Observational study of operating room times for knee and hip replacement surgery at nine U.S. community hospitals.
Knee (N = 185) and hip (N = 140) replacement cases were studied at nine community hospitals in the midwestern United States to determine whether certain management interventions could decrease case durations and reduce labor costs. Substantive (10 min) reductions in operating room (OR) time per case were not associated with: 1) increases in OR staffing, such as the addition of a surgical assistant; 2) complete elimination of all delays; or 3) increases in anesthesiologists' presence in the ORs. Substantive (10 min) increases in OR time per case were not associated with: 1) reductions in anesthesiologists' presence in the ORs or 2) changes in case scheduling to run fewer ORs, with some cases starting later in the day. Even if these factors had been associated with differences in OR time per case, any changes resulting from management interventions would still not have reduced labor costs. At these hospitals, OR nursing and anesthesia labor costs were fixed costs, because the OR workload averaged only 5.6 hr of cases per day.


Screening of novel immunostimulatory CpG ODNs and their anti-leukemic effects as immunoadjuvants of tumor vaccines in murine acute lymphoblastic leukemia.
Acute lymphoblastic leukemia (ALL) is a common malignant disease and a major cause of mortality due to recurrent disease. Immunotherapy is a promising strategy for eradicating minimal residual disease and thus preventing the relapse of leukemia. Apart from stem cell transplantation, CpG oligodeoxynucleotides (ODNs) are excellent candidates for the immunotherapy of leukemia. However, the number of usable CpG ODNs is limited. In this study, we tested a panel of CpG ODNs and obtained three CpG ODN sequences with strong immunostimulatory activity by comparing their capacity to activate lymphocytes. The data revealed that the flanking bases, the spacing of individual CpG motifs and polyguanosine ends, contribute to the immunostimulatory activity of a CpG ODN. In the immunotherapy of murine leukemia with the novel ODN as the adjuvant, we found that CpG Seqs 14 and 19 were effective in the treatment of a leukemia model by prolonging survival span, augmenting natural killer cell and CTL cytotoxicity, as well as increasing the number of long-term survivors. The ability of CpG ODN to induce both strong innate and adaptive anti-leukemic immune activity could render it an appropriate agent for therapeutic applications in acute leukemia. This study demonstrates the feasibility of active immunotherapy with CpG ODNs in patients with acute leukemia and thus represents a potential alternative therapeutic strategy for eradicating residual disease which is resistant to conventional cytoreductive treatment.


Hepatic angiomyolipoma mimicking hepatocellular carcinoma: magnetic resonance imaging and clinical pathological characteristics in 9 cases.
Hepatic angiomyolipoma (HAML) is a rare mesenchymal tumor of the liver with marked histological diversity. The present study was to review the magnetic resonance imaging (MRI) and clinical pathological features of HAML resembling hepatocellular carcinoma (HCC). Nine patients who underwent surgical resection and had pathological diagnosis of HAML were retrospectively analyzed. All of 9 patients (5 males and 4 females) had a solitary hepatic mass with a median size of 4 cm (from 1.4 cm to 15.3 cm). Seven cases were identified as incidental liver tumors during health screening and 2 patients were diagnosed for hepatic mass when visited hospitals with unspecific abdominal discomfort. Before resection, 6 cases were diagnosed as HCC on MRI. MRI on chemical shift imagings showed a large amount of lipids in 5 cases. The enhancement pattern of MRI was classified into 2 types: in 2 cases, lesions with small or no vessels that demonstrated prolonged enhancement (1 mixed subtype and 1 myomatous subtype) and in 7 cases, lesions with abundant central vessels that show rapid washout (3 mixed subtypes and 4 myomatous subtypes) in the portal venous/delayed phase. All patients underwent resection of hepatic tumor and no recurrence was observed during follow-up (range: 2-24 months) of median 10 months. By immunohistochemistry, the tumor cells demonstrated positive immunostaining for human melanoma black-45, smooth muscle actin, and CD34. In conclusion, all of 9 patients with HAML presented with none or nonspecific clinical manifestations. The diagnosis of HAML relies on disease and immunohistochemistry, but not MRI due to its resemblance to HCC.


Membranes from a transplantable osteogenic sarcoma responsive to parathyroid hormone and prostaglandins: regulation of adenylate cyclase and of hormone metabolism.
Adenylate cyclase activity in particulate fractions from a transplantable rat osteogenic sarcoma was stimulated in a dose-dependent manner by prostaglandins E1 and E2 (PGE1 and PGE2) and parathyroid hormone (PTH). Prostaglandin F2alpha was active at a high concentration (3 x 10(-4) mol/l). Pretreatment of membranes with collagenase plus hyaluronidase reduced the magnitude of the PTH effect but did not affect the size of the PGE1 effect. Guanosine 5'-triphosphate and its synthetic analogue 5'-guanylylimidodiphosphate (Gpp(NH)p) activated adenylate cyclase in particulate preparations from the osteogenic sarcoma. The latter agent produced much larger effects, although the concentrations required for half-maximal enzyme activation were the same for both agonists (approximately 2 x 10(-6) mol/l). The effects of PTH and Gpp(NH)p were supra-additive at some concentrations of hormone. The effects of PGE1 and Gpp(NH)p were supra-additive at all hormone concentrations tested. Pre-incubation of membrane particles for 6 min with PTH produced an enzyme activation which was not reversed by dilution through washing; pre-incubation with PGE1 did not produce this effect. The response of membrane adenylate cyclase to Gpp(NH)p (10(-4) mol/l) was 75% greater in preparations pre-incubated with PTH than in membranes pre-incubated in buffer alone or in buffer containing PGE1. The basal rate of cyclic AMP production in the adenylate cyclase assay system decreased over a 35 min incubation period. This decrease was prevented by addition of PTH or PGE1. Addition of NaF or Gpp(NH)p produced a steady increase in the rate of production of cyclic AMP with time. Membrane preparations did not reduce the biological activity of PTH and did not degrade 125I-labelled PTH. The results demonstrate that the PTH- and PGE-responsive adenylate cyclases of the osteogenic sarcoma have distinctly different properties and that particulate preparations of the tumour do not metabolize PTH.


Molecular characterization, expression and antimicrobial activities of two c-type lysozymes from manila clam Venerupis philippinarum.
Lysozymes play an important role in the innate immune responses with which mollusks respond to bacterial invasion through its lytic activity. In the present study, two c-type lysozymes (designed as VpCLYZ-1 and VpCLYZ-2, respectively) were identified and characterized from the manila clam Venerupis philippinarum. The full-length cDNA of VpCLYZ-1 and VpCLYZ-2 was of 629 and 736 bp, encoding a polypeptide of 156 and153 amino acid residues, respectively. The deduced amino acid sequences of VpCLYZs showed high similarity to other known invertebrate c-type lysozymes. Multiple alignments and phylogenetic relationship strongly suggested that VpCLYZ-1 and VpCLYZ-2 belonged to the c-type lysozyme family. Both VpCLYZ-1 and VpCLYZ-2 transcripts were constitutively expressed in a wide range of tissues with different levels. The VpCLYZ-1 transcript was dominantly expressed in hepatopancreas and hemocytes, while VpCLYZ-2 transcript was mainly expressed in the tissues of hepatopancreas and gills. Both the mRNA expression of VpCLYZ-1 and VpCLYZ-2 was significantly up-regulated at 12 h post Vibrio anguillarum challenge. The recombinant VpCLYZ-1 and VpCLYZ-2 (designed as rVpCLYZ-1 and rVpCLYZ-2) exhibited lytic activity against all tested bacteria, and rVpCLYZ-1 showed higher activities than rVpCLYZ-2 in killing Micrococcus luteus and V. anguillarum. Overall, our results suggested that VpCLYZ-1 and VpCLYZ-2 belonged to the c-type lysozyme family, and played important roles in the immune responses of manila clam, especially in the elimination of pathogens.


Body image, figure rating, and body mass index of girls enrolled in health, physical education, or athletics classes.
The aim was to examine associations among body-image, figure rating, and Body Mass Index of seventh grade girls who chose health, physical education, or athletics classes. Measurements were taken prior to and following the course. Class choice was significantly related to body-image satisfaction but not to figure rating or Body Mass Index. Research is needed to examine inaccurate self-perception of fatness in underweight girls, whether there is a higher risk for eating disorders for students in athletics and physical education classes, whether the curriculum is effective with students in physical education and athletics, and why girls who chose the health class began with higher body-image satisfaction than those in physical education or athletics, even though their Body Mass Index and figure-rating size did not differ.


Advances in Understanding and Harnessing the Molecular Regulatory Mechanisms of Vegetable Quality.
The quality of vegetables is facing new demands in terms of diversity and nutritional health. Given the improvements in living standards and the quality of consumed products, consumers are looking for vegetable products that maintain their nutrition, taste, and visual qualities. These requirements are directing scientists to focus on vegetable quality in breeding research. Thus, in recent years, research on vegetable quality has been widely carried out, and many applications have been developed via gene manipulation. In general, vegetable quality traits can be divided into three parts. First, commodity quality, which is most related to the commerciality of plants, refers to the appearance of the product. The second is flavor quality, which usually represents the texture and flavor of vegetables. Third, nutritional quality mainly refers to the contents of nutrients and health ingredients such as soluble solids (sugar), vitamin C, and minerals needed by humans. With biotechnological development, researchers can use gene manipulation technologies, such as molecular markers, transgenes and gene editing to improve the quality of vegetables. This review attempts to summarize recent studies on major vegetable crops species, with Brassicaceae, Solanaceae, and Cucurbitaceae as examples, to analyze the present situation of vegetable quality with the development of modern agriculture.


Managing Urological Disorders in Multiple Sclerosis Patients: A Review of Available and Emerging Therapies.
Multiple sclerosis (MS) is a progressive neurological autoimmune disease with a diverse range of urological symptomatology, and most MS patients experience 1 or more moderate to severe urinary symptoms, as well as bladder and/or sexual disorders. Urologists play the director's role in evaluating and treating these patients. Therefore, identifying the proper evaluation tools and the most suitable therapeutic options for specific patients requires a thorough understanding of this disease process.


