eHealth Search Patterns: A Comparison of Private and Public Health Care Markets Using Online Panel Data.
Patient and consumer access to eHealth information is of crucial importance because of its role in patient-centered medicine and to improve knowledge about general aspects of health and medical topics. The objectives were to analyze and compare eHealth search patterns in a private (United States) and a public (United Kingdom) health care market. A new taxonomy of eHealth websites is proposed to organize the largest eHealth websites. An online measurement framework is developed that provides a precise and detailed measurement system. Online panel data are used to accurately track and analyze detailed search behavior across 100 of the largest eHealth websites in the US and UK health care markets. The health, medical, and lifestyle categories account for approximately 90% of online activity, and e-pharmacies, social media, and professional categories account for the remaining 10% of online activity. Overall search penetration of eHealth websites is significantly higher in the private (United States) than the public market (United Kingdom). Almost twice the number of eHealth users in the private market have adopted online search in the health and lifestyle categories and also spend more time per website than those in the public market. The use of medical websites for specific conditions is almost identical in both markets. The allocation of search effort across categories is similar in both the markets. For all categories, the vast majority of eHealth users only access one website within each category. Those that conduct a search of two or more websites display very narrow search patterns. All users spend relatively little time on eHealth, that is, 3-7 minutes per website. The proposed online measurement framework exploits online panel data to provide a powerful and objective method of analyzing and exploring eHealth behavior. The private health care system does appear to have an influence on eHealth search behavior in terms of search penetration and time spent per website in the health and lifestyle categories. Two explanations are offered: (1) the personal incentive of medical costs in the private market incentivizes users to conduct online search; and (2) health care information is more easily accessible through health care professionals in the United Kingdom compared with the United States. However, the use of medical websites is almost identical, suggesting that patients interested in a specific condition have a motivation to search and evaluate health information, irrespective of the health care market. The relatively low level of search in terms of the number of websites accessed and the average time per website raise important questions about the actual level of patient informedness in both the markets. Areas for future research are outlined.


Induction of human T helper cell type 1 differentiation results in loss of IFN-gamma receptor beta-chain expression.
Differential expression of cytokine receptors accounts for an important regulatory mechanism in differentiation of Th1/Th2 subsets. Here, we report that human Th0 and Th2 clones constitutively express transcripts for the IFN-gammaR beta-chain, whereas mRNA for this signaling component of the IFN-gamma receptor is absent in Th1 clones. Activation of T cell clones, however, resulted in a transient induction or enhancement of IFN-gammaR beta-chain mRNA expression in Th1 clones and Th0/Th2 clones, respectively. IL-12-mediated Th1 cell differentiation of naive CD4+, CD45RA+ cord blood T cells, which constitutively express IFN-gammaR beta-chain mRNA, resulted in a loss of expression of this cytokine receptor chain after 6 to 12 days of culture. In contrast, Th2 populations, differentiated from CD4+, CD45RA+ cord blood T cells in the presence of IL-4, continued to express high levels of IFN-gammaR beta-chain transcripts. The loss of IFN-gammaR beta-chain expression in Th1 populations was accompanied by a failure of IFN-gamma to induce the expression of the IFN-gamma-inducible gene, IFN response factor-1, whereas IFN-gamma was effective in inducing IFN response factor-1 mRNA expression in Th0 and Th2 cells. These results indicate that down-regulation of the IFN-gammaR beta-chain correlates with impaired IFN-gamma-induced signaling in Th1 cells. Finally, Th2 populations, generated in the presence of both IL-4 and IFN-gamma, expressed levels of IFN-gammaR beta-chain transcripts similar to those produced by cells differentiated in the presence of IL-4 only, demonstrating that IFN-gamma does not modulate the expression of its receptor. Together, these data indicate that human Th0/Th2 and Th1 subsets, respectively, can be distinguished based on the expression of the IFN-gammaR beta-chain.


Bayesian wavelet-based image denoising using the Gauss-Hermite expansion.
The probability density functions (PDFs) of the wavelet coefficients play a key role in many wavelet-based image processing algorithms, such as denoising. The conventional PDFs usually have a limited number of parameters that are calculated from the first few moments only. Consequently, such PDFs cannot be made to fit very well with the empirical PDF of the wavelet coefficients of an image. As a result, the shrinkage function utilizing any of these density functions provides a substandard denoising performance. In order for the probabilistic model of the image wavelet coefficients to be able to incorporate an appropriate number of parameters that are dependent on the higher order moments, a PDF using a series expansion in terms of the Hermite polynomials that are orthogonal with respect to the standard Gaussian weight function, is introduced. A modification in the series function is introduced so that only a finite number of terms can be used to model the image wavelet coefficients, ensuring at the same time the resulting PDF to be non-negative. It is shown that the proposed PDF matches the empirical one better than some of the standard ones, such as the generalized Gaussian or Bessel K-form PDF. A Bayesian image denoising technique is then proposed, wherein the new PDF is exploited to statistically model the subband as well as the local neighboring image wavelet coefficients. Experimental results on several test images demonstrate that the proposed denoising method, both in the subband-adaptive and locally adaptive conditions, provides a performance better than that of most of the methods that use PDFs with limited number of parameters.


[Effect of phytoecdisteroids and anabolic steroids on liver mitochondrial respiration and oxidative phosphorylation in alloxan diabetic rats].
Administration of phytoecdisteroides ecdisterone and turkesterone in the dose of 5 mg/kg and anabolic steroid preparation nerobol in the dose 10 mg/kg in rats with experimental diabetes removes the activation of respiration under all metabolic conditions of rats liver mitochondria revealing at given pathology. The normalized effect of phytoecdisteroides on the cells energetic processes is observed on the 7th day of the administration. The same effect of nerobol is revealed at more prolonged (15 days) administration.


Impaired lusitropy-frequency in the aging mouse: role of Ca(2+)-handling proteins and effects of isoproterenol.
We examined the relationship between age-associated lusitropic impairment, heart rate, and Ca(2+)-handling proteins and assessed the efficacy of increasing left ventricular (LV) relaxation via beta-adrenergic stimulation in adult and aging mouse hearts. LV function was measured in isolated, isovolumic blood-perfused hearts from adult (5 mo), old (24 mo), and senescent (34 mo) mice. Hearts were paced from 5 to 10 Hz, returned to 7 Hz, exposed to 10(-6) M isoproterenol, and paced again from 7 to 10 Hz. Age-related alterations in Na(+)/Ca(2+) exchanger (NCX), sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a), and phospholamban (PLB) levels were assessed by immunoblot. Despite preserved contractile performance, aging caused impaired lusitropy. Increased pacing caused an elevation in end-diastolic pressure that progressively worsened with age. The time constant of isovolumic pressure decay (tau) was significantly prolonged in old and senescent hearts compared with adults. Relative to adult hearts, the SERCA2a-to-PLB ratios were reduced 68 and 69%, and NCX were reduced 37 and 58% in old and senescent hearts, respectively. Isoproterenol completely reversed the age-associated lusitropic impairments. These data suggest that impaired lusitropy in aging mouse hearts is related to a decreased rate of cytosolic Ca(2+) removal and that accelerating SR Ca(2+) resequestration via beta-adrenergic stimulation can reverse this impairment.


[Stress urinary incontinence in women. Our experience with 218 cases].
From November 1992 to March 1994, in the Gynaecological ward of the Obstetrical and Gynaecological section of Cannizzaro Hospital, 218 patients suffering from urinary stress incontinence (U.S.I.) were observed. Using computerized clinical cards, U.S.I. was found in the 71.79% cases. From the clinical evaluation 38.39% of patients were found to be suffering from 1st degree bladder prolapse, 34.82% from 2nd degree bladder prolapse and 16.97% from, 3rd degree. 9.82% of the patients did not manifest signs of bladder prolapse. Therapy was mainly surgical. Burch colposuspension was carried out on 65 patients. When necessary a total hysterectomy and perineal plastic surgery was carried out. A Perrin-Leger bladder neck suspension was carried out on 10 patients and a Pereyra-Raz on 5. Given the varied aspects of U.S.I., the Authors would conclude that the best results are obtained by combining medical, surgical and rehabilitative treatment.


A high-coverage Neandertal genome from Vindija Cave in Croatia.
To date, the only Neandertal genome that has been sequenced to high quality is from an individual found in Southern Siberia. We sequenced the genome of a female Neandertal from ~50,000 years ago from Vindija Cave, Croatia, to ~30-fold genomic coverage. She carried 1.6 differences per 10,000 base pairs between the two copies of her genome, fewer than present-day humans, suggesting that Neandertal populations were of small size. Our analyses indicate that she was more closely related to the Neandertals that mixed with the ancestors of present-day humans living outside of sub-Saharan Africa than the previously sequenced Neandertal from Siberia, allowing 10 to 20% more Neandertal DNA to be identified in present-day humans, including variants involved in low-density lipoprotein cholesterol concentrations, schizophrenia, and other diseases.


The adaptive immune response to sporadic cancer.
Most of the current experimental cancer models do not reflect the pathophysiology of real-life cancer. Cancer usually occurs sporadically and is clonal in origin. Between tumor initiation and progression, clinically unapparent pre-malignant cells may persist for years or decades in humans. Recently, mouse models of sporadic cancer have been developed. The mouse germ-line can be engineered with high precision so that defined genes can be switched on and off in the adult organism in a targeted manner. Analysis of the immune response against sporadic tumors requires the knowledge of a tumor antigen. Ideally, a silent oncogene, for which the mice are not tolerant, is stochastically activated in individual cells. This approach offers the opportunity to analyze the adaptive immune response throughout the long process of malignant transformation and most closely resembles cancer in humans. In such a model with the highly immunogenic SV40 large T antigen as a dormant oncogene, we discovered that sporadic cancer is recognized by the adaptive immune system at the pre-malignant stage, concomitant with the induction of tumor antigen-specific tolerance. These results demonstrated that even highly immunogenic sporadic tumors are unable to induce functional cytotoxic T lymphocytes. Based on this model, we conclude that immunosurveillance plays little or no role against sporadic cancer and that tumors must not escape immune recognition or destruction.


