypanosoma rangeli: characterization of a Mg-dependent ecto ATP-diphosphohydrolase activity.
In this work we describe the ability of living Trypanosoma rangeli to hydrolyze extracellular ATP. In these intact parasites whose viability was assessed before and after the reactions by motility and by Trypan blue dye exclusion, there was a low level of ATP hydrolysis in the absence of any divalent metal (1.53+/-0.12 nmol P(i)/h x 10(7) cells). The ATP hydrolysis was stimulated by MgCl(2) and the Mg-dependent ecto-ATPase activity was 5.24+/-0.64 nmol P(i)/h x 10(7) cells. The Mg-dependent ecto-ATPase activity was linear with cell density and with time for at least 60 min. This stimulatory effect on the ATP hydrolysis was also observed when MgCl(2) was replaced by MnCl(2), but not by CaCl(2), SrCl(2), and ZnCl(2). The apparent K(m) for Mg-ATP2- was 0.53+/-0.11 mM. The optimum pH for the T. rangeli Mg-dependent ecto-ATPase activity lies in the alkaline range. This ecto-ATPase activity was insensitive to inhibitors of other ATPase and phosphatase activities, such as oligomycin, sodium azide, bafilomycin A1, ouabain, furosemide, vanadate, molybdate, sodium fluoride, tartrate, and levamizole. To confirm that this Mg-dependent ATPase was an ecto-ATPase, we used an impermeant inhibitor, DIDS (4, 4'-diisothiocyanostylbene 2'-2'-disulfonic acid) as well as suramin, an antagonist of P2 purinoreceptors and inhibitor of some ecto-ATPases. These two reagents inhibited the Mg(2+)-dependent ATPase activity in a dose-dependent manner. This ecto-ATPase activity was stimulated by carbohydrates involved in the attachment/invasion of salivary glands of Rhodnius prolixus and by lipophorin, an insect lipoprotein circulating in the hemolymph.


Therapeutic Effect of Doxorubicin-Chlorin E6-Loaded Mesoporous Silica Nanoparticles Combined with Ultrasound on Triple-Negative Breast Cancer.
Sonodynamic Therapy (SDT) has good targeting and non-invasive advantages in solid cancers, but its antitumor effect is not sufficient to replace traditional treatments. Some studies that combined SDT with chemotherapy or nanoparticles have managed to enhance its efficiency and overcome the side effects of chemotherapy. In this study, we synthesized and characterized mesoporous silica nanoparticles (MSN-DOX-Ce6) loaded with doxorubicin (DOX) and sonosensitizer, chlorin e6 (Ce6). Then, we conducted in vitro and in vivo experiments to explore the antitumor effect of MSN-DOX-Ce6 under ultrasound (US) treatment. The characterization tests showed that the nanoparticles are uniformly sized spheres with mesoporous structure, resulting in a high drug-loading efficiency. In the in vitro experiments, MSN-DOX-Ce6 could effectively inhibit cell proliferation under US but not more than other treatment groups. However, the in vivo studies showed that MSN-DOX-Ce6+US has better antitumor effect than DOX+Ce6+US or DOX alone on xenograft tumor-bearing mice. In summary, MSNs showed a great potential for DOX and Ce6 delivery. We concluded that under US, MSN-DOX-Ce6 nanocomposites increase the antitumor effect of DOX and SDT and thereby are a potential treatment for solid tumors.