Single-molecule chemistry of metal phthalocyanine on noble metal surfaces.
To develop new functional materials and nanoscale electronics, researchers would like to accurately describe and precisely control the quantum state of a single molecule on a surface. Scanning tunneling microscopy (STM), combined with first-principles simulations, provides a powerful technique for acquiring this level of understanding. Traditionally, metal phthalocyanine (MPc) molecules, composed of a metal atom surrounded by a ligand ring, have been used as dyes and pigments. Recently, MPc molecules have shown great promise as components of light-emitting diodes, field-effect transistors, photovoltaic cells, and single-molecule devices. In this Account, we describe recent research on the characterization and control of adsorption and electronic states of a single MPc molecule on noble metal surfaces. In general, the electronic and magnetic properties of a MPc molecule largely depend on the type of metal ion within the phthalocyanine ligand and the type of surface on which the molecule is adsorbed. However, with the STM technique, we can use on-site molecular "surgery" to manipulate the structure and the properties of the molecule. For example, STM can induce a dehydrogenation reaction of the MPc, which allows us to control the Kondo effect, which describes the spin polarization of the molecule and its interaction with the complex environment. A specially designed STM tip can allow researchers to detect certain molecule-surface hybrid states that are not accessible by other techniques. By matching the local orbital symmetry of the STM tip and the molecule, we can generate the negative differential resistance effect in the formed molecular junction. This orbital symmetry based mechanism is extremely robust and does not critically depend on the geometry of the STM tip. In summary, this simple model system, a MPc molecule absorbed on a noble metal surface, demonstrates the power of STM for quantum characterization and manipulation of single molecules, highlighting the potential of this technique in a variety of applications.


Influence of dietary lysine on growth and carcass composition of high-lean-growth gilts fed from 34 to 72 kilograms.
One hundred eight high-lean-growth gilts (34.4 kg BW) were used to determine the dietary lysine requirement to maximize growth, carcass characteristics, and protein accretion from 34 to 72.5 kg BW. The experiment was a randomized complete block design; initial BW served as the blocking factor. Six dietary treatments were included, ranging from .54 to 1.04% (.10% increments) digestible lysine (.69 to 1.25% total lysine). Pigs were housed in pens of three, with six replicate pens per treatment. Pig weights and feed consumption were collected weekly to calculate ADG, ADFI, and gain:feed (G/F). Initially, five pigs were slaughtered to determine baseline carcass composition. When the mean weight for pigs in a pen reached 55 and 72.5 kg, one pig per pen was randomly selected and slaughtered for carcass measurements. The right side of each carcass was ground twice and sampled to determine carcass composition and tissue accretion rates. Average daily gain was increased by dietary lysine from 34 to 55 kg (linear, P < .01), from 55 to 72.5 kg (linear, P < .10), and from 34 to 72.5 kg (linear, P < .01). Although ADFI from 34 to 55 and from 55 to 72.5 kg was not influenced by dietary lysine, ADFI for the entire experiment tended to decrease (quadratic, P < .10) as digestible lysine increased. Increased dietary lysine resulted in improved G/F from 34 to 55 kg (linear, P < .01) and from 55 to 72.5 and 34 to 72.5 kg (quadratic, P < .01). Average backfat thickness was not influenced by dietary lysine at 55 kg but decreased (linear, P < .05) as dietary lysine increased at 72.5 kg. At 55 kg, longissimus muscle area was larger (linear, P < .05) for gilts fed increased digestible lysine. However, longissimus muscle area was similar for all treatments at 72.5 kg. Gilts fed increased digestible lysine had greater CP accretion from 34 to 55 kg (linear, P < .01), 55 to 72.5 kg (linear, P < .05; quadratic, P < .10), and from 34 to 72.5 kg (quadratic, P < .05). Based on the feed intake observed in this study, the high-lean-growth gilt requires at least 22 g/d total lysine intake from 34 to 72.5 kg to maximize CP accretion.


Alexithymia in substance abuse: relationship to depression.
Recently Giannini reported that substance abusers were significantly higher alexithymic scorers than healthy volunteers but that the alexithymia scores correlated positively with scores of mood states on the five-factor model for healthy volunteers not but for substance abusers. This suggested that researchers should not aggregate all substance abusers into one group. To check Giannini's suggestions, further examinations including mood changes in substance abusers seem needed.


[Risks from volatile anesthetics in operating rooms of Umbrian hospitals].
The present report is a research on air samples taken in the operating theatres environment in the hospitals of Umbria to control in order the concentration of anaesthetics in use and to define ambient pollution and to propose changes. The A.A. have divided operating theatres in for groups to analyze the data: 1) operating theatres where there were both systems: air change system and air intake system; 2) operating theatres where there was only the air-change system; 3) operating theatres where there was only the air intake system; 4) operating theatres where there were no systems. These data have been compared with the limit values advised by N.I.O.S.H. The lowest value of pollution have been recorded in those operating theatres with both systems. The A.A. have also compared the ethrane or other alogenated anaesthetics values in the air-change system equipped operating theatres with those (values) found in the intake-air system equipped operating theatres. The lowest values have been recorded in those operating theatres with normal air-change system. Where changes have been made to improve the operating theatres environment, the A.A. have effectuated new controls and found lower values of the anaesthetics levels. The concentration of anaesthetics appeared lower then before.


Biochemical characterization of chicken secretory component.
Human dimeric IgA was injected i.v. into chickens whose bile was then collected. The human IgA which had been transported across the hepatocytes of the chicken was subsequently purified from the bile and shown to be associated with a protein of 80 kDa and pI 4.6, which reacted with rabbit antisera to chicken bile proteins but not with an antiserum to human alpha chain. The chicken bile protein thus has functional and biochemical properties similar to those of mammalian secretory component.


Electrophysiological evidence for an antinociceptive effect of ketamine in the rat spinal cord.
The dissociative anesthetic ketamine also has antinociceptive effects. The mechanism and the site of action of such effect of ketamine have been, however, elusive and controversial. The present study was conducted to examine the effect of systemically administered ketamine on spinal nociceptive transmission. We investigated and compared the effects of ketamine (0.25-8 mg/kg) on the hamstring flexor reflex in intact, lightly anesthetized rats and spinally transected rats. The opioid receptor antagonist naloxone was used to examine the involvement of opioid receptors in the actions of ketamine. Finally, the effects of ketamine on dorsal horn neuronal activity to electrical stimulation of peripheral nerves were also studied. Ketamine caused similar dose-dependent depression of the hamstring flexor reflex recorded from spinally intact rats and from spinalized rats. Even the highest dose of ketamine failed to influence the monosynaptic reflex. The depressive effect of ketamine on the flexor reflex was not reversed by naloxone. Ketamine i.v. also exerted a relatively selective inhibition of the responses of dorsal horn wide-dynamic-range neurons to C-fiber input of electrical stimulation of the plantar nerve. Our present results support the notion that ketamine can exert a direct antinociceptive effect in rat spinal cord. Moreover, the data indicated that the spinal antinociceptive effect of ketamine does not involve naloxone-sensitive opioidergic mechanisms.


Histopathological features of the resected left atrial appendage as predictors of recurrence after surgery for atrial fibrillation in valvular heart disease.
A histopathological assessment of left atrial appendages (LAA) resected during surgical treatment for atrial fibrillation (AF) was made, with the aim of improving the prediction of postoperative AF recurrence. This clinicopathological study involved 57 surgical cases of valvular AF and 34 age- and sex-matched control autopsy cases with a history of sinus rhythm. LAA from the cases with valvular AF showed greater hypertrophy of cardiomyocytes (p<0.0001), greater nuclear enlargement (p<0.0001), more bizarre nuclei (BN; p<0.0001), and more intercellular fibrosis (ICF; p<0.001). Partial disarray of cardiomyocytes and fatty infiltration were recognized in both the AF and control groups. Thirty-seven cases had maintained sinus rhythm after surgery from 7 months to 10 years. AF recurred within a month of surgery in 17 and after a month in 3; there was no significant difference in histopathological features between them. These 20 cases had more cellular hypertrophy (p<0.025), nuclear enlargement (p<0.025), BN (p<0.01), and ICF (p<0.025) than those who maintained sinus rhythm after surgery. The histopathological findings for LAA reflected the underlying valvular diseases; however, the most reliable predictors of postoperative AF recurrence were hypertrophy of cardiomyocytes, bizarre shaped nuclei, and extensive ICF.


Developing an Educational Package to Improve Attitude of Medical Students Toward People With Mental Illness: A Delphi Expert Panel, Based on a Scoping Review.
The importance of stigma toward patients with mental illness in medical students as future physicians cannot be overemphasized. There is currently no formal training to reduce stigma toward mental illness in medical students in their educational curriculums in Iran like most other low and middle income countries. Therefore, aiming to provide a practical and effective training package focused on reducing stigma toward patients with mental illness in medical students, the current study conducted, as an expert panel with Delphi method, based on a scoping review, to develop an education package to improve attitude of medical students toward patients with mental illness. We surveyed the available international databases including PubMed, Google Scholar, Scopus, PsycINFO, Tripdatabase, Web of Science, Cochrane Database of Systematic Reviews as well as Persian databases including Iranmedex, SID, Irandoc and Magiran in February and March 2020. After an extensive review of related resources, 13 articles met our inclusion criteria. Then, we extracted the related data including type and duration of the interventions, sample size, mean and standard deviation of stigma scores before and after interventions. To develop the package among the included interventions, we asked 16 experts in psychology, psychiatry, and social medicine to rate the interventions based on a number of variables such as effectiveness, feasibility and applicability in a Delphi process. The selected intervention in Delphi method with consensus of experts included a set of four sequential interactive interventions: showing a movie and discussing it, psychiatric training including contact with people who affected psychiatric disorders, social communication with people who affected psychiatric disorders, and group discussion on defining stigma and personal experiences. In the present study, we recommend a set of interventions to reduce stigma toward patients with mental illness among medical students in the form of a package of combined, interactive and sequential interventions that have been previously been shown to be effective in reducing stigma related to mental illness. We expect that implementation of these interventions would reduce mental illness stigma in medical students; which needs further verification.


