Predicting Future Health Transitions Among Newly Admitted Nursing Home Residents With Heart Failure.
To understand how a heart failure diagnosis and admission health instability predict health transitions and outcomes among newly admitted nursing home residents. Retrospective cohort study of linked administrative data, including the Continuing Care Report System MDS 2.0 for nursing homes, the Discharge Abstract Database for hospitalized patients, and National Ambulatory Care Reporting System to track emergency department visits. Older adults, aged 65 years and above, admitted to nursing homes in Ontario, Alberta, and British Columbia, Canada, from 2010 to 2016. Mortality and hospitalization were plotted over 1 year. Multistate Markov models were used to estimate adjusted odds ratios (ORs) for transitions to different states of health in stability, hospitalization, and death, stratified by heart failure diagnosis and by interRAI Changes in Health and End-stage disease Signs and Symptoms (CHESS) score, at 90 days following admission to a nursing home. The final sample included 143,067 residents. Adverse events were most common in the first 90 days. A diagnosis of heart failure predicted worsening health instability, hospitalizations, and mortality. The effect of heart failure on hospitalizations and death was strongest for low baseline health instability (CHESS = 0; OR 1.63, 95% confidence interval (CI) 1.58-1.68, and OR 1.71, 95% CI 1.57-1.86, respectively), versus moderate instability (CHESS = 1-2; OR 1.36, 95% CI 1.32-1.39, and OR 1.48, 95% CI 1.41-1.55), versus high instability (CHESS = 3; OR 1.12, 95% CI 1.03-1.23, and OR 1.21, 95% CI 1.11-1.32). The magnitude of the impact of a heart failure diagnosis was greatest for lower baseline health instability. Residents with the highest degree of health instability were also most likely to die in hospital. A diagnosis of heart failure and health instability provide complementary information to predict transfers, deaths, and adverse outcomes. Clearly identifying these at-risk patients may be useful in targeting interventions in nursing homes.


Free tissue transfer for the treatment of facial paralysis.
Long-standing facial paralysis requires the introduction of viable, innervated dynamic muscle to restore facial movement. The options include regional muscle transfer and microvascular free tissue transfer. There are advantages and disadvantages of each. Briefly, the regional muscle transfer procedures are reliable and provide immediate return of movement. However, the movement is not of a spontaneous mimetic nature. Free tissue transfer, in contrast, offers the possibility of synchronous, mimetic movement. It does, however, require a prolonged healing time in comparison with that of regional muscle transfer. The choice is made by physician and patient together, taking into account their preferences and biases. Muscle-alone free tissue transfer is our preferred option for reanimation of uncomplicated facial paralysis without skin or soft tissue deficits. Combined muscle and other tissue (most are skin flap) is another preferred option for more challenging complex facial paralysis with skin or soft tissue deficits after tumor excision. Gracilis flap is the author's first choice of muscle transplantation for both reconstructions. From 1986 to 2006, gracilis functioning free muscle transplantation (FFMT) was performed at Chang Gung Memorial Hospital for facial reanimation in 249 cases of facial paralysis. The main etiology is postoperative complication and Bell's palsy. The innervating nerve comes mostly from contralateral facial nerve branches, few from ipsilateral facial nerve due to tumor ablation, and from ipsilateral motor branch to masseter or spinal accessory nerve due to Möbius syndrome. We have evolutionally used a short nerve graft (10 to 15 cm) to cross the face in the first stage; after a 6- to 9-month waiting period, gracilis FFMT was performed for the second stage of the reconstruction. The technique of evolution has shown encouraging results to achieve the goal of rapid restoration and fewer scars on the donor leg.


Evaluating the progression of osteolysis after total knee arthroplasty.
Osteolysis around the knee following total knee arthroplasty continues to be a leading cause for revision total knee arthroplasty. Risk factors for periprosthetic knee osteolysis are associated with excessive polyethylene wear and include, but may not be limited to, malalignment of the mechanical axis, early-generation polyethylene sterilization techniques, excessive backside polyethylene wear, metal-backed patellar components, patient age, and an elevated body mass index. The initial diagnosis of osteolysis is frequently discovered on routine surveillance radiographs. The location, size, progressive nature, and associated symptomatology of the defect guides treatment. Surgical indications and timing are predicated on the risk of failure with continued observation. Advanced imaging helps to quantitate the size and location of osteolytic lesions as accurately as possible and aids in preoperative planning. When deciding whether surgery or management with continued radiographic surveillance is indicated, a global assessment of the character and progression of the osteolysis must be weighed with the risk factors associated with the patient.


High-intensity intermittent exercise training with chlorella intake accelerates exercise performance and muscle glycolytic and oxidative capacity in rats.
The purpose of this study was to investigate the effect of chronic chlorella intake alone or in combination with high-intensity intermittent exercise (HIIE) training on exercise performance and muscle glycolytic and oxidative metabolism in rats. Forty male Sprague-Dawley rats were randomly assigned to the four groups: sedentary control, chlorella intake (0.5% chlorella powder in normal feed), HIIE training, and combination of HIIE training and chlorella intake for 6 wk (n = 10 each group). HIIE training comprised 14 repeats of a 20-s swimming session with a 10-s pause between sessions, while bearing a weight equivalent to 16% of body weight, 4 days/week. Exercise performance was tested after the interventions by measuring the maximal number of HIIE sessions that could be completed. Chlorella intake and HIIE training significantly increased the maximal number of HIIE sessions and enhanced the expression of monocarboxylate transporter (MCT)1, MCT4, and peroxisome proliferator-activated receptor γ coactivator-1α concomitantly with the activities of lactate dehydrogenase (LDH), phosphofructokinase, citrate synthase (CS), and cytochrome-c oxidase (COX) in the red region of the gastrocnemius muscle. Furthermore, the combination further augmented the increased exercise performance and the enhanced expressions and activities. By contrast, in the white region of the muscle, MCT1 expression and LDH, CS, and COX activities did not change. These results showed that compared with only chlorella intake and only HIIE training, chlorella intake combined with HIIE training has a more pronounced effect on exercise performance and muscle glycolytic and oxidative metabolism, in particular, lactate metabolism.


Prematurity and cardiovascular risk at early adulthood.
Theories of early stress exposure and allostatic load offer a lifespan perspective to adult health after prematurity based on these early stressors affecting endocrine and metabolic systems. In this study, we examine cardiovascular and metabolic risk by comparing two groups of preterm infants who experienced a full spectrum of neonatal illness and a term-born group at age 23. Of the 215 infants recruited at birth, 84% participated at age 23. The cohort included 45 full-term (FT), 24 healthy preterm (HPT), and 111 sick preterm (SPT) infants. Socio-economic status was equivalent across groups. Cardiovascular and metabolic outcomes were as follows: blood pressure (BP), fasting glucose and lipid profiles, weight, waist-hip ratio (WHR), and body mass index (BMI). Clinical and subclinical ranges were compared across neonatal groups and gender. At age 23, the HPT and SPT groups had higher systolic BP compared with the FT group. The SPT group had lower weight compared with the FT and HPT groups. No group differences were found on diastolic BP, glucose, total cholesterol, high-density lipids, low-density lipids, triglycerides, BMI, or WHR. Preterm males had more systolic hypertension and low high-density lipids than FT males. Former preterm males and females had high WHR ratios and BMI at 23 years. Subclinical prehypertensive rates were highest for the HPT female group, followed by the SPT females. Only one (4.2%) HPT adult male was clinically diabetic. As young adults, HPT and SPT infants had early indicators of cardiovascular risk but no indicators of metabolic risk. There is utility in using clinical and subclinical ranges to identify early cardiovascular risk in early adulthood.


Host Mucin Is Exploited by Pseudomonas aeruginosa To Provide Monosaccharides Required for a Successful Infection.
One of the primary functions of the mucosal barrier, found lining epithelial cells, is to serve as a first-line of defense against microbial pathogens. The major structural components of mucus are heavily glycosylated proteins called mucins. Mucins are key components of the innate immune system as they aid in the clearance of pathogens and can decrease pathogen virulence. It has also been recently reported that individual mucins and derived glycans can attenuate the virulence of the human pathogen Pseudomonas aeruginosa Here, we show data indicating that mucins not only play a role in host defense but that they can also be subverted by P. aeruginosa to cause disease. We found that the mucin MUL-1 and mucin-derived monosaccharides N-acetyl-galactosamine and N-acetylglucosamine are required for P. aeruginosa killing of Caenorhabditis elegans We also found that the defective adhesion of P. aeruginosa to human lung alveolar epithelial cells, deficient in the mucin MUC1, can be reversed by the addition of individual monosaccharides. The monosaccharides identified in this study are found in a wide range of organisms where they act as host factors required for bacterial pathogenesis. While mucins in C. elegans lack sialic acid caps, which makes their monosaccharides readily available, they are capped in other species. Pathogens such as P. aeruginosa that lack sialidases may rely on enzymes from other bacteria to utilize mucin-derived monosaccharides.IMPORTANCE One of the first lines of defense present at mucosal epithelial tissues is mucus, which is a highly viscous material formed by mucin glycoproteins. Mucins serve various functions, but importantly they aid in the clearance of pathogens and debris from epithelial barriers and serve as innate immune factors. In this study, we describe a requirement of host monosaccharides, likely derived from host mucins, for the ability of Pseudomonas aeruginosa to colonize the intestine and ultimately cause death in Caenorhabditis elegans We also demonstrate that monosaccharides alter the ability of bacteria to bind to both Caenorhabditis elegans intestinal cells and human lung alveolar epithelial cells, suggesting that there are conserved mechanisms underlying host-pathogen interactions in a range of organisms. By gaining a better understanding of pathogen-mucin interactions, we can develop better approaches to protect against pathogen infection.


