Evaluation of a wearable wireless device with artificial intelligence, iThermonitor WT705, for continuous temperature monitoring for patients in surgical wards: a prospective comparative study.
To evaluate a new-generation, non-invasive, wireless axillary thermometer with artificial intelligence, iThermonitor (WT705, Raiing Medical, Beijing, China), and to ascertain its feasibility for perioperative continuous body temperature monitoring in surgical patients. Departments of Biliary Surgery and Operating Room and the post-anaesthesia care unit of a university teaching hospital in Chengdu, China. A total of 526 adult surgical patients were consecutively enrolled. This was a prospective observational study. Axillary temperatures were continuously recorded with iThermonitor throughout the whole perioperative period. The temperatures of the contralateral armpit were measured with mercury thermometers at 8:00, 12:00, 16:00 and 20:00 every day and were used as references. The outcomes were the accuracy and precision of the temperatures measured with iThermonitor, the validity to detect fever and the feasibility of continuous wear. Pairs of temperatures were evaluated with Student's t-test, Pearson's correlation and repeated-measures Bland-Altman plot. A total of 3621 pairs of body temperatures were obtained. The temperatures measured with iThermonitor agreed with those measured with the mercury thermometers overall, with a mean difference of 0.03°C±0.35°C and a moderate correlation (r=0.755, p<0.001). The 95% limits of agreement (LoA) ranged from -0.63°C to 0.73°C, with 5.11% of the differences outside the 95% LoA. The intraclass correlation coefficient was 0.753. Continuous temperature monitoring captured more fevers than intermittent observation (117/526 vs 91/526, p<0.001), detected fever up to 4.35 hours earlier, and captured a higher peak temperature (0.29°C±0.27°C, 95% CI: 0.26-0.31). All subjects felt that wearing iThermonitor was more or less comfortable and did not affect their daily activities. iThermonitor is promising for continuous remote temperature monitoring in surgical patients. However, further developments are still needed to improve the precision of this device, especially for temperature detection in underweight patients and those with lower body temperature. ChiCTR1900024549; Results (registered on 5 July 2019).


Changes in the regional shape and volume of subcortical nuclei in patients with tinnitus comorbid with mild hearing loss.
Tinnitus, the perception of sound without an external source, is a prevalent disease, but its underlying mechanism has not been fully elucidated. Recent studies have suggested the involvement of subcortical nuclei in tinnitus generation. We investigated changes in the local shape and volume of subcortical nuclei in relation to tinnitus. The participants included 53 patients with tinnitus and 52 age- and gender-matched normal controls. Individual 3D T1-weighted structural images were obtained using 3-T magnetic resonance imaging. Surface-based vertex analysis (SVA) was performed with automated segmentation of the bilateral caudate nuclei, putamina, nucleus accumbens, thalami, pallidum, hippocampi, amygdalae, and brainstem. The scalar distances from the mean surface and volumes of 15 nuclei were compared between the tinnitus and control groups and correlated with tinnitus handicap score (THI) and tinnitus duration. SVA revealed regional contractions in the accessory basal and lateral nuclei of the right amygdala and expansions in the left medial and right ventral posterior nuclei and lateral dorsal nucleus of both thalami. The surface distances of the right nucleus accumbens were positively correlated with tinnitus duration, while those of the left nucleus accumbens and left hippocampus were negatively correlated with THI. Regional atrophy of the amygdala may indicate self-modulation of emotional response regulation to diminish tinnitus-related emotional distress. Thalamic regional expansion may signify dysfunctional auditory gating in the thalamus, where inhibition of the tinnitus signal at the thalamus level is disrupted due to abnormal changes in the limbic system, ultimately leading to the tinnitus percept.


Microbial oil - A plausible alternate resource for food and fuel application.
Microbes have recourse to low-priced substrates like agricultural wastes and industrial efflux. A pragmatic approach towards an emerging field- the exploitation of microbial oils for biodiesel production, pharmaceutical and cosmetic applications, food additives, biopolymer production will be of immense remunerative significance in the near future. Due to high free fatty acid, nutritive content and simpler solvent extraction processes of microbial oils with plant oil, microbial oils can back plant oils in food applications. The purpose of this review is to evaluate the opulence of lipid production in native and standard micro-organisms and also to emphasize the vast array of applications including food and fuel by obtaining maximum yield.


A celebration of Fred Brauer's legacy in mathematical biology.
Fred Brauer (1932-2021), one of the pioneers of mathematical population biology, shaped generations of researchers through his lines of research, his books which have become key references in the field, and his mentoring of junior researchers. This dedication reviews some of his work in population harvesting and epidemiological modeling, highlighting how this special collection reflects the impact of his legacy through both his research accomplishments and the formation of new researchers.


Extracellular matrix-induced changes in expression of cell cycle-related proteins and proteasome components in endometrial adenocarcinoma cells.
Extracellular matrix (ECM) components regulate growth and differentiation of epithelial cells, and impaired cell-ECM interaction may lead to increased cell proliferation and tumorigenesis. Whereas ECM has been shown to alter cellular morphology and reduce proliferation of HEC-1B endometrial adenocarcinoma cells, little is known about the underlying changes in gene expression. The purpose of this study was to investigate these changes. We studied by cDNA array the effects of ECM components, as present in Matrigel basement membrane cell culture matrix, on gene expression in HEC-1B endometrial adenocarcinoma cells in respect of the same cells cultured on conventional plastic surface. Some of the changes were confirmed by protein analyses. As expected, several growth-promoting genes were downregulated, while many genes associated with growth restriction were upregulated in Matrigel-grown carcinoma cells. Also, the expression of many 20S proteasome components was downregulated. The observed changes point to a less malignant phenotype of Matrigel-grown tumor cells, supported by reduced growth characteristics and morphology. The study provides further insight into the mechanisms whereby ECM components may participate in the regulation of cell growth--by reducing expression of growth-promoting genes and increasing expression of the genes associated with growth restriction.


Dental anomalies in cleft lip and/or palate children at age 10 - a retrospective review across three cleft centres: Part 1.
Introduction Children with oral clefts often present with dental anomalies which can impact function, aesthetics and complicate the patient's dental treatment and needs. An understanding of potential anomalies, along with early recognition and planning, is thus essential for effective care.Aim This paper is the first in a two-part three-centre series. This paper will assess the dental anomalies identified in 10-year-old patients attending three cleft centres in the UK.Method Retrospective review was undertaken of the clinical notes of 10-year-old patients attending South Wales (SW), Cleft NET East (CNE) and West Midlands (WM) cleft units, for their ten-year audit record appointment in 2016/2017.Results In total, 144 patients were reviewed (SW = 42; CNE = 52; WM = 50). Dental anomalies were recorded for 80.6% of patients (n = 116).Discussion The review gives insight into the dental complexities of UK oral cleft patients. These patients require specialist paediatric dental input and intensive preventive regimes.Conclusion Shared care between cleft team specialists and general dental practitioners is important when providing holistic care for cleft patients.


Radiographers and radiologists reporting plain radiograph requests from accident and emergency and general practice.
To assess selectively trained radiographers and consultant radiologists reporting plain radiographs for the Accident and Emergency Department (A&E) and general practitioners (GPs) within a typical hospital setting. Two radiographers, a group of eight consultant radiologists, and a reference standard radiologist independently reported under controlled conditions a retrospectively selected, random, stratified sample of 400 A&E and 400 GP plain radiographs. An independent consultant radiologist judged whether the radiographer and radiologist reports agreed with the reference standard report. Clinicians then assessed whether radiographer and radiologist incorrect reports affected confidence in their diagnosis and treatment plans, and patient outcome. For A&E and GP plain radiographs, respectively, there was a 1% (95% confidence interval (CI) -2 to 5) and 4% (95% CI -1 to 8) difference in reporting accuracy between the two professional groups. For both A&E and GP cases there was an 8% difference in the clinicians' confidence in their diagnosis based on radiographer or radiologist incorrect reports. For A&E and GP cases, respectively, there was a 2% and 8% difference in the clinicians' confidence in their management plans based on radiographer or radiologist incorrect reports. For A&E and GP cases, respectively, there was a 1% and 11% difference in effect on patient outcome of radiographer or radiologist incorrect reports. There is the potential to extend the reporting role of selectively trained radiographers to include plain radiographs for all A&E and GP patients. Further research conducted during clinical practice at a number of sites is recommended.


Morphological changes in the cat cerebral cortex produced by superfusion of ouabain.
The morphological changes following superfusion of the cat cerebral cortex with ouabain were studied. Autoradiography of [3H]ouabain was performed to study drug distribution. The resulting lesion consists of an upper vacuolated layer which is distinctly separated from an underlying region containing dark neurones. Ouabain is confined to the vacuolated layer. Swelling of apical dendrites and many presynaptic terminals are the main morphological changes occurring in the vacuolar layer. Depletion of synaptic vesicles, clustering of vesicles around the synaptic membrane, and the production of coated vesicles and cisternae are further changes found within presynaptic endings. Whilst swelling of fibrous astrocytes within the glialimitans occurs, this is not true of astrocytic processes elsewhere in ouabain exposed regions. Regions containing dark neurones are characterised by a general swelling of astroglial processes. The results strongly suggest that apical dendrites and presynaptic endings possess high activities of Na+, K+-ATPase whereas the activity on astroglial processes within the neuropil is relatively low. Astroglial swelling in areas of dark neurones is produced by some change in the chemical milieu surrounding the processes which appears unrelated to Na+, K+-ATPase inhibition.


Gene Fusion Detection and Characterization in Long-Read Cancer Transcriptome Sequencing Data with FusionSeeker.
Gene fusions are prevalent in a wide array of cancer types with different frequencies. Long-read transcriptome sequencing technologies, such as PacBio, Iso-Seq, and Nanopore direct RNA sequencing, provide full-length transcript sequencing reads, which could facilitate detection of gene fusions. In this work, we developed a method, FusionSeeker, to comprehensively characterize gene fusions in long-read cancer transcriptome data and reconstruct accurate fused transcripts from raw reads. FusionSeeker identified gene fusions in both exonic and intronic regions, allowing comprehensive characterization of gene fusions in cancer transcriptomes. Fused transcript sequences were reconstructed with FusionSeeker by correcting sequencing errors in the raw reads through partial order alignment algorithm. Using these accurate transcript sequences, FusionSeeker refined gene fusion breakpoint positions and predicted breakpoints at single bp resolution. Overall, FusionSeeker will enable users to discover gene fusions accurately using long-read data, which can facilitate downstream functional analysis as well as improved cancer diagnosis and treatment. FusionSeeker is a new method to discover gene fusions and reconstruct fused transcript sequences in long-read cancer transcriptome sequencing data to help identify novel gene fusions important for tumorigenesis and progression.