Validation of reference genes for quantitative RT-qPCR studies of gene expression in Atlantic cod (Gadus morhua l.) during temperature stress.
One important physiological response to environmental stress in animals is change in gene expression. To obtain reliable data from gene expression studies using RT-qPCR it is important to evaluate a set of possible reference genes as normalizers for expression. The expression of these candidate genes should be analyzed in the relevant tissues during normal and stressed situations. To find suitable reference genes it was crucial that the genes were stably expressed also during a situation of physiological stress. For poikilotermic animals like cod, changes in temperature are normal, but if the changes are faster than physiological compensation, the animals respond with typical stress responses. It has previously been shown that Atlantic cod show stress responses when elevation of water temperature is faster than 1 degree/day, for this reason we chose hyperthermia as stress agent for this experiment. We here describe the expression of eight candidate reference genes from Atlantic cod (Gadus morhua l.) and their stability during thermal stress (temperature elevation of one degree C/day for 5 days). The genes investigated were: Eukaryotic elongation factor 1 alpha, ef1a; 18s ribosomal RNA; 18s, Ubiquitin conjugate protein; ubiq, cytoskeletal beta-actin; actb, major histcompatibility complex I; MHC-I light chain, beta-2 -microglobulin; b2m, cytoskeletal alpha-tubulin; tba1c, acidic ribosomal phosphoprotein; rplp1, glucose-6-phosphate dehydrogenase; g6pd. Their expression were analyzed in 6 tissues (liver, head kidney, intestine, spleen, heart and gills) from cods exposed to elevated temperature and compared to a control group. Although there were variations between tissues with respect to reference gene stability, four transcripts were more consistent than the others: ubiq, ef1a, 18s and rplp1. We therefore used these to analyze the expression of stress related genes (heat shock proteins) induced during hyperthermia. We found that both transcripts were significantly upregulated in several tissues in fish exposed to increased temperature. This is the first study comparing reference genes for RT-qPCR analyses of expression during hyperthermia in Atlantic cod. ef1a, 18s, rplp1 and ubiq transcripts were found to be well suited as reference genes during these experimental conditions.


Inclusion of IL-3 during retrovirally-mediated transduction on stromal support does not increase the extent of gene transfer into long-term engrafting human hematopoietic progenitors.
Interleukin 3 (IL-3) supports the survival of multilineage hematopoietic progenitors, and increases the extent of retrovirally mediated gene transfer into colony-forming cells. However, effects from the supraphysiological levels used in ex-vivo expansion and gene-therapy protocols on subsequent differentiation of human progenitors have not been well defined. In the current studies, the extents of retrovirally mediated transduction and lineage development from CD34+ cells cultured ex vivo in the presence or absence of IL-3 were compared. All transductions were performed in the presence of an irradiated stromal support layer, IL-6 and SCF, with and without inclusion of 10 ng/ml IL-3. Following transduction, colony-forming (CFU) assays were done, and the remaining cells were transplanted into cohorts of sibling beige/nude/xid (bnx) mice. Marrow from the mice was harvested 9-10 months post transplantation. The average extent of human CD45+ cell engraftment in the bone marrow and the human hematopoietic lineages recovered from the mice in the +IL-3 and -IL-3 groups did not vary significantly. No deleterious effects on the extent of engraftment, lineage generation, or survival of clonogenic progenitors was observed with inclusion of IL-3 in the transductions performed on stromal support. The percentage of G418-resistant human progenitors recovered from mice was equivalent. The extent of marking by the neo gene in the marrow of the mice was equal in both groups, and inverse PCR revealed that primitive cells transduced in the absence of IL-3 had generated progeny with slightly better clonal diversity than progenitors transduced in the presence of IL-3. These data show that, while transduction of colony-forming progenitors may not always be apparent, primitive human hematopoietic cells can be transduced to significant levels in the absence of IL-3.


fMRI after Phalloplasty with Nerve Anastomosis in a Trans-Man Patient.
We report on a case of a trans-man patient, who underwent penile reconstruction with the use of a radial forearm flap, urethroplasty, vaginectomy and scrotoplasty, insertion of testicle implants, and penile erection implants, similar to previously described methods. One of the requirements for an ideal phalloplasty is the preservation of erogenous sensitivity, which is often demanded by the patients for fulfilling their sexual well-being. For the first time known to us, we use a functional magnetic resonance imaging following radial forearm flap phalloplasty with nerve anastomosis to assess the cortical activation after clitoral stimulation. The patient was poked with a plastic pen on the neophallus and the groin. Regular block design with T1 and BOLD-T2* images were used. The results contradict the classic Penfield and Rasmussen homunculus, that is, the activations in the primary somatosensory cortex (S1) were bilateral with a left-sided dominance in the lateral parts of the medial postcentral gyrus (same region as the groin), and no activations were observed in the mesial parts of the postcentral gyrus. We also reported bilateral activations with a left-sided dominance in the secondary somatosensory cortex (S2) and near Broca's area at the sylvian fissure just posterior to ramus ascendens. Our findings are similar to previous studies reporting on imaging related to genital sensitivity.


Age-dependent relationships between work ability, thinking of quitting the job, and actual leaving among Italian nurses: a longitudinal study.
Qualified nurses commonly report several work-related problems, which may threat their health and work ability, and may have an impact upon retention. The aim of the present study was to investigate whether perceived work ability is a predictor for different types of thinking of quitting and for actual exit from the workplace. A prospective study has been performed based on 3329 Italian registered nurses which responded to both measurements of the Nurses' Early Exit Study. Institutions were selected by means of a stratified sampling procedure. All the 7447 nurses working in that healthcare organizations were recruited for the study. Baseline questionnaire was collected from 5504 nurses. Response rate at follow-up was 63.4%. Two hundred and fifty-five nurses left the job in the course of the investigation. Several multiple logistic regression analyses were performed controlling for indicators of work-related well-being, socio-demographic, and labour-market characteristics. As a whole, our results show that among nurses younger than 45 years work ability is a significant predictor of different types of thinking of quitting, but not of actual exit from the workplace: a lower perceived work ability was associated with a higher desire to undertake further education (OR: 3.05; 95% CI: 1.30-7.18) and/or to change workplace (OR: 4.03; 95% CI: 1.84-8.83) or profession (OR: 6.67; 95% CI: 2.78-15.99). In contrast, among the older nurses (>45), only actual exit was predicted by lower work ability scores (OR: 7.14; 95% CI: 1.15-44.13), along with the perception of a larger availability of free nursing posts in the region (OR: 2.70; 95% CI: 1.13-6.43). Therefore, we conclude that in the relationship between low perceived work ability and intended or actual exit, a significant part is explained by age itself, but also by the age-related differences in occupational and life opportunities. This contribution concludes with some age-related policies aimed at boosting nurses' retention.


Long-Range Interactions Boost Singlet Exciton Diffusion in Nanofibers of π-Extended Polymer Chains.
Raising the distance covered by singlet excitons during their lifetimes to values maximizing light absorption (a few hundred nm) would solve the exciton diffusion bottleneck issue and lift the constraint for fine (∼10 nm) phase segregation in bulk heterojunction organic solar cells. In that context, the recent report of highly ordered conjugated polymer nanofibers featuring singlet exciton diffusion length, LD, in excess of 300 nm is both appealing and intriguing [Jin, X.; et al. Science 2018, 360 (6391), 897-900]. Here, on the basis of nonadiabatic molecular dynamics simulations, we demonstrate that singlet exciton diffusion in poly(3-hexylthiophene) (P3HT) fibers is highly sensitive to the interplay between delocalization along the polymer chains and long-range interactions along the stacks. Remarkably, the diffusion coefficient is predicted to rocket by 3 orders of magnitude when going beyond nearest-neighbor intermolecular interactions in fibers of extended (30-mer) polymer chains and to be resilient to interchain energetic and positional disorders.


Lopsided growth of Earth's inner core.
Hemispherical asymmetry is a prominent feature of Earth's inner core, but how this asymmetry relates to core growth is unknown. Based on multiple-scattering modeling of seismic velocity and attenuation measurements sampling the whole uppermost inner core, we propose that the growth of the solid core implies an eastward drift of the material, driven by crystallization in the Western Hemisphere and melting in the Eastern Hemisphere. This self-sustained translational motion generates an asymmetric distribution of sizes of iron crystals, which grow during their translation. The invoked dynamical process is still active today, which supports the idea of a young inner core.


Genetic profiling of Mycobacterium tuberculosis in Tunisia: predominance and evidence for the establishment of a few genotypes.
Typing analyses of 378 Mycobacterium tuberculosis isolates collected between the years 2001 and 2005 from three northern representative regions of Tunisia revealed a highly homogeneous population. Indeed, 84.9 % of all tuberculosis (TB) cases were attributed to the Haarlem, LAM or T families. Strikingly, within each family, more than 60 % of TB cases were due to a single genotype. ST50 (Haarlem3) and ST42 (LAM9) genotypes were exceptionally predominant, representing 46.3 % of all typed isolates. ST50 showed an increased tendency for clustering and was more predominant in the extreme north of the country. By contrast, the more widespread ST42, which was apparently prevalent 17 years ago, displayed weak cluster individualization and a low transmission rate, consistent with its stable association with the Tunisian population. It is believed that both mass BCG vaccination, strictly applied for four decades, and the high endogamy rate that characterizes the Tunisian population could have profoundly shaped the population structure of M. tuberculosis by concurrently favouring the selection and accommodation of particular genotypes.


Transcriptome Analyses Reveal Systematic Molecular Pathology After Optic Nerve Crush.
The function of glial cells in axonal regeneration after injury has been the subject of controversy in recent years. Thus, deeper insight into glial cells is urgently needed. Many studies on glial cells have elucidated the mechanisms of a certain gene or cell type in axon regeneration. However, studies that manipulate a single variable may overlook other changes. Here, we performed a series of comprehensive transcriptome analyses of the optic nerve head over a period of 90 days after optic nerve crush (ONC), showing systematic molecular changes in the optic nerve head (ONH). Furthermore, using weighted gene coexpression network analysis (WGCNA), we established gene module programs corresponding to various pathological events at different times post-ONC and found hub genes that may be potential therapeutic targets. In addition, we analyzed the changes in different glial cells based on their subtype markers. We revealed that the transition trend of different glial cells depended on the time course, which provides clues for modulating glial function in further research.