The Effects of Transversus Abdominis Plane (TAP) Block on Hemodynamic Parameters, Postoperative Analgesia, and Parental Satisfaction in Children.
To evaluate ultrasound-guided transversus abdominis plane (TAP) block, perioperative hemodynamic responses, postoperative analgesic efficacy, length of hospitalisation, and family satisfaction in children undergoing abdominal surgery. Randomised clinical trial. Place and Duration of the Study: Department of Anaesthesiology and Reanimation, Harran University Hospital, Turkiye, from June 2020 to June 2021. One hundred and eight patients aged 4-12 years in the American Society of Anaesthesiologists (ASA) 1-2 group who will undergo abdominal surgery (intra-abdominal and extra-abdominal) were included in the study. The patients were randomly divided into two groups as TAP to be performed (TAP+) and not to (TAP-) using the closed envelope method. General anaesthesia was given to the patients with standard anaesthesia protocol. Intraoperative and postoperative vitals, analgesic consumption in the first 24 hours postoperatively, length of hospitalisation, pain scores with Wong Baker Facial Pain Rating Scale (WBFPS), and parent satisfaction scores with Likert satisfaction scale were recorded. Perioperative SBP, DBP, and HR were significantly lower in the TAP+group (p <0.005). Postoperative analgesic consumption and Likert satisfaction scores were significantly higher in the TAP-group compared to the TAP+Group (p <0.001). Parental satisfaction was significantly higher in the TAP+Group than in the TAP-Group. The application of TAP block to children undergoing abdominal surgery; provided stable hemodynamics in the perioperative period, good analgesia in the postoperative period and increased parental satisfaction. In addition, can also shorten the hospital stays and may be routinely preferred in multimodal analgesia applications. Anaesthesia, Regional, Transversus abdominis plane block, Family satisfaction, Pain, Postoperative, Paediatric surgery.


[Relation factor analysis for the short-term preservation of ipsilateral renal function after partial nephrectomy].
Objectives: To analyze the factors relative to the short-term preservation of ipsilateral renal function after partial nephrectomy. Methods: The clinical data of 83 patients who were treated with partial nephrectomy from December 2014 to December 2019 in the Department of Urology, Sun Yat-sen University Cancer Center were retrospectively analyzed. There were 54 males and 29 females, aging (M (IQR)) 49 (17) years (range: 27 to 74 years). The ischemia time in operation was 25 (18) minutes (range: 10 to 67 minutes). Emission computed tomography scan and CT scan were performed before (within 1 month) and after (3 to 12 months) surgery. The volume of the ipsilateral and contralateral kidney was measured on the basis of preoperative and postoperative CT scans. The glomerular filtration rate (GFR) specifically in each kidney was estimated by emission computed tomography. Recovery from ischemia is determined by the formula: GFR preservation/volume saved×100%. Linear regression was used to explore the factors ralative to the short-term preservation of ipsilateral renal function after partial nephrectomy. Results: The GFR preservation of the ipsilateral kidney was 80.9 (25.2) % (range: 31.0% to 109.4%). The volume loss of the kidney resulted in a decrease of 12.0% (5.8 ml/(min×1.96 m2)) of GFR, while the ischemic injury resulted in a decrease of 6.5% (2.5 ml/(min×1.96 m2)) of GFR. The volume saved from the ipsilateral kidney was 87.1 (12.9) % (range: 27.0% to 131.7%). Recovery from ischemia was 93.5 (17.5) % (range:44.3% to 178.3%). In multivariate analysis, GFR preservation of the ipsilateral kidney was significantly correlated with the volume saved of the ipsilateral kidney (β=0.383, 95%CI: 0.144 to 0.622, P=0.002). It was not related to the ischemia time (β=-0.046, 95%CI:-0.383 to 0.475, P=0.831). Conclusion: In the condition of limited ischemic time, in the short term ipsilateral renal function after partial nephrectomy is mainly determined by the loss of kidney volume, while ischemic injury only plays a minor role.


Cemento-ossifying fibroma presenting as a mass of the parapharyngeal and masticator space.
We report a case of cemento-ossifying fibroma that presented as a large extraosseous mass in the masticator and parapharyngeal space. CT scanning and MR imaging showed a large extraosseous mass with central conglomerated, well-matured ossified nodules and fatty marrow. The central matured ossified nodules were of low density on CT scans and high signal intensity on T1- and T2-weighted MR images. Multiplanar reformatted CT scans revealed the origin of the mass to be at the extraction site of the right lower second molar tooth.


A frame of reference for assessing the intensity of exertional dyspnoea during incremental cycle ergometry.
Assessment of dyspnoea severity during incremental cardiopulmonary exercise testing (CPET) has long been hampered by the lack of reference ranges as a function of work rate (WR) and ventilation (V' E). This is particularly relevant to cycling, a testing modality which overtaxes the leg muscles leading to a heightened sensation of leg discomfort.Reference ranges based on dyspnoea percentiles (0-10 Borg scale) at standardised work rates and V' E were established in 275 apparently healthy subjects aged 20-85 years (131 men). They were compared with values recorded in a randomly selected "validation" sample (n=451; 224 men). Their usefulness in properly uncovering the severity of exertional dyspnoea were tested in 167 subjects under investigation for chronic dyspnoea ("testing sample") who terminated CPET due to leg discomfort (86 men).Iso-work rate and, to a lesser extent, iso-V' E reference ranges (5th-25th, 25th-50th, 50-75th and 75th-95th percentiles) increased as a function of age, being systematically higher in women (p<0.01). There were no significant differences in percentiles distribution between "reference" and "validation" samples (p>0.05). Submaximal dyspnoea-work rate scores fell within the 75th-95th or >95th percentiles in 108 out of 118 (91.5%) subjects of the "testing" sample who showed physiological abnormalities known to elicit exertional dyspnoea, i.e. ventilatory inefficiency and/or critical inspiratory constraints. In contrast, dyspnoea scores typically fell in the 5th-50th range in subjects without those abnormalities (p<0.001).This frame of reference might prove useful to uncover the severity of exertional dyspnoea in subjects who otherwise would be labelled as "non-dyspnoeic" while providing mechanistic insights into the genesis of this distressing symptom.


[Posttraumatic syringomyelia in 2 patients with thoracic spinal cord lesions].
Two patients, men aged 42 and 40 years, developed new neurological symptoms 3 months and 22 years, respectively, after a traumatic high thoracic spinal cord injury. The MRI scan showed a cavity in the central part of the spinal cord, on which the diagnosis of 'posttraumatic syringomyelia' could be based. In one of the patients a syringo-subarachnoidal shunt was created, the other was treated conservatively because of a severe concomitant thoracic kyphosis. Posttraumatic syringomyelia is a potentially life-threathening late complication of spinal cord injury and is characterized by development of new neurological symptoms after a variable time interval. The most typical symptom of non-traumatic syringomyelia, viz. diminution of vital sensitivity without loss of gnostic sensitivity, is not necessarily present in posttraumatic syringomyelia. Surgical treatment of posttraumatic syringomyelia is advocated if there is progressive neurological deterioration, and consists of drainage of the syrinx.


Bilateral lower palpebral demodicosis in a dairy cow.
A registered 3 year old Guernsey heifer, recently fresh, was examined for sudden appearance of diffuse, firm swelling beneath both eyes. Vital signs and physical examination were within normal limits; no lymphadenopathy was present. Biopsy revealed a chronic eosinophilic granulomatous cellulitis and degenerate Demodex bovis. the lesions selfresolved within three months.


In-depth analysis of a heterosexually acquired human immunodeficiency virus type 1 superinfection: evolution, temporal fluctuation, and intercompartment dynamics from the seronegative window period through 30 months postinfection.
Human immunodeficiency virus type 1 (HIV-1) superinfection refers to the acquisition of another strain by an already infected individual. Here we report a comprehensive genetic analysis of an HIV-1 superinfection acquired heterosexually. The infected individual was in a high-risk cohort in Tanzania, was exposed to multiple subtypes, and was systematically evaluated every 3 months with a fluorescent multi-region genotyping assay. The subject was identified in the window period and was first infected with a complex ACD recombinant strain, became superinfected 6 to 9 months later with an AC recombinant, and was monitored for >2.5 years. The plasma viral load exceeded 400,000 copies/ml during the first 9 months of infection but resolved to the set point of 67,000 copies/ml by 3 months after superinfection; the CD4 cell count was 377 cells/mul at 30 months. Viral diversity was evaluated with techniques designed to fully sample the quasi-species, permitting direct observation of the evolution, temporal fluctuation, and intercompartment dynamics of the initial and superinfecting strains and recombinants derived from them. Within 3 months of superinfection, seven different molecular forms were detected in gag and six were detected in env. The proportions of forms fluctuated widely over time in plasma and peripheral blood mononuclear cells, illustrating how challenging the detection of dually infected individuals can be. Strain-specific nested PCR confirmed that the superinfecting strain was not present until the 9 month follow-up. This study further defines the parameters and dynamics of superinfection and will foster appropriate studies and approaches to gain a more complete understanding of risk factors for superinfection and its impact on clinical progression, epidemiology, and vaccine design.


The influence of the depth of substrate dentin surface and thickness of the current restorative samples on bond strength.
The effect of sample thickness and dentin depth on bond strength of composite, compomer and resin modified glass ionomer have been investigated. The occlusal surfaces of 84 non carious human third molars were used for bonding. 4 subgroups were tested, superficial dentin with sample thickness 1 and 2 mm and deep dentin with sample thickness 1 and 2 mm respectively SBMP + /Z 100 composite showed 26 +/- 3.2, 22.3 +/- 4.5, 17 +/- 3.2 and 21.8 +/- 4.2 MPa shear bond strength to S. dentin 1 mm, deep dentin 1 and 2 mm and S. dentin 2 mm respectively. Compoglass reported 10.4 +/- 1.57, 9.1 +/- 2.3, 5.0 +/- 0.6 and 9.24 +/- 3.1 MPa while, Vitremer achieved 4.7 +/- 0.49, 3.2 +/- 0.39, 3.0 +/- 0.81 and 3.2 +/- 0.53 MPa. It is concluded that the highest bond strength can be achieved to superficial dentin in thickness or increments not more than 1 mm. And that both dentin depth and sample thickness might influence the quality of the bond to dentin with an effect that varies from one material to another depending upon the mechanism of bond of each material and its chemical composition.


The dirty dozen: twelve failures of the hurricane katrina response and how psychology can help.
This comprehensive analysis addresses the United States' alarming lack of preparedness to respond effectively to a massive disaster as evidenced by Hurricane Katrina. First, a timeline of problematic response events during and after Hurricane Katrina orients readers to some of the specific problems encountered at different levels of government. Second, a list of the "Dirty Dozen"--12 major failures that have occurred in prior disasters, which also contributed to inadequate response during and after Hurricane Katrina--is presented. Third, this article encourages expanding psychology's role beyond the treatment of trauma to encompass disaster planning and mitigation efforts from a broader public health perspective. Finally, areas for important interdisciplinary research in human behavior that will influence our nation's overall preparedness for future catastrophes are identified, and ways psychologists can become personally involved beyond treating casualties are discussed.