Respiratory work in elastase treated hamsters.
Biomechanical adaptations of the diaphragm in the hamster model of emphysema are similar to those observed in skeletal muscle with exercise training. The aim of this study was to evaluate whether the dynamic pressure-volume (PV) work of breathing in hamsters with elastase-induced emphysema may contribute to these adaptations. PV work in elastase treated animals was compared to healthy controls. The studies were performed in adult hamsters 14-16 months following intratracheal administration of elastase (elastase treated group, ET) or saline (control group, CTL). Airway and esophageal pressures and air flows were measured during spontaneous breathing in anesthetized, supine animals. Pulmonary work (WL) was computed from transpulmonary pressures and airflows. Functional residual capacity (FRC) and total lung capacity (TLC; defined as volume at 25 cmH2O) in ET were increased 2 and 1.8 times, respectively, compared with CTL. Averaged tidal volume (VT) and inspiratory flows were comparable between groups. Total work of breathing (WT) normalized per ml VT was not significantly affected with elastase treatment but the pulmonary elastance work (WE) was significantly less in ET animals than controls (0.88 +/- 0.61 g cm(-2) vs. 1.63 +/- 0.32). Pulmonary resistive work was not significantly different between ET and CTL animals. These results suggest that biomechanical adaptations of the diaphragm observed in ET hamsters are caused by mechanisms other than the changes in dynamic mechanical properties of the lung following elastase treatment.


Efficacy of olive leaves extract on the outcomes of hospitalized covid-19 patients: A randomized, triple-blinded clinical trial.
Since the emergence of the novel coronavirus, herbal medicine has been considered a treatment for COVID-19 patients. This study was done to determine the efficacy of olive leaf extract on the outcomes of COVID-19 patients. This randomized, triple-blinded clinical trial was conducted on hospitalized COVID-19 patients. Using block randomization, eligible patients were allocated to the following groups: intervention A received olive leaf extract (250 mg every 12 hours for five days), intervention B received olive leaf extract (500 mg every 12 hours for five days), and the control group received placebo (every 12 hours for five days). The outcomes (vital signs, laboratory tests, and length of hospitalization) were compared by group. Of the 150 patients randomized into groups, 141 completed the follow-up and were analyzed. On the fifth day of hospitalization, body temperature (MD=0.34, P<0.001), pulse rate (MD=5.42, P=0.016), respiratory rate (MD=1.66, P=0.001), ESR (MD=13.55, P<0.001), and CRP (MD=15.68, P<0.001) of intervention A were significantly lower than the control group, while oxygen saturation (MD= -1.81, P=0.001) of intervention A was significantly higher than the control group. Furthermore, body temperature (MD=0.30, P=0.001), pulse rate (MD=5.29, P=0.022), respiratory rate (MD=1.41, P=0.006), ESR (MD=14.79, P<0.001), and CRP (MD=16.28, P<0.001) of intervention B were significantly lower than the control group, while oxygen saturation (MD= -2.38, P<0.001) of intervention B was significantly higher than the control group. Olive leaf extract can improve the clinical status of the patients and decrease the length of hospitalization.


Advances in Alzheimer therapy: cholinesterase inhibitors.
After a decade of intense study of cholinergic therapies for Alzheimer's disease, three conditions in this field are apparent: 1) The potential that cholinergic agents will ameliorate the memory dysfunction of Alzheimer patients (as 1-dopa benefits Parkinson patients) is still a stimulus for research. 2) Cholinergic neuropharmacology and its impact on the therapy of memory disorders associated with cholinergic dysfunction needs to be further characterized and understood. 3) While there is still a search for a symptomatic treatment for AD, the path to find a treatment for the Alzheimer disease process must first pass through a phase of basic research to find the cause of Alzheimer's disease. At the meeting, there was an undercurrent of concern that the cholinergic deficit is too severe to be treated, that the cholinergic systems are too complex to respond to a pharmacologic therapy and that too many other systems are involved in Alzheimer's disease for a cholinergic treatment to be successful. However, this concern was balanced by the evidence of basic scientific experiments which indicate that the central cholinergic system mediating memory can be positively manipulated in animal lesion preparations and Alzheimer tissue. Also there were reports that improved pharmacological approaches and psychological measures are being developed. It appears that Alzheimer therapy is at the stage that cancer chemotherapy was 20 years ago: the promising agents cause nausea without producing clear effects but the basic laboratory studies strongly suggest that substantial benefits are possible and several agents have shown encouraging results. Meanwhile, patients and scientists are becoming increasingly interested in the field.(ABSTRACT TRUNCATED AT 250 WORDS)


[Experiments on suture material prolene 10-0 and vicryl 11-0 compared with nylon 10-0 in the rabbit cornea (author's transl)].
Synthetic absorbable suture material Vicryl 11-0 and not absorbable Prolene 10-0 are tolerated well by the corneal tissue as compared with nylon 10-0. Vicryl 11-0 sutures remained intact for only 13.2 days on an average, this is too short for normal corneal surgery. As nylon shows signs of absorption with time Prolene may be preferable to nylon where permanent sutures are necessary.


Quantitative Detection of Nucleoside Analogues by Multi-enzyme Biosensors using Time-Resolved Kinetic Measurements.
Fast, simple and cost-effective methods for detecting and quantifying pharmaceutical agents in patients are highly sought after to replace equipment and labor-intensive analytical procedures. The development of new diagnostic technology including portable detection devices also enables point-of-care by non-specialists in resource-limited environments. We have focused on the detection and dose monitoring of nucleoside analogues used in viral and cancer therapies. Using deoxyribonucleoside kinases (dNKs) as biosensors, our chemometric model compares observed time-resolved kinetics of unknown analytes to known substrate interactions across multiple enzymes. The resulting dataset can simultaneously identify and quantify multiple nucleosides and nucleoside analogues in complex sample mixtures.


Does Vitamin D Deficiency Really Increase the Risk of Post-surgical Hypoparathyroidism?
Postoperative hypoparathyroidism is the most frequent complication after total thyroidectomy. The identification of preoperative predictors could be helpful to identify patients at risk. The aim of this study is to determine if preoperative vitamin D levels are related to transient, protracted, and permanent hypoparathyroidism. A prospective, observational study that includes 100 patients who underwent total thyroidectomy. Transient hypoparathyroidism was present in 42% of patients, 11% developed protracted hypoparathyroidism and 5% permanent hypoparathyroidism. The median preoperative Vitamin D levels were higher in patients who developed transient hypoparathyroidism than in patients without this complication (24 ng/mL [RIQ 13-31] vs. 17 ng/mL [RIQ 10-24]; p = 0.024). Patients with preoperative vitamin D levels below 20 ng/mL had a lower percentage of transient hypoparathyroidism (31.4% vs. 53.1%; p = 0.028). The prevalence of protracted and permanent hypoparathyroidism in both groups was similar. Patients with preoperative vitamin D levels lower than 20 pg/mL had higher median PTH levels 24 h after surgery, (37.7 ± 28.2 pg/ml vs. 23.6 ± 18.6 pg/ml; p = 0.037), and suffered a lower postoperative PTH decline (46.2 ± 35.4% vs. 61 ± 29%; p = 0.026). Patients with vitamin D deficiency had a lower transient hypoparathyroidism rate, higher median PTH levels 24 h after surgery and a lower postoperative PTH decline. We found no association between preoperative vitamin D and the development of protracted or permanent hypoparathyroidism.


Targeted disruption of the leukotriene B(4) receptor in mice reveals its role in inflammation and platelet-activating factor-induced anaphylaxis.
Leukotrienes are derived from arachidonic acid and serve as mediators of inflammation and immediate hypersensitivity. Leukotriene B(4) (LTB(4)) and leukotriene C(4) (LTC(4)) act through G protein-coupled receptors LTB(4) receptor (BLTR) and Cys-LTR, respectively. To investigate the physiological role of BLTR, we produced mice with a targeted disruption of the BLTR gene. Mice deficient for BLTR (BLTR(-/-)) developed normally and had no apparent hematopoietic abnormalities. Peritoneal neutrophils from BLTR(-/-) mice displayed normal responses to the inflammatory mediators C5a and platelet-activating factor (PAF) but did not respond to LTB(4) for calcium mobilization or chemotaxis. Additionally, LTB(4) elicited peritoneal neutrophil influx in control but not in BLTR(-/-) mice. Thus, BLTR is the sole receptor for LTB(4)-induced inflammation in mice. Neutrophil influx in a peritonitis model and acute ear inflammation in response to arachidonic acid was significantly reduced in BLTR(-/-) mice. In mice, intravenous administration of PAF induces immediate lethal anaphylaxis. Surprisingly, female BLTR(-/-) mice displayed selective survival (6 of 9; P = 0.002) relative to male (1 of 11) mice of PAF-induced anaphylaxis. These results demonstrate the role of BLTR in leukotriene-mediated acute inflammation and an unexpected sex-related involvement in PAF-induced anaphylaxis.


Rapidly progressive renal disease as part of Wolfram syndrome in a large inbred Turkish family due to a novel WFS1 mutation (p.Leu511Pro).
Wolfram syndrome, also named "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is an inherited association of juvenile-onset diabetes mellitus and optic atrophy as key diagnostic criteria. Renal tract abnormalities and neurodegenerative disorder may occur in the third and fourth decade. The wolframin gene, WFS1, associated with this syndrome, is located on chromosome 4p16.1. Many mutations have been described since the identification of WFS1 as the cause of Wolfram syndrome. We identified a new homozygous WFS1 mutation (c.1532T>C; p.Leu511Pro) causing Wolfram syndrome in a large inbred Turkish family. The patients showed early onset of IDDM, diabetes insipidus, optic atrophy, sensorineural hearing impairment and very rapid progression to renal failure before age 12 in three females. Ectopic expression of the wolframin mutant in HEK cells results in greatly reduced levels of protein expression compared to wild-type wolframin, strongly supporting that this mutation is disease-causing. The mutation showed perfect segregation with disease in the family, characterized by early and severe clinical manifestations.