Pregnant women's knowledge of weight, weight gain, complications of obesity and weight management strategies in pregnancy.
Obesity is increasingly common in the obstetric population. Maternal obesity and excess gestational weight gain (GWG) are associated with increased perinatal risk. There is limited published data demonstrating the level of pregnant women's knowledge regarding these problems, their consequences and management strategies.We aimed to assess the level of knowledge of pregnant women regarding: (i) their own weight and body mass index (BMI) category, (ii) awareness of guidelines for GWG, (iii) concordance of women's own expectations with guidelines, (iv) knowledge of complications associated with excess GWG, and (v) knowledge of safe weight management strategies in pregnancy. 364 pregnant women from a single center university hospital antenatal clinic were interviewed by an obstetric registrar. The women in this convenience sample were asked to identify their weight category, their understanding of the complications of obesity and excessive GWG in pregnancy and safe and/or effective weight management strategies in pregnancy. Nearly half (47.8%) of the study population were overweight or obese. 74% of obese women underestimated their BMI category. 64% of obese women and 40% of overweight women overestimated their recommended GWG. Women's knowledge of the specific risks associated with excess GWG or maternal obesity was poor. Women also reported many incorrect beliefs about safe weight management in pregnancy. Many pregnant women have poor knowledge about obesity, GWG, their consequences and management strategies. Bridging this knowledge gap is an important step towards improving perinatal outcomes for all pregnant women, especially those who enter pregnancy overweight or obese.


The ethnic custom of tooth adornment in rural Bhutan: report of a case.
The practice of tooth modification dates back thousands of years and continues to be performed in some contemporary societies. There is limited information available about the dental customs in Bhutan. A 70-year-old Bhutanese woman presented with a gold disk on her maxillary anterior tooth. Both central incisors had been adorned when she was a teenager and subsequently the gold disk on the right incisor had broken off. They were placed for religious worship, promotion of peace, and to bring good luck. In addition to this case report, a brief literature review of ethnic alterations of the dentition is provided in this article. Recognition of the various practices of tooth modification can enhance cultural sensitivity and add to our general knowledge of social customs.


The LYMFASIM simulation program for modeling lymphatic filariasis and its control.
The LYMFASIM modeling framework for the transmission and control of the tropical parasitic disease lymphatic filariasis is described and its use in the context of an endemic community in north-eastern Brazil is illustrated. Lymphatic filariasis is a disease with a complex natural history with many unknowns. This complicates decision making with respect to control strategies. With LYMFASIM, a variety of hypotheses can be tested about the life history of the parasite Wuchereria bancrofti, its transmission from man to man through mosquitoes, the role of the immune system in regulating parasite numbers, the development of disease symptoms, and the effects of control measures (drug treatment or mosquito control). The implications of alternative assumptions and uncertainty about the quantification of parameters for the effectiveness of control strategies can be investigated. Thanks to the use of stochastic microsimulation, LYMFASIM is highly flexible and can be adapted and extended as new knowledge emerges.


In vivo "hot spot" MR imaging of neural stem cells using fluorinated nanoparticles.
To optimize (19)F MR tracking of stem cells, we compared cellular internalization of cationic and anionic perfluoro-15-crown-5-ether (PFCE) nanoparticles using cell culture plates with different surface coatings. The viability and proliferation of anionic and cationic PFCE-labeled neural stem cells (NSCs) did not differ from unlabeled cells. Cationic PFCE nanoparticles ((19)F T1/T2 = 580/536 ms at 9.4 Tesla) were superior to anionic particles for intracellular fluorination. Best results were obtained with modified polystyrene culture dishes coated with both carboxylic and amino groups rather than conventional carboxyl-coated dishes. After injecting PFCE-labeled NSCs into the striatum of mouse brain, cells were readily identified in vivo by (19)F MRI without changes in signal or viability over a 2-week period after grafting. These results demonstrate that neural stem cells can be efficiently fluorinated with cationic PFCE nanoparticles without using transfection agents and visualized in vivo over prolonged periods with an MR sensitivity of approximately 140 pmol of PFCE/cell.


A possible role for complement in the pathogenesis of chronic chagasic cardiomyopathy.
The membrane attack complex (MAC) of complement participates in several inflammatory and proliferative processes by releasing pro-inflammatory cytokines and growth factors from target cells. Chronic Chagasic cardiomyopathy (CCH) is a parasitic dilated cardiopathy, characterized by severe fibrosis and inflammation, which differs from idiopathic dilated cardiomyopathy (DCM). Trypanosoma cruzi, the pathogenic organism of CCH, is a strong complement activator and can also induce alternative pathway activation by mammalian cells. This study explored whether the myocardium in CCH patients has increased MAC deposition, an expression of complement activation, compared to DCM patients. MAC was semi-quantified in endomyocardial human samples (29 CCH subjects, 18 DCM subjects, and four controls) by immunohistochemistry. MAC was present in the sarcolemma of 38% of CCH, 5.5% of DCM (p<0.02), and 0% of controls, and in interstitial inflammatory cells of CCH. No difference was observed in the expression of the complement regulatory protein CD59, indicating that increased MAC deposition is likely to be the result of complement activation rather than decreased protection. It is proposed that the increased MAC deposition found in CCH, but not in DCM or controls, may help to explain the diffuse myocardial fibrosis and inflammation characteristic of the disease.


Pathogenesis and therapy of Pseudomonas aeruginosa keratitis.
Considerable progress has been made recently in understanding the pathogenesis of pseudomonas keratitis including its adhesion, invasion and the role of the glycocalyx. Adhesion to epithelial cells has been shown in vitro to depend on pili but their relationship to the glycocalyx biofilm has yet to be explored. The actions of its toxins and proteases have been established by studying the effects of deletion mutants. However, in animal models pseudomonads have been unable to cause an invasive infection in the presence of an intact corneal epithelium and have required associated trauma. Why early necrosis of the cornea can occur in an immunocompetent individual is still not clear but may reflect the delayed access of polymorphonuclear cells (PMNs) in an avascular tissue. Whether the corneal necrosis that later occurs is then due to the PMNs or pseudomonas toxins is not established. Topical fortified gentamicin therapy remains the treatment of choice for early infection. The use of medical and surgical adjunctive therapy is often needed to cope with the complications of advanced disease and has been reviewed.


Differences between Proxy and Patient Assessments of Cancer Care Experiences and Quality Ratings.
To assess the impact of proxy survey responses on cancer care experience reports and quality ratings. Secondary analysis of data from Cancer Care Outcomes Research and Surveillance (CanCORS). Recruitment occurred from 2003 to 2005. The study was a cross-sectional observational study. The respondents were patients with incident colorectal or lung cancer or their proxies. Analyses used linear regression models with an independent variable for proxy versus patient responses as well as study site and clinical covariates. The outcomes were experiences with medical care, nursing care, care coordination, and care quality rating. Multiple imputation was used for missing data. Among 6,471 respondents, 1,011 (16 percent) were proxies. The proportion of proxy respondents varied from 6 percent to 28 percent across study sites. Adjusted proxy scores were modestly higher for medical care experiences (+1.28 points [95 percent CI:+ 0.05 to +2.51]), but lower for nursing care (-2.81 [95 percent CI: -4.11 to -1.50]) and care coordination experiences (-2.98 [95 percent CI: -4.15 to -1.81]). There were no significant differences between adjusted patient and proxy ratings of quality. Proxy responses have small but statistically significant differences from patient responses. However, if ratings of care are used for financial incentives, such differences could be exaggerated across practices or areas if proxy use varies.


Deletion of the mucin-like molecule muc1 enhances dendritic cell activation in response to toll-like receptor ligands.
Dendritic cells (DC) are potent professional antigen-presenting cells that drive primary immune responses to infections or other agonists perceived as 'dangerous'. Muc1 is the only cell surface mucin or MUC gene product that is expressed in DC. Unlike other members of this glycoprotein family, Muc1 possesses a unique cytosolic region capable of signal transduction and attenuating toll-like receptor (TLR) activation. The expression and function of Muc1 has been intensively investigated on epithelial and tumor cells, but relatively little is known about its function on DC. We hypothesized that Muc1 would influence in vitro generation and primary DC activation in response to the TLR4 and TLR5 ligands lipopolysaccharide and flagellin. Compared with Muc1(+/+) DC, we found that Muc1(-/-) DC were constitutively activated, as determined by higher expression of co-stimulatory molecules (CD40, CD80 and CD86), greater secretion of immunoregulatory cytokines (TNF-alpha and VEGF), and better stimulation of allogeneic naïve CD4+ T cell proliferation. After activation by either LPS or flagellin and co-culture with allogeneic CD4+ T cells, Muc1(-/-) DC also induced greater secretion of TNF-alpha and IFN-gamma compared to similarly activated Muc1(+/+) DC. Taken together, our results indicate that deletion of Muc1 promotes a heightened functional response of DC in response to TLR4 and TLR5 signaling pathways, and suggests a previously under-appreciated role for Muc1 in regulating innate immune responses of DC.


Selective inhibition of apicoplast tryptophanyl-tRNA synthetase causes delayed death in Plasmodium falciparum.
The malaria parasite Plasmodium falciparum relies on efficient protein translation. An essential component of translation is the tryptophanyl-tRNA synthetase (TrpRS) that charges tRNA(trp). Here we characterise two isoforms of TrpRS in Plasmodium; one eukaryotic type localises to the cytosol and a bacterial type localises to the remnant plastid (apicoplast). We show that the apicoplast TrpRS aminoacylates bacterial tRNA(trp) while the cytosolic TrpRS charges eukaryotic tRNA(trp). An inhibitor of bacterial TrpRSs, indolmycin, specifically inhibits aminoacylation by the apicoplast TrpRS in vitro, and inhibits ex vivo Plasmodium parasite growth, killing parasites with a delayed death effect characteristic of apicoplast inhibitors. Indolmycin treatment ablates apicoplast inheritance and is rescuable by addition of the apicoplast metabolite isopentenyl pyrophosphate (IPP). These data establish that inhibition of an apicoplast housekeeping enzyme leads to loss of the apicoplast and this is sufficient for delayed death. Apicoplast TrpRS is essential for protein translation and is a promising, specific antimalarial target.