Benfluorex and unexplained valvular heart disease: a case-control study.
Recent case reports suggest that benfluorex, a fenfluramine derivative used in the management of overweight diabetic patients and dyslipidemia, is associated with cardiac valve regurgitation. We conducted a case-control study. Eligible patients were those admitted in the cardiology or the cardiac surgery units of our hospital between January, 1(st) 2003 and June 30(th) 2009, with mitral insufficiency diagnostic codes (ICD-10 I340 and I051). Patients with either a primary cause (degenerative, known rheumatic heart disease, infectious endocarditis, congenital, radiation-induced valvular disease, associated connective and/or vasculitis disease, trauma, tumor) or a secondary (functional) cause were considered as having an "explained" mitral regurgitation. Other patients were considered as having an "unexplained" mitral regurgitation and were included as cases. For each case, two controls were matched for gender and for the closest date of birth, among a list of patients with an "explained" mitral regurgitation. Drug exposures were assessed blindly regarding the case or control status, through contacts with patients, their family and/or their physicians. Out of the 682 eligible patients, 27 cases and 54 matched controls were identified. The use of benfluorex was reported in 22 patients: 19 of the 27 cases, versus 3 of the 54 controls, odds-ratio 17.1 (3.5 to 83), adjusted for body mass index, diabetes and dexfenfluramine use. The use of benfluorex is associated with unexplained mitral regurgitation.


Squamous papillomas of the conjunctiva: a retrospective clinicopathological study.
There is very limited literature on squamous papillomas of the conjunctiva from Nigeria and sub-Saharan Africa. In an attempt to contribute to the literature on the subject, we studied the clinicopathological characteristics of patients histologically diagnosed with squamous papilloma of the conjunctiva in Ibadan, Nigeria. Clinical and pathological records of patients with histological diagnosis of squamous papilloma of the conjunctiva made in the Department of Pathology, University College Hospital, Ibadan, between January 1985 and December 2004, were reviewed. There were totally 26 cases. Patients' ages ranged from 2 to 58 years with a mean age of 32 years. Male to female ratio was 1.4:1. Size of tumors ranged from 2 to 10 mm. Duration of presenting complaints was from 2 months to 10 years. The lesions in 10 cases were located in the medial canthus, at or close to the limbus in another 10 cases, and in the tarsal conjunctiva in a single case. Five cases had no documentation of location. Sixteen cases (61.5%) had multiple papillomas. Four cases had a history of chemical injury (alkaline based - hair relaxer in a single case, acid based - wet cell car battery fluid in two cases, and unknown chemical in a single case) preceding the lesion by at least 6 weeks. Fourteen cases had koilocytosis on histology suggestive of Human Papilloma Virus (HPV) etiology. HIV screening test was negative in the three patients who had the screening done. Preoperative clinical diagnosis was squamous papilloma in 16 cases, pterygium in 6 cases and squamous cell carcinoma in 2 cases. In the environment where we practice, conjunctival squamous papilloma occurs most commonly in the fourth decade of life. Only very few cases are submitted for histological diagnosis. HPV infection and chemical injury are the main etiology. We strongly advocate that all excisions of the conjunctiva, irrespective of the clinical impression, should be submitted routinely for histological assessment.


Effects of Acute Aerobic and Resistance Exercise on Cognitive Function and Salivary Cortisol Responses.
This study aimed to determine the comparative effectiveness of aerobic vs. resistance exercise on cognitive function. In addition, salivary cortisol responses, as an indicator of arousal-related neuroendocrine responses, were assessed as a potential mechanism underlying the effects of these 2 modes of acute exercise on cognition. Forty-two young adults were recruited and performed the Stroop task after 1 session of aerobic exercise, resistance exercise, and a sedentary condition performed on separate days. Saliva samples were collected at baseline and immediately and 30 min after treatment conditions. Acute exercise, regardless of exercise modality, improved multiple aspects of cognitive function as reflected by the Stroop task. Cortisol responses were higher after both modes of acute exercise compared with the sedentary condition and were higher at baseline and 30 min afterward compared with immediately after treatment conditions. These findings suggest that acute exercise of moderate intensity facilitates cognitive function, and, although salivary cortisol is influenced by acute exercise, levels were not related to improvements in cognition.


An evaluation of the nephrology nursing research literature: 1979-1989.
The purposes of this project were: to describe the research designs, areas of study, and major dependent variables of nephrology nursing research conducted between 1979 and 1989; and to evaluate the quality of this research. Of the 284 publications included, 34.9% of the research designs were descriptive; 45.4% analytical observational; 4.9% methodological; 14.1% experimental; and 0.7% historical. Content analysis was conducted to classify the area of study and dependent variables. Nurse experts assessed the quality of the research studies using Georgopoulos' (1975) Quality Index.


Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease.
To describe the clinical characteristics of nonalcoholic fatty liver disease (NAFLD) in children, including insulin resistance, and to test for correlation with liver pathology. A retrospective review of children with biopsy-proven NAFLD at Children's Hospital San Diego from 1999 to 2002. Liver biopsy specimens were independently reviewed by two pathologists. Children with NAFLD (n=43) were mostly male (70%), Hispanic American (53%) and obese (88%). The criteria for insulin resistance were met by 95% of subjects. Steatosis was predicted by the combination of quantitative insulin sensitivity check index, age, and ethnicity (P<.0001). Portal inflammation was predicted by the combination of ALT and fasting insulin (P=.0009). Perisinusoidal fibrosis was predicted by the combination of AST, fasting insulin, and BMI Z score (P<.0001). Portal fibrosis was predicted by the combination of right upper quadrant pain and homeostasis model assessment of insulin resistance (P=.0028). We identified significant predictors of liver pathology in children with NAFLD. Children being evaluated for NAFLD should be screened for insulin resistance, which is nearly universal and correlates with liver histology.


CPR in the elderly: when should it be performed?
Data comparing the success of CPR in elderly hospitalized persons, those living in the community, and those in long-term care facilities show varying results. In general, elderly patients who receive CPR following arrest do not fare as well as younger patients, but there appears to be a subgroup of elderly in whom the success rate is relatively high. Specifically, patients who demonstrate ventricular fibrillation or ventricular tachycardia are more likely to survive than are those demonstrating asystole or electromechanical dissociation. Most studies have not shown a difference in mental or functional impairment between older and younger survivors of cardiac arrest.


Acquired haemophilia as a paraneoplastic manifestation of pancreatic cancer.
Acquired haemophilia is a severe haematological disorder characterised by the presence of anti-factor VIII antibodies. Although rare, it can lead to serious bleeding complications. Acquired haemophilia can be seen in patients with malignancies as a paraneoplastic phenomenon. This is a case of a 52-year-old patient who presented with haematuria and retroperitoneal bleeding soon after being diagnosed with pancreatic adenocarcinoma and subsequently was found to have acquired haemophilia. The treatment of underlying malignancy with chemotherapy may accelerate the eradication of anti-factor VIII antibodies.


[Refractory glaucoma: peculiarities of treatment].
Refractory glaucoma is a clinical variety of glaucoma remarkable for its resistance to therapy. This determined special approaches to choice of drugs and methods ensuring a stable hypotensive effect as one of the conditions of preserving the visual functions. Original methods for surgical treatment of refractory glaucoma are proposed. New effective operations prevent excessive cicatrices at the site of intervention, one of the major causes of failure of antiglaucoma operations. Ultrasonic cyclodialysis is an effective method for surgical treatment of glaucoma in an aphakic eye. A principally new approach to treatment of refractory glaucoma is based on the use of high-frequency focussed ultrasound, a noninvasive method (sclerocyclodestruction) for attaining the hypotensive effect. The efficiency of the natural cytokine complex in the treatment of refractory glaucoma is due to effects of immunopeptides on repair processes at the site of intervention, which inhibit cell growth and prevent excessive development of cicatricial tissue round newly created routes of humor discharge.


Pectolinarigenin prevents bone loss in ovariectomized mice and inhibits RANKL-induced osteoclastogenesis via blocking activation of MAPK and NFATc1 signaling.
Osteoporosis (OP) is a metabolic disease caused by multiple factors, which is characterized by a reduction of bone mass per unit volume and destruction of bone microstructure. Aberrant osteoclast function is the main cause of OP, therefore, regulating the differentiation and function of osteoclast is one of the treatment strategies for OP. Pectolinarigenin (PEC) is a medicinal implant isolated from Fragrant Eupatorium. Our experimental data showed that PEC was able to inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in vitro, by tartrate-resistant acid phosphatase (TRAcP) staining, Fibrous actin ring formation, and hydroxyapatite resorption assays. In terms of mechanism, PEC inhibited the expression of the osteoclastogenesis-related gene, including cathepsin K (Ctsk), matrix metalloproteinase 9 (Mmp9), and TRAcP (Acp5). Western blot analysis demonstrated that PEC could significantly block the activation of RANKL-induced mitogen-activated protein kinase signaling cascades and was able to suppress the protein expression of nuclear factor of activated T-cells and c-Fos. Meanwhile, the intracellular reactive oxygen species levels were also reduced by PEC in a concentration-dependent manner. Further, PEC could prevent the ovariectomy-induced bone loss in vivo. Summarizing all, our data suggested that PEC inhibits osteoclast formation and function and RANKL signaling pathways, and thus could potentially be used in the treatment the osteoclast-related bone loss diseases.