Horseshoe crab (Limulus polyphemus) lectin but not garden snail (Helix pomatia) lectin elicits insulin-like activities in vitro.
Lectins from the horseshoe crab (Limulus polyphemus) and the garden snail (Helix pomatia) were tested for insulinomimetic activities in isolated rat epididymal adipocytes. The sialic acid binding horseshoe crab lectin suppressed epinephrine-induced lipolysis and augmented lipogenesis from D-[3-3H]-glucose while the N-acetylgalactosamine binding snail lectin was inactive. The results suggest that the insulin receptor on rat adipocytes contains sialic acid in its carbohydrate moiety but does not possess non-reducing alpha-D-galactopyranosyl or 2-acetamido-2-deoxy-alpha-D-galactopyranosyl end groups.


Interplay of hydrophobic and hydrophilic interactions in sequence-dependent cell penetration of spontaneous membrane-translocating peptides revealed by bias-exchange metadynamics simulations.
Spontaneous Membrane Translocating Peptides (SMTPs) can translocate silently across the bilayer and, thus, have the best potential to improve the delivery of therapeutic molecules to cells without toxicity. However, how their translocation mechanisms are affected by a specific peptide sequence remains poorly understood. Here, bias-exchange metadynamics simulations were employed to investigate the translocation mechanisms of five SMTPs with the same composition of amino acids (LLRLR, LRLLR, LLLRR, RLLLR, and LRLRL). Simulation results yield sequence-dependent free energy barrier using the FESs along the z-directional distance. An in-depth analysis of sequence-dependent interactions in different regions of the bilayers indicates that the free-energy barrier height of a specific sequence is resulted from the accessibility balance of isolated or clustered hydrophobic residues (L) and hydrophilic residues (R) that leads to different levels of resistance for moving of a peptide into the hydrophobic center of the membrane. At the maximal of the free-energy barrier, all peptides have a conformation parallel to the membrane surface with the barrier height determined by their affinity to the hydrophobic region. The appropriate bilayer perturbation and GDM+ pairing are beneficial for peptide translocation. These results provide an improved microscopic understanding of how peptide sequence influences the translocation efficiency and mechanism.


Therapeutic correction of hemophilia A by transplantation of hPSC-derived liver sinusoidal endothelial cell progenitors.
Liver sinusoidal endothelial cells (LSECs) form the predominant microvasculature in the liver where they carry out many functions including the secretion of coagulation factor VIII (FVIII). To investigate the early origins of this lineage, we develop an efficient and scalable protocol to produce human pluripotent stem cell (hPSC)-derived LSEC progenitors characterized as venous endothelial cells (VECs) from different mesoderm subpopulations. Using a sensitive and quantitative vascular competitive transplantation assay, we demonstrate that VECs generated from BMP4 and activin A-induced KDR+CD235a/b+ mesoderm are 50-fold more efficient at LSEC engraftment than venous cells from BMP4 and WNT-induced KDR+CD235a/b- mesoderm. When transplanted into immunocompromised hemophilia A mice (NSG-HA), these VECs engraft the liver, proliferate, and mature to functional LSECs that secrete bioactive FVIII capable of correcting the bleeding phenotype. Together, these findings highlight the importance of appropriate mesoderm induction for generating hPSC-derived LSECs capable of functioning in a preclinical model of hemophilia A.


Reducing corruption in a Mexican medical school: impact assessment across two cross-sectional surveys.
Corruption pervades educational and other institutions worldwide and medical schools are not exempt. Empirical evidence about levels and types of corruption in medical schools is sparse. We conducted surveys in 2000 and 2007 in the medical school of the Autonomous University of Guerrero in Mexico to document student perceptions and experience of corruption and to support the medical school to take actions to tackle corruption. In both 2000 and 2007 medical students completed a self-administered questionnaire in the classroom without the teacher present. The questionnaire asked about unofficial payments for admission to medical school, for passing an examination and for administrative procedures. We examined factors related to the experience of corruption in multivariate analysis. Focus groups of students discussed the quantitative findings. In 2000, 6% of 725 responding students had paid unofficially to obtain entry into the medical school; this proportion fell to 1.6% of the 436 respondents in 2007. In 2000, 15% of students reported having paid a bribe to pass an examination, not significantly different from the 18% who reported this in 2007. In 2007, students were significantly more likely to have bribed a teacher to pass an examination if they were in the fourth year, if they had been subjected to sexual harassment or political pressure, and if they had been in the university for five years or more. Students resented the need to make unofficial payments and suggested tackling the problem by disciplining corrupt teachers. The university administration made several changes to the system of admissions and examinations in the medical school, based on the findings of the 2000 survey. The fall in the rate of bribery to enter the medical school was probably the result of the new admissions system instituted after the first survey. Further actions will be necessary to tackle the continuing presence of bribery to pass examinations and for administrative procedures. The social audit helped to draw attention to corruption and to stimulate actions to tackle it.


Nonketotic Hyperglycinemia of Infants in Taiwan.
Nonketotic hyperglycinemia (NKH) is a rare, inherited disease, with very poor outcome. It is difficult to confirm the diagnosis due to nonspecific presentations and rapid progression. The incidence was reported in a few countries. We report the clinical and genetic features of typical neonatal NKH with novel splicing mutation, c.1058+3A>C, in the intron 7 of the glycine decarboxylase (GLDC) gene. Furthermore, this study aimed to delineate the estimated incidence and clinical characteristics of NKH in the Taiwanese population. Reports of Health Promotion Administration, Ministry of Health and Welfare of Taiwan, during the period from 2000 to 2013; the Human Gene Mutation Database; and literature regarding NKH in Taiwan were reviewed. Demographic information, age of onset, clinical characteristics, genetic analysis, electroencephalography examinations, and outcome of the patients were analyzed. The estimated incidence of NKH in the Taiwanese population was 7.2 cases per 1,000,000 live births. Among the 12 cases reported in Taiwan, more than 90% were of neonatal type. Fifty-five percent of affected patients died within 5 years, and all survivors had severe neurologic outcomes. Only three infants underwent genetic analysis during the study period. Two neonatal NKH infants had mutation in the GLDC gene, and the other one, who had late-onset NKH, had mutation in the glutaredoxin 5 gene. Compared with other countries, the estimated incidence of NKH was relatively rare in the Taiwanese population. It is important to characterize all index cases at the genetic level. With more awareness of NKH, increased knowledge of gene mutation, and improvement of diagnostic tools, NKH can be diagnosed more accurately.


Caregivers' utilization of health services: results from the Medicare Alzheimer's Disease Demonstration, Illinois site.
The purpose of this study is to examine the effect of the Medicare Alzheimer's Disease Demonstration and Evaluation (MADDE) conducted in Illinois on the use of health services and Medicare expenditures by caregivers of persons with dementia. Prospective randomized clinical trial. The MADDE (1989-1994), Illinois site. A cohort of 412 Medicare-eligible caregivers of persons with dementia. Medicare claims files provided data on the number of hospitalizations, hospital bed days, emergency department visits, and total Medicare Part A expenditures. After adjustment for baseline variables, the caregivers in the treatment group, when compared with those in the comparison group, had a lower likelihood of any hospitalization during the study period (odds ratio 0.58 (95% confidence interval (CI)=0.35-0.97), P= .037) and a reduced, but not significant, likelihood of emergency department use (odds ratio 0.66 (95% CI=0.40-1.08), P= .095). For those who were hospitalized, there were no significant differences between the treatment and comparison group caregivers in the number of hospitalizations, hospital length of stay, or Medicare payments. These results suggest that enhanced chronic illness case management directed at persons with dementia and their caregivers can reduce the need for acute hospital care.


Differences in the capacity of simian virus 40 (SV40) tumor antigens on cells, membranes and in soluble form to induce transplantation immunity in hamsters and mice.
The immunogenicity of the SV40 tumor-specific transplantation antigen (TSTA) on cells, cell particulates and solubilized membranes was studied in mice and in Syrian hamsters. Immunizations were done with various concentrations of tissue-culture-passaged, non-virus-releasing transformed cells, purified cell membranes and in some cases purified nuclei and papain-solubilized membranes obtained from several species, including the mouse, hamster, man, and sheep. All transformed cell lines were T-antigen-positive. The immunosensitive mKSA line of BALB/c mice and the immunosensitive SV34 cell line of the hamster were used for tumor challenge. All materials, regardless of source and of type of preparation, were strikingly immunogenic in the mouse but only SV40 virus and SV34 (hamster) cells provided protection against tumor cell challenge in the hamster. Also, in a limited study, BKV-transformed hamster cells and purified cell membranes and JCV-transformed hamster cells were found to be immunogenic by the tumor rejection assay in the mouse but not in the hamster. SV40 immunization did not protect the hamster against BKV- and JCV-transformed hamster cells. These results are discussed in terms of possible different specificities resident on the TSTA molecule.


Affinity zone identification approach for joint control of PM2.5 pollution over China.
In recent years, the Chinese government has made great efforts to jointly control and prevent air pollution, especially fine particulate matter (PM2.5). However, these efforts are challenged by technical constraints due to the significant temporal and spatial heterogeneity of PM2.5 across China. In this study, the Affinity Zone Identification Approach (AZIA), which combines rotated principal component analysis (RPCA) with revised clustering analysis, was developed and employed to regionalize PM2.5 pollution in China based on data from 1496 air quality monitoring sites recorded from 2013 to 2017. Two clustering methods, cluster analysis with statistical test (CAST) and K-center-point (K-medoids) clustering, were compared and revised to eliminate unspecified sites. Site zonation was finally extended to the municipality scale for the convenience of the controlling measures. The results revealed that 17 affinity zones with 5 different labels from clean to heavily polluted areas could be identified in China. The heavily polluted areas were mainly located in central and eastern China as well as Xinjiang Province, with regional average annual PM2.5 concentrations higher than 66 μg/m3. The new approach provided more comprehensive and detailed affinity zones than obtained in a previous study (Wang et al., 2015b). The North China Plain and Northeastern China were both further divided into northern and southern parts based on different pollution levels. In addition, five affinity zones were first recognized in western China. The findings provide not only a theoretical basis to further display the temporal and spatial variations in PM2.5 but also an effective solution for the cooperative control of air pollution in China.