Establishment of Full-Length cDNA Clones and an Efficient Oral Infection Model for Feline Coronavirus in Cats.
Feline infectious peritonitis virus (FIPV) is the etiologic agent of feline infectious peritonitis (FIP) and causes fatal disease in cats of almost all ages. Currently, there are no clinically approved drugs or effective vaccines for FIP. Furthermore, the pathogenesis of FIP is still not fully understood. There is an urgent need for an effective infection model of feline infectious peritonitis induced by FIPV. Here, we constructed a field type I FIPV full-length cDNA clone, pBAC-QS, corresponding to the isolated FIPV QS. By replacing the FIPV QS spike gene with the commercially available type II FIPV 79-1146 (79-1146_CA) spike gene, we established and rescued a recombinant virus, designated rQS-79. Moreover, we constructed 79-1146_CA infectious full-length cDNA pBAC-79-1146_CA, corresponding to recombinant feline coronavirus (FCoV) 79-1146_CA (r79-1146_CA). In animal experiments with 1- to 2-year-old adult cats orally infected with the recombinant virus, rQS-79 induced typical FIP signs and 100% mortality. In contrast to cats infected with rQS-79, cats infected with 79-1146_CA did not show obvious signs. Furthermore, by rechallenging rQS-79 in surviving cats previously infected with 79-1146_CA, we found that there was no protection against rQS-79 with different titers of neutralizing antibodies. However, high titers of neutralizing antibodies may help prolong the cat survival time. Overall, we report the first reverse genetics of virulent recombinant FCoV (causing 100% mortality in adult cats) and attenuated FCoV (causing no mortality in adult cats), which will be powerful tools to study pathogenesis, antiviral drugs, and vaccines for FCoV. IMPORTANCE Tissue- or cell culture-adapted feline infectious peritonitis virus (FIPV) usually loses pathogenicity. To develop a highly virulent FIPV, we constructed a field isolate type I FIPV full-length clone with the spike gene replaced by the 79-1146 spike gene, corresponding to a virus named rQS-79, which induces high mortality in adult cats. rQS-79 represents the first described reverse genetics system for highly pathogenic FCoV. By further constructing the cell culture-adapted FCoV 79-1146_CA, we obtained infectious clones of virulent and attenuated FCoV. By in vitro and in vivo experiments, we established a model that can serve to study the pathogenic mechanisms of FIPV. Importantly, the wild-type FIPV replicase skeleton of serotype I will greatly facilitate the screening of antiviral drugs, both in vivo and in vitro.


An FGFR inhibitor converts the tumor promoting effect of TGF-β by the induction of fibroblast-associated genes of hepatoma cells.
Tumors consistently mimic wound-generating chronic inflammation; however, why they do not heal like wounds with fibrotic scars remains unknown. The components of the tumor microenvironment, such as transforming growth factor β (TGF-β) and fibroblast growth factors (FGFs), may account for this phenomenon. Tumor formation involves continuous activation of the FGF pathway, whereas the repair of tissue injury is a self-limiting process accompanied with controlled activation of the FGF pathway. In the tumor microenvironment TGF-β increases the secretion of FGFs, further promoting the malignant biological properties of tumors. However, during wound healing, sufficient TGF-β together with moderate FGFs lead to matrix deposition and the formation of fibrotic scars. In the present study, TGF-β1 combined with AZD4547, an FGF receptor (FGFR) inhibitor, transformed hepatoma cells into less malignant fibroblast-like cells with respect to morphology, physiological properties, and gene expression profiles. In vivo experiments showed that TGF-β1 combined with AZD4547 not only inhibited tumor growth but also promoted tumor parenchyma fibrosis. Our results indicate that FGFR inhibitor treatment converts the effect of TGF-β on the hepatocellular carcinoma cells from tumor promotion into tumor inhibition by enhancing the induction effect of TGF-β on some fibroblast-associated genes. Converting human liver cancer cells into less malignant fibroblast-like cells and inducing tumor parenchyma cell fibrosis provides an alternative strategy for limiting tumor progression.


Perturbation analysis for the rotational spectrum of the NiBr radical in the X2Pi3/2 and A2Delta5/2 states.
The millimeter- and submillimeter-wave spectra of the NiBr radical in the X (2)Pi(3/2) and A (2)Delta(5/2) states were observed by a source-modulated microwave spectrometer. The NiBr radical was generated in a dc glow discharge through the mixture of Br(2) vapor and Ar gas by the sputtering reaction with a Ni cathode. Observed transition frequencies were independently analyzed for both electronic states using a standard polynomial expression of a Hund's case (c) approximation. Anomalous behavior of the effective molecular constants in the X (2)Pi(3/2) state was interpreted as the result of the perturbation between the X (2)Pi(3/2) and A (2)Delta(5/2) states. The deperturbed molecular constants were derived using a simplified supermultiplet Hamiltonian including the interaction terms between the two electronic states.


High-field THz source centered at 2.6 THz.
We demonstrate a table-top high-field terahertz (THz) source based on optical rectification of a collimated near-infrared pulse in gallium phosphide (GaP) to produce peak fields above 300 kV/cm with a spectrum centered at 2.6 THz. The experimental configuration, based on tilted-pulse-front phase matching, is implemented with a phase grating etched directly onto the front surface of the GaP crystal. Although the THz generation efficiency starts showing a saturation onset as the near-infrared pulse energy reaches 0.57 mJ, we can expect our configuration to yield THz peak fields up to 866 kV/cm when a 5 mJ generation NIR pulse is used. This work paves the way towards broadband, high-field THz sources able to access a new class of THz coherent control and nonlinear phenomena driven at frequencies above 2 THz.


Self-Propelled Micro-/Nanomotors Based on Controlled Assembled Architectures.
Synthetic micro-/nanomotors (MNMs) are capable of performing self-propelled motion in fluids through harvesting different types of energies into mechanical movement, with potential applications in biomedicine and other fields. To address the challenges in these applications, a promising strategy that combines controlled assembly (bottom-up approaches) with top-down approaches for engineering autonomous, multifunctionalized MNMs is under investigation, beginning in 2012. These MNMs, derived from layer-by-layer assembly or molecular self-assembly, display the advantages of: i) mass production, ii) response to the external stimuli, and iii) access to multifunctionality, biocompatibility, and biodegradability. The advance on how to integrate diverse functional components into different architectures based on controlled assemblies, to realize controlled fabrication, motion control (including the movement speed, direction, and state), and biomedical applications of MNMs, directed by the concept of nanoarchitectonics, are highlighted here. The remaining challenges and future research directions are also discussed.


Ru-, Rh- and Ir-Catalyzed Enantioselective sp3 C-H Functionalization.
The development of novel methodologies that enable the construction of complex chiral molecular scaffolds in an atom and step-economic manner has always been an area of immense interest and significant synthetic value. The transition metal-catalyzed enantioselective sp3 C-H activation and functionalization reactions serve as an expeditious means for introducing diverse functionalities in a straightforward manner. However, controlling the chemo- and stereoselectivity of these reactions is a significant challenge owing to their ubiquity and low reactivity. In this review, we present a comprehensive account on the recent advances in inter- and intramolecular asymmetric sp3 C-H bond functionalization utilizing ruthenium, rhodium, and iridium catalysts and get insights into the mechanistic aspects of these transformations.


Reparameterization of the Weibull model for practical uses in food science.
The reparameterization of the Weibull cumulative distribution function and its survival function was performed to obtain meaningful parameters in food and biological sciences such as the lag phase (λ), the maximum rate ( μ max ${\mu _{{\rm{max}}}}$ ), and the maximum increase/decrease of the function (A). The application of the Lambert function was crucial in order to achieve an explicit mathematical solution. Since the reparameterized model is applicable only when the shape parameter (α) is greater than one, the Weibull model was modified with the introduction of a new parameter ( μ β ${\mu _\beta }$ ) that represents the model rate at time β (scale parameter). All models were applied to literature data on food technology and microbiology topics: Microbial growth, thermal microbial inactivation, thermal degradation kinetics, and particle size distributions. The Weibull model and the reparameterized versions showed identical fitting performance in terms of coefficient of determination, residual mean standard error, values of residuals, and estimated values of the parameters. Some faults in the datasets used in this study permitted to re-mark the criticality of a good experimental plan when data modeling is approached. The parameter μ β ${\mu _\beta }$ resulted in an interesting new rate parameter that is not correlated with the scale parameter ( | r ¯ | $| {\bar{r}} |$ = 0.64 ± 0.37) and highly correlated with the shape parameter ( | r ¯ | $| {\bar{r}} |$ = 0.90 ± 0.11). Also, the reparameterization of the Weibull probability density function was performed by using both the standard and new parameters and applied to experimental data and gave useful information from the distribution curve, such as the value of the mode ( μ max ${\mu _{{\rm{max}}}}$ ) and a measure of the curve skewness (λ).


Barriers and facilitators to maintaining a high level of polypharmacy adherence in people living with HIV: A scoping review.
Objectives: With the prolongation of life span and increasing incidence of comorbidities, polypharmacy has become a challenge for people living with HIV/AIDS (PLWH). This review aimed to identify barriers and facilitators to maintaining a high level of polypharmacy adherence in people living with HIV/AIDS. Methods: Nine electronic databases were searched for studies from 1996 to October 2021. Studies were included if they were conducted with adults living with HIV/AIDS and reported barriers and facilitators to maintaining a high level of polypharmacy adherence. This review presents a conceptual framework model to help understand the barriers and facilitators. Results: Twenty-nine studies were included. The majority of publications were observational studies. Eighty specific factors were identified and further divided into five categories, including individual factors, treatment-related factors, condition-related factors, healthcare provider-related factors, and socioeconomic factors, based on the multidimensional adherence model (MAM). Conclusion: Eighty factors associated with polypharmacy adherence among people living with HIV/AIDS were identified and grouped into five major categories. Healthcare providers can make decisions based on the five categories of relevant factors described in this paper when developing interventions to enhance polypharmacy adherence. It is recommended that medications be evaluated separately and that an overall medication evaluation be conducted at the same time to prevent inappropriate polypharmacy use.


[Unusual aberrant location of a left internal jugular catheter].
Although aberrant locations were classical complications of central venous catheterization, the left superior diaphragmatic vein was an exceptional one. A case of this particular complication occurring after left internal jugular venous catheterization is described. The venous dilatation due to portal hypertension was probably partly responsible for this.