Poliovirus infection of established human blood cell lines: relationship between the differentiation stage and susceptibility of cell killing.
The replication of type 1 poliovirus in 13 established human blood cell lines differing in the differentiation stage and cell lineage was investigated. Three T (CCRF-CEM, CCRF-HSB-2, and Molt-3) and three B (Raji, CCRF-SB, and RPMI 8226) cell lines showed no cytopathic effects (CPE) or virus production. CPE associated with virus production were detected in the other seven cell lines: HL-60, ML-1, and KG-1 (granulocytic lineage), U-937 and THP-1 (monocytic lineage), K-562 (erythroid lineage), and Molt-4 (T cell lineage). These susceptible cell lines greatly differed in the speed at which the CPE progressed. The progression of CPE was faster in relatively well-differentiated cell lines such as HL-60 and U-937, independently of the multiplicity of infection, than in less differentiated cell lines such as K-562, KG-1, and THP-1. Thus, for the same lineage, the speed at which CPE progressed became proportionally higher with subsequent differentiation stages. In the K-562 cell culture, CPE were not observed until at least 5 days postinfection (p.i.), while more than 80% of HL-60 cells were killed within 3 days p.i. There were no significant differences between infected HL-60 and K-562 cells in the efficiency of infection determined at 8 hr p.i. by the indirect immunofluorescent technique, the rate of virus growth, or the amount of viral capsid protein synthesized. This indicated that there were similar viral replication cycles in the two cell lines. These observations suggest that the killing function of the virus is expressed more slowly in K-562 cells than in HL-60 cells.


The human motor control system's response to mechanical perturbation: should it, can it, and does it ensure stability?
From among the diverse meanings of stability, the one the author adopts here is that the effects of a perturbation are opposed, and therefore small effects remain small. Except in linear systems, however, instability need not lead to unbounded motion and may actually be desirable when maneuverability is important. Moreover, properties of nerves, muscles, and tendons present serious challenges to stabilization. A review of observations from the motor control literature reveals that responses to perturbations in many common situations assist rather than resist the perturbation and are therefore presumably destabilizing. The observations encompass situations of position maintenance as well as impending or ongoing movement. The author proposes that the motor control system responds to a sudden perturbation by a pattern of muscle activity that mimics an accustomed voluntary movement, oblivious of stability considerations. What prevents runaway motion in the face of short-term instability appears to be voluntary intervention.


Tumor response to neoadjuvant chemoradiation therapy for rectal adenocarcinoma is mediated by p53-dependent and caspase 8-dependent apoptotic pathways.
We tested the hypothesis that rectal tumors are most responsive to neoadjuvant therapy if they possess p53 and/or caspase 8 activity. Fifty patients diagnosed with biopsy-proven rectal cancer underwent neoadjuvant chemoradiation therapy consisting of 5-fluorouracil (300 mg/m(2) daily) and radiation (4,500 cGy). Endorectal ultrasonography was performed before and after neoadjuvant therapy along with digital rectal examination and/or sigmoidoscopy for staging purposes and to evaluate response to therapy. All patients underwent resection with specimens submitted for gross and microscopic review. Pretreatment biopsy specimens were subjected to immunohistochemical staining for mutated p53 and caspase 8 bioactivity. The study population consisted of 32 men and 18 women. There were 17 complete responses (CRs; 34%), 17 partial responses (PRs; 34%), and 16 cases of no response (NR; 32%). There were 10 stage I tumors (20%), 22 stage II tumors (44%), and 18 stage III tumors (36%) in the cohort at the time of initial diagnosis. p53 protein staining (ie, mutated p53) was positive in 31 tumors (62%; CR, n = 8; PR, n = 11; NR, n = 12); caspase 8 positivity was apparent in 30 specimens (60%; CR, n = 13; PR, n = 13; NR, n = 4). In terms of pretreatment predictions, we scored 3 separate levels of response (CR, 3; PR, 2; NR, 1) and compared them with the expected responses (ie, p53 positivity and caspase 8 negativity should yield NR, whereas all other combinations should yield responses). Wilcoxon 2-sample tests yielded a 1-sided P value of 0.007. The present study highlights a possible mechanism for tumor response to neoadjuvant manipulation, namely that dual mechanisms for apoptotic cell death are working in concert to cause tumor regression; one is p53 transcription-dependent, and the other is p53 transcription-independent.