Sleeping through COVID-19: a longitudinal comparison of 2019 and 2020 infant auto-videosomnography metrics.
With the outbreak of the COVID-19 pandemic, pediatric experts called attention to the potential adverse effects of living restrictions (e.g., lockdown) on child well-being, but at the same time- acknowledged their possible benefits. To date, only few data-driven reports have been published on child sleep during COVID-19, and all have been based on parent- or self-reports. This study used auto-videosomnography to capture the effects of COVID-19 stay-at-home orders imposed in the USA on objectively measured infant sleep. Auto-videosomnography metrics of infants assessed nightly between January and May 2020 were compared with metrics of an equivalent infant cohort, assessed in the corresponding 2019 period. A total of 610 infants (50.7% girls) aged 6-18 months (M = 11.8, SD = 3.6) were included, with 71,472 analyzed nights. Multilevel models were applied to assess differences between 2019 and 2020 infant sleep pre- and during-lockdown. Whereas infant cohorts were equivalent in demographic and January-March/April sleep characteristics, during the 2020 lockdown infants had longer nighttime sleep durations (Mdifference = 11.0 min, p = .01), later morning rise times (Mdifference = 9.5 min, p = .008), and later out-of-crib times (Mdifference = 12.3 min, p < .0001), compared to the equivalent 2019 period. In addition, weekday-weekend differences in sleep onset and midpoint times were diminished during 2020 home-confinement compared to the equivalent 2019 period (2019: Mdifference = 5.5 min, p < .0001; Mdifference = 4.5 min, p < .0001; 2020: Mdifference = 2.3 min, p = .01; Mdifference = 3.1 min, p < .0001, respectively). Notwithstanding the negative implications of COVID-19 living restrictions in other domains, our findings indicate that there might be a silver lining-in promoting longer and more consistent infant sleep. These benefits should be considered in determining policy for the current and future pandemics.


A survey of transcriptome complexity in Sus scrofa using single-molecule long-read sequencing.
Alternative splicing (AS) and fusion transcripts produce a vast expansion of transcriptomes and proteomes diversity. However, the reliability of these events and the extend of epigenetic mechanisms have not been adequately addressed due to its limitation of uncertainties about the complete structure of mRNA. Here we combined single-molecule real-time sequencing, Illumina RNA-seq and DNA methylation data to characterize the landscapes of DNA methylation on AS, fusion isoforms formation and lncRNA feature and further to unveil the transcriptome complexity of pig. Our analysis identified an unprecedented scale of high-quality full-length isoforms with over 28,127 novel isoforms from 26,881 novel genes. More than 92,000 novel AS events were detected and intron retention predominated in AS model, followed by exon skipping. Interestingly, we found that DNA methylation played an important role in generating various AS isoforms by regulating splicing sites, promoter regions and first exons. Furthermore, we identified a large of fusion transcripts and novel lncRNAs, and found that DNA methylation of the promoter and gene body could regulate lncRNA expression. Our results significantly improved existed gene models of pig and unveiled that pig AS and epigenetic modify were more complex than previously thought.


Coverage and prior authorization of psychotropic drugs under Medicare Part D.
This study examined formulary coverage and use of utilization management tools for three classes of psychotropic medications (antidepressants, antipsychotics, and anticonvulsants) among Medicare Part D prescription drug plans serving individuals dually eligible for the Medicare and Medicaid programs. Plans must cover "all or substantially all" molecules (distinct drugs) in these classes. Plans serving "dual eligibles" generally covered at least one formulation of all molecules in the three classes. However, certain product formulations were not covered by a number of plans, and use of prior authorization was common for a minority of plans. The effect of Part D will depend on the restrictiveness of the prior authorization and appeals processes, which is currently unknown.


Overexpression of PKMYT1 indicates the poor prognosis and enhances proliferation and tumorigenesis in non-small cell lung cancer via activation of Notch signal pathway.
The protein kinase, membrane‑associated tyrosine/threonine 1 (PKMYT1) has been implicated as an important factor promoting the tumorigenesis of hepatocellular carcinoma and colorectal cancer. The current study was designed to explore the functional role of PKMYT1 in non-small cell lung cancer (NSCLC) cell behaviors and to investigate the possible molecular mechanisms. The expression levels of PKMYT1 in NSCLC tissues and cell lines were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The clinical and prognostic significance of PKMYT1 in 153 cases of NSCLC was determined. We also evaluated the effects of KMYT1 on NSCLC cell proliferation, migration, and invasion in vitro. Western blot was performed to assure whether PKMYT1 affected the Notch signal pathway and MET pathway. We observed that PKMYT1 expression was significantly up-regulated in both NSCLC tissues and cell lines. Higher expression of PKMYT1 was associated with clinical stage and lymph nodes metastasis. Clinical survival assays demonstrated that patients with high PKMYT1 expression had a shorter overall survival time than those with low PKMYT1 expression. Moreover, the multivariate analysis confirmed that increased expression of PKMYT1 was an independent predictor of overall survival. Functionally, knockdown of PKMYT1 in the NSCLC cell lines A549 and H1299 suppressed NSCLC cells proliferation, invasion and migration, and promoted apoptosis. In addition, the down-regulation of PKMYT1 resulted in the inhibition of EMT in NSCLC cells. Further mechanistic studies revealed that when PKMYT1 was silenced, the expression levels of Notch1, p21, and Hes1 were respectively downregulated, suggesting that PKMYT1 could promote the activity of the Notch signal pathway. PKMYT1 plays a significant role in NSCLC aggressiveness and clinical outcome, and may serve as a promising therapeutic target for this disease.


Acute and long‑term psychiatric symptoms associated with COVID‑19 (Review).
Coronavirus disease 2019 (COVID-19) started spreading at the end of 2019 and despite the immediate actions of various governments with strict control, more and more individuals became infected daily. Due to the uncertainty and insecurity that still exists around this pandemic, there is an acute need for information and knowledge of what severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection entails. Respiratory and other physical symptoms received most of the medical attention, however, infected patients were also at risk for developing psychiatric and mental health disorders, such as depression, anxiety, and sleep disturbances. Available research reports a so-called 'post-COVID-19 syndrome', which refers to new and/or persistent signs and symptoms for over 12 weeks, following SARS. The aim of the present review was to provide a general overview of the psychiatric symptoms developed during SARS-CoV-2 infection and their long-term outcome, highlighting that, through follow-up with surviving patients it was revealed that some of the psychiatric symptoms of COVID-19 persisted for a long time after discharge and were also associated with negative effects on global functioning and lower quality of life.


Repeated exposure to severely limited sleep results in distinctive and persistent physiological imbalances in rats.
Chronic sleep disruption in laboratory rats leads to increased energy expenditure, connective tissue abnormalities, and increased weights of major organs relative to body weight. Here we report on expanded findings and the extent to which abnormalities become long-lasting, potentially permanent changes to health status after apparent recuperation from chronic sleep disruption. Rats were exposed 6 times to long periods of disrupted sleep or control conditions during 10 weeks to produce adaptations and then were permitted nearly 4 months of undisturbed sleep. Measurements were made in tissues from these groups and in preserved tissue from the experimental and control groups of an antecedent study that lacked a lengthy recuperation period. Cycles of sleep restriction resulted in energy deficiency marked by a progressive course of hyperphagia and major (15%) weight loss. Analyses of tissue composition in chronically sleep-restricted rats indicated that protein and lipid amounts in internal organs were largely spared, while adipose tissue depots appeared depleted. This suggests high metabolic demands may have preserved the size of the vital organs relative to expectations of severe energy deficiency alone. Low plasma corticosterone and leptin concentrations appear to reflect low substrate availability and diminished adiposity. After nearly 4 months of recuperation, sleep-restricted rats were consuming 20% more food and 35% more water than did comparison control rats, despite normalized weight, normalized adipocytes, and elevated plasma leptin concentrations. Plasma cholesterol levels in recuperated sleep-restricted rats were diminished relative to those of controls. The chronically increased intake of nutriments and water, along with altered negative feedback regulation and substrate use, indicate that internal processes are modified long after a severe period of prolonged and insufficient sleep has ended.


[Improved visualization of long-axis black-blood imaging of the carotid arteries using phase sensitive inversion recovery combined with 3D IR-T₁TFE].
The purpose of this study was to improve the visualization of long-axis black-blood imaging of the carotid arteries. We experimented on phantom and in-vivo study of 3 dimension (3D) inversion recovery T(1) turbo field echo combined with phase sensitive inversion recovery (PSIR-3D IR-T(1)TFE) at 3.0 Tesla. As a result, the contrast has been improved by calculated images of PSIR-3D IR-T(1)TFE set to inversion time (TI) 350 ms that is shorter than null point of blood. This displays that the contrast between blood and tissues can be improved when the longitudinal magnetization of blood is a negative. Therefore, the visualization of long-axis black-blood imaging of the carotid arteries has been improved by the calculated images of PSIR-3D IR-T(1)TFE set to TI that is shorter than null point of blood.


Effectiveness and Utility of Visual Scene Displays as Communication Supports for Adults and Children With Complex Communication Needs: Perspectives of Clinicians and Researchers.
Purpose The aims of this research study were to describe the perspectives of clinicians and researchers regarding the effectiveness of visual scene displays (VSDs) as communication supports in order to inform the translation of research to clinical practice. Method An online survey was completed by 298 clinicians and nine VSD researchers. Participants rated the effectiveness of VSDs in supporting a variety of communication functions and their strength of agreement regarding statements of VSD utility. Results Regardless of population served, clinicians and researchers rated VSDs as effective at supporting a range of communication functions. Participants also tended to agree with statements of VSD utility. Conclusions The current study highlights the perceptions of clinicians and researchers regarding the uses and benefits of VSDs for adults and children with complex communication needs and provides an initial measure of the current translation of research to clinical practice. Results indicate that VSDs can be used to support a variety of communication functions and utilities; however, further work is necessary to explore additional communication functions and delineate similarities and differences of VSD uses for differing populations. Supplemental Material https://doi.org/10.23641/asha.14551344.


Mosquito vector control and biology in Latin America--a tenth symposium. Abstracts.
The 10th annual Latin American symposium presented by the American Mosquito Control Association (AMCA) was held as part of the 66th Annual Meeting in Atlantic City, NJ, in March 2000. The principal objective, as for the previous 9 symposia, was to promote participation in the AMCA by vector control specialists, public health workers, and academicians from Latin America. This publication includes summaries of 57 presentations that were given orally in Spanish or presented as posters by participants from 9 countries in Latin America. Topics addressed in the symposium included results from chemical and biological control programs and studies; studies of insecticide resistance; and molecular, ecological, and behavioral studies of vectors of dengue (Aedes aegypti). malaria (Anopheles albimanus and Anopheles aquasalis). leishmaniasis (Lutzomyia), and Chagas' disease (Triatoma). Related topics included biology and control of scorpions and Chironomus plumosus.