An electrochemical immunosensor for an alpha-fetoprotein cancer biomarker on a carbon black/palladium hybrid nanoparticles platform.
The early detection of cancer is a key step in cancer survival. Thus, there is a need to develop low-cost technologies, such as electrochemical immunosensor technologies, for timely screening and diagnostics. The discovery of alpha-feto protein (AFP) as a tumour-associated antigen lends AFP as a biomarker for cancer detection and monitoring. Thus, immunosensors can be developed to target AFP in cancer diagnostics. Hence, we report the application of a hybrid nanocomposite of carbon black nanoparticles (CBNPs) and palladium nanoparticles (PdNPs) as a platform for the electrochemical immunosensing of cancer biomarkers. The hybrid carbon-metal nanomaterials were immobilised by using the drop-drying and electrodeposition technique on a glassy carbon electrode, followed by the immobilisation of the anti-AFP to fabricate an immunosensor. The nanoparticles were characterised with electron microscopy, voltammetry, and electrochemical impedance spectroscopy (EIS). Square wave voltammetry (SWV) and EIS were used to study the immunosensor signal toward the bio-recognition of the AFP cancer biomarker. The hybrid nanoparticles enhanced the immunosensor performance. A linear detection range from 0.005 to 1000 ng mL-1 with low detection limits of 0.0039 ng mL-1 and 0.0131 ng mL-1 were calculated for SWV and EIS, respectively. The immunosensor demonstrated good stability, reproducibility, and selectivity. Its real-life application potential was tested with detection in human serum matrix.


[Severe acute asthma: its management in emergency visits and intensive care].
All patients with asthma are at risk of suffering an acute asthma attack over their lifetime, and these may finally be fatal. Hospitalizations and emergency department visits and intensive care account for a large proportion of the health-care cost burden of asthma. Thus, it is especially important to establish plans for prevention, education and therapeutic rationalization of primary care that establishes the disease and decreases its worsening. The severity of the exacerbations may vary from a mild to life threatening. The mortality is basically linked to inadequate assessment of the patient's severity. This leads to inadequate treatment in the emergency and delay in the patient's hospitalization. This review describes the epidemiology, costs, pathophysiology, mortality and management of adult acute asthma patients in the emergency department and intensive care, especially that related to non-invasive mechanical ventilation and conventional forms of mechanical respiratory care, with the current changes in its operational strategy.


Three-dimensional and four-dimensional fetal echocardiography: a new frontier.
One of the difficulties of conventional two-dimensional cardiac imaging is the inability to examine fetal cardiac anatomy from multiple angle planes. Three-dimensional and four-dimensional ultrasound allows the fetal examiner to more accurately accomplish this task. Currently, multiple disciplines may be involved in the examination of the fetal heart (pediatric cardiologists, obstetricians, maternal-fetal medicine specialists, and radiologists). The three-dimensional and four-dimensional imaging equipment used by these specialty physicians varies greatly. The purpose of this communication is to review techniques using three-dimensional and four-dimensional imaging that the pediatric cardiologist may not be exposed to in the clinical environment, however, in consulting with colleagues needs to have an understanding of these imaging modalities. The reconstruction of cardiac structures using this technology allows the examiner to view cardiac anatomy in a manner that was limited by previous two-dimensional imaging. Volume datasets are obtained in the three-dimensional static mode (no cardiac motion) or using four-dimensional - the three-dimensional heart is observed contracting during one or multiple cardiac cycles. Therefore, the fourth dimension is time. Using either three-dimensional or four-dimensional technology datasets are acquired, followed by image reconstruction. The image reconstruction enables the examiner to evaluate a two-dimensional image using multiple views, evaluate intracardiac anatomy at different depth planes, and recreate casts of blood flow of the chambers and great vessels. This new technology has enhanced the ability of the examiner to identify normal and complex fetal heart anatomy during the early second to the late third trimesters of pregnancy.


Kinetic speciation and bioavailability of copper and nickel in mangrove sediments.
An attempt was made to establish a mechanistic linkage between chemical speciation of copper and nickel, and their bioavailability in mangrove ecosystem. Kinetic speciation study was performed to determine the concentrations of labile metal-complexes and their dissociation rate constants in mangrove sediments. Concentrations of copper and nickel in the mangrove roots were used as indicators of their bioavailability. It was found that the bioaccumulation of both the metals gradually increased with the increasing concentrations of the labile metal complexes and their dissociation rate constants in the mangrove sediments. This study shows that concentration of labile metal (copper and nickel) complexes and their dissociation rate constants in mangrove sediment can be a good indicator of their bioavailability.


A videotape analysis procedure for assessing conversational fluency in hearing-impaired adults.
This article describes a method for analyzing conversational difficulties and communication breakdown management in hearing-impaired adults and their communicative partners. The focus of the analysis is placed on the examination of conversational floor control, the proportion of repaired and nonrepaired communication breakdowns, and the strategies used by each member of the dyad to repair breakdowns. A case study illustrating the application of the procedure for aural rehabilitation is presented.


Ultrasonographic anatomy of the normal canine calcaneal tendon.
To provide a series of detailed ultrasonographic images of the canine calcaneal tendon, greyhound cadaver pelvic limbs were scanned with a high-resolution transducer, and images compared with dissected specimens. The three components of the calcaneal tendon are the tendons of insertion of the gastrocnemius, superficial digital flexor, and a conjoined tendon formed by tendons from the biceps femoris, semitendinosus, and gracilis. Each of these three tendons was visible in transverse ultrasound images, each measuring 2.4-3.2-mm thick at mid-calcaneal tendon. Improved understanding of the anatomy of the calcaneal tendon will support clinical ultrasonography of this region.


Dextran sulphate induced arthritis in rabbits.
Persistent effects of a short course of intra-articular dextran sulphate, dextrans, or chondroitin sulphate were examined in rabbit knees. Only dextran sulphate produced gross arthritis, associated with high synovial acid phosphatase and beta-glucuronidase activities. Synovial degradative capacity in synovium-cartilage cocultures was increased 2-fold by dextran sulphate and 1.5-fold by chondroitin sulphate treatments. Stimulation of cartilage breakdown in vitro paralleled the content of synovial marker enzyme at death of the animal, but the 2 responses could be dissociated.


Mechanical properties across hypomineralized/hypoplastic enamel of first permanent molar teeth.
The aims of the present study were to investigate the mechanical properties of first permanent molars affected with enamel hypomineralization or hypoplasia, and to describe the appearance of these lesions under scanning electron microscopy. Eight first permanent molar test teeth and two unaffected premolars (controls) were enclosed in resin, then sectioned axially and polished. The hardness and modulus of elasticity was determined from a single array of indentations made parallel to the amelo-dentinal junction using an Ultra-Micro-Indentation system. The teeth were then examined using the scanning electron microscope. The mechanical properties of the test teeth in the unaffected cervical region (hardness and modulus range, 2.03-4.99 GPa and 50.39-96.87 GPa, respectively) were similar to those of the control enamel (hardness and modulus range, 2.71-4.15 GPa and 62.06-95.77 GPa, respectively). Between the unaffected cervical enamel and the hypomineralized region there was a transitional area of 500-600 microm where the mechanical properties in the experimental teeth decreased linearly. The mechanical properties of the hypomineralized region of each experimental tooth were significantly lower than those of the control or cervical regions (hardness and modulus range, 0.07-1.74 GPa and 3.26-40.96 GPa, respectively). The scanning electron microscopy views revealed disorganized enamel with poorly demarcated prism boundaries in the affected regions. In conclusion, the hardness and modulus of elasticity of hypomineralized enamel in first permanent molars is significantly less than in unaffected areas of the same tooth. The reason for this is unclear but may be related to the lack of organization of the enamel crystals.


Application of array-based genomic and epigenomic technologies to unraveling the heterogeneous nature of breast tumors: on the road to individualized treatment.
The recent application of genomic microarray technology to the molecular profiling of breast tumors has clearly demonstrated their heterogeneous nature. Targeted treatment strategies are having a clear impact on patient survival. It has also become apparent that accumulated mutations, genomic instability, epigenetic phenomena, genetic variability and environmental factors all contribute to the uniqueness of a patient's tumor. Novel genomic and epigenetic-based technologies have been or are being developed in order to greatly enhance the analysis of tumor samples including those samples previously thought unusable due to the fixation process, such as archival formalin-fixed paraffin-embedded (FFPE) samples. Patients and their tumors can now be studied with regard to genetic variation, genomic instability, gene expression, gene mutations, and methylation patterns. These areas of research are being made more accessible through genome-wide screening technologies and will, in the near future, rapidly expand our understanding of what contributes to the unique properties of each tumor and lead to the identification of genes that could be potential therapeutic targets for specific tumor subtypes. Application of these technologies to our understanding of breast cancer will undoubtedly have an impact on the individualization of treatment for breast cancer patients in the not to distant future.


Tartrate-resistant acid phosphatase activity in tibial osteoclasts and cells elicited by ectopic bone and suture implants in normal and osteopetrotic rats.
Bone-induced multinucleated cells have been suggested as surrogates for the study of osteoclastic lineage and function. This study evaluates this proposal by comparing acid phosphatase localization in tibial osteoclasts (in situ) with that of cell populations elicited by subcutaneous implantation of devitalized trabecular bone chips from two week old rats and suture into normal and osteopetrotic (ia) rats, emphasizing tartrate-resistant acid phosphatase, an osteoclastic marker. The ia rat mutation of osteopetrosis is characterized by defective osteoclasts which typically express enhanced TRAP activity when compared to normal; ia macrophage populations do not share the same osteoclastic defect and demonstrate normal amounts of acid phosphatase reactivity. The majority of the acid phosphatase activity expressed by implant-elicited mononuclear cells was tartrate sensitive. An increase in the percentage of tartrate-sensitive, but not TRAP-positive, mononuclear cells was observed during the 14-day implantation period, suggesting the mononuclear cells did not undergo osteoclastic differentiation. Both normal and ia osteoclasts contained high concentrations of TRAP reaction product (++) while bone- and suture-induced multinucleated cells examined at 14 days post-implantation were negative (0) or mildly (+) TRAP reactive. We conclude that devitalized bone matrix implanted at this ectopic site is capable of the formation of TRAP-positive (+) multinucleated cells, but when compared on the basis of strength of TRAP activity, the bone-induced multinucleated cells do not resemble active osteoclasts, but are similar to suture-elicited macrophage polykaryons. Therefore, we suggest caution in the use of bone-induced multinucleated cells as surrogates for the study of osteoclasts and normal bone resorption. Instead, these cells may represent a population of cells involved in pathological bone loss due to inflammation.