The Arkansas Active Kids Study: Identifying contributing factors to metabolic health and obesity status in prepubertal school-age children.
We report the design, protocol and statistical analysis plan for the Arkansas Active Kids (AAK) Study. The study investigates the complex relationships between factors that contribute to metabolic health and obesity status in prepubertal school-age children in the state of Arkansas. We aim to identify modifiable behavioral and environmental factors and phenotypes related to metabolic health that are associated with obesity status that, if addressed effectively, can aid in designing effective intervention strategies to improve fitness and reduce obesity in children. We analyzed dietary and physical activity data from two national surveys (National Survey of Children's Health and Youth Risk Behavior Surveillance System). We then conducted detailed surveys to collect dietary, physical activity, socio-demographic, and environmental data from a sample of 226 prepubertal Arkansas children. In the same sample of prepubertal children, we also collected extensive physiologic data to further study associations between physical activity and metabolic health. All study visits included detailed measures of vital signs, energy expenditure, components of physical fitness, body composition and the collection of biological samples for determination of metabolic analytes. The observational, environmental and physiological results will be used to craft multivariate statistical models to identify which variables define 'phenotype signatures' that associate with fitness level and obesity status.


Evaluation of QT dispersion in epileptic patients and its association with SUDEP risk.
Mortality in epileptic patients was attributed to sudden unexpected death in epilepsy (SUDEP). The precise pathophysiology of SUDEP is not fully understood, yet prolongation of ventricular repolarization particularly QTc interval suggested to be one of the contributing risk factor for SUDEP. We aimed at evaluation of QTc and QT dispersion (QTD) in patients with epilepsy (both refractory and well-controlled epilepsy) and their association with the epileptic severity and sudden unexplained death (SUDEP) risk. The study included eighty epileptic patients (40 controlled epileptic patients and 40 refractory epileptic patients) compared to thirty non-epileptic volunteers as the control group (patients with history of cardiovascular comorbidities or exposure to antiarrhythmic drugs were excluded from the study). All participants were subjected to clinical evaluation including detailed epileptic history with assessment of SUDEP 7 risk, severity scale, 12 leads surface ECG to measure QTc & QTD, 24 h Holter monitoring to assess heart rate variability (HRV) parameters. Controlled and refractory epileptic patients demonstrated increased average QTc and QTD values compared to control group (450.1 ± 18.9 vs. 412.3 ± 12.3 ms, p < 0.0001, 452.1 ± 19.0 vs. 412.3 ± 12.3 ms, p < 0.0001 respectively) (45.6 ± 14.9 vs. 15.4 ± 6.8 ms, p < 0.001, 70.6 ± 18.1 vs. 15.4 ± 6.8 ms, p < 0.0001 respectively). Refractory epileptic patients had a significantly higher incidence of abnormal QTD > 50 ms compared to controlled epileptic patients (32.5% vs. 90%, p < 0.005). Refractory epileptic patients with generalized form had significantly higher severity scale in addition to significantly impaired rMSSD and pNN50 compared to those with focal form (1072.7 ± 722.7 vs. 429.1 ± 180.4, p < 0.03, 17.11 ± 4.6 vs. 26.4 ± 7.9 ms, p < 0.004 and 2.9 ± 1.8 vs. 7.8 ± 4.1%, p < 0.003 respectively). Among refractory epileptic patients, the duration of epilepsy, rMSSD and QTD significantly correlated with SUDEP-7 risk (r2 =0.199, p < 0.005, r2 =0.623, p < 0.0001 and r2=0.44, p < 0.0001 respectively). The current study stands out the importance of evaluating QTc and QTD in 12-lead ECG recordings in epileptic patients and signifying their association with SUDEP-7 risk among refractory epileptic patients.


Predictors of caregiver feeding practices differentiating persistently obese from persistently non-overweight adolescents.
Understanding the contribution of caregiver feeding practices to adolescent diet and weight is important to refining caregiver roles within the context of adolescent obesity prevention and treatment. This secondary data analysis examined whether feeding practices of female caregivers differentiated persistently non-overweight (n = 29) from persistently obese (n = 47) adolescents. Families who previously participated in a cross-sectional study on correlates of obesity were recruited for this follow-up study. At the time of the follow-up study, anthropometric measures were taken for all female caregivers and adolescents, and caregivers completed the Child Feeding Questionnaire-Adolescent version. Socioeconomic, demographic, female caregiver anthropometric, and psychological (caregiver perceived self-weight and concern for adolescent overweight) variables were examined as predictors of feeding practices found to differentiate the two groups. Female caregivers of persistently obese adolescents reported significantly greater use of restriction and monitoring compared to female caregivers of persistently non-overweight adolescents. Restriction was predicted by female caregiver age and concern for adolescent overweight whereas monitoring was predicted by concern for adolescent overweight only. Caregiver feeding strategies may be an important target for adolescent obesity prevention and intervention efforts particularly among those with heightened concern about their teen's weight status.