Racial/ethnic, age and sex disparities in leukemia survival among adults in the United States during 1973-2014 period.
There has been marked improvement in leukemia survival, particularly among children in recent time. However, the long-term trends in survival among adult leukemia patients and the associated sex and racial survival disparities are not well understood. We, therefore, evaluated the secular trends in survival improvement of leukemia patients from 1973 through 2014, using Surveillance Epidemiology and End-Result Survey Program (SEER) data. ICD-O-3 morphology codes were used to group leukemia into four types: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML). Survival analysis for each leukemia type stratified by race/ethnicity, age, sex was performed to generate relative survival probability estimates for the baseline time period of 1973 through 1979. Hazard ratios (HR) and respective 95% confidence intervals (CIs) for survival within subsequent 10-year time periods by race, age and sex were calculated using Cox proportional hazard models. Of the 83,255 leukemia patients for the current analysis, the 5-year survival of patients with ALL, AML, CLL, and CML during 1973-1979 were 42.0%, 6.5%, 66.5%, and 20.9%, respectively. Compared to the baseline, there were substantial improvements of leukemia-specific survival in 2010-2014 among African-American (81.0%) and Asian (80.0%) patients with CML and among 20-49 year of age with CLL (96.0%). African-American patients, those with AML and those older than 75 years of age had the lowest survival improvements. Asians experienced some of the largest survival improvements during the study period. Others, including African-American and the elderly, have not benefited as much from advances in leukemia treatment.


The Surgical White Matter Chassis: A Practical 3-Dimensional Atlas for Planning Subcortical Surgical Trajectories.
The imperative role of white matter preservation in improving surgical functional outcomes is now recognized. Understanding the fundamental white matter framework is essential for translating the anatomic and functional literature into practical strategies for surgical planning and neuronavigation. To present a 3-dimensional (3-D) atlas of the structural and functional scaffolding of human white matter-ie, a "Surgical White Matter Chassis (SWMC)"-that can be used as an organizational tool in designing precise and individualized trajectory-based neurosurgical corridors. Preoperative diffusion tensor imaging magnetic resonance images were obtained prior to each of our last 100 awake subcortical resections, using a clinically available 3.0 Tesla system. Tractography was generated using a semiautomated deterministic global seeding algorithm. Tract data were conceptualized as a 3-D modular chassis based on the 3 major fiber types, organized along median and paramedian planes, with special attention to limbic and neocortical association tracts and their interconnections. We discuss practical implementation of the SWMC concept, and highlight its use in planning select illustrative cases. Emphasis has been given to developing practical understanding of the arcuate fasciculus, uncinate fasciculus, and vertical rami of the superior longitudinal fasciculus, which are often-neglected fibers in surgical planning. A working knowledge of white matter anatomy, as embodied in the SWMC, is of paramount importance to the planning of parafascicular surgical trajectories, and can serve as a basis for developing reliable safe corridors, or modules, toward the goal of "zero-footprint" transsulcal access to the subcortical space.


Withanolide D Exhibits Similar Cytostatic Effect in Drug-Resistant and Drug-Sensitive Multiple Myeloma Cells.
In spite of recent therapeutic advances, multiple myeloma (MM) remains a malignancy with very low curability. This has been partly attributed to the existence of a drug-resistant subpopulation known as cancer stem cells (CSCs). MM-CSCs are equipped with the necessary tools that render them highly resistant to virtually all conventional therapies. In this study, the growth inhibitory effects of withanolide D (WND), a steroidal lactone isolated from Withania somnifera, on drug-sensitive tumoral plasma cells and drug-resistant MM cells have been investigated. In MTT/XTT assays, WND exhibited similar cytostatic effects between drug-resistant and drug-sensitive cell lines in the nM range. WND also induced cell death and apoptosis in MM-CSCs and RPMI 8226 cells, as examined by the calcein/ethidium homodimer and annexin V/propidium iodide stainings, respectively. To determine whether P-glycoprotein (P-gp) efflux affected the cytostatic activity of WND, P-gp was inhibited with verapamil and results indicated that the WND cytostatic effect in MM-CSCs was independent of P-gp efflux. Furthermore, WND did not increase the accumulation of the fluorescent P-gp substrate rhodamine 123 in MM-CSCs, suggesting that WND may not inhibit P-gp at the tested relevant doses. Therefore, the WND-induced cytostatic effect may be independent of P-gp efflux. These findings warrant further investigation of WND in MM-CSC animal models.


[Factors Influencing "Face" in People With Dementia: A Systematic Review of the Literature].
Face (self-esteem) is an issue that involves socially endowed status, identity roles, and self-image management and maintenance. People with dementia and their family members often experience social isolation due to diminished self-image, which affects disease progression. Better understanding the factors that influence the self-image of people with dementia may promote the ability of caregivers to maintain self-image and promote public understanding and empathy toward people with dementia. The aim of this study was to explore the factors influencing self-image in people with dementia using a systematic review of the literature. A systematic review was used. Articles were retrieved from electronic databases including PubMed, CINAHL, Airiti Library, and Cochrane Library. The following keywords and MeSH terms were used to search for articles on dementia, face, self-esteem, respect, and self-concept. A total of 3,050 articles published prior to September 2018 that matched the search criteria were extracted. After screening the topics, deleting repetitions, and doing critical appraisals, eight articles were selected for analysis. Research quality was appraised using the Joanna Briggs Institute and the Melnyk and Fineout-Overholt for Evidence-Based Medicine Level of Evidence. Two themes related to the factors influencing self-image in people with dementia were extracted from the selected articles. The first theme was "loss of self-identity". As people with dementia gradually lose their cognitive function and memory ability, they are increasingly incapable of handling and managing their current role tasks. The second theme was "negative public perception". The public believes that people with dementia are at risk to others and that their behaviors are unpredictable, resulting in the deprivation of the rights to which people with dementia are entitled. Because of disease progression, people with dementia gradually lose their self-identity and become unable to perform their life-role tasks. This is accompanied by negative perceptions of the disease among the public, which, in turn, damages the self-image of people with dementia and their families. The results of this review may provide a reference for caregivers planning future person-centered care approaches for people with dementia. In addition, these results may help facilitate the establishment of a more friendly environment for people with dementia in both public and private spaces.


Clinical implications of mandible and neck measurements in non-obese asian snorers: ansan city general population-based study.
Anthropometric abnormalities of the mandible and neck may contribute to snoring in non-obese Asians. The study evaluated the clinical implications of mandible and neck measurements in non-obese Asian snorers. The external mandible and neck measurements (neck circumference, two lengths of neck, mandibular body angle, and lengths of mandibular ramus and body) were compared between snorers and non-snorers in a sample of 2,778 non-obese Koreans (1,389 males, 1,389 females) aged 40 to 69 years (mean, 48.47±7.72 years). The overall prevalence of snoring was 64.7% (899/1,389) and 48.3% (671/1,389) in non-obese male and female subjects, respectively. In non-obese males, snorers had significantly a greater neck circumference (P<0.0001) and shorter mandibular body length (P=0.0126) than non-snorers. In non-obese females, snorers had significantly greater neck circumferences (P=0.0165), compared with non-snorers. However, there were no statistically significant differences in other variables between non-snorers and snorers. Anthropometric abnormalities of the mandible and neck, including thick neck circumference in both genders and small mandible size in males, may be relevant contributing factors to snoring in non-obese Asian snorers.


[The high content of palmitinic fatty acid in food as a major cause of increase of concentration of cholesterol and low density lipoproteins and atheromatous plaques of arteries' intima].
The positioning of individual triglycerides of blood serum in palmitinic and oleic lipoproteins ofvery low density in the order ofincrease of the rate constant of their hydrolysis under action of post-heparin lipoprotein leads to the sequence as follows: palmitoil-palmitoil-palmitate-->palmitoil-palmitoil-oleate-->palmitoil-oleil-palmitat-->oleil-palmitoil-palmitate-->oleil-palmitate-palmitate-->oleil-oleil-palmitate-->oleil-oleil-oleate. The shift to the left and to the right is discerned with this spectrum of isoforms of triglycerides. The shift to the left into direction of palmitinicc triglycerides occurs in case of eating of animal food (i.e. beef andfoodstuf of fat saw milk) when the content of palmitinic saturated fatty acid supersedes 15% of fatty acids total and under the development of endogenic syndrome of insulin resistance. The content of low density lipoproteins cholesterol is high in blood The shift to the right with prevalence of oleinic triglycerides occurs in case of low content of beef and foodstuff of fat saw milk in food, fish eating, seafood and olive oil. The physiologic levels of carbohydrates in food and insulin function are present too. The shift to the right initiates the action of insulin, ometa-3 essential polyenic fatty acids, glytazones and fibrates. They increase the activity of delta9-stearil-KoA-desaturase-2 and the transformation of palmitine saturated fatty acid into mono unsaturated oleinic fatty acid. The shift to the left forms the palmitine alternative of metabolism of substrate to supply cells with energy. The shift to the right is a more effective oleinic alternative.


[Electrophysiologic actions of mexiletine (Kö-1173) in man].
Electrophysiologic studies have been performed in 11 patients before and 12 minutes after intravenous administration of 250 mg of mexiletine. All patients had crisis of paroxysmal tachycardia. The cases with conduction defects at any level, as ascertained by surface ECG or basal electrophysiologic recordings, were excluded from treatment. The results obtained do not show significant variations in any of the parameters studied. It is concluded that mexiletine is an antiarrhythmic drug with an action typical of group I of the classification of Vaughan Williams, and that it reduces the maximum velocity of systolic depolarization. In the absence of conduction defects, its behaviour is similar to that of lidocaine or diphenylhydantoin.


Design, characterization, and aerosolization of organic solution advanced spray-dried moxifloxacin and ofloxacin dipalmitoylphosphatidylcholine (DPPC) microparticulate/nanoparticulate powders for pulmonary inhalation aerosol delivery.
The aim of this study was to design and develop respirable antibiotics moxifloxacin (MOXI) hydrochloride and ofloxacin (OFLX) microparticles and nanoparticles, and multifunctional antibiotics particles with or without lung surfactant 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) for targeted dry powder inhalation delivery as a pulmonary nanomedicine. Particles were rationally designed and produced by advanced spray-drying particle engineering from an organic solution in closed mode (no water) from dilute solution. Scanning electron microscopy indicated that these particles had both optimal particle morphology and surface morphology, and the particle size distributions were suitable for pulmonary delivery. Comprehensive and systematic physicochemical characterization and in vitro aerosol dispersion performance revealed significant differences between these two fluoroquinolone antibiotics following spray drying as drug aerosols and as cospray-dried antibiotic drug: DPPC aerosols. Fourier transform infrared spectroscopy and confocal Raman microspectroscopy were employed to probe composition and interactions in the solid state. Spray-dried MOXI was rendered noncrystalline (amorphous) following organic solution advanced spray drying. This was in contrast to spray-dried OFLX, which retained partial crystallinity, as did OFLX:DPPC powders at certain compositions. Aerosol dispersion performance was conducted using inertial impaction with a dry powder inhaler device approved for human use. The present study demonstrates that the use of DPPC offers improved aerosol delivery of MOXI as cospray-dried microparticulate/nanoparticulate powders, whereas residual partial crystallinity influenced aerosol dispersion of OFLX and most of the compositions of OFLX:DPPC inhalation powders.