Polymerase chain reaction amplification products separated on rehydratable polyacrylamide gels and stained with silver.
Separation of polymerase chain reaction (PCR) amplification of specific fragment length polymorphisms was carried out on rehydratable polyacrylamide gels on a horizontal flat slab system. A discontinuous sulfate-borate buffer system was employed on 5-8% T gels crosslinked with 3.5% C. Samples were diluted in leading sulfate ion buffer at 1/10 the ionic strength of the separating gel buffer and placed directly onto the surface of the rehydrated gels in 0.5-10 microliters volumes. The trailing ion and counterion were contained in a gel plug and placed directly onto the anodal and cathodal ends of the gel, and the electrodes placed directly onto the surface of the gel plugs. Filter paper wicks, soaked in diluted leading ion buffer, were placed along each side to lower the ionic strength of the edges, thereby increasing mobility at the edge and thus preventing smile effects. The gel-gel contact of the plug and separating gel prevent the production of a junction potential which occurs between dissimilar materials such as a paper wick and the gel. Ten- to 20-cm separations were carried out from 2-5 h, respectively, and resolution in the 20 cm system was 1.6-4 bp (base pairs) between 100 and 500 bp, 4-7 bp between 500 and 1000 bp, 12-20 bp between 1000 and 2000 bp and about 50 bp between 2000 and 3000 bp. Between 3000 and 4000 bp, resolution fell off to +/- 100 bp. Sensitivity, using a silver stain, indicated that one could readily distinguish less than 10 pg of DNA per mm width on the gels.(ABSTRACT TRUNCATED AT 250 WORDS)


A rare and extensive summer bloom enhanced by ocean eddies in the oligotrophic western North Pacific Subtropical Gyre.
The North Pacific Subtropical Gyre (NPSG) is the largest ecosystem on Earth, and it plays a critical role in global ocean productivity and carbon cycling. Here, we report a rare and striking ~2000-km-long phytoplankton bloom that lasted over one month in the western part of the NPSG in summer 2003. The bloom resulted from the co-occurrence of a northward-shifted North Equatorial Current (NEC) supplying additional phosphate, and strong eddy activity that fueled productivity and spread chlorophyll mainly through horizontal stirring. The extensive one-month bloom had a maximum Chl concentration of six times the summer mean value and collectively fixed an additional five teragrams (5 × 1012 g) of carbon above the summer average. An increase in the pCO2 during the bloom suggests that most of the additionally fixed carbon was rapidly consumed.


Prevention of capsular contracture with Guardix-SG(®) after silicone implant insertion.
Capsular contracture is the most common side effect of breast implant insertion and the problem that breast surgeons seek to avoid the most. Previous animal studies have proved that an antiadhesive barrier solution (AABS) prevents peri-implant capsule formation. In this study, the authors sought to explore the effect that Guardix-SG(®), an AABS that can encapsulate implants in the form of a gel, can have on capsular contracture. This study used 12 female New Zealand white rabbits weighing 2.5-3 kg. Implants were inserted into the subpanniculus carnosus plane through an incision in the bilateral midback area. Once the implant was inserted, 3 g of Guardix-SG(®) and normal saline were instilled into the left and right sides, respectively. The rabbits were killed 6 months after the procedure. The intracapsular pressure was measured using tonometry with a 38.2-g circular glass piece, and capsular thickness was measured by dyeing the biopsy specimen with hematoxylin and eosin and Masson's trichrome stain. The myofibroblasts were quantitatively analyzed through monoclonal anti-alpha smooth muscle actin antibody immunohistochemistry staining. The intracapsular pressure in the control group (4.51 ± 0.98 mmHg) was significantly higher (p = 0.002) than in the study group (3.51 ± 0.4 mmHg). The average capsular thickness was significantly greater in the control group (0.33 ± 0.15 mm; p = 0.015). In the analysis, the interrelation between capsular thickness and intracapsular pressure was insignificant in both groups, as was the number of myofibroblasts in both groups (p = 0.582). Through this study, the authors were able to demonstrate that capsular contracture can be suppressed in the rabbit model by instilling Guardix-SG(®) after insertion of cohesive gel implants in the subpanniculus carnosus plane. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Dental caries risk in relation to dietary habits and dental services in two industrial populations.
Environmental hazards contribute to the poor oral health in many occupations. Among the earliest occupations mentioned are those of the baker and confectionery worker. To determine appropriate ways of promoting oral health in places of work, factors affecting caries susceptibility were studied. Dental caries status, dietary and dental health behaviors, and salivary microbiologic findings in 338 confectionery and 101 shipyard workers were compared. A caries risk index based on salivary findings was used in log-linear models where the effects of sex, diet, use of dental services, and work environment were studied. Caries experience was found to be high in both populations. Dietary habits were the most important factor affecting caries occurrence and susceptibility. Similar dietary behaviors were found in both groups. The confectionery industry did not seem to be an exceptionally hazardous environment for dental health in general. However, the screening of high-risk workers should be organized. Reimbursement of costs had no major effect on use of dental services or caries risk. Oral health promotion should be integrated with existing occupational health services to improve oral health in industrial populations.


[Pregnancy following cytostatic treatment of trophoblast tumor].
Observation of 18 pregnancies in 13 women who had undergone treatment for trophoblastic neoplasm with cytostatic drugs confirmed reports according to which the risk of miscarriage, premature birth, stillbirth, and severe congenital anomalies is not increased. Seven low-risk patients who had been treated with methotrexate gave birth to 10 children who were mature except for one pair of premature twins. Only one child had an anomaly, i.e. celiac disease, but this could not be linked to the prior treatment. Three high-risk patients who had been treated with methotrexate or methotrexate with actinomycin-D gave birth to four children, all of whom were mature and healthy. Intensive prenatal care, and in particular diagnosis at the beginning of pregnancy, are of great importance. At least one year must elapse between termination of chemotherapy and the beginning of a pregnancy. Effective contraception must be assured during this time.


Exercise, energy expenditure and energy balance, as measured with doubly labelled water.
The doubly labelled water method for the measurement of total daily energy expenditure (TDEE) over 1-3 weeks under daily living conditions is the indicated method to study effects of exercise and extreme environments on energy balance. Subjects consume a measured amount of doubly labelled water (2H2 18O) to increase background enrichment of body water for 18O and 2H, and the subsequent difference in elimination rate between 18O and 2H, as measured in urine, saliva or blood samples, is a measure for carbon dioxide production and thus allows calculation of TDEE. The present review describes research showing that physical activity level (PAL), calculated as TDEE (assessed with doubly labelled water) divided by resting energy expenditure (REE, PAL = TDEE/REE), reaches a maximum value of 2·00-2·40 in subjects with a vigorously active lifestyle. Higher PAL values, while maintaining energy balance, are observed in professional athletes consuming additional energy dense foods to compete at top level. Exercise training can increase TDEE/REE in young adults to a value of 2·00-2·40, when energy intake is unrestricted. Furthermore, the review shows an exercise induced increase in activity energy expenditure can be compensated by a reduction in REE and by a reduction in non-exercise physical activity, especially at a negative energy balance. Additionally, in untrained subjects, an exercise-induced increase in activity energy expenditure is compensated by a training-induced increase in exercise efficiency.


Parental programming: how can we improve study design to discern the molecular mechanisms?
The contribution of inherited non-genetic factors to complex diseases is of great current interest. The ways in which mothers and fathers can affect their offspring's health clearly differ as a result of the intimate interactions between mother and offspring during pre- and postnatal life. There is, however, potential for some overlap in mechanisms, particularly epigenetic mechanisms. A small number of epidemiological studies and animal models have investigated the non-genetic contribution of the parents to offspring health. Discovering new mechanisms of disease inheritance is technically difficult, especially in genetically, socially and environmentally heterogeneous human populations. Therefore, rigorous experimental design, appropriate sample numbers and the use of high-throughput technologies are necessary to provide convincing evidence. Based on recent examples from the literature, here we propose several ways to improve human studies that aim to identify the underlying mechanisms of transgenerational inheritance of metabolic disease.


Lévy-type diffusion on one-dimensional directed Cantor graphs.
Lévy-type walks with correlated jumps, induced by the topology of the medium, are studied on a class of one-dimensional deterministic graphs built from generalized Cantor and Smith-Volterra-Cantor sets. The particle performs a standard random walk on the sets but is also allowed to move ballistically throughout the empty regions. Using scaling relations and the mapping onto the electric network problem, we obtain the exact values of the scaling exponents for the asymptotic return probability, the resistivity, and the mean-square displacement as a function of the topological parameters of the sets. Interestingly, the system undergoes a transition from superdiffusive to diffusive behavior as a function of the filling of the fractal. The deterministic topology also allows us to discuss the importance of the choice of the initial condition. In particular, we demonstrate that local and average measurements can display different asymptotic behavior. The analytic results are compared to the numerical solution of the master equation of the process.


Identification and Comparative Analysis of Long Non-Coding RNA in the Skeletal Muscle of Two Dezhou Donkey Strains.
Long non-coding RNA (lncRNA) has been extensively studied in many livestock. However, compared with other livestock breeds, there is less research regarding donkey lncRNA function. It has been reported that lncRNA plays an important role in the timing control of development, aging, and death of livestock. Therefore, the study of donkey skeletal muscle lncRNA is of great significance for exploring donkey meat production performance. In this study, RNA-Seq was used to perform high-throughput sequencing of skeletal muscle (longissimus dorsi and gluteus) of two Dezhou donkey strains (SanFen and WuTou). The differentially expressed lncRNAs were screened between different strains and tissues. Then candidate genes for conjoint analysis were screened based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, the accuracy of the sequencing data was verified by real-time quantitative polymerase chain reaction (RT-qPCR). Herein, we identified 3869 novel lncRNAs and 73 differentially expressed lncRNAs. Through the comparison between groups, the specific expression of lncRNAs were found in different strains and muscle tissues. Importantly, we constructed the lncRNA-miRNA-mRNA interaction network and found three important candidate lncRNAs (MSTRG.9787.1, MSTRG.3144.1, and MSTRG.9886.1) and four candidate genes (ACTN1, CDON, FMOD, and BMPR1B). Analysis of the KEGG pathway indicates that the TGF-β signaling pathway plays a pivotal role in the growth and development of skeletal muscle in Dezhou donkey strains.


[Outcome of intensive care].
The mean hospital mortality of patients after intensive therapy in Germany is about 15%, the mortality within the intensive care unit about 8%. Short-term prognosis is mainly determined by severity of disease, type of disease and patient age. The impact of disease severity is measured by acute physiology score systems. The significance of disease categories becomes apparent in disease states with a continuing high mortality. Age is an independent risk factor. The higher risk of older patients cannot be explained by different diagnosis, and it is not secondary to a less aggressive therapy. The same factors mainly determine long-term prognosis. The 5-year-survival rate after intensive therapy is around 60%, a 3-fold increase as compared to the general population. Dependent upon the disease category, survival curves of intensive care patients parallel survival curves of the general population 2 years after admission. Analysis of quality of life is based upon objective measurement and subjective estimation of health-related life quality in the physical, psychological, and social life domain. Patients after intensive therapy experience a moderate but significant decrease in quality of life. This is the case in global estimations of quality of life as well as in investigations of different life domains. The remaining quality of life is tolerable. This is in accordance with the positive overall judgement of intensive care by patients themselves. The chief problem of intensive care remain diseases with continuing high mortality.