Meeting the 1990 hypertension objectives for the nation--a progress report.
The National High Blood Pressure Education Program (NHBPEP) effort got underway in 1972 following hypertension research findings and continues to be influenced and, when necessary, redirected, by further findings. Its coordinating committee is composed of representatives from 32 national organizations, and the program itself includes several Federal agencies, all State health departments, and more than 2,000 community-based programs. The goals of NHBPEP and the 1990 prevention objectives for the nation center around the same basic theme: high blood pressure is a serious condition leading to major diseases and premature death. It can be easily detected and effectively brought under control. In the summer of 1984, Admire and co-workers provided a general review and status report of the 1990 Hypertension Objectives and the progress made in meeting those objectives. In the remarkably short period of time since that review, there is even more progress to report. There is good evidence of progress in preventing disease and premature death from hypertension, in bringing hypertension under long term control, and in giving Americans a better understanding of the consequences of uncontrolled high blood pressure. There is also evidence in the fact that while visits to physicians generally have increased only slightly, hypertension visits have increased more markedly. And there is evidence that stroke mortality continues to decline in an almost linear fashion.


[Giant cell arteritis (temporal arteritis, Horton's arteritis): clinical characteristics and management].
Giant cell arteritis can cause diagnostic difficulties due to its heterogeneous symptomatology. Characteristic ophthalmic and systemic symptoms of Horton's disease are discussed. The clinical course is described on the basis of typical patients, which shows that generic symptoms do not have to coexist. The Horton's arteritis potentially represents a systemic vasculitis that requires early diagnosis and treatment in order to avoid dramatic ophthalmic consequences, in worst cases blindness. The erythrocyte sedimentation rate (ESR) represents the most important laboratory parameter. Although temporal artery biopsy remains the only confirmatory procedure for a definite diagnosis, imaging procedures such as sonography, magnetic resonance imaging, ultrasound biomicroscopy are useful in supporting the clinical diagnosis. Highly dosed corticosteroid therapy should always be indicated when suspicious clinical symptoms are present, even without any dramatic laboratory parameter changes. Initial high dosages are indicated up to 1 gram daily depending on the severity of the disease. Subsequently a slow ESR titrated reduction of the dose is necessary under control of inflammation values, symptomatology and side effects. Occasionally a lifelong immunsuppressive therapy is indispensable. The long-term treatment should take place in close cooperation with the general practitioner, rheumatologist, neurologist and if necessary further specialists.


A revised prediction model for natural conception.
One of the aims in reproductive medicine is to differentiate between couples that have favourable chances of conceiving naturally and those that do not. Since the development of the prediction model of Hunault, characteristics of the subfertile population have changed. The objective of this analysis was to assess whether additional predictors can refine the Hunault model and extend its applicability. Consecutive subfertile couples with unexplained and mild male subfertility presenting in fertility clinics were asked to participate in a prospective cohort study. We constructed a multivariable prediction model with the predictors from the Hunault model and new potential predictors. The primary outcome, natural conception leading to an ongoing pregnancy, was observed in 1053 women of the 5184 included couples (20%). All predictors of the Hunault model were selected into the revised model plus an additional seven (woman's body mass index, cycle length, basal FSH levels, tubal status,history of previous pregnancies in the current relationship (ongoing pregnancies after natural conception, fertility treatment or miscarriages), semen volume, and semen morphology. Predictions from the revised model seem to concur better with observed pregnancy rates compared with the Hunault model; c-statistic of 0.71 (95% CI 0.69 to 0.73) compared with 0.59 (95% CI 0.57 to 0.61).


Interactional theory of childhood problematic media use.
The growth of mobile device access and ownership has yielded many opportunities and challenges for raising healthy digital media consumers. As adoption of mobile and internet-connected devices has increased among children, concerns for healthy child development have been expressed regarding excessive or problematic use. Although much theoretical and empirical work has been conducted evaluating adolescents' and adults' risks for dependence on various screen media (e.g., Gaming Disorder, Internet Addiction), little theoretical consideration has been expounded regarding the etiology and maintenance of problematic media use earlier in childhood (i.e., under age 12 years). The purpose of this paper is to propose a theoretical framework through which to investigate problematic media use in early childhood. Our theory, the Interactional Theory of Childhood Problematic Media Use (IT-CPU) merges developmental and clinical psychology theories, with communication and human-computer interaction perspectives. We outline distal and proximal factors that we hypothesize contribute to the development of problematic media use in childhood, and emphasize maintaining factors that could be targets for intervention. Finally, we provide recommendations for an interdisciplinary research agenda to test our proposed theory and inform experimental trials to prevent and treat childhood problematic media use.


Effect of gluten-free diet on splenic hypofunction of adult coeliac disease.
Splenic function has been serially measured by counting pitted red cells in 15 coeliac patients, before and during a gluten-free diet. The basal percentage values of pitted cells decreased significantly during treatment but no correlation was observed between the duration of the gluten-free diet and the percentage of recovery of splenic function over basal values. Out of six coeliacs with pitted cell values consistent with splenic hypofunction, three showed a total recovery after gluten withdrawal. Our data suggest that, contrary to recent reports, hyposplenism in adult coeliac disease is improved by a gluten-free diet, and that environmental factors may be important in determining and maintaining this complication.


Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy.
Although highly active antiretroviral therapy (HAART) in the form of triple combinations of drugs including protease inhibitors can reduce the plasma viral load of some HIV-1-infected individuals to undetectable levels, it is unclear what the effects of these regimens are on latently infected CD4+ T cells and what role these cells play in the persistence of HIV-1 infection in individuals receiving such treatment. The present study demonstrates that highly purified CD4+ T cells from 13 of 13 patients receiving HAART with an average treatment time of 10 months and with undetectable (<500 copies HIV RNA/ml) plasma viremia by a commonly used bDNA assay carried integrated proviral DNA and were capable of producing infectious virus upon cellular activation in vitro. Phenotypic analysis of HIV-1 produced by activation of latently infected CD4+ T cells revealed the presence in some patients of syncytium-inducing virus. In addition, the presence of unintegrated HIV-1 DNA in infected resting CD4+ T cells from patients receiving HAART, even those with undetectable plasma viremia, suggests persistent active virus replication in vivo.


Inflammatory changes in the plasma and cerebrospinal fluid of patients with persistent pain and postpartum depression after elective Cesarean delivery: an exploratory prospective cohort study.
Severe acute pain after Cesarean delivery increases the risk of developing persistent pain (~20% incidence) and postpartum depression (PPD) (~15% incidence). Both conditions contribute to maternal morbidity and mortality, yet early risk stratification remains challenging. Neuroinflammation has emerged as a key mechanism of persistent pain and depression in nonobstetric populations. Nevertheless, most studies focus on plasma cytokines, and the relationship between plasma and cerebrospinal fluid (CSF) cytokine levels is unclear. Our primary aim was to compare inflammatory marker levels between patients who developed the composite outcome of persistent pain and/or PPD vs those who did not. We recruited term patients with singleton pregnancies undergoing elective Cesarean delivery under neuraxial anesthesia into an exploratory prospective cohort study. We collected baseline demographic, obstetric, and Edinburgh Postnatal Depression Scale information, and performed quantitative sensory tests. Plasma was collected preoperatively and 48 hr postoperatively. In the operating room, 10 mL of CSF was collected, followed by a standardized anesthetic. Intra- and postoperative management were according to standard practice. We obtained Edinburgh Postnatal Depression Scale and pain scores at six weeks and three months after delivery. The primary outcome was persistent pain and/or PPD at three months. We analyzed the difference in inflammatory marker levels between the groups (primary aim) using two-sided Mann-Whitney tests. Eighty participants were enrolled, and 63 patients completed the study; 23 (37%) experienced the primary outcome at three months. Preoperative plasma transforming growth factor beta 1 (TGF-β1) concentration was higher in patients who developed the primary outcome compared with those who did not (median [interquartile range (IQR)], 2,879 [2,241-5,494] vs 2,292 [1,676-2,960] pg·mL-1; P = 0.04), while CSF IL-1β concentration was higher in patients who developed the primary outcome than in those who did not (median [IQR], 0.36 [0.29-0.39] vs 0.30 [0.25-0.35] pg·mL-1; P = 0.03). We observed differential levels of plasma and CSF inflammatory biomarkers in patients who developed persistent pain and PPD compared with those who did not. We showed the feasibility of collecting plasma and CSF samples at Cesarean delivery, which may prove useful for future risk-stratification. ClinicalTrials.gov (NCT04271072); registered 17 February 2020.


Cloning, nucleotide sequencing, and analysis of the AcrAB-TolC efflux pump of Enterobacter cloacae and determination of its involvement in antibiotic resistance in a clinical isolate.
Enterobacter cloacae is an emerging clinical pathogen that may be responsible for nosocomial infections. Management of these infections is often difficult, owing to the high frequency of strains that are resistant to disinfectants and antimicrobial agents in the clinical setting. Multidrug efflux pumps, especially those belonging to the resistance-nodulation-division family, play a major role as a mechanism of antimicrobial resistance in gram-negative pathogens. In the present study, we cloned and sequenced the genes encoding an AcrAcB-TolC-like efflux pump from an E. cloacae clinical isolate (isolate EcDC64) showing a broad antibiotic resistance profile. Sequence analysis showed that the acrR, acrA, acrB, and tolC genes encode proteins that display 79.8%, 84%, 88%, and 82% amino acid identities with the respective homologues of Enterobacter aerogenes and are arranged in a similar pattern. Deletion of the acrA gene to yield an AcrA-deficient EcDC64 mutant (EcDeltaacrA) showed the involvement of AcrAB-TolC in multidrug resistance in E. cloacae. However, experiments with an efflux pump inhibitor suggested that additional efflux systems also play a role in antibiotic resistance. Investigation of several unrelated isolates of E. cloacae by PCR analysis revealed that the AcrAB system is apparently ubiquitous in this species.


