Conflict-of-interest, copyright and other declarations.
Declarations of exclusive publication, author contribution, conflict-of-interest and copyright transfer are important formalities required by most biomedical journals. Conflict-of-interest may be personal, commercial, political, academic or financial. It is particularly important for authors to provide a full and complete disclosure of any financial relationship with a commercial organisation that may have an interest in the contents of the submitted manuscript. Editors, editorial board members and reviewers should also declare any possible conflicts-of-interest. The handling of conflict-of-interest during manuscript preparation, peer review and editorial decision making impacts the credibility of published articles and scientific research in general.


Caregiver involvement in behavioural health services in the context of child welfare service referrals: a qualitative study.
Human service agencies serve a growing number of adults with behavioral health needs. Despite these agencies' key role in identifying need and facilitating services, many individuals do not receive care or end services prematurely. Few studies have explored the experiences of families referred to behavioral health services by such agencies or the extent to which families' perceptions of service need align with those of treatment providers and frontline workers. This study presents findings from a qualitative study of caregivers involved with child welfare agencies who were referred to behavioral health services. Researchers reviewed agencies' case records and conducted in-depth interviews with 16 caregivers, 9 child welfare caseworkers, and 12 behavioral health treatment counselors. Findings suggest that when deciding to engage in services, caregivers weigh not only their individual and family behavioral health needs but also potential agency intervention, including loss of child custody. Many professionals reported that involvement with a child welfare agency hindered the caregiver's disclosure of behavioral health care needs. Implications for managers and practitioners are discussed.


W7-X magnetic diagnostics: Rogowski coil performance for very long pulses.
Stellerators can be operated without the need of significant plasma current for generation of poloidal magnetic field components. Wendelstein 7-X (W7-X) is optimized for stiff magnetic configurations by minimizing pressure driven currents, such as bootstrap and Pfirsch-Schluter currents. In Addition to the largely reduced plasma currents, the HELIAS-type device is a low magnetic shear configuration required for magnetic boundary islands. However, the diverting magnetic field structure is already influenced by small net plasma currents. In particular, the W7-AS divertor results revealed a significant sensitivity of the X-point location with respect to favorable edge plasma states. Thus, a precise X-point control for W7-X is envisaged and, although expected net plasma currents range in the order of 10-100 kA only, stabilization by adaptive controllers is foreseen to an accuracy of about 1 kA. This stabilization should be reliable even after 2000 s of plasma operation. A precondition for achieving this is a reliable current detection. For this purpose, W7-X will be equipped with Rogowski of which the first has now been assembled onto one of the plasma vessel sectors. The integral performance and sensitivity inhomogeneities have been tested by employing the digital integrator of W7-X [A. Werner, Rev. Sci. Instrum. 77, 10E307 (2006)] and a cable energized with 200 A, representing the plasma current.


Age-Dependent Effects of Prenatal Dexamethasone Exposure on Immune Responses in Male Rats.
Prenatal glucocorticoid therapy is indicated in preterm delivery to prevent respiratory distress. This study was designed to evaluate the age-dependent effects of prenatal dexamethasone (DEX) therapy on the immune system using a rat model. Pregnant Sprague-Dawley rats received an intraperitoneal injection of DEX (0.1 mg/kg/day) or saline (VEH) over gestational days 14-20. Male offspring were sacrificed at postnatal day 7 (D7; infant stage), D120 (young adult stage), and D180 (adult stage) for evaluation of leukocyte subsets and isolation of splenocytes. The production of innate and adaptive immune cytokines was assessed from the culture supernatants of splenocytes, stimulated with lipopolysaccharide and concanavalin A, respectively. For innate cytokines, the levels of interferon gamma inducible protein 10 were significantly higher, but those of tumor necrosis factor-α were significantly lower, in the culture medium of splenocytes prepared from the DEX group at D120 than those in the VEH group. For adaptive cytokines, the levels of interleukin-4 (IL-4) were significantly higher at D7 and those of IL-10 were significantly higher at D120 after prenatal exposure to DEX. We also showed that the expression level of IL-4 mRNA was significantly higher in splenocytes prepared from the DEX group at D7, compared with the VEH group. Importantly, the mRNA expression level of T-bet, a key transcription factor for immune cells, was greatly decreased in the spleen of the DEX group at D7, compared with the VEH group. In conclusion, prenatal dexamethasone exposure shows the greater impact on immune responses of their male offspring in early life.