The efficacy of different anti-vascular endothelial growth factor agents and prognostic biomarkers in monitoring of the treatment for myopic choroidal neovascularization.
To evaluate anatomical and visual results of eyes with naive myopic choroidal neovascularization (mCNV) in patients treated with intravitreal anti-vascular endothelial growth factor (VEGF) therapies. This is a retrospective, non-randomized, comperative, intervetional study. One hundred fourteen eyes of 114 patients with mCNV who underwent intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR) or intravitreal aflibercept (IVA) monotherapy injections were enrolled into the study. The best corrected visual acuity (BCVA), central macular thickness (CMT) and subfoveal choroidal thickness (SFCT) were compared among the groups during the follow-up periods at the beginning, months 1, 3, 6, 12, and the final visit. The mean age of the patients was 47.76 ± 10.57 years (range, 33-72 years) and the mean follow-up period was 23.34 ± 6.81 months (range, 13-38 months). The mean BCVA denoted a significantly improve at each group (p < 0.05). In terms of an inter-group analysis of all 3 groups, at months 1, 6, and 12 and final visit, the BCVA were statistically significantly better in the IVA group when compared to both IVB and IVR groups (p = 0.021, p = 0.032, p = 0.024, p = 0.012). There was a significant decrease in CMT following IVB (236.49 ± 40.91 μm-190.74 ± 50.12 μm), IVA (232.91 ± 46.29 μm-193.73 ± 46.81 μm) and IVR (234.78 ± 45.37 μm-192.21 ± 37.27 μm) between baseline and final visit (p = 0.018, p = 0.002, p < 0.001, respectively). There was a statistically significant decrease in SFCT values between baseline and final examination only in the IVA group (p < 0.001). The mean number of injections were 9.18 ± 3.18 (range; 3 to 13) in IVB, 6.46 ± 2.93 (range; 3-11) in IVR and 4.45 ± 1.42 (range; 2-7) in IVA (p = 0.028). All three anti-VEGFs were found to be effective in terms of visual results in patients with mCNV. However, we demonstrated that IVA reduces the need for anti-VEGF when compared to patients who received both IVB and IVR. Furthermore, IVA induced a prominent reduction in SFCT, whereas IVR and IVB did not have a significant action on SFCT.


Overexpression of X Intrinsic Protein 1;1 in Nicotiana tabacum and Arabidopsis reduces boron allocation to shoot sink tissues.
Major Intrinsic Proteins (MIP) are a family of channels facilitating the diffusion of water and/or small solutes across cellular membranes. X Intrinsic Proteins (XIP) form the least characterized MIP subfamily in vascular plants. XIPs are mostly impermeable to water but facilitate the diffusion of hydrogen peroxide, urea and boric acid when expressed in heterologous expression systems. However, their transport capabilities in planta and their impact on plant physiology are still unknown. Here, we demonstrated that overexpression of NtXIP1;1 in Nicotiana tabacum by the En2pPMA4 or the 35S CaMV promoter and in Arabidopsis, which does not contain any XIP gene, by the 35S CaMV promoter, resulted in boron (B)-deficiency symptoms such as death of the shoot apical meristem, infertile flowers, and puckered leaves. Leaf B concentrations in symptomatic tissues and B xylem sap concentrations were lower in the overexpressors than in control plants. Importantly, expression of NtXIP1;1 under the control of the AtNIP5;1 promoter complemented the B deficiency phenotype of the Atnip5;1 knockout mutant, defining its ability to act as a boric acid channel in planta. Protein quantification analysis revealed that NtXIP1;1 was predominantly expressed in young B-demanding tissues and induced under B-deficient conditions. Our results strongly suggest that NtXIP1;1 plays a role in B homeostasis and its tissue-specific expression critically contributes to the distribution of B within tobacco.


Coping, PTSD symptoms, and alcohol involvement in trauma-exposed college students in the first three years of college.
The objective of the present study was to examine prospective, bidirectional associations among posttraumatic stress disorder (PTSD) symptoms, coping style, and alcohol involvement (use, consequences) in a sample of trauma-exposed students just entering college. We also sought to test the mechanistic role that coping may play in associations between PTSD symptoms and problem alcohol involvement over time. Participants (N = 734) completed measures of trauma exposure, PTSD symptoms, coping, and alcohol use and consequences in September of their first college year and again each September for the next 2 years. We observed reciprocal associations between PTSD and negative coping strategies. In our examination of a mediated pathway through coping, we found an indirect association from alcohol consequences and PTSD symptoms via negative coping, suggesting that alcohol consequences may exacerbate posttraumatic stress over time by promoting negative coping strategies. Trauma characteristics such as type (interpersonal vs. noninterpersonal) and trauma reexposure did not moderate these pathways. Models were also invariant across gender. Findings from the present study point to risk that is conferred by both PTSD and alcohol consequences for using negative coping approaches, and through this, for posttraumatic stress. Interventions designed to decrease negative coping may help to offset this risk, leading to more positive outcomes for those students who enter college with trauma exposure.


[Effects of hFRNK on E-cadherin/beta-catenin in colon cancer cells in vitro].
To explore the effects of human FRNK gene on E-cadherin/beta-catenin complex in colon cancer cell line Colo320WT cells stimulated with extrinsic gastrinl7. AdEasy system was used to construct pAdhFRNK expressing human FRNK gene by recombination in E. coli. BJ5283. pCR3.1/GR plasmid expressing gastrin receptor CCK-2 was transfected into colon cancer cell line Colo320 cells by Lipofectamine 2000 and expressing stably CCK-2R clones were screened by G418 (500 pg/ml). The expression levels of gastrin receptor in Colo320 cells and the transfected Colo320WT cells were assayed by RT-PCR. Colo320WT cells were treated by 10(-8) mol/L gastrinl7 for 12 h; and after Colo320WT cells were infected by pAdhFRNK (MOI: 100) for 2 d the cells were treated by gastrin17 for 12 h again. The expression levels of E-cadherin and beta-catenin in TX-100 soluble fraction and TX-100 insoluble fraction of Colo320WT cells were assayed by co-immunoprecipation and Western blot. E-cadherin and beta-catenin's distribution in Colo320WT cells were detected by immunocytochemistry. When 10(-8) mol/L gastrin17 stimulated Colo320WT cells for 12 h, the expression levels of E-cadherin and beta-catenin in TX-100-soluble fraction decreased apparently, while the expression levels of E-cadherin and beta-catenin in TX-100-insoluble fraction increased markedly. When pAdhFRNK infected Colo320WT cells for 2 d and 10(-8) mol/L gastrin17 treated the cells for 12 h, the expression levels of E-cadherin and beta-catenin in TX-100-soluble fraction increased apparently again, and the expression levels of E-cadherin and beta-catenin in TX-100-insolutble fraction decreased markedly. Immunocytochemistry showed that the distribution of E-cadherin and beta-catenin was translocated from plasma membrane into cytoplasm and nucleus in the cells stimulated with gastrinl7, and after the cells were infected with pAdhFRNK and stimulated by gastrinl7 again. beta-catenin was mainly observed in cytoplasm and little nuclear immunoreactivity. An adenovirus vector pAdhFRNK can inhibit abnormal distribution of E-cadherin and beta-catenin in the gastrin17-stimulated cells. The mechanism is probably that hFRNK can disphosphorylate phosphorylated FAK and block FAK pathway.


A critical subset model provides a conceptual basis for the high antiviral activity of major HIV drugs.
Control of HIV-1 replication was first achieved with regimens that included a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI); however, an explanation for the high antiviral activity of these drugs has been lacking. Indeed, conventional pharmacodynamic measures like IC(50) (drug concentration causing 50% inhibition) do not differentiate NNRTIs and PIs from less active nucleoside reverse transcriptase inhibitors (NRTIs). Drug inhibitory potential depends on the slope of the dose-response curve (m), which represents how inhibition increases as a function of increasing drug concentration and is related to the Hill coefficient, a measure of intramolecular cooperativity in ligand binding to a multivalent receptor. Although NNRTIs and PIs bind univalent targets, they unexpectedly exhibit cooperative dose-response curves (m > 1). We show that this cooperative inhibition can be explained by a model in which infectivity requires participation of multiple copies of a drug target in an individual life cycle stage. A critical subset of these target molecules must be in the unbound state. Consistent with experimental observations, this model predicts m > 1 for NNRTIs and PIs and m = 1 in situations where a single drug target/virus mediates a step in the life cycle, as is the case with NRTIs and integrase strand transfer inhibitors. This model was tested experimentally by modulating the number of functional drug targets per virus, and dose-response curves for modulated virus populations fit model predictions. This model explains the high antiviral activity of two drug classes important for successful HIV-1 treatment and defines a characteristic of good targets for antiviral drugs in general, namely, intermolecular cooperativity.


Implantation of Implantable Collamer Lenses After Radial Keratotomy.
To assess the predictability, efficacy, and safety of posterior chamber phakic implantable collamer lens (ICL) implantation after radial keratotomy. In a retrospective non-comparative interventional case series, outcomes in 6 consecutive eyes of 4 patients with residual refraction after radial keratotomy were analyzed after the implantation of ICLs. All of the lenses were implanted to correct the residual refractive error, ranging from -12.00 to +3.50 diopters (D) for sphere and from -0.75 to -3.75 D for cylinder. The mean uncorrected distance visual acuity after ICL implantation was 0.31 ± 0.36 logMAR and the corrected distance visual acuity was 0.12 ± 0.10 logMAR. The mean efficacy index was 0.86. No eyes lost lines of visual acuity, two eyes did not change after surgery, two eyes gained one line, and two eyes gained two lines. The mean safety index was 1.17. No intraoperative complications were found and ICL explantation or repositioning was not required during the follow-up. No cases of cataract, pigment dispersion glaucoma, pupillary block, or other vision-threatening complications were found. ICL implantation may be considered a reasonable surgical procedure for correcting residual refractive errors after radial keratotomy. [J Refract Surg. 2017;33(6):395-398.].