Prophylactic simvastatin increased survival during endotoxemia and inhibited granulocyte trafficking in a cell-intrinsic manner.
Cross sectional studies have shown that statin-users have improved odds of surviving severe sepsis. Meanwhile controlled clinical trials failed to demonstrate improved sepsis survival with acute statin administration following hospitalization. Here, a lethal murine peritoneal lipopolysaccharide (LPS) endotoxemia model was used to assess the efficacy of chronic versus acute simvastatin on survival. Mirroring clinical observations, chronic but not acute treatment with simvastatin significantly increased survival. At a pre-mortality time point in LPS-treated mice, chronic simvastatin suppressed granulocyte trafficking in to the lungs and peritoneum without otherwise suppressing emergency myelopoiesis, myeloid cells in circulation, or inflammatory cytokines. Chronic simvastatin treatment significantly downregulated inflammatory chemokine gene signature in the lungs of LPS-treated mice. Thus, it was unclear if simvastatin was inhibiting granulocyte chemotaxis in a cell intrinsic or extrinsic manner. Adoptive transfer of fluorescently labeled granulocytes from statin and vehicle treated mice into LPS-treated mice showed that simvastatin inhibited lung-granulocyte trafficking in a cell intrinsic manner. Congruent with this, chemotaxis experiments using in vitro macrophages and ex vivo granulocytes demonstrated that simvastatin inhibited chemotaxis in a cell-intrinsic manner. Collectively, chronic but not acute simvastatin treatment improved survival in murine endotoxemia, and this was associated with cell-intrinsic inhibition of granulocyte chemotaxis.


EBV lytic infection enhances transformation of B-lymphocytes infected with EBV in the presence of T-lymphocytes.
Epstein-Barr virus (EBV) establishes lifelong latency in B-lymphocytes following infection. Although in immune-competent individuals EBV remains in a quiescent state, in immunodeficient individuals, such as those with AIDS or transplant recipients, B-lymphocytes infected with EBV proliferate to give rise to lymphoproliferative diseases. Similarly, in vitro, EBV transforms human B-lymphocytes into indefinitely growing lymphoblastoid cell lines (LCLs) in the absence of cytotoxic T-lymphocytes. Although LCLs harbor the entire EBV genome as an episome, in most cells the virus remains in a latent state expressing a fraction of EBV genes, and lytic infection occurs spontaneously but only in a small percentage of cells. Here, we report that lytic infection contributes to EBV-induced lymphoproliferation by a paracrine mechanism. An EBV immediate-early protein, BZLF1, induces IL-13, thus facilitating the proliferation of EBV-transformed B-lymphocytes in the presence of T-lymphocytes. These data suggest that lytic gene products could contribute to virus-induced oncogenesis by a paracrine mechanism.


Optimization and validation of two multiplex qPCR assays for the rapid detection of microorganisms commonly invading the amniotic cavity.
Microbial invasion of the amniotic cavity (MIAC) leading to infection is strongly associated with adverse pregnancy and neonatal outcomes. Limitations of current diagnostic assays to detect MIAC rapidly and accurately have hindered the ability of obstetricians to identify and treat intra-amniotic infections. We developed, optimized, and validated two multiplex quantitative polymerase chain reaction (qPCR) assays for the simultaneous detection and quantification of microbial taxa commonly associated with MIAC. The first assay allows for the quantification of general bacterial and fungal loads in amniotic fluid and includes a human reference gene to allow for assessing the integrity of clinical samples and the DNA extraction process. The second assay allows for the detection and quantification of four specific bacterial taxa commonly associated with MIAC: Ureaplasma spp., Mycoplasma hominis, Streptococcus agalactiae, and Fusobacterium nucleatum. The qPCR assays were validated by using both microbial isolates and clinical amniotic fluid samples. The assays were further validated by comparing qPCR amplification results to those from the microbial culture and bacterial 16S rRNA gene sequencing of amniotic fluid. Both assays demonstrated high reproducibility and are sensitive and specific to their intended targets. Therefore, these assays represent promising molecular diagnostic tools for the detection of MIAC. Most importantly, these assays may allow for administration of timely and targeted antibiotic interventions to reduce adverse perinatal outcomes attributed to intra-amniotic infections.


T-2 mycotoxin Induces male germ cell apoptosis by ROS-mediated JNK/p38 MAPK pathway.
T-2 mycotoxin, a type A trichothecene toxin that, specifically, causes male and female reproductive toxicity. We evaluated T-2 toxin toxicity in testes from neonatal testes after in vitro tissue cultured. Additionally, current study focuses on the molecular mechanism of toxicity and germ cell damage in GC-1 spermatogonial cells. Mouse testicular fragments were subjected to T-2 toxin (0-20 nM) during days 5 of in vitro culture. Testicular germ cell number were reduced and downregulated the expression of corresponding markers depending on the exposure concentration of T-2 toxin; however, Sertoli cell markers and steroidogenic enzyme expression increased when treated with 20 nM T-2 toxin. The cell viability decreased, apoptosis increased, and pro-apoptotic protein expression increased in 5-20 nM T-2 toxin-exposed spermatogonia. Moreover, T-2 toxin generated reactive oxygen species (ROS) and induced mitochondrial dysfunction, indicating that activation of p38 MAPK signaling triggered by ROS is involved in the apoptotic molecular mechanism of T-2 toxin. T-2 toxin induced the phosphorylation of ERK1/2, c-Jun, JNK/SAPK, p38, and p53, and the subsequent inhibition of AKT phosphorylation. The upregulation of genes related to apoptosis and MAPK/JNK signaling was consistently observed in cells exposed to T-2 toxin. These results indicate that T-2 toxin triggers apoptotic cell death in germ cells through the triggering of ROS-mediated JNK/p38-MAPK signaling pathways.


Detection of mRNA for the cytokines, interleukin-1 alpha and interleukin-8, in corneas from patients with pseudophakic bullous keratopathy.
Cytokines have been implicated in corneal inflammatory diseases. The authors sought to determine if corneal diseases with different patterns of inflammation are accompanied by characteristic patterns of cytokine expression. The authors used reverse transcription-polymerase chain reaction to detect mRNA for 12 specific cytokines from patients with Fuch's dystrophy (n = 7), pseudophakic bullous keratopathy (n = 12), or normal corneas (n = 4). Using Wilcoxon rank sum analysis, mRNA for interleukin (IL)-1 alpha or IL-8 was significantly more abundant in corneas from patients with pseudophakic bullous keratopathy relative to either comparison group. mRNA for the T-cell marker, CD4, and for T-cell derived cytokines, IL-2, IL-4, and interferon gamma, could not be detected in any corneal sample. Message for IL-1 receptor antagonist and transforming growth factor-beta 1 or -beta 2 was readily detectable in most corneas regardless of diagnosis. The findings indicate that the pattern of cytokine mRNA expression reflects differences in the pathogenesis of these corneal diseases.


Impaired expression of indoleamine 2, 3-dioxygenase in monocyte-derived dendritic cells in response to Toll-like receptor-7/8 ligands.
The effects of immunostimulatory RNAs (isRNAs) on the expression of immuno-suppressive factors are largely unknown. Indoleamine 2,3-dioxygenase (IDO) is a key negative regulator of immune responses and it has been implicated in hampering immunity against tumours. Here we show that the activation of Toll-like receptors (TLR)-7/8 with isRNAs or R848, a specific ligand for TLR7/8, can induce IDO expression in human monocytes, but not in monocyte-derived dendritic cells (moDC). In contrast to TLR7/8 agnosists, treatment of the same moDC with interferon-gamma-induced IDO expression. Treatment of monocytes with 2'-O-methyl uridine-modified isRNAs alone does not induce IDO, but totally abrogated the effects of unmodified isRNAs. Like isRNAs, synthetic viral RNAs and cytomegalovirus (CMV) induced IDO in monocytes, whereas TLR2 ligand lipopeptide Pam3Cys exhibited no effect. Furthermore, IDO positive monocytes suppressed autologous T-cell activation. Collectively, these data indicate for first time that the potency of TLR7/8 signalling pathways to induce IDO expression in monocytes is silenced when the cells are programmed to differentiate into dendritic cells. The immunosuppressive properties of IDO might confer an advantage to CMV-infected monocytes to escape T-cell responses. The findings that 2'-O-methyl modified RNAs can block isRNA-induced IDO expression would facilitate the design of new TLR inhibitors.


Characterizing soil salinity at multiple depth using electromagnetic induction and remote sensing data with random forests: A case study in Tarim River Basin of southern Xinjiang, China.
Tarim River Basin is experiencing heavy soil degeneration in a long term because of the extreme natural conditions, added with improper human activities such as reclamation and rejected field repeatedly, which hindered the soil health. One of the mainly form is soil salinization. Spatial distribution and variation of soil salinity is essential both for agricultural resource management and local economic development. However, knowledge of the spatial distribution of soil salinization in this region has not been updated since 1980s while land use and climate have undergone major changed. Electromagnetic induction (EMI) has been successfully used to directly measurement the spatial distribution of targeting soil property at field- scale, and apparent electrical conductivity (ECa, mS m-1) has become a surrogate of soil salinity (EC, dS m-1) studied by many researchers at local scale. However, the effectiveness of this equipment has not been verified in the typical soil salinization areas in southern Xinjiang, especially on a large scale. This study was aimed to test the performance of ECa jointed with Random Forest (RF) for soil salinity regional-scale mapping at a typical arid area, taking Tarim River Basin as an example. The result showed that ECa together with environmental derivative variables and with RF were suited for regional-scale soil salinity mapping. Predicted accuracy of EC was higher at surface (0-20 cm, R2 = 0.65, RMSE = 5.59) and deeper soil depth (60-80 cm, R2 = 0.63, RMSE = 2.00, and 80-100 cm, R2 = 0.61, RMSE = 1.73), lower at transitional zone (20-40 cm, R2 = 0.55, RMSE = 2.66, and 40-60 cm, R2 = 0.51, RMSE = 2.49). When ECa is involved in modeling, the prediction accuracy of multiple depths of EC is improved by 13.33%-61.54%, of which the most obvious depths are 60-80 cm and 0-20 cm. The results of variable importance show that SoilGrids were also favored the power EC model. Hence, we strongly recommended to joint EMI reads with remote sensing imagery for soil salinity monitoring at large scale in southern Xinjiang. These EC and ECa map can provide a data source for environmental modeling, a benchmark against which to evaluate and monitor water and salt dynamics, and a guide for the design of future soil surveys.