Accuracy of Doppler echocardiography to estimate key hemodynamic variables in subjects with normal left ventricular ejection fraction.
The accuracy of Doppler echocardiography to estimate key hemodynamic parameters in subjects with normal left ventricular ejection fraction (LVEF) has not been fully investigated. Thirty-six subjects with LVEF >50% (median age 62 years), with a broad clinical profile, underwent Doppler echocardiography immediately followed by right heart catheterization. Correlation coefficients between invasive and noninvasive right atrial pressure (RAP), systolic (sPAP) and mean (mPAP) pulmonary artery pressure, cardiac output (CO), and pulmonary vascular resistance (PVR) were 0.39, 0.70, 0.72, 0.57, and 0.60 (P < .001 for all). There was no significant correlation between invasive and noninvasive (based on the peak early transmitral to peak early septal mitral annular velocity ratio) pulmonary capillary wedge pressure (PCWP; r = 0.23; P = .18). Bland-Altman plots revealed variable bias but with consistently large limits of agreement for all noninvasive parameters, particularly PCWP. Areas under the receiver operating characteristic curve for noninvasive sPAP, CO, PVR, and PCWP to predict an invasively assessed mPAP ≥25 mm Hg, cardiac index <2.5 L min(-1) m(-2), PVR >3 Wood units, and PCWP ≤15 mm Hg, respectively, were 0.92, 0.83, 0.70, and 0.58. Single Doppler echocardiography parameters are not accurate enough to reliably estimate key hemodynamic parameters, particularly PCWP, in subjects with normal LVEF.


Motion-detection thresholds for first- and second-order gratings and plaids.
The two-stage decomposition-recombination model of 2D motion perception has been criticised on the basis that the direction of plaid stimuli can be accurately discriminated at speeds so low that the direction of their Fourier components is not discriminable. The nature of this gap in performance between gratings and plaids was investigated across a range of spatial frequencies and durations for first- and second-order stimuli. Motion-detection thresholds were obtained using a 2AFC, constant stimuli procedure and it was found that although thresholds for detection of plaid motion were often lower than those for gratings, the gap in performance between first-order plaids and gratings was unreliable, varying in magnitude and occasionally direction with the spatial frequency of the stimulus, presentation duration and observer. Curiously, an analogous gap found between purely second-order gratings and second-order plaids was more reliable and stable. It has been suggested that the gap is the result of 'local motion detectors' or broadly tuned V1 cells. The data presented here suggest that second-order mechanisms are responsible for the gap and that first-order information may even disrupt it.


Quaternary stereocentres via an enantioconvergent catalytic SN1 reaction.
The unimolecular nucleophilic substitution (SN1) mechanism features prominently in every introductory organic chemistry course. In principle, stepwise displacement of a leaving group by a nucleophile via a carbocationic intermediate enables the construction of highly congested carbon centres. However, the intrinsic instability and high reactivity of the carbocationic intermediates make it very difficult to control product distributions and stereoselectivity in reactions that proceed via SN1 pathways. Here we report asymmetric catalysis of an SN1-type reaction mechanism that results in the enantioselective construction of quaternary stereocentres from racemic precursors. The transformation relies on the synergistic action of a chiral hydrogen-bond-donor catalyst with a strong Lewis-acid promoter to mediate the formation of tertiary carbocationic intermediates at low temperature and to achieve high levels of control over reaction enantioselectivity and product distribution. This work provides a foundation for the enantioconvergent synthesis of other fully substituted carbon stereocentres.