Meningiomas of the pediatric skull base: a review.
Pediatric skull base meningiomas are rare and complex clinical entities. Meningioma is a relatively uncommon brain tumor in children, and only ∼ 27% involve the skull base. Some evidence suggests that these tumors are more likely to be atypical or malignant in children than adults. The absence of female preponderance in pediatric meningiomas is reflected in the skull base subpopulation. Skull base meningiomas in children are most likely to be found in the anterior or middle fossa base, or involving the orbit and optic nerve sheath. Petroclival, suprasellar/parasellar, cerebellopontine angle, cavernous sinus, and foramen magnum tumors are very rare. Meningiomas constitute a small proportion of reported cases of pediatric skull base pathology, and they are entirely absent from many case series. Initial gross total resection is consistently associated with superior outcomes. Surgical approaches to the pediatric skull base must take additional factors into consideration including relatively smaller anatomy, immature dentition, incompletely aerated sinuses and air cells, and altered configurations of structures such as the pterional bony complex. Multidisciplinary expertise is essential to optimizing treatment outcomes.


Quantum Bayesianism as the basis of general theory of decision-making.
We discuss the subjective probability interpretation of the quantum-like approach to decision making and more generally to cognition. Our aim is to adopt the subjective probability interpretation of quantum mechanics, quantum Bayesianism (QBism), to serve quantum-like modelling and applications of quantum probability outside of physics. We analyse the classical and quantum probabilistic schemes of probability update, learning and decision-making and emphasize the role of Jeffrey conditioning and its quantum generalizations. Classically, this type of conditioning and corresponding probability update is based on the formula of total probability-one the basic laws of classical probability theory.


Manidipine for hypertension not controlled by dual therapy in patients with diabetes mellitus: a non-comparative, open-label study.
Little is known about the effects of the calcium channel antagonist manidipine when it is added as a third drug in non-controlled hypertensive patients with diabetes mellitus receiving dual antihypertensive therapy. The aim of this study was to evaluate the response in terms of blood pressure (BP) and microalbuminuria when manidipine is administered to patients with type 2 diabetes and uncontrolled hypertension who are already being treated with a combination of a low-dose diuretic plus an ACE inhibitor or an angiotensin II type 1 receptor antagonist (angiotensin receptor blocker [ARB]). We also evaluated the effects of addition of manidipine on plasma fasting glucose, glycosylated haemoglobin (HbA(1c)), serum uric acid, the lipid profile, serum creatinine and creatinine clearance. This was a non-comparative, open-label study of hypertensive diabetic patients with systolic/diastolic BP >130/80 mmHg. All patients had been receiving treatment for ≥3 months with stable doses of a diuretic plus an ACE inhibitor or ARB. Manidipine 10 mg/day was added, increasing to 20 mg/day if the target BP was not reached after 3 months' treatment. The follow-up period was 6 months. Patient compliance was verified by tablet count. The doses of statins being taken by patients prior to commencement of the trial were not modified during the study. All patients were treated with oral antihyperglycaemic agents only; patients receiving insulin were excluded from the study. 136 patients were enrolled in the trial and completed the study; 41.9% of the patients were males, the mean ± SD age of the study population was 64.4 ± 12.3 years, and the mean ± SD body mass index was 30.2 ± 4.9 kg/m(2). The mean ± SD BP at baseline was 158.6 ± 15.6/86.7 ± 11.2 mmHg compared with 136.8 ± 12.0/78.0 ± 11.2 (-21.8/-8.7, respectively) mmHg at the end of the study period (p < 0.001). A total of 63.6% of the patients attained a BP of <140/90 mmHg and 20.9% attained a BP of <130/80 mmHg. The mean ± SD heart rate decreased from 75.1 ± 11.2 at baseline to 72.8 ± 11.2 beats/min at the end of the study (p = 0.06; not significant). Fifty percent (95% CI 41.6, 58.4) of the patients had microalbuminuria at baseline compared with 31.3% (95% CI 23.0, 39.6) at study end (p = 0.006). Reductions in mean ± SD fasting glucose levels (-10.2 ± 50.3 mg/dL; p < 0.05), HbA(1c) (-0.19 ± 0.97%; p = 0.05), total cholesterol (-11.9 ± 35.2 mg/dL; 95% CI -18.1, -5.8; p < 0.005), triglycerides (-10.8 ± 51.1 mg/dL; 95% CI -19.7, -1.8; p = 0.018) and low-density lipoprotein-cholesterol (-8.1 ± 27.7 mg/dL; 95% CI -13.2, -2.9; p = 0.002) were observed. No patients dropped out of the study because of adverse effects. The most frequent adverse effect encountered was malleolar oedema (9%). Manidipine added as the third drug to a renin-angiotensin system inhibitor plus a low dose of diuretic significantly reduces BP, improves renal function, has favourable effects on the lipid and glucose profiles, and reduces microalbuminuria in uncontrolled hypertensive patients with type 2 diabetes. Long-term trials are necessary to evaluate time-related effects.


Efficacy of a screening radioallergosorbent test.
Controversy over the routine use of the radioallergosorbent test (RAST) for initial inhalant allergy diagnosis largely concerns expense to the patient. Presented is a method for utilizing the RAST, with all its inherent advantages, at a competitive cost to both negatively and positively responding patients. The initial use of a "screening" RAST that utilizes approximately one third the number of tests in the usual full RAST battery is recommended. When all responses on the screening RAST battery are negative, further RAST testing proves generally unnecessary. For positive responders, the screening RAST often eliminates the need of additional pollen and/or mold allergen testing, a further cost-containment feature. The presented study illustrates the efficacy of this technique. A background section is provided to familiarize the reader with the common modalities available for testing and treating IgE-mediated inhalant allergies.


LineUp: statistical detection of chromosomal homology with application to plant comparative genomics.
The identification of homologous regions between chromosomes forms the basis for studies of genome organization, comparative genomics, and evolutionary genomics. Identification of these regions can be based on either synteny or colinearity, but there are few methods to test statistically for significant evidence of homology. In the present study, we improve a preexisting method that used colinearity as the basis for statistical tests. Improvements include computational efficiency and a relaxation of the colinearity assumption. Two algorithms perform the method: FullPermutation, which searches exhaustively for runs of markers, and FastRuns, which trades faster run times for exhaustive searches. The algorithms described here are available in the LineUp package (http://www.igb.uci.edu/ approximately baldig/lineup). We explore the performance of both algorithms on simulated data and also on genetic map data from maize (Zea mays ssp. mays). The method has reasonable power to detect a homologous region; for example, in >90% of simulations, both algorithms detect a homologous region of 10 markers buried in a random background, even when the homologous regions have diverged by numerous inversion events. The methods were applied to four maize molecular maps. All maps indicate that the maize genome contains extensive regions of genomic duplication and multiplication. Nonetheless, maps differ substantially in the location of homologous regions, probably reflecting the incomplete nature of genetic map data. The variation among maps has important implications for evolutionary inference from genetic map data.


Mindfulness-based cognitive therapy for bipolar disorder: a feasibility trial.
The present open study investigates the feasibility of Mindfulness-based cognitive therapy (MBCT) in groups solely composed of bipolar patients of various subtypes. MBCT has been mostly evaluated with remitted unipolar depressed patients and little is known about this treatment in bipolar disorder. Bipolar outpatients (type I, II and NOS) were included and evaluated for depressive and hypomanic symptoms, as well as mindfulness skills before and after MBCT. Patients' expectations before the program, perceived benefit after completion and frequency of mindfulness practice were also recorded. Of 23 included patients, 15 attended at least four MBCT sessions. Most participants reported having durably, moderately to very much benefited from the program, although mindfulness practice decreased over time. Whereas no significant increase of mindfulness skills was detected during the trial, change of mindfulness skills was significantly associated with change of depressive symptoms between pre- and post-MBCT assessments. MBCT is feasible and well perceived among bipolar patients. Larger and randomized controlled studies are required to further evaluate its efficacy, in particular regarding depressive and (hypo)manic relapse prevention. The mediating role of mindfulness on clinical outcome needs further examination and efforts should be provided to enhance the persistence of meditation practice with time.


Leveraging the complementary nature of RNA-Seq and shotgun proteomics data.
RNA sequencing (RNA-Seq) and MS-based shotgun proteomics are powerful high-throughput technologies for identifying and quantifying RNA transcripts and proteins, respectively. With the increasing affordability of these technologies, many projects have started to apply both to the same samples to achieve a more comprehensive understanding of biological systems. A major analytical challenge for such integrative projects is how to effectively leverage the complementary nature of RNA-Seq and shotgun proteomics data. RNA-Seq provides comprehensive information on mRNA abundance, alternative splicing, nucleotide variation, and structure alteration. Sample-specific protein databases derived from RNA-Seq data can better approximate the real protein pools in cell and tissue samples and thus improve protein identification. Meanwhile, proteomics data provide essential confirmation of the validity and functional relevance of novel findings from RNA-Seq data. At the quantitative level, mRNA and protein levels are only modestly correlated, suggesting strong involvement of posttranscriptional regulation in controlling gene expression. Here, we review recent studies at the interface of RNA-Seq and proteomics data. We discuss goals, accomplishments, and challenges in RNA-Seq-based proteogenomics. We also examine the current status and future potential of parallel transcriptome and proteome quantification in revealing posttranscriptional regulatory mechanisms.


Health care needs of community-dwelling older adults.
To identify, assess, and rank the importance of health care needs of community-dwelling older adults. A structured telephone interview with 107 respondents (physicians, direct service providers and administrators) about the importance of a list of 31 health care needs of older adults. Respondents also identified the single most important health issue facing local older adults now and in the next 5 to 10 years. The five most important health care needs, in descending order, are: care-giver support services, community long-term care services, services for people with dementia/Alzheimer's disease, palliative/end-of-life care, and services for cancer patients and their families. Community long-term care services were identified as the single most important health issue both now and in the next 5 to 10 years. The study findings should be of value to health and social service researchers, planners, providers and administrators regarding the needs of community-dwelling older adults.