The prognostic role of peritoneal cytology in stage IA endometrial endometrioid carcinomas.
Debates exist about the effects of peritoneal cytology and its treatment on the survival of early endometrial cancer. This study is to explore the prognostic role of peritoneal cytology and relevant therapy in patients with stage IA endometrial endometrioid carcinomas in a retrospective cohort study. From June 1, 2010, to June 1, 2017, in a teaching hospital, all the cases of pathologically confirmed stage IA endometrioid endometrial cancer were reviewed. Patients were followed up to February 1, 2019. The survival outcomes were compared among patients with negative peritoneal cytology, positive peritoneal cytology and no peritoneal cytology outcomes. In total, 1284 patients were included in the study, and 754 (58.7%) had peritoneal cytology evaluations with 22 (2.9%) of positive peritoneal cytology. After a median follow-up of 57.4 months, 1257 patients (97.9%) had definite survival outcomes. None of the patients with positive peritoneal cytology had recurrence or mortality. The appearance of positive peritoneal cytology had no impact on the disease-free, overall and cancer-specific overall survivals in univariate and multivariate analyses. No risk factors, including the adjuvant therapy, were found to be relevant with the appearance and survival in patients with positive peritoneal cytology. In patients with stage IA endometrial endometrioid carcinoma, the prevalence of positive peritoneal cytology was very low without know risk factor. Positive peritoneal cytology did not influence the survival outcomes of whole population, and adjuvant therapy did not influence the survival outcomes of patients with positive peritoneal cytology in such population. Mini Abstract The appearance of positive peritoneal cytology in stage IA endometrial endometrioid carcinomas had no clinical significance and need no adjuvant therapy.


Detection of the novel HLA-B*51:232:02 variant in an inhabitant from the island of Crete.
Characterization of the HLA-B*51:232:02 allele in a Greek individual of Cretan origin.


Worksite Environmental Interventions for Obesity Prevention and Control: Evidence from Group Randomized Trials.
Worksites provide multiple advantages to prevent and treat obesity and to test environmental interventions to tackle its multiple causal factors. We present a literature review of group-randomized and non-randomized trials that tested worksite environmental, multiple component interventions for obesity prevention and control paying particular attention to the conduct of formative research prior to intervention development. The evidence on environmental interventions on measures of obesity appears to be strong since most of the studies have a low (4/8) and unclear (2/8) risk of bias. Among the studies reviewed whose potential risk of bias was low, the magnitude of the effect was modest and sometimes in the unexpected direction. None of the four studies describing an explicit formative research stage with clear integration of findings into the intervention was able to demonstrate an effect on the main outcome of interest. We present alternative explanation for the findings and recommendations for future research.


Evaluation of developmental toxicity of safinamide in zebrafish larvae (Danio rerio).
Monoamine oxidase-B (MAO-B), as a principal metabolizing enzyme, plays important roles in the metabolism of catecholamines and xenobiotics in the central nervous system and peripheral tissues. Safinamide, the third-generation reversible MAO-B inhibitor, has potential to alleviate many neurological diseases such as Parkinson's disease (PD) and depression. Exposure to clinical psychotropic drugs often has adverse effects on fetuses. Currently, a variety of studies of safinamide focus on its curative effect and pharmacological effect, while its side effect of embryonic development is barely studied. In this study, we used zebrafish as a model to evaluate the embryonic developmental toxicity of safinamide. Our results revealed that higher concentrations (30 μM) of safinamide treatment caused a decrease in hatching rate and an increase in malformation and mortality in zebrafish larvae. Meanwhile, we observed that lower safinamide exposure (10 μM) increased the body length of zebrafish larvae and resulted in hyperactivity-like behaviors. In addition, an increased trend in dopamine (DA) level was found in 3.3 μM and 10 μM safinamide-exposed groups. Transcriptome analysis identified that safinamide exposure may disturb a variety of physiological processes such as neuroactive ligand-receptor interaction signaling pathway. In summary, our study reveals that safinamide may cause developmental defects in zebrafish larvae and provides insights into its toxic reactions in early develoment.


β-Sitosterol Inhibits The Proliferation of Endometrial Cells via Regulating Smad7-Mediated TGF-β/Smads Signaling Pathway.
To investigate the effect of β-sitosterol on endometrial cells to understand the underlying mechanism. This is a laboratory-based experimental study conducted on animals and cells. Histological assays were performed to determine the effect of β-sitosterol on endometrial cells. The CCK-8 assay was used to assess the inhibitory effect of β-sitosterol on the proliferation of ectopic endometrial stromal cells (hEM15A). Flow cytometry was performed to evaluate the induction of apoptosis by β-sitosterol in hEM15A cells. The transwell invasion assay was conducted to measure the suppression of hEM15A cell migration by β-sitosterol. Western blot analyses were performed to analyze the effect of β-sitosterol on the expression of Smad family member 7 (Smad7) and the activity of transforming growth factor-β (TGF-β1), as well as the phosphorylation of Smad2 and Smad3. Histological assays showed that β-sitosterol regulates histopathology and induces apoptosis of endometrial cells in vivo. The CCK-8 assay revealed that β-sitosterol could inhibit the proliferation of hEM15A in human endometriosis patients. Flow cytometry showed that apoptosis was triggered by β-sitosterol in hEM15A. The transwell invasion assay indicated that the hEM15A migration under the β-sitosterol treatment group was suppressed. Western blot analyses suggested that β-sitosterol increased the expression of Smad7, decreased the activity of TGF-β1, and reduced the phosphorylation of Smad2 and Smad3. The effect of β-sitosterol was weakened by the silence of Smad7. The results suggest that β-sitosterol can inhibit the proliferation of endometrial cells and relieve endometriosis by inhibiting TGF-β-induced phosphorylation of Smads through regulation of Smad7.


Sexual Risk Behaviors Among Youth in the Child Welfare System.
This study uses data from the National Survey of Child and Adolescent Well-Being (NSCAW) to provide estimates of sexual risk behaviors for 877 youth, age 11-14 at baseline, in the child welfare system. It examines the association between baseline psychosocial risk and protective factors on engagement in sexual risk behaviors after 36 months. It further compares rates of sexual risk behaviors between youth placed in out-of-home care and those who remained with their biological family. Key findings include a high rate of pregnancy, a high percentage of youth who initiated sexual activity at or before age 13 as well as a limited role of protective factors in moderating sexual risk behaviors. A history of placement into out-of-home care is not significantly associated with greater engagement in sexual risk behaviors. Implications for intervention development and child welfare policy for this population are discussed.


Recent Advances in the Microbial Synthesis of Hemoglobin.
Hemoglobin is a cofactor-containing protein with heme that plays important roles in transporting and storing oxygen. Hemoglobins have been widely applied as acellular oxygen carriers, bioavailable iron-supplying agents, and food-grade coloring and flavoring agents. To meet increasing demands and overcome the drawbacks of chemical extraction, the biosynthesis of hemoglobin has become an attractive alternative. Several hemoglobins have recently been synthesized by various microorganisms through metabolic engineering and synthetic biology. In this review, we summarize the novel strategies that have been used to biosynthesize hemoglobin. These strategies can also serve as references for producing other heme-binding proteins.


Effects of acquisition method and reconstruction algorithm for CT number measurement on standard-dose CT and reduced-dose CT: a QIBA phantom study.
To compare the effect of different acquisition and reconstruction methods on the radiation dose and accuracy of CT number measurements, using a 320-detector row CT and a Quantitative Imaging Biomarker Alliance (QIBA) recommended phantom. Acquisitions were performed on a 320-detector row CT, as 64- and 80-detector row helical and wide detector step-and-shoot (i.e., wide volume) acquisitions with tube currents of 400 mA, 100 mA, 50 mA, 20 mA, and 10 mA. Image was reconstructed with the filtered back projection (FBP), adaptive iterative dose reduction using 3D processing (AIDR 3D), and forward projected model-based iterative reconstruction (FIRST) methods. The difference between measured CT numbers and the actual -856HU value of the phantom insert was determined by each CT acquisition protocol. Differences in actual and measured CT numbers were compared among acquisitions and among reconstruction methods by means of Tukey's HSD test. The CT number obtained with 64-detector row helical acquisition was significantly larger than that obtained with others (p < 0.0001). At each tube current, the CT number reconstructed with FIRST was significantly smaller than that with others (p < 0.0001). Acquisition and reconstruction methods are significantly affecting radiation dose reduction and accuracy of CT number measurements on a phantom study.


Assessment of copper, iron, zinc and manganese status and speciation in patients with Parkinson's disease: A pilot study.
The objective of this pilot study was to assess iron (Fe), copper (Cu), zinc (Zn), and manganese (Mn) status (hair, serum, and urine) and speciation (serum) in Parkinson's disease (PD) patients. A pilot study involving a total of 27 subjects (13 PD patients, 14 controls) was performed. Serum, urine, and hair metal content was assessed using ICP-MS. Speciation analysis of Cu, Zn, Fe, and Mn was performed using a hybrid HPLC-ICP-MS system. Group comparisons did not reveal any significant group difference in serum Cu, Zn, Fe, and Mn total metal level between PD patients and controls. Speciation analysis revealed a significant decrease in Cu/ceruloplasmin copper in association with elevation of low-molecular weight species (amino acids)-bound copper. It is proposed that in PD, binding of Cu(II) ions to ceruloplasmin is reduced and free copper ions coordinate with low molecular weight ligands. The level of Mn-albumin complexes in PD patients was more than 4-fold higher as compared to the respective value in the control group. The observed difference may be considered as a marker of redistribution between high and low molecular weight ligands. Metal speciation is significantly affected in serum of PD-patients. These findings are indicative of the potential role of metal metabolism and PD pathogenesis, although the exact mechanisms of such associations require further detailed studies.


Facial shape; height and width in the second and third trimester of pregnancy.
The objective of this study is to calculate on 3D volumes obtained from 16 weeks' gestation normative data of facial height (FH), facial width (FW) and their ratio and to test these parameters in pathological cases. In total, 228 volumes were analyzed: 207 from normal and 21 from pathological cases. After multiplanar correction to the exact midsagittal plane FH was measured from the nasion to the gnathion and FW between the most lateral points on the zygomatic arch. For both FH and FW the intra- and inter-observer intraclass correlation coefficient variability was 0.99 and the difference between paired measurements was less than 0.3 cm in 95% of the cases. FH increased from 1.48 to 5.08 cm (FH = -16.10 + 3.78 × log(GA), R2: 0.93) and FW from 2.20 to 6.42 cm (FW: 4.19-17.18 × log(GA), R2: 0.85). The ratio increased steadily until about 25 weeks and less thereafter (ratio: (1/GA) × 26.44 + 0.92, R2: 0.23). In pathological cases 16.6% of measurements were outside the normal range. This study provides normative data for FH and FW measurements and insight in normal facial growth after 16 weeks' gestation. FH exceeds FW growth especially before 25 weeks.


The role of body image in patient compliance and education.
This study investigated the relation between one aspect of body image (body cathexis) and the achievement of knowledge about life after a heart attack, as well as subsequent compliance with posthospitalization prescriptions. There was no significant correlation between body cathexis and achieved knowledge. The hypothesis which proposed that a relationship exists between body cathexis and compliance with posthospitalization prescriptions was statistically significant, body-cathexis effects are inferred to be present in compliance behaviors, and the hypothesis was supported. A statistically significant correlation was not found to exist between achieved knowledge and subsequent compliance behavior.