Three potential neurovascular pathways driving the benefits of mindfulness meditation for older adults.
Mindfulness meditation has been shown to be beneficial for a range of different health conditions, impacts brain function and structure relatively quickly, and has shown promise with aging samples. Functional magnetic resonance imaging metrics provide insight into neurovascular health which plays a key role in both normal and pathological aging processes. Experimental mindfulness meditation studies that included functional magnetic resonance metrics as an outcome measure may point to potential neurovascular mechanisms of action relevant for aging adults that have not yet been previously examined. We first review the resting-state magnetic resonance studies conducted in exclusively older adult age samples. Findings from older adult-only samples are then used to frame the findings of task magnetic resonance imaging studies conducted in both clinical and healthy adult samples. Based on the resting-state studies in older adults and the task magnetic resonance studies in adult samples, we propose three potential mechanisms by which mindfulness meditation may offer a neurovascular therapeutic benefit for older adults: (1) a direct neurovascular mechanism via increased resting-state cerebral blood flow; (2) an indirect anti-neuroinflammatory mechanism via increased functional connectivity within the default mode network, and (3) a top-down control mechanism that likely reflects both a direct and an indirect neurovascular pathway.


The effects of counter-ion condensation and co-ion depletion upon the rates of chemical repair of poly(U) radicals by thiols.
Bimolecular rate constants for reactions of poly(U) radicals with a series of thiols of varying net charge (Z) were measured by pulse radiolysis with conductivity detection at low ionic strength. At pH 7 and 18 degrees C the values of k2 (M-1s-1) were: reduced glutathione (Z = -1), less than 500; 2-mercaptoethanesulphonic acid (Z = -1), 1.5 x 10(3); 2-mercaptoethanol (Z = 0), 1.8 x 10(5); cysteine (Z = 0), 2.0 x 10(5); cysteamine (Z = +1), 4.1 x 10(7). Values determined at pH 4 were: 2-mercaptoethanol, 6.1 x 10(5); cysteamine 2.2 x 10(8); N-(2-mercaptoethyl)-1,3-diaminopropane (WR-1065, Z = +2), 4.6 x 10(8). The variation in rate with structure could not reasonably be attributed to inherent reactivity differences in the thiols and was ascribed to inhomogeneous distributions of the thiols in solution resulting from electrostatic interactions. Thus, cationic thiols are concentrated approximately 100-fold near poly(U), relative to neutral thiols, as a consequence of counter-ion condensation, whereas anionic thiols have approximately 100-fold lower concentration near poly(U) than neutral thiols as a result of co-ion depletion. These results show that the ability of a thiol to repair radical sites in a polyanion is dramatically influenced by its net charge as a consequence of the counter-ion condensation and co-ion depletion phenomena.


Periodontal status of patients with abnormalities of the immune system. II. Observations over a 2-year period.
Patients with IgA deficiency and agammaglobulinemia were pair-matched to immunocompetent subjects by age and Plaque Index. Clinical examinations performed initially and after 2 years included the Plaque Index, Gingival Index, Periodontal Disease Index, caries experience (DMF-T) and full mouth radiographic surveys. Therapy during the 2-year period included oral hygiene instructions, prophylaxis and indicated restorative treatment. Immunodeficient patients manifested consistently lower levels of gingival inflammation than matched immunocompetent patients at both examination periods. Caries experience of immunodeficient patients was also less during the study interval, and five of these patients demonstrated DMF-T scores of zero. No developmental abnormalities, acute gingival or mucosal lesions, or attachment loss associated with periodontitis was observed in either group.


A rare cause of delayed contrast enhancement on cardiac magnetic resonance imaging: infective endocarditis.
Although there have been a few reports about the magnetic resonance (MR) imaging features of infective endocarditis (IE), delayed contrast enhancement attributable to fibrosis has not been previously described. The case of a 4-year-old girl who was diagnosed with IE based on positive blood culture results and echocardiographic findings is presented. At cardiac MR imaging, late phase contrast-enhanced images revealed a significant enhancement suggesting fibrosis secondary to IE.