Time Course of Endothelial Dysfunction Induced by Decompression Bubbles in Rats.
Decompression stress can cause endothelial injury, leading to systematic inflammation and prothrombotic phenomena. Our previous work found that endothelial injury following decompression correlated positively with bubble formation. This study aimed to investigate the time course of endothelial injury and the relationship with bubble amounts. Rats were subjected to a simulated air dive to 7 ATA for 90 min with rapid decompression. Bubbles were detected ultrasonically at the root of pulmonary arteries following decompression. Surviving rats were randomly divided into six groups according to sampling time following decompression (2, 6, 12, 24, 48, and 72 h). Three parameters, serum levels of malondialdehyde (MDA), endothelin-1 (ET-1), and intercellular cell adhesion molecule-1 (ICAM-1) were identified from our previous study and measured. The level of MDA reached a peak level at 12 h post decompression, and then decreased gradually to control level before 72 h. For both ET-1 and ICAM-1, the greatest expression appeared at 24 h following surfacing, and the increases lasted for more than 72 h. These changes correlated positively with bubble counts at most detection time points. This study reveals the progress of endothelial dysfunction following decompression which provides guidance for timing the determination at least for the current model. The results further verify that bubbles are the causative agents of decompression induced endothelial damage and bubble amounts are an objective and suitable parameter to predict endothelial dysfunction. Most importantly, levels of endothelial biomarkers post dive may serve as sensitive parameters for assessing bubble load and decompression stress.


[Relation between the breakfast quality and the academic performance in adolescents of Guadalajara (Castilla-La Mancha)].
To study the relationship between the breakfast quality and skipping it on academic performance of a population of adolescents. A nutritional study on the breakfast quality has been performed in a population of adolescents from Guadalajara (467 young people; age: 12-17 years) by means of questionnaires of seven-day consumption frequency. Besides, we have collected socio-demographic data and academic scores of these people. Most of the students interviewed take a deficient breakfast since only 4.88% have a complete breakfast. The girls aged 15-17 years are those taking the poorest quality breakfast since 8.33% of them skip this meal. 68.29% take breakfasts which quality may be improved. The breakfast quality is directly related with the mean score obtained during the course 2003-04. This relationship is not so clear-cut when the different mandatory subjects in the different academic orientations are considered since it depends on the type of subject (comprehension, memory, concentration, physical activity...). The population studied consumes a poor breakfast, which may affect the academic outcomes, especially those for certain subjects.


It is time to authenticate the Microbiome Sciences with accredited educational programs and departments.
The Microbiome Sciences are at a crucial maturation stage. Scientists and educators should now view the Microbiome Sciences as a flourishing and autonomous discipline, creating degree programs and departments that are conducive to cohesive growth.


Power calculation for cross-sectional stepped wedge cluster randomized trials with variable cluster sizes.
Standard sample size calculation formulas for stepped wedge cluster randomized trials (SW-CRTs) assume that cluster sizes are equal. When cluster sizes vary substantially, ignoring this variation may lead to an under-powered study. We investigate the relative efficiency of a SW-CRT with varying cluster sizes to equal cluster sizes, and derive variance estimators for the intervention effect that account for this variation under a mixed effects model-a commonly used approach for analyzing data from cluster randomized trials. When cluster sizes vary, the power of a SW-CRT depends on the order in which clusters receive the intervention, which is determined through randomization. We first derive a variance formula that corresponds to any particular realization of the randomized sequence and propose efficient algorithms to identify upper and lower bounds of the power. We then obtain an "expected" power based on a first-order approximation to the variance formula, where the expectation is taken with respect to all possible randomization sequences. Finally, we provide a variance formula for more general settings where only the cluster size arithmetic mean and coefficient of variation, instead of exact cluster sizes, are known in the design stage. We evaluate our methods through simulations and illustrate that the average power of a SW-CRT decreases as the variation in cluster sizes increases, and the impact is largest when the number of clusters is small.


Peginterferon alfa-2a and ribavirin for chronic hepatitis C genotype 1 infections in black patients: safety, tolerability and impact on sustained virologic response.
HCV infections are two-times more prevalent in black Americans than in whites. We previously reported that treatment with peginterferon alfa-2a plus ribavirin produced a sustained virologic response (SVR) rate of 26% in blacks, a lower efficacy compared with the SVR in whites. Here we detail the safety profile of peginterferon alfa-2a plus ribavirin and the relationship between treatment adherence, defined by cumulative drug exposure, and SVR in 78 black patients infected with HCV genotype 1. Sixty-two (79%) patients completed 48 weeks of combination treatment. Peginterferon alfa-2a dose was modified for neutropenia in 36 patients (46%), whereas ribavirin dose was modified due to anemia in 31 patients (40%). The SVR rate was related to medication exposure, based on the percentage of the planned doses of peginterferon and ribavirin that the patients received. The SVR rates were 33, 25 and 0% in patients who received >80, 61-80 and <or=60% of the planned peginterferon, respectively. The SVR rates were 28, 33 and 18% in patients who received >80, 61-80 and <or=60% of the planned ribavirin. The SVR rate was 29% (11 of 38) in patients who received >80% of the total planned doses of both peginterferon and ribavirin and 7% (1 of 14) in patients who received <or=80% of both medicines. The SVR was 30% in patients who received >60% exposure to both, and 0% in patients with <or=60% exposure. In conclusion, peginterferon alfa-2a plus ribavirin demonstrated good safety and tolerability profiles in blacks infected with HCV genotype 1. Adherence to at least >60% of the planned peginterferon alfa-2a and ribavirin doses for 48 weeks was associated with a greater SVR in black patients with HCV genotype 1 infections.


Autologous stem cell transplantation in multiple myeloma patients <60 vs >/=60 years of age.
The role of autologous stem cell transplantation (AuSCT) in older multiple myeloma patients is unclear. Using data from the Autologous Blood and Marrow Transplant Registry, we compared the outcome of 110 patients >/=the age of 60 (median 63; range 60-73) years, undergoing AuSCT with that of 382 patients <60 (median 52; range 30-59) years. The two groups were similar except that older patients had a higher beta(2)-microglobulin level at diagnosis (P=0.016) and fewer had lytic lesions (P=0.007). Day 100 mortality was 6% (95% confidence interval 4-9) and 1-year treatment-related mortality (TRM) was 9% (6-13) in patients <60 years, compared with 5% (2-10) and 8% (4-14), respectively, in patients >/=60 years. The relapse rate, progression-free survival (PFS) and overall survival (OS) in the two groups were also similar. Multivariate analysis of all patients identified only an interval from diagnosis to AuSCT >12 months and the use of two prior chemotherapy regimens within 6 months of AuSCT as adverse prognostic factors. Our results indicate that AuSCT can be safely performed in selected older patients: the best results were observed in patients undergoing AuSCT relatively early in their disease course.


Developmental dyscalculia: a prospective six-year follow-up.
To determine the natural history of developmental dyscalculia (DC) and factors impacting on its prognosis, we performed a prospective six-year longitudinal study. One hundred and forty children of normal intelligence diagnosed with DC in the fifth grade of elementary school were re-examined for dyscalculia three and six years later, in eighth (n=123) and eleventh (n=104; 41 males, 63 females) grades respectively. Mean age of the children in fifth grade was 11 years 1 month (SD 4 months), in eighth grade 14 years 2 months (SD 1 month), and in eleventh grade 17 years 2 months (SD 5 months). The assessment included standardized arithmetic, reading and writing tests, behavioural rating scales, information on socioeconomic status, educational interventions, and familial learning problems. Participants in eleventh grade were recategorized as having DC if their score on the arithmetic test was not more than the fifth centile for grade. At the six-year follow-up, 99/104 (95%) children diagnosed with dyscalculia in fifth grade were still performing poorly in arithmetic, scoring within the lowest quartile for their grade, and 42/104 (40%) were recategorized with DC. Chronicity of DC was associated with severity of the dyscalculia in fifth grade (p<0.05), lower IQ (p<0.01), inattention (p<0.01), and writing problems (p<0.01). Thus, DC is an enduring specific learning difficulty, persisting into late adolescence in almost half of affected individuals.


Liquid drugs and high dead space syringes may keep HIV and HCV prevalence high - a comparison of Hungary and Lithuania.
Despitevery similar political, drug policy and HIV prevention backgrounds, HIV and HCV prevalence is considerably different in Hungary (low HIV and moderate HCV prevalence) and Lithuania (high HCV and moderate HIV prevalence). Wecompared the drug use profile of Hungarian (n = 215) and Lithuanian (n = 300) injecting drug users (IDUs). Overall, compared with IDUs in Hungary, IDUs in Lithuania often injected opiates purchased in liquid form ('shirka'), used and shared 2-piece syringes (vs. 1-piece syringes) disproportionately more often, were less likely to acquire their syringes from legal sources and had significantly more experience with injected and less experience with non-injected drugs. It may not be liquid drugs per se that contribute to a higher prevalence of HCV and/or HIV, but it is probably factors associated with the injecting of liquid drugs, such as the wide-spread use and sharing of potentially contaminated 2-piece syringes acquired often from non-legal sources, and syringe-mediated drug sharing with 2-piece syringes. Scaling up substitution therapy, especially heroin replacement, combined with reducing the supply of liquid drugs may decrease the prevalence of high-risk injecting behaviours related to the injecting of liquid drugs and drug injecting-related infections among IDUs in Lithuania.