A 29-mer site regulates transcription of the initiator gene as well as function of the replication origin of Vibrio cholerae chromosome II.
The region responsible for replication of Vibrio cholerae chromosome II (chrII) resembles those of plasmids that have repeated initiator binding sites (iterons) and an autorepressed initiator gene. ChrII has additional features: Its iterons require full methylation for initiator (RctB) binding, which makes them inactive for a part of the cell cycle when they are hemi-methylated. RctB also binds to a second kind of site, called 39-mers, in a methylation independent manner. This binding is inhibitory to chrII replication. The site that RctB uses for autorepression has not been identified. Here we show that a 29-mer sequence, similar to the 39-mers, serves as that site, as we find that it binds RctB in vitro and suffices to repress the rctB promoter in vivo. The site is not subject to methylation and is likely to be active throughout the cell cycle. The 29-mer, like the 39-mers, could inhibit RctB-dependent mini-chrII replication in Escherichia coli, possibly by coupling with iterons via RctB bridges, as was seen in vitro. The 29-mer thus appears to play a dual role in regulating chrII replication: one independent of the cell cycle, the other dependent upon iteron methylation, hence responsive to the cell cycle.


The employed unemployed: the subterranean economy in Spain.
This paper discusses the relationship between the subterranean economy and unemployment. Clandestine economic activity provides jobs at low incomes, but also bad and dangerous working conditions and job insecurity. Governments and even trade unions tend to ignore the wider implications of the underground economy. Three main forms of submerged economy are identified.


Love moderates the relationship between partner type and condom use among women engaging in transactional vaginal sex.
Background Relationship characteristics and day-to-day variation in affective state have been associated with HIV risk behaviour. However, no research has assessed the impact of these factors on event-level condom use among women engaging in transactional sex. Twenty-six women engaging in transactional sex were enrolled in a prospective study of their sexual health. They completed diaries about multi-level predictors of condom use during vaginal sex twice, daily. Over 4 weeks, 18 participants reported 87 paid/traded vaginal intercourse events. Of these, 51.7% were condom protected. The majority of paid/traded events (81.5%) occurred with a non-romantic partner. After controlling for partner type, feeling in love on a given day was associated with higher odds of condom use during paid/traded sexual events, while having sex on the weekend and at night were associated with lower odds of condom use (all P≤0.05). There was a significant interaction between being in love and using condoms during transactional sex (P<0.01). In paid/traded sexual events with romantic partners, the frequency of condom use was 71.4% (5/7) when women did not report love and 40% (4/10) when love was reported. In sexual events with non-romantic partners, the frequency of condom use was 43.8% (14/32) when women did not report love and 59.5% (22/37) when love was reported. Women were less likely to report protected sex with romantic partners and more likely to report protected sex with non-romantic partners when they are in love. Interventions focusing on the link between day-to-day variation in affective state on condom use may help women with risk management across partner types.


[Coronary arterial stent implantation proceeding noncardiac surgical procedures. Is it safe; can we recommend it?].
Patients undergoing non-cardiac surgical procedures who carry coronary artery stents have to be classified as high risk patients. Perioperative myocardial infarction and severe bleeding are possible. Therefore, anaesthetic management directed by invasive monitoring, ECG ST analysis, transesophageal echocardiography and referral to an intensive care unit are absolutely justified. The urgency of the surgical procedure, perioperative risk and an antiplatelet regimen have to be discussed with the patient and the surgeon in advance. In the case of cardiac complications, rapid therapy by an interventional cardiologist must be available.


Peroral endoscopic myotomy (POEM) is safe and effective in the setting of prior endoscopic intervention.
We aimed to determine the safety and feasibility of peroral endoscopic myotomy (POEM) in the setting of prior endoscopic interventions. This study involves 40 consecutive patients undergoing POEM. POEM was performed for esophageal motility disorders, including achalasia, nutcracker with nonrelaxing lower esophageal sphincter (LES), hypertensive lower esophageal sphincter, and diffuse esophageal spasm. Outcome measures include length of procedure (LOP), intraoperative complications, and dysphagia relief. Forty patients, with a mean age of 54 ± 19 years, underwent POEM. The pre-POEM intervention group consisted of 12 patients (nine achalasia, two nutcracker with nonrelaxing LES, and one diffuse esophageal spasm) who also had previous endoscopic treatment, while the pre-POEM non-intervention group consisted of 28 patients (22 achalasia, 3 hypertensive LES, 2 nutcracker with nonrelaxing LES, and 1 diffuse esophageal spasm). Ten patients had botox injections and two patients had large caliber balloon dilations prior to POEM. The median preoperative Eckardt score was 5 in the pre-POEM intervention group vs 6 in the pre-POEM non-intervention group (p value = 0.4). There was no statistical difference in the mean LOP (134 ± 43 vs 131 ± 41, p = 0.8) or the incidence of intraoperative complications (17 vs 3 %, p = 0.2) between the two groups. There was also no difference in the 6-month postoperative median Eckardt scores between the two groups (1 vs 1, p = 0.4). POEM is safe and effective even following preoperative endoscopic large caliber balloon dilations or botox injection. These interventions do not seem to contribute to increased adverse intraoperative or postoperative clinical outcomes.


Brainatomy: A Novel Way of Teaching Sphenoid Bone Anatomy With a Simplified 3-Dimensional Model.
The diagnosis and treatment of diseases at and around the sphenoid bone demands throughout understanding of its anatomy in 3-dimensional (3-D) space. However, despite the complex anatomic nature of the sphenoid bone, the current educational resources for its 3-D anatomy are insufficient for fast and long-term retention of the anatomic relationships. To provide a simplified 3-D model of the sphenoid bone that anyone can easily learn and recall as an internal mental model. Various studies on the anatomy of the sphenoid bone were analyzed. The collected data included the shape, foramina, canals, fissures, and minute details of the sphenoid bone. The gained detailed knowledge was subsequently used to create a 3-D model of the sphenoid bone with the help of 3-D computer software. A live lecture was given with this same software and simultaneously recorded with a microphone and a computer-screen recorder. A novel approach in lecturing, building the sphenoid bone from the scratch in a piecemeal fashion, was utilized. The sphenoid bone was recreated as an horizontally elongated box without a superior and posterior wall. All its foramina, canals, and fissures are visually easy to follow. Understanding its neuroanatomic terminologies based on their anatomic nature and relationships is enhanced. This simplified 3-D model, along with the video lecture, will enhance the efficiency of studying sphenoid bone anatomy. The educational resources of this study can be obtained by medical students, radiologists, neurologists, neurosurgeons, neuroscientists, or anyone else seeking for fundamental understanding of sphenoid bone anatomy.


Questions on causality and responsibility arising from an outbreak of Pseudomonas aeruginosa infections in Norway.
In 2002, Norway experienced a large outbreak of Pseudomonas aeruginosa infections in hospitals with 231 confirmed cases. This fuelled intense public and professional debates on what were the causes and who were responsible. In epidemiology, other sciences, in philosophy and in law there is a long tradition of discussing the concept of causality. We use this outbreak as a case; apply various theories of causality from different disciplines to discuss the roles and responsibilities of some of the parties involved. Mackie's concept of INUS conditions, Hill's nine viewpoints to study association for claiming causation, deterministic and probabilistic ways of reasoning, all shed light on the issues of causality in this outbreak. Moreover, applying legal theories of causation (counterfactual reasoning and the "but-for" test and the NESS test) proved especially useful, but the case also illustrated the weaknesses of the various theories of causation.We conclude that many factors contributed to causing the outbreak, but that contamination of a medical device in the production facility was the major necessary condition. The reuse of the medical device in hospitals contributed primarily to the size of the outbreak. The unintended error by its producer--and to a minor extent by the hospital practice--was mainly due to non-application of relevant knowledge and skills, and appears to constitute professional negligence. Due to criminal procedure laws and other factors outside the discourse of causality, no one was criminally charged for the outbreak which caused much suffering and shortening the life of at least 34 people.


5-Aminolevulinic acid ameliorates cadmium-induced morphological, biochemical, and ultrastructural changes in seedlings of oilseed rape.
Due to its prolific growth, oilseed rape (Brassica napus L.) can be grown successfully for phytoremediation of cadmium (Cd)-contaminated soils. Nowadays, use of plant growth regulators against heavy metals stress is one of the major objectives of researchers. The present study evaluates the ameliorate effects of 5-aminolevulinic acid (ALA, 0, 0.4, 2, and 10 mg/l) on the growth of oilseed rape (B. napus L. cv. ZS 758) seedlings under Cd stress (0, 100, and 500 μM). Results have shown that Cd stress hampered the seedling growth by decreasing the radical and hypocotyls length, shoot and root biomass, chlorophyll content, and antioxidants enzymes. On the other hand, Cd stress increased the level of malondialdehyde (MDA) and production of H2O2 and accumulation of Cd in the shoots. The microscopic study of leaf mesophyll cells showed that toxicity of Cd totally destroyed the whole cell structure, and accumulation of Cd also appeared in micrographs. Application of ALA at lower dosage (2 mg/l) enhanced the seedling growth and biomass. The results showed that 2 mg/l ALA significantly improved chlorophyll content under Cd stress and decreased the level of Cd contents in shoots. Application of ALA reduced the MDA and H2O2 levels in the cotyledons. The antioxidants enzymes (ascorbate peroxidase, peroxidase, catalase, glutathione reductase, and superoxide dismutase) enhanced their activities significantly with the application of 2 mg/l ALA under Cd stress. This study also indicated that higher dosage of ALA (10 mg/l) imposed the negative effect on the growth of oilseed rape. Microscopic study showed that application of ALA alleviated the toxic effects of Cd in the mesophyll cell and improved the cell structure. Use of 2 mg/l ALA under 500 μM Cd was found to be more effective, and under this dosage, cell structure was clear, with obvious cell wall and cell membrane as well as a big nucleus, which was found with well-developed two or more nucleoli. Chloroplast was almost round in shape and contained thylakoids membranes and grana, but starch grains were not found in chloroplast comparatively to other treatments. On the basis of our results, we can conclude that ALA has a promotive effect which could improve plant survival under Cd stress.