Pediatric hepatitis B treatment.
Although the introduction of hepatitis B vaccine has been contributing to the reduction in the prevalence of hepatitis B virus (HBV) carriers worldwide, the treatment of children with chronic HBV infection is a challenge to be addressed. HBeAg seroconversion, which induces low replication of HBV, is widely accepted as the first goal of antiviral treatment in children with chronic hepatitis B. However, spontaneous HBeAg seroconversion is highly expected in children with chronic HBV infection. Therefore, the identification of children who need antiviral treatment to induce HBeAg seroconversion is essential in the management of chronic HBV infection. Guidelines and experts' opinion show how to identify children who should be treated and how to treat them. If decompensated cirrhosis is absent, interferon-alpha is the first-line antiviral treatment. Nucleos(t)ide analogues (NAs), such as lamivudine, adefovir, entecavir and tenofovir, are also available for the treatment of children, although the approval age differs among them. If decompensated cirrhosis is present, NAs are the first-line antivirals. When the emergence of drug-resistant HBV variants is taken into consideration, entecavir (approved for age 2 years or older) and tenofovir (age 12 years or older), which have high genetic barriers, will play a central role in the treatment of HBV infection. However, the optimal duration of NA treatment and adverse events of long-term NA treatment remain unclear in children. In resource-constrained countries and regions, the financial burden of visiting hospitals, receiving routine blood examination and purchasing antiviral drugs is heavy. Moreover, there is no clear evidence that the induction of HBeAg seroconversion by antiviral treatment prevents the progression of liver disease to cirrhosis and hepatocellular carcinoma in children with chronic HBV infection. It is thus imperative to clarify the clinical impact of antiviral treatment in children with HBV infection.


Influence of well-being variables and recovery state in physical enjoyment of professional soccer players during small-sided games.
This study aimed to assess the effects of the total quality of recovery and well-being indices (self-ratings of sleep during the preceding night, stress, fatigue and delayed onset muscle soreness) on rating of perceived exertion (RPE) and physical enjoyment (PE) during small-sided games. A total of 20 professional soccer players (25 ± 0.8 years) completed four 5-a-side game sessions of 25-min duration each (4 × 4 min work with 3-min passive recovery in-between). All variables were collected before each game session with the exception of RPE and Physical Activity Enjoyment Scale that were collected after. The results demonstrate that recovery state and pre-fatigue states were not contributing signals of affected internal intensity and enjoyment of players. The study established the objectivity and utility of RPE as a useful tool for determining internal intensity during soccer-specific training as well as PE for assessing emotional response during exercise or training session.


The free and the beta 2-microglobulin-associated heavy chains of HLA-A, B alloantigens share the antigenic determinant recognized by the monoclonal antibody Q1/28.
Serological and immunochemical assays have shown that the monoclonal antibody Q1/28 recognizes an antigenic determinant which is expressed on the heavy chain of subsets of HLA-A, B antigens and is distinct from those defining the serological polymorphism of this system. Association of the HLA-A, B heavy chain with beta 2-microglobulin is not required for expression of the antigenic determinant recognized by the monoclonal antibody Q1/28, since this antibody can immunoprecipitate a 45 000 m.w. component from radiolabeled lymphoid-cell glycoproteins immunodepleted with either an anti-human beta 2-microglobulin xenoantiserum or the MoAb W6/32 to framework determinants of HLA-A, B, C antigens. Furthermore, the MoAb Q1/28 can immunoprecipitate a 45 000 m.w. component from an NP40 lysate of radiolabeled Daudi cells, which lack the genetic information for beta 2-microglobulin. The determinant recognized by the MoAb Q1/28 is relatively resistant to denaturing treatments and does not appear to be carbohydrate in nature. The MoAb Q1/28 is the first example of an antibody which recognizes an antigenic determinant expressed on both the beta 2-microglobulin-associated and free HLA-A, B heavy chains.


Harnessing gradient gelatin nanocomposite hydrogels: a progressive approach to tackling antibacterial biofilms.
Infectious wounds pose significant challenges due to their susceptibility to bacterial infections, hindering tissue repair. This study introduces gradient gelatin nanocomposite hydrogels for wound healing and antibacterial biofilm management. These hydrogels, synthesized via UV light polymerization, incorporate copper-doped polydopamine nanoparticles (PDA-Cu) and GelMA (gelatin methacrylate). The hydrogels have a unique structure with a porous upper layer and a denser lower layer, ensuring superior swelling (over than 600%) and effective contact with bacterial biofilms. In vitro experiments demonstrate their remarkable antibacterial properties, inhibiting S. aureus and E. coli biofilms by over 45% and 53%, respectively. This antibacterial action is attributed to the regulation of reactive oxygen species (ROS) production, an alternative mechanism to bacterial cell wall disruption. Moreover, the hydrogels exhibit high biocompatibility with mammalian cells, making them suitable for medical applications. In vivo evaluation in a rat wound infection model shows that the gradient hydrogel treatment effectively controls bacterial biofilm infections and accelerates wound healing. The treated wounds have smaller infected areas and reduced bacterial colony counts. Histological analysis reveals reduced inflammation and enhanced granulation tissue formation in treated wounds, highlighting the therapeutic potential of these gradient nanocomposite hydrogels. In summary, gradient gelatin nanocomposite hydrogels offer promising multifunctional capabilities for wound healing and biofilm-related infections, paving the way for innovative medical dressings with enhanced antibacterial properties and biocompatibility.