Intercalated duct cells in the rat parotid gland may behave as tissue stem cells.
This study was conducted to determine whether intercalated duct cells in the rat parotid gland have the properties of tissue stem cells. After induction of cellular proliferation by repeated administration of isoproterenol (IPR), a beta-adrenergic agonist, proliferation activity in acinar, intralobular, and intercalated ductal cells was quantified using Ki-67 immunohistochemistry. The total number of each type of component cell in a gland was also estimated in the course of IPR treatment. IPR was found to induce proliferation of acinar and intercalated duct cells, but not intralobular duct cells. The total number of acinar cells in a gland on day 5 of IPR treatment was 1.6 times of that at day 0 (baseline). In contrast, the total numbers of intercalated and intralobular duct cells did not change from baseline, indicating a high possibility that the proliferated intercalated duct cells differentiated into acinar cells. On days 2 to 3 of IPR treatment, intercalated duct cells with amylase-positive secretory granules were recognized in a region very close to the acini, and were suspected of being transitional cells from intercalated duct to acinar cells. This quantitative study indicates that intercalated duct cells may have the properties of tissue stem cells upon IPR stimulation.


Antimicrobial susceptibility testing of porcine Brachyspira (Serpulina) species isolates.
No standardized method for susceptibility testing of Brachyspira spp. is currently available. A broth dilution procedure was evaluated and used to test the activities of six antimicrobial agents for 108 isolates of Swedish porcine Brachyspira spp. representing biochemical groups I, II, and III. Group I corresponds to Brachyspira hyodysenteriae, group II corresponds to B. intermedia, and group III corresponds to B. murdochii and B. innocens. A panel was designed with the antimicrobial agents dried in tissue culture trays with wells that allowed a liquid volume of 0.5 ml in each and agitation of the broth when incubated on a shaker. The MICs were determined by using brain heart infusion broth with 10% fetal calf serum. For 10 isolates, the results obtained in broth were compared to the MICs obtained on two different types of agar. Different inoculum densities and incubation times were also compared. The concentrations at which 90% of the B. hyodysenteriae isolates (n = 72) were inhibited in the broth dilution test by tiamulin (0.25 micro g/ml), tylosin (>256 micro g/ml), erythromycin (>256 micro g/ml), clindamycin (>4 micro g/ml), virginiamycin (4 micro g/ml), and carbadox (0.06 micro g/ml) were determined. The MICs tended to be lower in broth than on agar. Differences in inoculum densities and incubation times had little influence on the MICs. The evaluated broth dilution test was simple to perform, the end points were easily read, and the results were reproducible and reliable. No isolates with decreased susceptibility to tiamulin were found among the Swedish isolates tested.


Cystatin C and Creatinine Concentrations Are Uninformative Biomarkers of Sarcopenia: A Cross-Sectional NHANES Study.
Differences in creatinine and cystatin C-based estimates of glomerular filtration rate (eGFRDiff = eGFRCr - eGFRCysC) may reflect differences in muscle mass. We sought to determine if eGFRDiff (1) reflects lean mass, (2) identifies sarcopenic individuals beyond estimates based on age, body mass index (BMI), and sex; and (3) demonstrates associations differently in those with and without chronic kidney disease (CKD). This cross-sectional study included 3,754 participants, ages 20-85 years, with creatinine and cystatin C concentration levels, and dual-energy X-ray absorptiometry scans from National Health and Nutrition Examination Survey data (1999-2006). Dual-energy X-ray absorptiometry-derived appendicular lean mass index (ALMI) estimated muscle mass. Non-race-based CKD Epidemiology Collaboration equations estimated glomerular filtration rate using eGFRCr, eGFRCysC, and both biomarkers (eGFRCysC&Cr). CKD was defined as eGFRCysC&Cr <60 mL/minute/1.73 m2. ALMI sex-specific T-scores (compared with young adult) < -2.0 defined sarcopenia. In estimating ALMI, we compared the coefficient of determination (R2) values from: 1) eGFRDiff, 2) clinical characteristics (age, BMI, and sex), and 3) clinical characteristics plus eGFRDiff. Using logistic regression, we evaluated each model's C-statistic to diagnose sarcopenia. eGFRDiff was negatively and weakly associated with ALMI (No CKD: R2 = 0.006, p-value 0.002; CKD: R2 = 0.001, P value .9). Clinical characteristics explained most of the variation in ALMI (No CKD: R2 = 0.851, CKD: R2 = 0.828), and provided strong discrimination of sarcopenia (No CKD C-statistic: 0.950; CKD C-statistic: 0.943). Adding eGFRDiff improved the R2 by 0.025, and the C-statistic by 0.003. Tests for interaction between eGFRDiff and CKD were not significant (all P values > .05). Although eGFRDiff has statistically significant associations with ALMI and sarcopenia in univariate analyses, multivariate analyses demonstrate that eGFRDiff does not capture more information beyond routine clinical characteristics (age, BMI, and sex).