The accuracy of the 'triple test' in the diagnosis of papillary lesions of the breast.
The literature on fine-needle aspiration (FNA) cytology for papillary lesions presents a very mixed picture. Many authors advocate mandatory excision of these lesions. This recommendation is largely based on the 'atypical' nature of the FNA report. The aim of this work is to see if breast papillomas can be treated conservatively. We report a retrospective study of outcomes for patients with a provisional diagnosis of a 'papillary breast lesion' based on assessment by palpation (no clinically suspicious features), sonography (benign or probably benign according to the Breast Imaging Reporting and Data System 'BI-RADS®'), and FNA (benign cytological category with a papillary architecture) findings from one integrated breast service. Thirty-six cases were identified over a period of 6 years. Thirty-four of the patients had surgical excision. All of the 34 surgical cases were confirmed to be benign in nature on histopathology (intraduct papilloma). The remaining 2 cases were stable on follow-up. We believe that a policy of mandatory excision of papillary lesions of the breast is unnecessarily cautious.


Food and non-food reinforcement among pregnant women.
Excessive gestational weight gain (GWG) in pregnancy may be driven in part by greater motivation to eat, and studying the relative reinforcing value of food versus non-food commodities may provide insight into factors important for excessive GWG. This study was a cross-sectional examination of the relationship between women meeting the Institute of Medicine (IOM) guidelines for GWG and the relative reinforcing value of food vs. non-food commodities during pregnancy. Two-hundred and thirty-three pregnant women (1st trimester, n = 44; 2nd trimester, n = 105; 3rd trimester, n = 84), aged 18-40, were recruited via a crowdsourcing platform and completed an online survey. Relative food reinforcement (RRVfood), relative non-food activity reinforcement (RRVactive) and relative non-food cognitively enriching activity reinforcement (RRVcognitive) were measured by a questionnaire at the point of contact. Self-reports of gestational age and weight gain during pregnancy were collected. The relationship between food and non-food reinforcement was assessed based on IOM classifications for weight gain during pregnancy. After adjustment for women's education level and parity, higher RRVfood (p = 0.036) and lower RRVcognitive (p = 0.040) responses were associated with greater GWG. Food reinforcing ratio (FRR) analysis was then conducted to systematically examine the effect of non-food behaviors on GWG when food reinforcement was accounted for. Women who gained below the IOM weight gain guidelines had significantly higher FRRcognitive than those gaining above (p = 0.013), indicating cognitively enriching activities may better compete with food among pregnant women. Interventions that help to increase the reinforcing value of cognitively enriching activities may be a new avenue to regulate eating to minimize GWG.


Crystallization of GST2, a human class alpha glutathione transferase.
Single crystals of human GST2, a class alpha glutathione transferase have been grown in polyethylene glycol 2000 by the hanging-drop vapour diffusion method. The crystals belong to space group C2 and have cell dimensions a = 100.8 A, b = 95.4 A, c = 105.2 A and beta = 92.4 degrees. The X-ray diffraction pattern extends to better than 3 A resolution.


Design, synthesis and bioactivity evaluation of tribactam beta lactamase inhibitors.
Known carbapenem compounds with inhibitory effect towards beta-lactamase enzymes are formed from bicyclical beta lactam structural scaffolds. On the basis of results from theoretical computational methods and molecular modelling we have designed and developed a synthetic route towards novel, biologically active tricyclic derivatives of carbapenems.


The influence of efavirenz on the pharmacokinetics of a twice-daily combination of indinavir and low-dose ritonavir in healthy volunteers.
This study evaluated the effect of multiple-dose efavirenz on the steady-state pharmacokinetics of the combination of indinavir (800 mg) and low-dose ritonavir (100 mg) twice a day, in which ritonavir is used to increase indinavir plasma concentrations. Eighteen healthy male volunteers participated in this multiple-dose, 1-arm, 2-period interaction study. They took a combination of 800 mg indinavir and 100 mg ritonavir with food for 15 days. From days 15 to 29, a once-daily administration of 600 mg efavirenz was added to the combination. Pharmacokinetics of indinavir and ritonavir on days 15 and 29 were compared. Fourteen volunteers completed the study. The addition of efavirenz resulted in significant reductions (P <.01) in indinavir area under the curve (AUC, -25%), trough concentration (C(min), -50%), and maximum concentration (C(max), -17%). All indinavir C(min) levels on day 29 remained equivalent to or above the mean C(min) value described for the regimen of 800 mg indinavir three times a day, without ritonavir (0.15 mg/L). Changes in ritonavir AUC, C(min), and C(max) were -36%, -39%, and -34%, respectively. Pharmacokinetics of efavirenz on day 29 were comparable with published data. The addition of efavirenz to a combination of 800 mg indinavir and 100 mg ritonavir twice daily results in significant decreases in AUC, C(max), and especially C(min) of indinavir. The dose of indinavir or ritonavir should be increased to maintain similar indinavir drug levels after addition of efavirenz to the indinavir-ritonavir combination. Dose modifications may not be needed in antiretroviral-naive human immunodeficiency virus-infected patients if the reference C(min) of the regimen of 800 mg indinavir 3 times a day is considered to be adequate.


Exosomes and Extracellular RNA in Muscle and Bone Aging and Crosstalk.
Extracellular vesicles (EV), which include exosomes and microvesicles, are membrane-bound particles shed by most cell types and are important mediators of cell-cell communication by delivering their cargo of proteins, miRNA, and mRNA to target cells and altering their function. Here, we provide an overview of what is currently known about EV composition and function in bone and muscle cells and discuss their role in mediating crosstalk between these two tissues as well as their role in musculoskeletal aging. Recent studies have shown that muscle and bone cells produce EV, whose protein, mRNA, and miRNA cargo reflects the differentiated state of the parental cells. These EV have functional effects within their respective tissues, but evidence is accumulating that they are also shed into the circulation and can have effects on distant tissues. Bone- and muscle-derived EV can alter the differentiation and function of bone and muscle cells. Many of these effects are mediated via small microRNAs that regulate target genes in recipient cells. EV-mediated signaling in muscle and bone is an exciting and emerging field. While considerable progress has been made, much is still to be discovered about the mechanisms regulating EV composition, release, uptake, and function in muscle and bone. A key challenge is to understand more precisely how exosomes function in truly physiological settings.


Evidence for phosphoprotein microspheres in bone.
Bone sialoprotein and osteopontin are 'bone-specific' phosphoproteins, but their function is uncertain and their ultrastructural associations remain unclear. Insight into their role was sought by special attention to their general distribution and specific morphology under the high-power optical microscope. Their extracellular staining characteristics were examined in cryosections of adult rat skeletal tissues using two immunohistochemical methods. The two proteins were clearly evident in immature woven bone of endochondral and intramembranous origin (although cartilage was negative, even when calcified). In mature lamellar bone, bone sialoprotein remained ubiquitous, while osteopontin was confined to cement lines and other relatively discrete sites of past and present resorption activity, particularly near blood vessels. In neither case was the distribution of the stain structureless and diffuse. Invariably (except when non-specific), it was sharply defined and had the form of microspheres measuring approximately 1 microm in diameter. In both immature and mature regions, these objects appeared in sheets, chains or groups in a pattern that was evidently coincident with a similar structural arrangement found within the inorganic phase of bone. It was concluded that phosphoproteins are not randomly located throughout the collagenous matrix but are apparently integral to calcified microsphere populations, and it is suggested that these structures are well placed to control the chemical state of the mineral over their surfaces and influence remodelling.


Conformational ensemble view of G protein-coupled receptors and the effect of mutations and ligand binding.
G protein-coupled receptors (GPCRs) are integral membrane proteins that can convert an extracellular signal into multiple intracellular signaling processes. This pleiotropy of GPCRs is enabled by their structural flexibility manifested in thermally accessible multiple conformations, each of which may be capable of activating a different signaling cascade inside the cell (Kenakin & Miller, 2010). Different subsets of conformations can be potentially stabilized through mutations, or binding to various ligands (inverse agonists, antagonists, and agonists), or binding to G proteins, etc. Structure determination efforts have led to a small subset of these receptors being crystallized in one or two distinct conformations, but computational methods can predict an ensemble of conformations that characterize the full thermodynamic landscape of the receptor. Mutations in the receptor or binding of ligands can modulate this energy landscape, by stabilizing a unique set of conformations under different conditions, which may correspond to a specific downstream physiological function. These studies can provide testable hypotheses on the structural basis of GPCR activation and functional selectivity.


Physical mapping of bacteriophage lambda DNA with restriction endonuclease HpaI.
The restriction endonuclease from Haemophilus parainfluenzae, endoR.HpaI cleaves lambdacI857s7 DNA into 14 fragments. The sizes of these fragments were determined and a physical map was constructed. The ordering of the fragments was carried out using different deletion and substitution mutants of lambda phage, double cleavages with another restriction enzyme, endoR.BamHI, and partial protection of individual HpaI recognition sites by the antibiotics distamycin A and actinomycin D. HpaI produces fragments from the left arm of the lambda DNA genome, which may help in investigating the structure and function of this part of the phage.


Evaluating the phytoplankton, nitrate, and ammonium interactions during summer bloom in tributary of a subtropical reservoir.
The rational eutrophication management largely depends on the knowledge of the dynamics in the dissolved inorganic nutrients especially nitrogen forms which trigger exponential primary productivity in eutrophic systems. The present study investigated the phytoplankton interactions with the dissolved N forms, nitrate (NO3) and ammonium (NH4) in a sub-tropical Yangtze River tributary, China vulnerable to multiple anthropogenic stressors following the impoundment of the largest hydraulic structure, the Three Gorges Dam. Results indicated strong NO3 inhibition by the low NH4 pool exerting toxic effects on the major phytoplankton groups, particularly the Bacilliariophyta (relative abundance < 1%) while significant Cyanophyta proliferation prevailed (relative abundance ≥ 90%). Strong N limitation exacerbated by NH4 deficit and P replete condition characterizes the summer bloom in the tributary. The biomass attenuation kinetics revealed significantly fast NH4 metabolism, half-life (t1/2= 1.4 d, K = 0.00750 ± 0.004 d-1) as the first-order rate adequately fitted into the experimental data although, the second-order rate also demonstrated considerable goodness of fit. The growth responses induced by the Si enrichment potentially suggested possible secondary limitation by Si with the likelihood of intensification should the ecosystem phytoplankton community dominance shifts from Cyanophyta to the Bacilliariophyta. The response of P enrichment on growth was attributed to luxury consumption rather than limitation as responses only became significant towards the end of the study. The study, therefore, presents the first report of biomass ageing rate worthy of incorporation into the recent bloom management protocol for the development of predictive ecosystem dynamics.