Advantages of minimal incision laparoscopic cholecystectomy.
Modifications to conventional laparoscopic cholecystectomy (CLC) are aimed at decreasing abdominal wall trauma and improving cosmetic outcome. Although single-incision laparoscopic surgery (SILS) provides excellent cosmetic results, the procedure is technically challenging and expensive compared to the conventional laparoscopic approach. To describe a novel, hybrid technique combining SILS and conventional laparoscopy using minimal abdominal wall incisions. Fifty patients diagnosed with symptomatic cholelithiasis were operated using two reusable 5 mm trocars inserted through a single 15 mm umbilical incision and a single 2-3 mm epigastric port. This technique was clubbed "minimal incision laparoscopic cholecystectomy" (MILC). MILC was completed in 49 patients (98%). In five patients an additional 3 mm trocar was used and in 2 patients the epigastric trocar was switched to a 5 mmtrocar. The procedure was converted to CLC in one patient. Mean operative time was 29 minutes (range 18-60) and the average postoperative hospital stay was 22 hours (range 6-50). There were no postoperative complications and the cosmetic results were rated excellent by the patients. MILC is an intuitive, easy-to-learn and reproducible technique and requires small changes from CLC. As such, MILC may be an attractive alternative, avoiding the cost and complexity drawbacks associated with SILS.


The association of assault military sexual trauma and sexual function among partnered female service members and veterans: the mediating roles of depression and sexual self-schemas.
Background: Military sexual trauma (MST) that involves assault is associated with poorer sexual function in U. S. women service members/veterans (SM/Vs). Theory of sexual function suggests that the presence of higher depression severity and more negative sexual self-schemas may contribute to sexual dysfunction. This has yet to be examined in partnered women SM/Vs who are survivors of MST. Objective: Using path analysis, the current study examined the associations of MST type, depression, sexual self-schemas, and sexual function in 818 partnered women SM/Vs. Method: Three separate mediation models were tested, all testing indirect effects of depression and sexual self-schemas on the association of MST type and sexual function. In Model 1, the mediation model assumed that exposure to MST predicted more severe depression, which then predicted more negative sexual self-schemas. More negative sexual self-schemas, in turn, predicted poorer sexual function. In Model 2, the mediation model assumed that exposure to MST predicted more negative sexual self-schemas, which then predicted more severe depression. More severe depression, in turn, predicted poorer sexual function. In Model 3, the mediation model assumed a parallel mediation in that exposure to MST predicted more severe depression and more negative sexual self-schemas, which in turn, predicted poorer sexual function. Results: The best fitting model suggested a parallel mediation of higher depression severity (estimate: -1.30, confidence interval: -1.91,-.69) and more negative sexual self-schemas (estimate: -2.09, confidence interval: -2.94,-1.24) on the association of assault MST and poorer sexual function (Model 3). Harassment-only MST was unrelated to sexual function through mediated pathways. Conclusions: Interventions to improve sexual function among MST survivors who experienced assault should address negative sexual self-schemas related to sexual performance and depressive symptoms. Cognitive behavioural interventions that include challenging maladaptive cognitions may be well suited to address this clinical need.


Use of antisense techniques in rat renal medulla.
The experiments outlined in this chapter utilized a novel infusion technique to deliver an antisense oligonucleotide (and an enzyme inhibitor) directly into the renal medullary interstitial space of conscious rats. Antisense treatment led to a selective decrease in nNOS protein and reduced total NOS enzymatic activity in the renal medulla of the infused rats while three other gene products found in the renal medulla (iNOS, eNOS, and beta-actin) were unaltered. Physiological studies in rats demonstrated that infusion of the antisense oligonucleotide into the renal medullary interstitial space increased mean arterial pressure. The increase in blood pressure was dependent on the sodium intake of the rats, was not mimicked when a scrambled oligonucleotide was infused, and was reversible when the antisense infusion was stopped. To confirm the functional data obtained with the antisense oligonucleotide, renal medullary interstitial infusion of the nNOS enzyme inhibitor 7-NI was also shown to lead to a similar increase in arterial pressure and decrease in total NOS activity in the renal medulla. Together, the antisense oligonucleotide, the enzyme inhibitor, and the interstitial infusion technique were used to demonstrate that nNOS found in the renal medulla is important in the chronic regulation of arterial pressure. The experiments summarized in this chapter outline a strategy that can potentially be used to examine the functional effects of many different proteins in this region of the body. Through the use of antisense oligonucleotides and other pharmacological agents, we can hope to gain a more comprehensive understanding of the factors that control renal medullary tubular and vascular function and consequently fluid and electrolyte homeostasis and blood pressure.


Effect of polyvalent ions in the formation of ionic-liquid-based aqueous biphasic systems.
Two main approaches were combined aiming at evaluating the impact of polyvalent salt cations on the formation of ionic-liquid-based aqueous biphasic systems (ABS): (i) experimental determination of a large array of ternary phase diagrams composed of sodium-, magnesium-, and aluminum-based salts with 1-butyl-3-methylimidazolium-based ionic liquids and (ii) determination of the ions speciation in each of these systems. The results here reported show, for the first time, that the phase behavior of ionic-liquid-based aqueous biphasic systems is not only dominated by the ability of the strong and "free" salting-out ions to interact with water creating thus hydration complexes but also a result of the interactions occurring between the different ions and, particularly, on their speciation in aqueous solutions. The gathered data indicate that the higher the salt ion valence, the more complex is its speciation with a number of different species in aqueous media present. Further results based on NMR spectroscopy and a proper analysis of the pH influence clearly demonstrated the impact of ion speciation through the phase separation and ABS formation.


A datalogger to identify vocalizing dolphins.
A datalogger was developed to identify vocalizing dolphins within socially interacting captive groups. Every 50 ms the logger stores data on the level and frequency of detected sound. Dataloggers are temporarily attached to dolphins by suction cups for data collection sessions lasting up to 45 min. Later, computer analysis of data from the dataloggers reveals which dolphin produced each vocalization recorded during the session. Results from use of dataloggers with two captive bottlenose dolphins (Tursiops truncatus) at the New England Aquarium in Boston, MA are presented. The possible use of dataloggers with wild dolphins is discussed.


Three-dimensional direct femtosecond laser writing of second-order nonlinearities in glass.
We demonstrate that direct femtosecond laser writing in silver-containing zinc and gallium phosphate glass enables generation of three-dimensional (3D) optical second-order nonlinear microstructures having an χ(2) value about 2.5 times that of quartz. The proposed physical model involves photo-reduction, photo-dissociation, and migration of silver species within the glass matrix. 3D laser-written second-order nonlinear structures could become a new class of nonlinear optical components.


Unveiling the effects of A-site substitutions on the oxygen ion migration in A2-xA'xNiO4+δ by first principles calculations.
The effects of A-site substitutions on the interstitial oxygen formation energy and the migration energy in layered A2-xA'xNiO4+δ (A = selected lanthanides, A' = Ba, Sr, Ca) are investigated by first principles calculations. The interstitial oxygen formation energy is negative, in the range of -4.81 eV to -3.45 eV, strongly supporting easiness of formation of the interstitial oxygen defects in the (A,A')O rock salt plane. The Pr2NiO4+δ compound shows the lowest formation energy, indicating the highest amount of interstitial oxygen. Doping with alkaline earth cations (A') increases the formation energy of the interstitial oxygen, which prefers to be located far away from the dopants. Nevertheless, Ca seems to be the best choice, due to relatively low formation energy. Calculations for the four kinds of diffusion paths allow it to be predicted that the oxygen transport in A2-xA'xNiO4+δ is governed by the interstitialcy mechanism in the ab plane, because of the significantly lower energy barriers for this mechanism. An interesting finding is achieved for A2NiO4+δ (A = Pr, Nd, Sm), for which the energy barriers for the interstitialcy transport are negative (-0.47 eV, -0.33 eV and -0.02 eV, respectively), implying that the transition state is more stable than the assumed initial state. A new structural configuration is proposed in this work, with the adjacent apical oxygen located at the adjacent interstitial site, which shows ca. 0.5 eV lower free energy than that of the initial model. This result provides a new understanding for the location of the interstitial and the adjacent apical oxygens from an energetic point of view and supports previously published experimental data. It is found that alkaline earth doping at the A-site deteriorates the interstitial oxygen diffusion in La2-xA'xNiO4.25 materials, but concerning overall transport properties, Ca seems to be a good dopant from an energetic point of view, when compared with Ba and Sr.


Taking Open Innovation to the Molecular Level - Strengths and Limitations.
The ever-growing availability of large-scale open data and its maturation is having a significant impact on industrial drug-discovery, as well as on academic and non-profit research. As industry is changing to an 'open innovation' business concept, precompetitive initiatives and strong public-private partnerships including academic research cooperation partners are gaining more and more importance. Now, the bioinformatics and cheminformatics communities are seeking for web tools which allow the integration of this large volume of life science datasets available in the public domain. Such a data exploitation tool would ideally be able to answer complex biological questions by formulating only one search query. In this short review/perspective, we outline the use of semantic web approaches for data and knowledge integration. Further, we discuss strengths and current limitations of public available data retrieval tools and integrated platforms.


Preservation of normal lung regions in the adult respiratory distress syndrome. Analysis by computed tomography.
In this report, we challenge the commonly held assumption that the adult respiratory distress syndrome (ARDS) is a homogeneous process associated with generalized and relatively uniform damage to the alveolar capillary membrane. We studied 13 patients with ARDS, comparing the pulmonary parenchymal changes seen by standard bedside chest roentgenograms with those seen by computed tomography of the chest. Three patients demonstrated generalized lung involvement by both radiologic techniques. In another eight patients, despite the appearance of generalized involvement on the standard chest x-ray film, the computed tomographic scans showed patchy infiltrates interspersed with areas of normal-appearing lung. Two patients showed patchy involvement by both techniques. The fact that ARDS spares some regions of lung parenchyma is useful knowledge in understanding the gas-exchange abnormalities of ARDS, the variable responsiveness to positive end-expiratory pressure, and the occurrence of oxygen toxicity. The problem of regional inhomogeneity should also be kept in mind when interpreting lung biopsy specimens or bronchoalveolar lavage fluid in patients with ARDS.