Plastic Waste and the Environmental Crisis Industry.
Our relationship with plastic is complex. While the societal benefits of plastic are undeniable, plastic has also come to occupy a central role within a culture of waste and disposable living that constitutes a significant problem for health and the natural environment. Public awareness of the harms asociated with plastic is high, thanks, in part, to a range of sustained media exposure. This, however, has so far failed to materialize in any significant global reduction in plastic pollution. Meaningful regulatory change that adressess the harms of plastic at the point of production is curiously absent, while some apparent gains have been rolled back-against a backdrop of a global pandemic and a rehabilitation of plastic. This article highlights the assemblage of media, government and corporate interests that performs the role of what we identify as the "Environmental Crisis Industry" ("ECI"), which perpetuates stasis in the face of environmental catastrphe. The ECI manages our anxieties through media discourses of precarity and danger, while at the same time, offering us attainable "solutions" that exist well within the logic of consumer capitalism-in effect, compelling us (at least morally) to become eco-consumers. In this way, the political energy of grassroots climate resistance is "pre-corporated," so to speak, into the product design of major corporations, dissipating the chance of real progressive change in favor of a new green spirit of capitalism.


Development of 3D-QSAR models for predicting the activities of chemicals to stimulate muscle growth via β2-adrenoceptor.
β2-adrenoceptor (β2AR) agonists can stimulate skeletal muscle growth. Their illegal use in food-producing animals, human athletes and bodybuilders causes adverse health effects. In the present study, we developed 3D-QSAR models for predicting the activity of chemicals which can stimulate skeletal muscle growth through β2AR. The activity of 25 β2AR agonists was measured by β2AR-cAMP response element (CRE) -luciferase (Luc) reporter assay. The 3D-QSAR models were built using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The CoMFA and CoMSIA models displayed high external predictability (R2 0.996 and 0.992, respectively) and good statistical robustness, and revealed that electrostatic effects were the most prominent forces influencing the activity of β2AR agonists. The CoMFA and CoMSIA contour plots provided clues regarding the main chemical features responsible for the activity variations and also resulted in predictions which correlate very well with the observed activity. In vitro study with differentiated myotubes showed that the potency orders of β2AR agonists in activating the β2AR-CRE-Luc reporter and in upregulating CREB target genes related to muscle growth were consistent. These 3D-QSAR models provide tools for predicting the activity of chemicals which might be illegally used in livestock or humans to stimulate skeletal muscle growth.


Primary infective spondylodiscitis caused by Lactococcus garvieae and a review of human L. garvieae infections.
We report the first case of primary infective spondylodiscitis due to Lactococcus garvieae, confirmed by 16S rRNA gene sequencing, in the absence of concomitant endocarditis in a patient with long-standing gastritis on famotidine. He responded to a 6-week course of ampicillin. The gastrointestinal tract is probably the source of infection.


Computed tomography image reconstruction using stacked U-Net.
Since the development of deep learning methods, many researchers have focused on image quality improvement using convolutional neural networks. They proved its effectivity in noise reduction, single-image super-resolution, and segmentation. In this study, we apply stacked U-Net, a deep learning method, for X-ray computed tomography image reconstruction to generate high-quality images in a short time with a small number of projections. It is not easy to create highly accurate models because medical images have few training images due to patients' privacy issues. Thus, we utilize various images from the ImageNet, a widely known visual database. Results show that a cross-sectional image with a peak signal-to-noise ratio of 27.93 db and a structural similarity of 0.886 is recovered for a 512 × 512 image using 360-degree rotation, 512 detectors, and 64 projections, with a processing time of 0.11 s on the GPU. Therefore, the proposed method has a shorter reconstruction time and better image quality than the existing methods.