Inhibition of cytolysin activity in large granular lymphocyte granules by lipids: evidence for a membrane insertion mechanism of lysis.
The ability of various compounds to inhibit the lytic activity of purified cytoplasmic granules from LGL tumors was tested. The lytic activity of granule cytolysin was modestly inhibited by inorganic phosphate, and various monophosphoesters, with I50 values in the range of 8-20 mM. Among monophosphoesters, choline phosphate was exceptionally potent, with an I50 of 1.4 mM. In contrast to the inhibition by phosphate esters, the parent compounds such as neutral sugars, glycerol, and choline, showed no detectable inhibition at 50 mM. A lysolipid bearing a short aliphatic chain and some detergents were inhibitory with I50 values in the range of 1 mM. Lysolipids with longer aliphatic chains, phospholipids as liposomes, and related lipid compounds were found to display potent inhibition of the hemolytic activity of LGL granule cytolysin, with I50 values in the range of 0.2-30 microM. Soluble globular proteins inhibited LGL granule cytolysin hemolytic activity with I50 of 0.07-0.4 mg/ml. However, lipoproteins were 2-3 orders of magnitude more potent inhibitors, with L50 values of less than 1 microgram/ml. The observed potent inhibition by lipid compounds lends support to a model of the lytic action of granule cytolysin in which soluble cytolysin molecules insert into the membrane lipid bilayer during the course of the lytic event.


Infective endocarditis in 13 cats.
To describe the clinical presentation, clinicopathological abnormalities and outcomes of a series of cats diagnosed with infective endocarditis (IE) at two tertiary care referral institutions. Thirteen client-owned cats presenting to the cardiology or emergency services of tertiary referral institutions with a diagnosis of endocarditis based on the modified Duke criteria. Retrospective case series. Medical records were reviewed to extract relevant data. In addition, cases that had cardiac tissue available were evaluated by polymerase chain reaction for the presence of Bartonella DNA. Prevalence of feline IE was 0.007%. Cats with endocarditis tended to be older (median age: 9 years, range: 2-12 years) and no sex or breed was overrepresented. Commonly encountered clinical signs included respiratory distress (n = 5) and locomotor abnormalities of varying severity (n = 5). Echocardiographic examination detected valvular lesions consistent with endocarditis on the aortic (n = 8) or mitral (n = 5) valves. Nine cats were diagnosed with congestive heart failure at the time of endocarditis diagnosis. Overall, prognosis was grave with a median survival time of 31 days. In contrast to dogs, cats with IE typically present with clinical signs consistent with cardiac decompensation and locomotor abnormalities suggestive of either thromboembolic disease or inflammatory arthritis. Given the advanced state of disease when diagnosis typically occurs, prognosis is grave.


Biomechanical analysis of simultaneous distal and proximal radio-ulnar joint instability.
Simultaneous dislocation of the proximal and distal radio-ulnar joints without bony injuries has been reported, but the mechanism remains unclear. We investigated concurrent proximal and distal radio-ulnar joint instability after sequential sectioning of the annular ligament, triangular fibrocartilage complex, and quadrate ligament. We performed this biomechanical study with six fresh-frozen cadaveric upper extremities. Proximal and distal radio-ulnar joint displacement was measured using an electromagnetic tracking device during passive mobility testing with anterior, lateral, and posterior loads on the radial head with pronation, supination, and neutral rotation. Measurements were statistically analyzed using the generalized linear mixed model. Proximal radio-ulnar joint instability was significantly greater after sectioning of the annular (lateral: 1.4%, P < .05; posterior: 0.7%, P < .05) and quadrate (lateral: 43.7%, P < .05; posterior: 29.5%, P < .05) ligament. Distal radio-ulnar joint instability was significantly greater in every sequential stage (final stage: anterior: 24.1%, P < .05; lateral 21.0%, P < .05; posterior: 31.3%, P < .05). Finally, significant simultaneous instability of the joints was observed after sectioning of the annular ligament, triangular fibrocartilage complex, and quadrate ligament, and neutral rotation potentially induced gross instability. Our ligament injury model induced simultaneous proximal and distal radio-ulnar joint instability without bony or interosseous membrane injury, probably induced by severe soft tissue injury. Proximal radio-ulnar joint instability may influence distal radio-ulnar joint instability from pivoting of the interosseous membrane. Our findings will help surgeons evaluate the magnitude of soft tissue injury and plan surgery for patients with simultaneous proximal and distal radio-ulnar joint instability.


Beyond rescue: Implementation and evaluation of revised naloxone training for law enforcement officers.
This study describes the implementation and evaluation of revised opioid overdose prevention and education of naloxone training for law enforcement officers (LEOs) that added: (1) a recovery testimony and (2) the process for deputy-initiated referrals postnaloxone administration. Evaluation regarding the naloxone training included a pre- and postopioid overdose knowledge surveys (N = 114) and subsequent 1-year postnaloxone training outcomes. Pre- and posttest scores for all knowledge outcome measures were statistically significant (p < .001) with favorable comments pertaining to the recovery testimony. Out of 31 individuals who received naloxone, 6 individuals (19.4%) continue to be in treatment or received some treatment services. The most common symptoms reported were unconsciousness/unresponsiveness (40.5%), abnormal breathing patterns (24.3%), and blue lips (16.2%). The majority of the calls (65.6%) were to a residential area, and the time for naloxone revival ranged <1-10 min (M = 3.48; SD = 2.27). As nearly 20% of individuals sought treatment after a LEO-initiated referral, it is recommended that other agencies consider the referral process into the training. Future research will investigate the impact of the recovery testimony in reducing the stigma of addiction.


A meta-analysis of the diagnostic performance of machine learning-based MRI in the prediction of axillary lymph node metastasis in breast cancer patients.
Despite that machine learning (ML)-based MRI has been evaluated for diagnosis of axillary lymph node metastasis (ALNM) in breast cancer patients, diagnostic values they showed have been variable. In this study, we aimed to assess the use of ML to classify ALNM on MRI and to identify potential covariates that might influence the diagnostic performance of ML. A systematic research of PubMed, Embase, Web of Science, and the Cochrane Library was conducted until 27 December 2020 to collect the included articles. Subgroup analysis was also performed. Fourteen studies assessing a total of 2247 breast cancer patients were included in the analysis. The overall AUC for ML in the validation set was 0.80 (95% confidence interval [CI] 0.76-0.83) with a negative predictive value of 0.83. The pooled sensitivity and specificity were 0.79 (95% CI 0.74-0.84) and 0.77 (95% CI 0.73-0.81), respectively. In the subgroup analysis of the validation set, T1-weighted contrast-enhanced (T1CE) imaging with ML yielded a higher sensitivity (0.80 vs. 0.67 vs. 0.76) than the T2-weighted fat-suppressed (T2-FS) imaging and diffusion-weighted imaging (DWI). Support vector machines (SVMs) had a higher specificity than linear regression (LR) and linear discriminant analysis (LDA) (0.79 vs. 0.78 vs. 0.75), whereas LDA showed a higher sensitivity than LR and SVM (0.83 vs. 0.70 vs. 0.77). MRI sequences and algorithms were the main factors that affect the diagnostic performance of ML. Although its results were encouraging with the pooled sensitivity of around 0.80, it meant that 1 in 5 women that would go with undetected metastases, which may have a detrimental effect on the overall survival for 20% of patients with positive SLN status. Despite that a high NPV of 0.83 meant that ML could potentially benefit those with negative SLN, it might also translate to 1 in 5 tests being false negative. We would like to suggest that ML may not be yet usable in clinical routine especially when patient survival is used as a primary measurement of its outcome.


The Impact of Race on Intensity of Care Provided to Older Adults in the Medical Intensive Care Unit.
African-Americans and Hispanics receive disproportionately less aggressive non-critical treatment for chronic diseases than their Caucasian counterparts. However, when it comes to end-of-life care, minority races are purportedly treated more aggressively in Medical Intensive Care Units (MICU) and are more likely to die there. We sought to determine the impact of race on the intensity of care provided to older adults in the Medical Intensive Care Unit (MICU) using the Therapeutic Intervention Scoring System-28 (TISS-28) and other MICU interventions. This is a prospective study of a cohort of 309 patients aged 60 years and older in the MICU. Interventions such as mechanical ventilation, vasopressors, new onset dialysis, feeding tubes, and pulmonary artery catheterization were recorded. Primary outcomes were TISS-28 scores and MICU interventions. Non-white patients were younger and had more dementia and delirium although there was no difference in ICU mortality. The amount of critical care delivered to non-white and white patients were equivalent at p ≤ 0.05 based on their respective TISS-28 scores. Non-white patients received more renal replacement therapy than white patients. Our study adds to the growing body of literature demonstrating that the relationship between race, patient preference, and the intensity of care provided in MICUs is multifaceted. Although prior studies have reported that non-white populations often opt for more aggressive care, the similar proportions of non-white and white "full code" patients in this study suggests that this idea is overly simplistic.


Ultrafast Brain MRI: Clinical Deployment and Comparison to Conventional Brain MRI at 3T.
To compare an ultrafast brain magnetic resonance imaging (MRI) protocol to the conventional protocol in motion-prone inpatient clinical settings. This retrospective study was HIPAA compliant and approved by the Institutional Review Board with waived inform consent. Fifty-nine inpatients (30 males, 29 females; mean age 55.1, range 23-93 years)who underwent 3-Tesla brain MRI using ultrafast and conventional protocols, both including five sequences, were included in the study. The total scan time for five ultrafast sequences was 4 minutes 59 seconds. The ideal conventional acquisition time was 10 minutes 32 seconds but the actual acquisition took 15-20 minutes. The average scan times for ultrafast localizers, T1-weighted, T2-weighted, fluid-attenuated inversion recovery (FLAIR), diffusion-weighted, T2*-weighted sequences were 14, 41, 62, 96, 80, 6 seconds, respectively. Two blinded neuroradiologists independently assessed three aspects: (1) image quality, (2) gray-white matter (GM-WM) differentiation, and (3) diagnostic concordance for the detection of six clinically relevant imaging findings. Wilcoxon signed-rank test was used to compare image quality and GM-WM scores. Interobserver reproducibility was calculated. The ultrafast T1-weighted sequence demonstrated significantly better image quality (P = .005) and GM-WM differentiation (P < .001) compared to the conventional sequence. There was high agreement (>85%) between both protocols for the detection of mass-like lesion, hemorrhage, diffusion restriction, WM FLAIR hyperintensities, subarachnoid FLAIR hyperintensities, and hydrocephalus. The ultrafast protocol achieved at least comparable image quality and high diagnostic concordance compared to the conventional protocol. This fast protocol can be a viable option to replace the conventional protocol in motion-prone inpatient clinical settings.