Growth Performance, Diet Digestibility, and Chemical Composition of Mealworm (Tenebrio molitor L.) Fed Agricultural By-Products.
Humanity's growing demand for animal protein exceeds the capacity of traditional protein sources to support growing livestock production. Insects offer promising partial substitutes, converting low-nutritional quality materials into high-value biomass. Hence, the bioconversion ability of Tenebrio molitor larvae was assessed by using three types of agricultural by-products (broccoli by-product, tigernut pulp, and grape pomace) at different inclusion levels (0%, 25%, 50%, and 100%) in a carbohydrate-based diet. Ten diets were formulated to assess their impact on the growth, diet digestibility, and nutritional composition of the larvae. For each treatment, eight replicates were employed: five for the growth-performance-digestibility trial and three for the complementary test of uric acid determination. The growth was influenced by the type of diet administered. The broccoli by-product resulted in higher larvae weight and a better feed conversion ratio. However, diets based solely on a single by-product (100%) compromised the productivity and diet digestibility. The larvae changed their nutritional composition depending on the rearing substrate, although the amino acid profile remained consistent. In conclusion, the studied by-products have the potential for use in T. molitor rearing as part of the diet but not as the exclusive ingredients, indicating promising opportunities for using agricultural by-products in T. molitor rearing and production.


Lysyl oxidase-like 2 as a new poor prognosis marker of squamous cell carcinomas.
Lysyl oxidase-like 2 (Loxl2) interacts with and stabilizes Snai1 transcription factor, promoting epithelial-mesenchymal transition. Either Loxl2 or Snai1 knock-down blocks tumor growth and induces differentiation, but the specific role of each factor in tumor progression is still unknown. Comparison of the gene expression profiles of the squamous cell carcinoma cell line HaCa4 after knocking-down Loxl2 or Snai1 revealed that a subset of epidermal differentiation genes was specifically up-regulated in Loxl2-silenced cells. In agreement, although both Loxl2- and Snai1-knockdown cells showed reduced in vivo invasion, only Loxl2-silenced cells exhibited a skin-like epidermal differentiation program. In addition, we show that expression of Loxl2 and Snai1 correlates with malignant progression in a two-stage mouse skin carcinogenesis model. Furthermore, we found that increased expression of both LOXL2 and SNAI1 correlates with local recurrence in a cohort of 256 human laryngeal squamous cell carcinomas. We describe for the first time that high levels of LOXL2 are associated with decreased overall and disease-free survival in laryngeal squamous cell carcinomas, lung squamous cell carcinoma, and lymph node-negative (N(0)) breast adenocarcinomas. Altogether, our results show that LOXL2 can be used as a new poor prognosis indicator in human squamous cell carcinomas promoting malignant transformation by both SNAI1-dependent and SNAI1-independent pathways.


Single-Cell RNA-seq Reveals Angiotensin-Converting Enzyme 2 and Transmembrane Serine Protease 2 Expression in TROP2+ Liver Progenitor Cells: Implications in Coronavirus Disease 2019-Associated Liver Dysfunction.
The recent coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2. COVID-19 was first reported in China (December 2019) and is now prevalent across the globe. Entry of severe acute respiratory syndrome coronavirus 2 into mammalian cells requires the binding of viral Spike (S) proteins to the angiotensin-converting enzyme 2 receptor. Once entered, the S protein is primed by a specialized serine protease, transmembrane serine protease 2 in the host cell. Importantly, besides the respiratory symptoms that are consistent with other common respiratory virus infections when patients become viremic, a significant number of COVID-19 patients also develop liver comorbidities. We explored whether a specific target cell-type in the mammalian liver could be implicated in disease pathophysiology other than the general deleterious response to cytokine storms. Here, we used single-cell RNA-seq to survey the human liver and identified potentially implicated liver cell-type for viral ingress. We analyzed ~300,000 single cells across five different (i.e., human fetal, healthy, cirrhotic, tumor, and adjacent normal) liver tissue types. This study reports on the co-expression of angiotensin-converting enzyme 2 and transmembrane serine protease 2 in a TROP2+ liver progenitor population. Importantly, we detected enrichment of this cell population in the cirrhotic liver when compared with tumor tissue. These results indicated that in COVID-19-associated liver dysfunction and cell death, a viral infection of TROP2+ progenitors in the liver might significantly impair liver regeneration in patients with liver cirrhosis.


Reduced costs of reproduction in females mediate a shift from a male-biased to a female-biased lifespan in humans.
The causes underlying sex differences in lifespan are strongly debated. While females commonly outlive males in humans, this is generally less pronounced in societies before the demographic transition to low mortality and fertility rates. Life-history theory suggests that reduced reproduction should benefit female lifespan when females pay higher costs of reproduction than males. Using unique longitudinal demographic records on 140,600 reproducing individuals from the Utah Population Database, we demonstrate a shift from male-biased to female-biased adult lifespans in individuals born before versus during the demographic transition. Only women paid a cost of reproduction in terms of shortened post-reproductive lifespan at high parities. Therefore, as fertility decreased over time, female lifespan increased, while male lifespan remained largely stable, supporting the theory that differential costs of reproduction in the two sexes result in the shifting patterns of sex differences in lifespan across human populations. Further, our results have important implications for demographic forecasts in human populations and advance our understanding of lifespan evolution.


Power comparison of regression methods to test quantitative traits for association and linkage.
George et al. [1999 Am J Hum Genet 65:236-245] proposed a regression-based TDT method for quantitative traits consisting of regressing the trait on the parental transmission of a marker allele. Zhu and Elston [2000] also developed a TDT method for quantitative traits by defining a linear transformation to condition out founder information. Both methods test the null hypothesis of no linkage or association and can be applied to general pedigree structures. In this paper, we compare the power of these two methods through simulation, sampling those nuclear families with at least one heterozygous parent. Overall, we find that a variant of Zhu and Elston's method with 2 d.f. is more powerful. However, if the mode of inheritance is known, then a most powerful test with 1 d.f. can be found. All these regression TDT tests require linkage to detect association, but a test that does not require linkage will be more powerful.


Real-Time Standard View Classification in Transthoracic Echocardiography Using Convolutional Neural Networks.
Transthoracic echocardiography examinations are usually performed according to a protocol comprising different probe postures providing standard views of the heart. These are used as a basis when assessing cardiac function, and it is essential that the morphophysiological representations are correct. Clinical analysis is often initialized with the current view, and automatic classification can thus be useful in improving today's workflow. In this article, convolutional neural networks (CNNs) are used to create classification models predicting up to seven different cardiac views. Data sets of 2-D ultrasound acquired from studies totaling more than 500 patients and 7000 videos were included. State-of-the-art accuracies of 98.3% ± 0.6% and 98.9% ± 0.6% on single frames and sequences, respectively, and real-time performance with 4.4 ± 0.3 ms per frame were achieved. Further, it was found that CNNs have the potential for use in automatic multiplanar reformatting and orientation guidance. Using 3-D data to train models applicable for 2-D classification, we achieved a median deviation of 4° ± 3° from the optimal orientations.


Effect of altered tissue binding on the disposition of barbital in the isolated perfused rat liver: application of the axial dispersion model.
To examine the dependence of hepatic dispersion on tissue binding, the distribution kinetics of barbital under varying conditions of barbiturate perfusate concentrations was studied in the isolated perfused rat liver preparation (n = 5). The in situ liver was perfused in a single-pass mode with protein-free Krebs bicarbonate medium (15 mL/min). During steady-state infusion with various barbiturate concentrations (barbital, 1 g/L; butethal, 0.1, 1 g/L), a bolus containing [3H]water (cellular space marker) and [14C]barbital was injected into the portal vein. The recoveries of [3H]water and [14C]barbital were complete. The mean transit time and hence the volume of distribution for barbital in the absence of bulk barbiturate concentration (56 s and 1.24 mL/g) were about 2-fold higher than those for water (29 s and 0.58 mL/g), and they decreased progressively as the perfusate barbiturate concentration increased, indicating a decrease in tissue binding. However, the relative dispersion values (CV2H) of water (0.60) and barbital (0.66) were about the same magnitude and independent of the bulk concentration of barbiturate. The one-compartment dispersion model adequately described the data of barbital with a constant DN (dispersion number) value of 0.35. The results indicate that varying the tissue binding of barbital does not change the magnitude of DN; as such it offers a new experimental approach to examine the hepatic dispersion of solutes with a large distribution volume.


The significance of tumor contamination in the bone marrow from high-risk primary breast cancer patients treated with high-dose chemotherapy and hematopoietic support.
We studied the incidence and significance of tumor cell contamination of the bone marrow or peripheral blood progenitor cells of patients who had high risk primary breast cancer involving 10 or more axillary lymph nodes and who received high dose cyclophosphamide, cisplatin, and carmustine with hematopoietic support as consolidation following standard dose adjuvant chemotherapy. The autologous hematopoietic cell products were evaluated in 85 eligible patients. Eighty-three samples were available from the time of bone marrow harvest, and peripheral blood progenitor cells were evaluated from 57 of the 65 patients who additionally received these products. The screening technique utilized a panel of four anti-breast cancer monoclonal antibodies and an immunohistochemical technique. Thirty (36%) of the 83 evaluable patients had tumor cell contamination of the bone marrow. Only 2 (4%) of the 57 patients had tumor cell contamination of the peripheral blood progenitor cells. Tumor cell contamination of the bone marrow was associated with shorter disease-free survival and overall survival. In addition, the higher the number of tumor cells identified, the shorter disease-free and overall survival. There was no relationship between the tumor cell contamination of the bone marrow and the site of relapse. The combination of the log of the number of tumor cells +1 and number of positive lymph nodes predicted both disease-free and overall survival. Tumor cell contamination of the bone marrow from the harvest is associated with shorter disease-free and overall survival for patients who were treated with standard dose chemotherapy followed by consolidation with high dose alkylating agents and hematopoietic support. It is unclear what role the contaminating tumor cells have in relapse, and they may just be a high-risk marker. A comparison with other prognostic factors and characteristics of the tumor may determine the significance of the tumor contamination of the bone marrow.