Regional dynamic signal changes during controlled hyperventilation assessed with blood oxygen level-dependent functional MR imaging.
To quantitate the amplitude changes and temporal dynamics of regional functional MR imaging signals during voluntary hyperventilation using blood oxygen level-dependent contrast echo-planar imaging. Seven male subjects were studied during voluntary hyperventilation (PetCO2 = 20 mm Hg) regulated by capnometry. Measurements were made on multisection echo-planar MR images obtained with parameters of 1000/66 (repetition time/echo time), flip angle of 30 degrees, and voxel size of 3 x 3 x 5 mm3. Sensitivity of the functional MR imaging signal to changes in PetCO2, time delays in relation to PetCO2 changes, and time constants of functional MR imaging signal changes were assessed on a region-by-region basis. Within 20 seconds of starting hyperventilation, rapid and substantial decreases in the functional MR imaging signal (by as much as 10%) were measured in areas of gray matter, which were significantly greater than the modest changes observed in white matter. Regional-specific effects in areas of the frontal, occipital, and parietooccipital cortex were stronger than in subcortical regions or in the cerebellum. Signal decreases measured with functional MR imaging were significantly delayed with respect to the reduction in PetCO2. Apparent differences between regional time constants did not reach statistical significance. Regional and gray-white matter differences in functional MR imaging signal changes during controlled hyperventilation may reflect differences in metabolic activity, vascular regulation, and/or capillary density. When measuring brain activation with functional MR imaging, arterial PCO2 differences due to unregulated respiration may confound interpretation of activation-related functional MR imaging signal changes.


Changes in retinal nerve fiber layer thickness in patients with cerebral infarction: evidence of transneuronal retrograde degeneration.
We aimed to evaluate the thicknesses of the retinal nerve fiber layer (RNFL) in patients with cerebral infarction (CI) by using optical coherence tomography. This cross-sectional study evaluated 45 patients with CI (patient group) and 45 healthy subjects (control group). All subjects underwent a complete ophthalmic examination including optical coherence tomography. The average, temporal, nasal, inferior, and superior quadrant RNFL thicknesses and in each of 12 sectors around the optic nerve head were obtained. The side with the infarction was compared to the contralateral side among the patients with cerebral infarction, and their measurements were also compared to those of the control group. Patients who had CI only in the middle cerebral artery (MCA) and posterior cerebral artery (PCA) were included in this study. Correlations between the RNFL thicknesses and infarction features were also evaluated. The mean age of the patients was 61.6 ± 12.4 years, and the mean age of the controls was 59.6 ± 11.8 years (p = 0.65). Of the 45 patients with cerebral infarction, 35 (77.7 %) had infarction in the MCA territory, 10 (22.2 %) had infarction in the PCA territory and the mean duration of the disease was 20.2 ± 29.1 months. The average, superior, inferior, and nasal RNFL thicknesses were significantly thinner in both eyes of the patients with CI than in the eyes of the control group (p < 0.05). The average and inferior RNFL thicknesses were significantly more affected in the ipsilateral eyes than in the contralateral eyes (p < 0.031 and p < 0.006, respectively). The amount of reduction in the RNFL thicknesses was not correlated with the infarction features. Significant thinning of the RNFL in patients with CI may result from transneuronal retrograde degeneration. Optical coherence tomography may provide useful information to confirm the process of trans-synaptic retrograde degeneration.


[Rethoracotomies in the postoperative period].
The authors have performed 22 rethoracotomies. The causes of rethoracotomies were as follows: intrapleural bleedings, coagulated hemothorax, hermetic lung tissue, gangrene of the lung, bronchial fistula, atelectasis of the middle lobe and an error in diagnosis. Of great significance is the diagnosing of the postoperative complication and establishment of indications for rethoracotomy. Errors and problems in it show that the indication for reoperation should be established as early as possible.


The isolation of lymphocyte mitochondria and their regulation of extramitochondrial free Ca2+ concentration.
1. A method for the isolation of functionally intact mitochondria from lymphocytes is described. It involves digitonin breakage of the plasma membrane, followed by differential centrifugation. The yield was 36 mg of mitochondrial protein/200 g of pig mesenteric lymph node (6 mg of mitochondrial protein/10(9) lymphocytes). The mitochondrial had a respiratory-control ratio of 2--3.5 with succinate as substrate. 2. Ca2+ transport by these mitochondria was investigated. They were able to regulate the extramitochondrial free [Ca2+] very precisely, by buffering any displacements from the steady-state. The exact extramitochondrial free [Ca2+] of this steady-state depended on the conditions of incubation. In a medium designed to resemble the cytoplasmic environment, with added Ca2+, lymphocyte mitochondria maintained a steady-state free [Ca2+] of 0.63 microM (pCa of 6.2). The rates of Ca2+ uptake and efflux under these conditions, with both lymphocyte and liver mitochondria, were very much lower than those in a less complex medium. 3. Lymphocyte mitochondria were shown to possess an Na+-independent Ruthenium Red-insensitive efflux pathway similar to that of liver mitochondria. Ruthenium Red totally inhibited the electrophoretic uniporter. Although Na+ had no effect on the steady-state maintained by lymphocyte mitochondria, they were shown to possess an Na+/H+ antiporter.


Domain-Adversarial Transformer Network for Multiphase Liver Tumor Segmentation.
Accurate liver tumor segmentation is a prerequisite for data-driven tumor analysis. Multiphase computed tomography (CT) with extensive liver tumor characteristics is typically used as the most crucial diagnostic basis. However, the large variations in contrast, texture, and tumor structure between CT phases limit the generalization capabilities of the associated segmentation algorithms. Inadequate feature integration across phases might also lead to a performance decrease. To address these issues, we present a domain-adversarial transformer (DA-Tran) network for segmenting liver tumors from multiphase CT images. A DA module is designed to generate domain-adapted feature maps from the non-contrast-enhanced (NC) phase, arterial (ART) phase, portal venous (PV) phase, and delay phase (DP) images. These domain-adapted feature maps are then combined with 3D transformer blocks to capture patch-structured similarity and global context attention. The experimental findings show that DA-Tran produces cutting-edge tumor segmentation outcomes, making it an ideal candidate for this co-segmentation challenge.


Clusterization of patients with idiopathic pulmonary fibrosis with chemokine receptors: a possible role in the diagnostic work-up of idiopathic pulmonary fibrosis?
Background and objective: Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible interstitial lung disease whose diagnosis often requires surgical lung biopsies (SLB) in cases without consistent radiological findings. We previously published that the expression of the chemokine receptors CXCR3 and CCR4 on T cells is significantly different in bronchoalveolar lavage (BAL) of IPF patients from other interstitial lung diseases. The aim of the study was to evaluate cut-off values of CXCR3 and CCR4 receptors expressed on bronchoalveolar lavage (BAL) and peripheral blood (PB) T cells useful for a differential diagnosis. Methods: Ninety-three patients were enrolled: 35 IPF, 36 interstitial lung diseases (nIPF) and 22 sarcoidosis. CXCR3 and CCR4 were evaluated on BAL and PB T lymphocytes with flow cytometry. Results: Among PB and BAL variables considered, the values of the ratio of BAL and PB CXCR3 on CD4 cells were clustered in the most informative way to obtain a classification rule for the diagnosis of patients without steroid therapy (n = 66/93). Patients with a CXCR3 ratio BAL/PB on CD4 T cells lower or equal than 1.43 were assigned to the IPF group with sensitivity = 0.87 and specificity = 0.90. All the other variables considered showed lower sensitivity and specificity in discriminating IPF patients. Conclusions: The evaluation of chemokine receptors on BAL and PB T lymphocytes could aid to discriminate IPF in subjects without steroid therapy, particularly in those patients with a high-resolution computed tomography (HRCT) non typical for Usual Interstitial Pneumonia (UIP). (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 35-43).


Deciphering the pivotal role of people with high-frequency occupational animal exposure in antibiotic resistance transmission between humans and animals.
The spread of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) among humans and food-producing animals has been widely reported. However, the transmission routes and associated risk factors remain incompletely understood. Here, we used commensal Escherichia coli bacteria strains from faeces of pigs and local citizens [HEG: high exposure group (pig breeders, butchers or restaurant chefs) and LEG: low exposure group (other occupations)] to explore the dynamics of ARB and ARG transmission between animals and humans. Most ARGs (96%) present in pigs were shared with humans. Carriage rates of the shared ARGs suggest two transmission patterns among pigs, the HEG and LEG: one pattern was highest in pigs, gradually decreasing in the HEG and LEG (e.g. floR and cmlA1); the other pattern was increasing from pigs to the HEG but then decreasing in the LEG (e.g. mcr-1.1). Carriage rates of the HEG were higher than in the LEG in both patterns, implicating the HEG as a crucial medium in transmitting ARB and ARGs between food-producing animals and humans. Moreover, frequent inter/intragroup transmission via strains, plasmids and/or mobile elements was evident. Carriage of mcr-1.1 on human-gut-prevalent plasmids possibly promoted its enrichment in the HEG. The HEG is a crucial factor in transmitting ARB and ARGs between food-producing animals and humans. Rational measures to contain the risks of occupational exposure are urgently needed to keep dissemination of antibiotic resistance in check and safeguard public health.


Dam-Infant Rhesus Macaque Pairs to Dissect Age-Dependent Responses to SARS-CoV-2 Infection.
The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease (COVID-19) has led to a pandemic of unprecedented scale. An intriguing feature of the infection is the minimal disease in most children, a demographic at higher risk for other respiratory viral diseases. To investigate age-dependent effects of SARS-CoV-2 pathogenesis, we inoculated two rhesus macaque monkey dam-infant pairs with SARS-CoV-2 and conducted virological and transcriptomic analyses of the respiratory tract and evaluated systemic cytokine and Ab responses. Viral RNA levels in all sampled mucosal secretions were comparable across dam-infant pairs in the respiratory tract. Despite comparable viral loads, adult macaques showed higher IL-6 in serum at day 1 postinfection whereas CXCL10 was induced in all animals. Both groups mounted neutralizing Ab responses, with infants showing a more rapid induction at day 7. Transcriptome analysis of tracheal airway cells isolated at day 14 postinfection revealed significant upregulation of multiple IFN-stimulated genes in infants compared with adults. In contrast, a profibrotic transcriptomic signature with genes associated with cilia structure and function, extracellular matrix composition and metabolism, coagulation, angiogenesis, and hypoxia was induced in adults compared with infants. Our study in rhesus macaque monkey dam-infant pairs suggests age-dependent differential airway responses to SARS-CoV-2 infection and describes a model that can be used to investigate SARS-CoV-2 pathogenesis between infants and adults.