Corneal-Reflection Eye-Tracking Technique for the Assessment of Horizontal Sound Localization Accuracy from 6 Months of Age.
The evaluation of sound localization accuracy (SLA) requires precise behavioral responses from the listener. Such responses are not always possible to elicit in infants and young children, and procedures for the assessment of SLA are time consuming. The aim of this study was to develop a fast, valid, and objective method for the assessment of SLA from 6 months of age. To this end, pupil positions toward spatially distributed continuous auditory and visual stimuli were recorded. Twelve children (29 to 157 weeks of age) who passed the universal newborn hearing screening and eight adults (18 to 40 years of age) who had pure-tone thresholds ≤20 dB HL in both ears participated in this study. Horizontal SLA was measured in a sound field with 12 loudspeaker/display (LD)-pairs placed in an audiological test room at 10 degrees intervals in the frontal horizontal plane (±55 degrees azimuth). An ongoing auditory-visual stimulus was presented at 63 dB SPL(A) and shifted to randomized loudspeakers simultaneously with pauses of the visual stimulus. The visual stimulus was automatically reintroduced at the azimuth of the sounding loudspeaker after a sound-only period of 1.6 sec. A corneal-reflection eye-tracking technique allowed the acquisition of the subjects' pupil positions relative to the LD-pairs. The perceived azimuth was defined as the median of the intersections between gaze and LD-pairs during the final 500 msec of the sound-only period. Overall SLA was quantified by an Error Index (EI), where EI = 0 corresponded to perfect match between perceived and presented azimuths, whereas EI = 1 corresponded to chance. SLA was rapidly measured in children (mean = 168 sec, n = 12) and adults (mean = 162 sec, n = 8). Visual inspection of gaze data indicated that gaze shifts occurred in sound-only periods. The medians of the perceived sound-source azimuths either coincided with the presenting sound-source azimuth or were offset by a maximum of 20 degrees in children. In contrast, adults revealed a perfect match from -55 to 55 degrees, except at 15 degrees azimuth (median = 20 degrees), with 9/12 of the quartile ranges = 0 degrees. Children showed a mean (SD) EI of 0.42 (0.17), which was significantly higher than that in adults (p < 0.0001). However, children revealed a distinct age-related EI improvement of 16 percentage points per year (r = -0.68, p = 0.015, n = 12), suggesting an ongoing maturation of SLA in the studied age range (29 to 157 weeks). The eight adults showed high SLA and high reliability as demonstrated by the low mean (SD) EI (0.054 [0.021]) and the low variability in test-retest differences (95% confidence interval = -0.020 to 0.046). Corneal-reflection eye-tracking provides an objective and fast assessment of horizontal SLA from about 6 months of age and may enable gaze to be used as an objective measure for sound localization in this age group. Infant SLA is immature and improvements are related to increasing age. Adults show high overall SLA and low intra- and intersubject variability in SLA. The technique may be used as a clinical tool for the evaluation of very early intervention in a young, preverbal population and throughout the life span.


Transcriptomes of parents identify parenting strategies and sexual conflict in a subsocial beetle.
Parenting in the burying beetle Nicrophorus vespilloides is complex and, unusually, the sex and number of parents that can be present is flexible. Such flexibility is expected to involve specialized behaviour by the two sexes under biparental conditions. Here, we show that offspring fare equally well regardless of the sex or number of parents present. Comparing transcriptomes, we find a largely overlapping set of differentially expressed genes in both uniparental and biparental females and in uniparental males including vitellogenin, associated with reproduction, and takeout, influencing sex-specific mating and feeding behaviour. Gene expression in biparental males is similar to that in non-caring states. Thus, being 'biparental' in N. vespilloides describes the family social organization rather than the number of directly parenting individuals. There was no specialization; instead, in biparental families, direct male parental care appears to be limited with female behaviour unchanged. This should lead to strong sexual conflict.


Relaxation and metastability in a local search procedure for the random satisfiability problem.
An analysis of the average properties of a local search procedure (RandomWalkSAT) for the satisfaction of random Boolean constraints is presented. Depending on the ratio alpha of constraints per variable, reaching a solution takes a time T(res) growing linearly [T(res) approximately tau(res)(alpha)N, alpha<alpha(d)] or exponentially (T(res) approximately exp[N zeta(alpha)], alpha>alpha(d)) with the size N of the instance. The relaxation time tau(res)(alpha) in the linear phase is calculated through a systematic expansion scheme based on a quantum formulation of the evolution operator. For alpha>alpha(d), the system is trapped in some metastable state, and resolution occurs from escape from this state through crossing of a large barrier. An annealed calculation of the height zeta(alpha) of this barrier is proposed. The polynomial to exponential cross-over alpha(d) approximately =2.7 is not related to the onset of clustering among solutions occurring at alpha approximately =3.86.


Segmentation of MR Brain Images Through Hidden Markov Random Field and Hybrid Metaheuristic Algorithm.
Image segmentation is one of the most critical tasks in Magnetic Resonance (MR) images analysis. Since the performance of most current image segmentation methods is suffered by noise and intensity non-uniformity artifact (INU), a precise and artifact resistant method is desired. In this work, we propose a new segmentation method combining a new Hidden Markov Random Field (HMRF) model and a novel hybrid metaheuristic method based on Cuckoo search (CS) and Particle swarm optimization algorithms (PSO). The new model uses adaptive parameters to allow balancing between the segmented components of the model. In addition, to improve the quality of searching solutions in the Maximum a posteriori (MAP) estimation of the HMRF model, the hybrid metaheuristic algorithm is introduced. This algorithm takes into account both the advantages of CS and PSO algorithms in searching ability by cooperating them with the same population in a parallel way and with a solution selection mechanism. Since CS and PSO are performing exploration and exploitation in the search space, respectively, hybridizing them in an intelligent way can provide better solutions in terms of quality. Furthermore, initialization of the population is carefully taken into account to improve the performance of the proposed method. The whole algorithm is evaluated on benchmark images including both the simulated and real MR brain images. Experimental results show that the proposed method can achieve satisfactory performance for images with noise and intensity inhomogeneity, and provides better results than its considered competitors.


Classifying End-of-Life Patterns: Evidence From the National Health and Aging Trends Study.
End-of-life (EOL) care quality encompasses multiple domains, which are typically studied in silos. This paper explores interrelationships across domains and how they simultaneously shape patterns of EOL care quality. Secondary analysis using National Health and Aging Trends Study. Latent class analysis was used to identify subgroups of decedents according to quality of symptoms and needs management, care experience, care processes, and site of death. Multinomial logistic regression was employed to investigate the association between decedent characteristics and class membership. Five groups of decedents were identified. Multiple sites of death with high care coordination (Class 4: 35%) comprised decedents with least concerns regarding symptom management and care experience. Decedents in Predominantly home deaths with no hospice use (Class 1: 26%), predominantly hospital deaths with low hospice use (Class 2: 18%), and multiple sites of death with hospice use (Class 3: 7%) presented similar symptom management and care experience patterns. Multiple sites of death with low care coordination (Class 5: 14%) comprised decedents experiencing poor quality EOL care across multiple domains. Non-Hispanic Black and Hispanic decedents were more likely to be in Class 2 and decedents with dementia diagnosis in Class 4. There is considerable heterogeneity in EOL care patterns. Assessing quality based on discrete metrics in silos may lead to unintended consequences like stinting of necessary care or increased caregiving burden on families. There is a need for greater focus on patient-centeredness and how care processes and structures interact in the context of shifting care patterns, care preferences, and payment reforms.


Fungal infection associated with intravenous drug abuse: a case of localized cerebral phycomycosis.
The authors present a case of confusion and mood disturbance caused by a focal cerebral fungal (phycomycosis) infection in an otherwise healthy intravenous drug addict. A review of the literature found only 9 cases of phycomycosis with localized cerebral involvement. This report describes the sixth occurrence of phycomycosis in an intravenous drug addict (the fifth to localize in the basal ganglia). In addition to the human immunodeficiency virus, unusual infectious causes of confusion and mood disturbance may be increasing as the intravenous drug-using population expands. Recognition of the clinical features of a fungal infection in a high-risk population may lead to earlier diagnosis and more effective treatment of this uniformly fatal disease. The clinician should consider localized cerebral phycomycosis as a cause of confusion and mood disturbance in intravenous drug addicts, especially when there is evidence of basal ganglia involvement.


VLDL hydrolysis by hepatic lipase regulates PPARδ transcriptional responses.
PPARs (α,γ,δ) are a family of ligand-activated transcription factors that regulate energy balance, including lipid metabolism. Despite these critical functions, the integration between specific pathways of lipid metabolism and distinct PPAR responses remains obscure. Previous work has revealed that lipolytic pathways can activate PPARs. Whether hepatic lipase (HL), an enzyme that regulates VLDL and HDL catabolism, participates in PPAR responses is unknown. Using PPAR ligand binding domain transactivation assays, we found that HL interacted with triglyceride-rich VLDL (>HDL≫LDL, IDL) to activate PPARδ preferentially over PPARα or PPARγ, an effect dependent on HL catalytic activity. In cell free ligand displacement assays, VLDL hydrolysis by HL activated PPARδ in a VLDL-concentration dependent manner. Extended further, VLDL stimulation of HL-expressing HUVECs and FAO hepatoma cells increased mRNA expression of canonical PPARδ target genes, including adipocyte differentiation related protein (ADRP), angiopoietin like protein 4 and pyruvate dehydrogenase kinase-4. HL/VLDL regulated ADRP through a PPRE in the promoter region of this gene. In vivo, adenoviral-mediated hepatic HL expression in C57BL/6 mice increased hepatic ADRP mRNA levels by 30%. In ob/ob mice, a model with higher triglycerides than C57BL/6 mice, HL overexpression increased ADRP expression by 70%, demonstrating the importance of triglyceride substrate for HL-mediated PPARδ activation. Global metabolite profiling identified HL/VLDL released fatty acids including oleic acid and palmitoleic acid that were capable of recapitulating PPARδ activation and ADRP gene regulation in vitro. These data define a novel pathway involving HL hydrolysis of VLDL that activates PPARδ through generation of specific monounsaturated fatty acids. These data also demonstrate how integrating cell biology with metabolomic approaches provides insight into specific lipid mediators and pathways of lipid metabolism that regulate transcription.