Can bacterial endotoxin exposure reverse atopy and atopic disease?
Studies have shown that endotoxin exposure in childhood is associated with a reduced risk of atopy and atopic asthma. It is commonly assumed that these effects only occur in early life. However, recent epidemiologic studies suggest that immune deviation might take place throughout life. Assuming that the immune system is not fixed after the first years of life, we hypothesize that endotoxin exposure might not only inhibit the development of atopic sensitization and disease at any time throughout life but might also reverse this process. This novel extension of the hygiene hypothesis is primarily based on the indirect evidence of several epidemiologic observations showing a reduction in atopy in adults highly exposed to endotoxin that is unlikely to be explained by protective effects alone. In addition, some animal studies demonstrated the potential of endotoxin to downregulate pre-existing airway eosinophilia and hyperreactivity. However, there is currently little direct evidence that endotoxin might reverse atopy and allergic diseases. Observational studies and randomized trials to test this hypothesis could ultimately lead to the development of novel treatments for atopic diseases, such as allergic asthma, hay fever, and eczema.


Validation of Diagnostic Coding for Asthma in an Electronic Health Record System in Hong Kong.
Electronic health record (EHR) databases can facilitate epidemiology research into various diseases including asthma. Given the diagnostic challenges of asthma, the validity of the coding in EHR requires clarification. We aimed to assess the validity of International Classification of Diseases, 9th Revision (ICD-9) code algorithms for identifying asthma in the territory-wide electronic medical health record system of the Clinical Data Analysis and Reporting System (CDARS) in Hong Kong. Adult patients who had the diagnosis of asthma input from all public hospitals in Hong Kong and those from Queen Mary Hospital in 2011-2020 were identified using the ICD-9 code of 493 (493.0, 493.1, 493.2, and 493.9) by CDARS. Patients' clinical record and spirometry were reviewed by two respiratory specialists to confirm the presence of asthma in the randomly selected cases. There were 43,454 patients who had the diagnostic code of asthma among all public hospitals in Hong Kong and 1852 in Queen Mary Hospital in the same period. A total of 200 cases were randomly selected and validated using medical record and spirometry review by a respiratory specialist. The overall positive predictive value (PPV) was 85.0% (95% CI 80.1-89.9%). This was the first ICD-9 code validation for CDARS (EHR) in Hong Kong on asthma. Our study demonstrated that using ICD-9 code (493.0, 493.1, 493.2 and 493.9) to identify asthma can result in a PPV that was reliable to support the utility of the CDARS database for further research on asthma among the Hong Kong population.


The lose-lose dilemmas of Barcelona's platform delivery workers in the age of COVID-19.
The abrupt lockdown experienced by a big part of the world population due to the COVID-19 pandemic has bestowed upon home delivery services an unexpected importance. Officially considered amongst "essential services", their workers circulate freely while most people are advised (when not forced) to stay in their homes. The present paper explores how this context helps to shed light on the precarious situation of the majority of the platform delivery workers (PDW). This is done through in-depth, semi-structured interviews and digital ethnography of the interactions within a WhatsApp group. The main finding is that the COVID-19 context deepened the precarization of the PDW confronting them with four dilemmas from which there is no way out.


An evaluation of three in vitro cytotoxicity assays.
A number of methods for determining the general toxic effects of test chemicals on cells in culture are now at the validation stage. Three such methods based on measurement of total cell protein or neutral red uptake and on the detection of morphological effects have been compared. The cell line used was 3T3-L1 (a continuous fibroblast cell line derived from mouse embryos). The results obtained in a blind trial with 30 coded chemicals indicated a close correlation between the relative cytotoxicities of chemicals tested by all three methods.