Cost-Effectiveness Analysis of Deep Brain Stimulation in Patients with Parkinson's Disease in Japan.
Deep brain stimulation (DBS) is an effective surgical option for treating Parkinson's disease (PD). DBS is invasive, with a high initial cost. In Japan, questions have been raised about its cost-effectiveness and the resulting improvements in outcome. The aim of this study was to evaluate the cost-effectiveness of DBS for PD in Japan, particularly whether early or late DBS is more cost-effective. We used a Markov cohort simulation to follow the clinical course of DBS for PD. We conducted a survey to capture QOL scores among healthy Japanese volunteers. Transition probabilities were estimated from randomized clinical trials. We determined direct medical costs from the perspective of the Japanese health care system. Outcomes were assessed as quality-adjusted life years. We conducted univariate and probabilistic sensitivity analyses. DBS costs an additional 10.3 million Japanese yen (US$85,100; exchange rate on October 28, 2015 was 121 yen to $1) for a gain of 3.2 quality-adjusted life years. The incremental cost-effectiveness ratio was 3.1 million yen ($25,600). The incremental cost-effectiveness ratio was 8.5 million yen ($70,200) for early DBS, 3.1 million yen ($25,600) for intermediate DBS, and 3.3 million yen ($27,200) for late-stage DBS. Our model suggests that DBS is cost-effective in the Japanese health care system. DBS is more cost-effective if performed in the intermediate rather than early or late stages of PD.


Temporal Trends in Early Pediatric Cochlear Implantations in California from 2018 to 2020.
To characterize the demographics of children receiving cochlear implantations, identify factors associated with delayed implantations, and trend these factors over time. Retrospective cross-sectional study. Healthcare Cost and Utilization Project California State Ambulatory Surgery Database for calendar years 2018-2020. Children 5 years or younger undergoing cochlear implantation. Cochlear implantation. The population-controlled number of cochlear implantations was calculated and stratified by race and insurance. Early implantation was defined as implantation at age 2 years or younger. A mixed-effects logistic regression model was generated to identify factors associated with early implantation and how that association changed from 2018 to 2020. The final cohort included 467 children. The number of implantations increased from 141 to 175 implants from 2018 to 2020 (24.1% increase); 229 (49.0%) children were implanted at 2 years or younger. Medicaid insurance was associated with decreased odds of early implantation (odds ratio, 0.18 [95% confidence interval, 0.15-0.23], p < 0.001); this association with Medicaid insurance was significant when stratified across all racial groups. The percentage of children with Medicaid who were implanted at 2 years or younger increased from 20.9 to 62.0% from 2018 to 2020. Among children in California, socioeconomic factors, in particular public insurance, are correlated with age of cochlear implantation. These disparities improved significantly from 2018 to 2020. Further investigation into changes and initiatives in California during this time frame may aid in directing national efforts to improve pediatric cochlear implantation access.


Prevalence of mental disorders in South Asia: An umbrella review of systematic reviews and meta-analyses.
Mental disorders are highly prevalent in eight South Asian countries, yet there is a gap of a synthesized overview of the prevalence of mental disorders in this region. This umbrella review aims to summarize the prevalence of mental disorders from systematic reviews and meta-analyses of South Asian studies. A systematic search of 11 major databases and additional sources was conducted until December 11, 2019. Articles were included if they were systematic reviews or meta-analyses, reported the prevalence of mental disorders, and reported primary studies conducted in South Asian countries only. Among 2591 citations, a total of 23 reviews met all the criteria of this umbrella review. The synthesized findings from those reviews suggest high prevalence rates for mental disorders, including depressive disorders, anxiety disorders, mood disorders, suicidal behavior and self-harm, schizophrenia, substance use disorders, neurodevelopmental disorders, dementia, and other mental health problems. Also, findings suggest a high burden of maternal depression, psychiatric comorbidities in chronic physical illnesses, and various mental disorders among children, elderly adults, refugees, and other vulnerable populations. Most studies were from India whereas evidence from Afghanistan, Bhutan, and Maldives was limited. The findings of this review are constrained with heterogeneity in prevalence estimations, methodologies, sampling issues, and limitations in the existing literature, which should be addressed in future research. The evidence synthesized in this review provides national and regional overview of the prevalence of mental disorders, which may inform better policymaking and practice advancing mental health in South Asia.


Percutaneous closure of paravalvular mitral regurgitation with Vascular Plug III under the guidance of real-time three-dimensional transesophageal echocardiography.
Transcatheter closure of mitral prosthetic paravalvular leak (PVL) has been hampered by technical challenges and the lack of closure devices specifically designed for this purpose. The oblong cross-sectional shape of the Amplatzer Vascular Plug III device (AVP) may be a more appropriate choice to be deployed for mitral PVL's. Real-time three-dimensional transesophageal echocardiography (RT-3D TEE) has emerged as an efficient tool that provides essential information concerning leakage size, location, and shape as well as navigation of catheters and wires. We assessed the feasibility and short, mid, and long-term efficacy of transcatheter mitral PVL closure using AVP-III under the guidance of RT-3D TEE. Three patients with severe symptomatic mitral PVL at high risk for repeat surgery underwent transcatheter leak closure with AVP III. Transfemoral approaches were used under RT-3D TEE guidance. Transcatheter closure of mitral PVLs was performed successfully in 3 patients using 5 devices. The first patient with 2 devices deployed had residual mitral regurgitation resulting in re-operation at the sixth month. The second patient had improved normally with a functioning prosthesis after the deployment of two devices, but had progressively worsening mitral regurgitation for which re-operation at the sixteenth month of follow-up was necessary. The third patient had no residual leak, with normal prosthetic function. At 24 months follow-up, all patients were in satisfactory clinical status. Although RT-3D TEE plays an essential role in guidance of transcatheter closure of mitral PVLs with AVP III, the absence of a specific closure device limits mid and long-term success rates.


Angiopoietin-1 promotes LYVE-1-positive lymphatic vessel formation.
Angiopoietin (Ang) signaling plays a role in angiogenesis and remodeling of blood vessels through the receptor tyrosine kinase Tie2, which is expressed on blood vessel endothelial cells (BECs). Recently it has been shown that Ang-2 is crucial for the formation of lymphatic vasculature and that defects in lymphangiogenesis seen in Ang-2 mutant mice are rescued by Ang-1. These findings suggest important roles for Ang signaling in the lymphatic vessel system; however, Ang function in lymphangiogenesis has not been characterized. In this study, we reveal that lymphatic vascular endothelial hyaluronan receptor 1-positive (LYVE-1(+)) lymphatic endothelial cells (LECs) express Tie2 in both embryonic and adult settings, indicating that Ang signaling occurs in lymphatic vessels. Therefore, we examined whether Ang-1 acts on in vivo lymphatic angiogenesis and in vitro growth of LECs. A chimeric form of Ang-1, cartilage oligomeric matrix protein (COMP)-Ang-1, promotes in vivo lymphatic angiogenesis in mouse cornea. Moreover, we found that COMP-Ang-1 stimulates in vitro colony formation of LECs. These Ang-1-induced in vivo and in vitro effects on LECs were suppressed by soluble Tie2-Fc fusion protein, which acts as an inhibitor by sequestering Ang-1. On the basis of these observations, we propose that Ang signaling regulates lymphatic vessel formation through Tie2.


Controls on Interspecies Electron Transport and Size Limitation of Anaerobically Methane-Oxidizing Microbial Consortia.
About 382 Tg yr-1 of methane rising through the seafloor is oxidized anaerobically (W. S. Reeburgh, Chem Rev 107:486-513, 2007, https://doi.org/10.1021/cr050362v), preventing it from reaching the atmosphere, where it acts as a strong greenhouse gas. Microbial consortia composed of anaerobic methanotrophic archaea and sulfate-reducing bacteria couple the oxidation of methane to the reduction of sulfate under anaerobic conditions via a syntrophic process. Recent experimental studies and modeling efforts indicate that direct interspecies electron transfer (DIET) is involved in this syntrophy. Here, we explore a fluorescent in situ hybridization-nanoscale secondary ion mass spectrometry data set of large, segregated anaerobic oxidation of methane (AOM) consortia that reveal a decline in metabolic activity away from the archaeal-bacterial interface and use a process-based model to identify the physiological controls on rates of AOM. Simulations reproducing the observational data reveal that ohmic resistance and activation loss are the two main factors causing the declining metabolic activity, where activation loss dominated at a distance of <8 μm. These voltage losses limit the maximum spatial distance between syntrophic partners with model simulations, indicating that sulfate-reducing bacterial cells can remain metabolically active up to ∼30 μm away from the archaeal-bacterial interface. Model simulations further predict that a hybrid metabolism that combines DIET with a small contribution of diffusive exchange of electron donors can offer energetic advantages for syntrophic consortia.IMPORTANCE Anaerobic oxidation of methane is a globally important, microbially mediated process reducing the emission of methane, a potent greenhouse gas. In this study, we investigate the mechanism of how a microbial consortium consisting of archaea and bacteria carries out this process and how these organisms interact with each other through the sharing of electrons. We present a process-based model validated by novel experimental measurements of the metabolic activity of individual, phylogenetically identified cells in very large (>20-μm-diameter) microbial aggregates. Model simulations indicate that extracellular electron transfer between archaeal and bacterial cells within a consortium is limited by potential losses and suggest that a flexible use of electron donors can provide energetic advantages for syntrophic consortia.


Zoonotic Endocarditis in a Man, the Netherlands.
In 2017, endocarditis caused by Streptococcus equi subspecies zooepidemicus was diagnosed in a man in the Netherlands who had daily contact with horses. Whole-genome sequencing of isolates from the man and his horses confirmed the same clone, indicating horse-to-human transmission. Systematic reporting of all zoonotic cases would help with risk assessment.


Technical note: Noninvasive monitoring of normal tissue radiation damage using spectral quantitative ultrasound spectroscopy.
While radiation therapy (RT) is a critical component of breast cancer therapy and is known to decrease overall local recurrence rates, recent studies have shown that normal tissue radiation damage may increase recurrence risk. Fibrosis is a well-known consequence of RT, but the specific sequence of molecular and mechanical changes induced by RT remains poorly understood. To improve cancer therapy outcomes, there is a need to understand the role of the irradiated tissue microenvironment in tumor recurrence. This study seeks to evaluate the use of spectral quantitative ultrasound (spectral QUS) for real time determination of the normal tissue characteristic radiation response and to correlate these results to molecular features in irradiated tissues. Murine mammary fat pads (MFPs) were irradiated to 20 Gy, and spectral QUS was used to analyze tissue physical properties pre-irradiation as well as at 1, 5, and 10 days post-irradiation. Tissues were processed for scanning electron microscopy imaging as well as histological and immunohistochemical staining to evaluate morphology and structure. Tissue morphological and structural changes were observed non-invasively following radiation using mid-band fit (MBF), spectral slope (SS), and spectral intercept (SI) measurements obtained from spectral QUS. Statistically significant shifts in MBF and SI indicate structural tissue changes in real time, which matched histological observations. Radiation damage was indicated by increased adipose tissue density and extracellular matrix (ECM) deposition. Our findings demonstrate the potential of using spectral QUS to noninvasively evaluate normal tissue changes resulting from radiation damage. This supports further pre-clinical studies to determine how the tissue microenvironment and physical properties change in response to therapy, which may be important for improving treatment strategies.


The subcellular distribution of dystrophin in mouse skeletal, cardiac, and smooth muscle.
We use a highly specific and sensitive antibody to further characterize the distribution of dystrophin in skeletal, cardiac, and smooth muscle. No evidence for localization other than at the cell surface is apparent in skeletal muscle and no 427-kD dystrophin labeling was detected in sciatic nerve. An elevated concentration of dystrophin appears at the myotendinous junction and the neuromuscular junction, labeling in the latter being more intense specifically in the troughs of the synaptic folds. In cardiac muscle the distribution of dystrophin is limited to the surface plasma membrane but is notably absent from the membrane that overlays adherens junctions of the intercalated disks. In smooth muscle, the plasma membrane labeling is considerably less abundant than in cardiac or skeletal muscle and is found in areas of membrane underlain by membranous vesicles. As in cardiac muscle, smooth muscle dystrophin seems to be excluded from membrane above densities that mark adherens junctions. Dystrophin appears as a doublet on Western blots of skeletal and cardiac muscle, and as a single band of lower abundance in smooth muscle that corresponds most closely in molecular weight to the upper band of the striated muscle doublet. The lower band of the doublet in striated muscle appears to lack a portion of the carboxyl terminus and may represent a dystrophin isoform. Isoform differences and the presence of dystrophin on different specialized membrane surfaces imply multiple functional roles for the dystrophin protein.


Microbial synthesis of the energetic material precursor 1,2,4-butanetriol.
The lack of a route to precursor 1,2,4-butanetriol that is amenable to large-scale synthesis has impeded substitution of 1,2,4-butanetriol trinitrate for nitroglycerin. To identify an alternative to the current commercial synthesis of racemic d,l-1,2,4-butanetriol involving NaBH4 reduction of esterified d,l-malic acid, microbial syntheses of d- and l-1,2,4-butanetriol have been established. These microbial syntheses rely on the creation of biosynthetic pathways that do not exist in nature. Oxidation of d-xylose by Pseudomonas fragi provides d-xylonic acid in 70% yield. Escherichia coli DH5alpha/pWN6.186A then catalyzes the conversion of d-xylonic acid into d-1,2,4-butanetriol in 25% yield. P. fragi is also used to oxidize l-arabinose to a mixture of l-arabino-1,4-lactone and l-arabinonic acid in 54% overall yield. After hydrolysis of the lactone, l-arabinonic acid is converted to l-1,2,4-butanetriol in 35% yield using E. coli BL21(DE3)/pWN6.222A. As a catalytic route to 1,2,4-butanetriol, microbial synthesis avoids the high H2 pressures and elevated temperatures required by catalytic hydrogenation of malic acid.


Complete Genome Sequence of the Fire Blight Pathogen Strain Erwinia amylovora Ea1189.
Erwinia amylovora causes fire blight, the most devastating bacterial disease of apples and pears in the United States and worldwide. The model strain E. amylovora Ea1189 has been extensively used to understand bacterial pathogenesis and molecular mechanisms of bacterial-plant interactions. In this work, we sequenced and assembled the de novo genome of Ea1189, using a combination of long Oxford Nanopore Technologies and short Illumina sequence reads. A complete gapless genome assembly of Ea1189 consists of a 3,797,741-bp circular chromosome and a 28,259-bp plasmid with 3,472 predicted genes, including 78 transfer RNAs, 22 ribosomal RNAs, and 20 noncoding RNAs. A comparison of the Ea1189 genome to previously sequenced E. amylovora complete genomes showed 99.94 to 99.97% sequence similarity with 314 to 946 single nucleotide polymorphisms. We believe that the availability of the complete genome sequence of strain Ea1189 will further support studies to understand evolution, diversity and structural variations of Erwinia strains, as well as the molecular basis of E. amylovora pathogenesis and its interactions with host plants, thus facilitating the development of effective management strategies for this important disease.


Confirmation of linkage to and localization of familial colon cancer risk haplotype on chromosome 9q22.
Genetic risk factors are important contributors to the development of colorectal cancer. Following the definition of a linkage signal at 9q22-31, we fine mapped this region in an independent collection of colon cancer families. We used a custom array of single-nucleotide polymorphisms (SNP) densely spaced across the candidate region, performing both single-SNP and moving-window association analyses to identify a colon neoplasia risk haplotype. Through this approach, we isolated the association effect to a five-SNP haplotype centered at 98.15 Mb on chromosome 9q. This haplotype is in strong linkage disequilibrium with the haplotype block containing HABP4 and may be a surrogate for the effect of this CD30 Ki-1 antigen. It is also in close proximity to GALNT12, also recently shown to be altered in colon tumors. We used a predictive modeling algorithm to show the contribution of this risk haplotype and surrounding candidate genes in distinguishing between colon cancer cases and healthy controls. The ability to replicate this finding, the strength of the haplotype association (odds ratio, 3.68), and the accuracy of our prediction model (approximately 60%) all strongly support the presence of a locus for familial colon cancer on chromosome 9q.


The protective effect of erythropoietin on renal injury induced by abdominal aortic-ischemia-reperfusion in rats.
Renal injury induced by aortic ischemia-reperfusion (IR) is an important factor in the development of postoperative acute renal failure following abdominal aortic surgery. The purpose of this study is to examine the effect of erythropoietin on renal injury induced by aortic IR in rats. Twenty-four Wistar-Albino rats were randomized into 3 groups (8 per group). The control group underwent laparotomy and dissection of the infrarenal abdominal aorta without occlusion. The aortic IR group underwent clamping of the infrarenal abdominal aorta for 30 min followed by 60 min of reperfusion. The aortic IR + erythropoietin group underwent the same aortic IR periods and was pretreated with 1000 U/kg subcutaneous erythropoietin 5 min before ischemia. In rat kidney specimens, tissue levels of malondialdehyde (MDA), superoxide dismutase, catalase, and glutathione peroxidase were measured. Histological evaluation of the rat kidney tissues was also done. Aortic IR significantly increased the levels of MDA and superoxide dismutase (P < 0.05 versus control). Erythropoietin significantly decreased the levels of MDA, superoxide dismutase, and catalase (P < 0.05 versus aortic IR). Histological evaluation showed that aortic IR significantly increased (P < 0.05 versus control), whereas erythropoietin significantly decreased (P < 0.05 versus aortic IR) the focal glomerular necrosis, dilation of Bowman's capsule, degeneration of tubular epithelium, necrosis in tubular epithelium, interstitial inflammatory infiltration, and congestion of blood vessels. The results indicate that erythropoietin has protective effects on renal injury induced by aortic IR in rats.


Including oncology outcomes of care in the computer-based patient record.
Changes in the health care system have caused a shift in research to outcomes of care, effectiveness, efficiencies, clinical practice guidelines, and costs. The greater use of computer systems, including decision support systems, quality assurance systems, effectiveness systems, cost containment systems, and networks, will be required to integrate administrative and patient care data for use in determining outcomes and resource management. This article describes developments to look forward to in the decade ahead, including the integration of outcomes data and clinical practice guidelines as content into computer-based patient records; the development of review criteria from clinical practice guidelines to be used in translating guidelines into critical paths; and feedback systems to monitor performance measures and benchmarks of care, and ultimately cost out cancer care.


Cyclic mRNA expression of thyrotropin subunits and deiodinases in red drum, Sciaenops ocellatus.
The role of thyrotropin (thyroid-stimulating hormone, TSH) in driving peripheral thyroid function in non-mammalian species is still poorly understood. Thyroxine (T₄), the principal hormone released from the thyroid gland in response to TSH stimulation, circulates with a robust daily rhythm in the teleost fish the red drum. Previous research suggests that the red drum T₄ cycle is circadian in nature, driven by TSH secretion in the early photophase and inhibited by T₄ feedback in the early scotophase. To determine whether TSH is produced in a pattern consistent with feedback inhibition by this T₄ cycle, we used quantitative real time PCR (qPCR) to quantify the daily cycle of expression of the pituitary TSH subunits GSUα, and TSHβ. We found that TSH expression cycled inversely to, and 6-12 h out of phase with, the T₄ cycle, consistent with the hypothesis that TSH secretion drives the T₄ cycle. To examine the potential role of deiodinases in negative feedback regulation of this TSH cycle, we also utilized qPCR to assess the pituitary expression patterns of the TH activating enzyme outer-ring deiodinase (Dio2) and the TH deactivating enzyme inner-ring deiodinase (Dio3). Dio2 was not expressed with an obvious daily cycle, whereas Dio3 expression mirrored the expression of TSH. These results are consistent with circulating T₄ providing the negative feedback signal controlling both TSH production and Dio3 expression in the pituitary, and suggest that TH inactivation by inner ring deiodination is an important component of TSH negative feedback control.


Two distinct domains of the beta-subunit of glucosidase II interact with the catalytic alpha-subunit.
Recent purification and cDNA cloning of the endoplasmic reticulum processing enzyme glucosidase II have revealed that it is composed of two soluble proteins: a catalytic alpha-subunit and a beta-subunit of unknown function, both of which are highly conserved in mammals. Since the beta-subunit, which contains a C-terminal His-Asp-Glu-Leu (HDEL) motif, may function to link the catalytic subunit to the KDEL receptor as a retrieval mechanism, we sought to map the regions of the mouse beta-subunit protein responsible for mediating the association with the alpha-subunit. By screening a panel of recombinant beta-subunit glutathione S-transferase fusion proteins for the ability to precipitate glucosidase II activity, we have identified two non-overlapping interaction domains (ID1 and ID2) within the beta-subunit. ID1 encompasses 118 amino acids at the N-terminus of the mature polypeptide, spanning the cysteine-rich element in this region. ID2, located near the C-terminus, is contained within amino acids 273-400, a region occupied in part by a stretch of acidic residues. Variable usage of 7 alternatively spliced amino acids within ID2 was found not to influence the association of the two sub-units. We theorize that the catalytic subunit of glucosidase II binds synergistically to ID1 and ID2, explaining the high associative stability of the enzyme complex.


Cancer Hallmarks Analytics Tool (CHAT): a text mining approach to organize and evaluate scientific literature on cancer.
To understand the molecular mechanisms involved in cancer development, significant efforts are being invested in cancer research. This has resulted in millions of scientific articles. An efficient and thorough review of the existing literature is crucially important to drive new research. This time-demanding task can be supported by emerging computational approaches based on text mining which offer a great opportunity to organize and retrieve the desired information efficiently from sizable databases. One way to organize existing knowledge on cancer is to utilize the widely accepted framework of the Hallmarks of Cancer. These hallmarks refer to the alterations in cell behaviour that characterize the cancer cell. We created an extensive Hallmarks of Cancer taxonomy and developed automatic text mining methodology and a tool (CHAT) capable of retrieving and organizing millions of cancer-related references from PubMed into the taxonomy. The efficiency and accuracy of the tool was evaluated intrinsically as well as extrinsically by case studies. The correlations identified by the tool show that it offers a great potential to organize and correctly classify cancer-related literature. Furthermore, the tool can be useful, for example, in identifying hallmarks associated with extrinsic factors, biomarkers and therapeutics targets. CHAT can be accessed at: http://chat.lionproject.net. The corpus of hallmark-annotated PubMed abstracts and the software are available at: http://chat.lionproject.net/about. firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


Efficacy of routine preoperative computed tomography scans in colon cancer.
A retrospective review of 180 patients who underwent surgery for primary colon carcinoma from August 1989 to August 1994 was performed to evaluate the necessity of preoperative CT scans in patients with known colon cancer. Sixty-seven patients had preoperative CT scans. Data were collected to evaluate the ability of the scan to detect hepatic metastases, lymph node involvement, and incidental findings that would possibly alter the planned surgical approach. In this study, CT had a sensitivity and specificity of 75 per cent and 88 per cent, respectively, in detecting hepatic metastases. Only 19 per cent of patients with lymph node involvement were correctly staged with CT scans as having lymphadenopathy. Only 3 of 67 patients had incidental findings on CT scans that ultimately changed the surgical approach. It is apparent that because CT scans detect only 75 per cent of hepatic and 19 per cent of hepatic and lymph node involvement and does not seem to alter the planned approach, it is not justified for routine preoperative evaluation of all patients. We, therefore, recommend a more selective approach to patients suspected of having advanced disease if the surgeon suspects that the information may alter the surgical approach.


Isolation, characterization, and organ-specific expression of two novel human zinc finger genes related to the Drosophila gene spalt.
The region-specific homeotic gene spalt (sal) of Drosophila specifies head and tail as opposed to trunk segments. During later stages of ontogenesis, sal is also expressed and required in a small number of tissues and organs in the developing embryo. sal encodes a zinc finger protein of unusual but characteristic structure. We made use of these unique features to isolate sal-like genes from humans. Here we report the isolation and molecular characterization of two sal-like transcription units, termed Hsal1 and Hsal2, which are located on chromosomes 16q12.1 and 14q11.1-q12.1, respectively. Their transcripts are expressed in a limited number of adult organs, including the brain. While Hsal2 is evenly expressed in different brain areas, Hsal1 transcripts preferentially accumulate in the corpus callosum and the substantia nigra. In the fetal brain, transcripts of both genes were detected in neurons. The arrangement of sal-like zinc finger domains and their high degree of sequence similarity suggest a novel and conserved subfamily of human zinc finger transcription factors that is closely related to the Drosophila gene product encoded by the gene sal.


NCCTG N0879 (Alliance): A randomized phase 2 cooperative group trial of carboplatin, paclitaxel, and bevacizumab ± everolimus for metastatic melanoma.
Despite the success of immune checkpoint and targeted therapy, many patients with melanoma ultimately require further treatment. The combination of carboplatin, paclitaxel, and bevacizumab (CPB) has demonstrated promising activity in a single-arm study. In the current study, the authors performed a randomized phase 2 study to confirm efficacy and to determine whether adding everolimus would increase the activity of the combination. Through the North Central Cancer Treatment Group, a total of 149 patients with unresectable AJCC 6th edition stage IV melanoma were randomized from May 2010 to May 2014 to either CPB or CPB with everolimus (CPBE). The primary endpoint was progression-free survival (PFS), with secondary endpoints of overall survival (OS), response rate, and tolerability. The CPB and CPBE treatment arms were balanced with regard to age (median age: 59 years vs 58 years) and high lactate dehydrogenase (48% vs 51%), but were unbalanced with regard to sex (male sex: 72% vs 55%; P = .03). Overall, there was no difference noted with regard to PFS, with a median PFS of 5.6 months for CPB versus 5.1 months for CPBE (hazard ratio [HR], 1.14; 95% confidence interval [95% CI], 0.81-1.62 [P = .44]), or for OS, with a median OS of 14.5 months for CPB versus 10.8 months for CPBE (HR, 1.16; 95% CI, 0.84-1.84). The confirmed response rate was 13% for CPB and 23% for CPBE (P = .13). Toxicity was higher for CPBE compared with CPB (83% for grade 3 + and 14% for grade 4 + vs 63% for grade 3 + and 11% for grade 4+, respectively) (toxicities were graded using the Cancer Therapy Evaluation Program of the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). Common grade 3 + toxicities were neutropenia, leukopenia, and fatigue, which occurred in both treatment arms with comparable frequency. Both experimental arms demonstrated activity, with a PFS of >5 months. However, the addition of everolimus to CPB failed to improve outcomes, with increased toxicity noted. These findings replicate the moderate antitumor activity of CPB, with future development possibly in combination with targeted or immunotherapy. Cancer 2018;124:537-45. © 2017 American Cancer Society.


Velocity tracking, a new and user independent method for detecting regional function of the left ventricle.
The use of two-dimensional echocardiography (2D echo) for detection of ischaemia is limited due to high user dependency. Longitudinal motion is sensitive for ischaemia and usable for quantitative measurement of longitudinal myocardial function but time consuming. Velocity tracking (VeT) is a new method that gives an easy three-dimensional understanding of both systolic and diastolic regional motion, using colour coded bull's eye presentation of longitudinal velocity, derived from colour coded tissue Doppler. The aim of this study was to test the accuracy of VeT in detecting ischaemia in non-ST-segment elevation myocardial infarction (NSTEMI) patients bedside. Twenty patients with NSTEMI and 10 controls were included. Echocardiography was performed within 24 h of symptoms and prior to coronary angiography. Bull's eye plots presenting the peak systolic velocity (PSV) and the sum of PSV and the E-wave-velocity (PSV+E) were created using our developed software. VeT was compared to expert wall motion scoring (WMS) and bedside echo. We used the clinical conclusion based on ECG, angiography and clinical picture as 'gold standard'. Sensitivity for ischaemia with VeT (PSV+E) was 85% and specificity 60%. The corresponding sensitivities for expert WMS were 75% (specificity 40%). For regional analysis VeT and WMS showed comparable results with correct regional outcome in 11/20 of patients both superior to bedside echo. Velocity tracking is a promising technique that provides an easily understandable three-dimensional bull's eye plot for assessment of regional left ventricular longitudinal velocity with great potential for detection of regional dysfunction and myocardial ischaemia.


"Forward-Thinking" in U.S. Biobanking.
Do biobanks enact policies and plans that allow them to anticipate and respond to potential challenges? If a biobank has one such policy or plan, is it likely to have more? Using survey data from 456 U.S. biobanks, we assess four possible indicators of such "forward-thinking." We present response frequencies and cross-tabulations regarding policies for return of results and ownership of specimens, and for having a formal business plan and a plan for what happens to specimens if the biobank closes. We analyze the relationships among these indicators, using chi-square for tests of statistical significance. Policies-Sixty-two percent of biobanks have a policy about returning individual research results; 70% have a policy designating ownership of specimens and/or technology. Having these two policies is significantly related (p < 0.001). Plans-34% of biobanks have a formal business plan; 26% have a written plan for what will happen to the specimens if the biobank closes. Having these two plans is significantly related (p < 0.001). Relationships among indicators-only 7% of biobanks are forward-thinking across all four indicators; 12% are forward-thinking across none. The two policies we examined tend to occur together, as do the two plans. These policies and plans seem to tap different aspects of accountability and responsiveness. Specifically, the policies reflect issues most commonly raised in the ethical and legal literature on biobanking, while the plans are indicators of sustainability, a separate area of concern in biobanking.


Immunoelectroosmophoresis in the diagnosis of meningococcal infections.
Specimens of cerebrospinal fluid and serum from 22 cases of meningococcal infection were examined by immunoelectroosmophoresis and the results compared with those obtained by microscopy and culture. The results were the same except that three of 10 cases of group B infection were not diagnosed by immunoelectroosmophoresis and two of 10 cases of group C infection were not diagnosed by culture. The sensitivity of the method depends on the potency of the antiserum used and antisera from commercial sources were satisfactory except for those prepared against group B meningococci. The method may be more sensitive than microscopy and culture under certain conditions, in particular, where the patient has already begun antibiotic treatment, where the specimens have become contaminated and, where the infecting organism is either a group A or group C meningococcus.


COX-2 inhibitor delivery system aiming intestinal inflammatory disorders.
Selective COX-2 inhibitors such as etoricoxib (ETX) are potentially indicated for the treatment of intestinal inflammatory disorders. However, their systemic administration provokes some off-site secondary effects, decreasing the desirable local effectiveness. To circumvent such limitations, herein an ETX delivery system based on electrospun fibrous meshes (eFMs) was proposed. ETX at different concentrations (1, 2, and 3 mg mL-1) was loaded into eFMs, which not affect the morphology and the mechanical properties of this drug delivery system (DDS). The ETX showed a burst release within the first 12 h, followed by a faster release until 36 h, gradually decreasing over time. Importantly, the ETX studied concentrations were not toxic to human colonic cells (i.e. epithelial and fibroblast). Moreover, the DDS loading the highest concentration of ETX, when tested with stimulated human macrophages, promoted a reduction of PGE2, IL-8 and TNF-α secretion. Therefore, the proposed DDS may constitute a safe and efficient treatment of colorectal diseases promoted by inflammatory disorders associated with COX-2.