Isomer abundance of small carbon clusters formed in buffer He gas.
We calculated the isomer spectrum of carbon clusters of 3-36 atoms, and performed molecular dynamics simulations of the cluster growth in buffer helium gas, showing that the isomers with potentials higher than those of the most stable clusters form with considerable probabilities under common experimental conditions.


Animal studies of potential chronic lung disease of workers in swine confinement buildings.
The pathologic changes in laboratory animals housed in a swine confinement building were studied to predict potential chronic health effects on persons working in these buildings. Rabbits and guinea pigs were maintained for 12 months either in a confined nursery-grower unit (test animals) or in conventional laboratory animal housing (controls). Necropsies and histopathologic examinations were performed on animals that died prematurely or were killed at termination of the study. Blood serum from the animals was examined for antibodies to extracts from swine confinement house dust. The confinement atmosphere was monitored for environmental pollutants. Concentrations of gases and dust in the air of the confinement building were comparable to those found in a typical swine confinement building. Pulmonic lesions seen in the test rabbits and guinea pigs included diffuse interstitial histiocytic pneumonia. Tracheal and nasal turbinate lesions included epithelial hyperplasia and metaplasia, with submucosal infiltration of plasma cells and heterophils. Blood from the test animals contained serum precipitins to dust extract from confinement houses. The presence of precipitins combined with the microscopic appearance of the lungs indicated that an immunologic process, such as hypersensitivity pneumonitis, may be used to explain the basis of the observed lung lesions. The tracheal and turbinate lesions are best explained as a reaction to a chronic low-grade irritation.


[Peri- and postmenopausal changes--body awareness, sexuality, and self- image of the middle-aged and older woman].
INTRODUCTION, METHODS: For the first time a study has been made, in a German urban population, of sexuality, body awareness and self-image of women between 50 and 82 years. A special anonymous questionnaire was designed by female gynaecologists and psychologists for this cross-sectional study in Munich. It focuses on body awareness, self imagery, sexual activity and psychological and physiological sexual feeling in their biographic context. 102 women took part. 53.9% are sexually active and 74.5% think of themselves as "a knowing woman", "middle aged" or "in the best years". Self perception of the body as being attractive correlates highly significantly with the psychological well-being. There is no correlation between women's psychological well-being and the perception of their general beauty. Women who find their body attractive think of themselves as more sensual than those, who do not find their body attractive. General and bodily perception of beauty are negatively correlated to the body mass index. Here, 61.8% of the women think they are overweight, but only 41.2 % have a body mass index over 25. 12.9% were sexually abused, and another 8.8% do not want to answer this question. There is a strong correlation between fear and sexual abuse. Only about 50% of the women speak about their sexuality and, of them, only 9.8% speak with their gynaeclologist. Sexuality is very important for the middle-aged and older woman, their body perception is as sensitive as in younger women and is of enormous importance for their psychological well-being. A Sexual history should be obligatory for older women. Fear of the examination can be a hint towards sexual abuse and should be taken seriously. All therapeutic interventions such as medication or operations should be discussed, and the patient's sexual wishes and expectations have to be taken into consideration.


Fast spin-echo MR images of the pelvis obtained with a phased-array coil: value in localizing and staging prostatic carcinoma.
The fast spin-echo pulse sequence allows T2-weighted MR images to be acquired more rapidly than is possible with conventional spin-echo sequences, and phased-array coils can provide a higher signal-to-noise ratio than is possible with the body coil. The combination of these methods permits higher resolution images to be obtained with more signal averages despite shorter imaging times. In this study, initial technical comparisons designed to confirm the advantage of combining fast spin-echo pulse sequences with a pelvic phased-array multicoil were followed by an assessment of the value of these methods for the localization and staging of prostatic carcinoma. Seventy-one men with known (60) or suspected (11) prostatic carcinoma were imaged with T2-weighted fast spin-echo pulse sequences in the axial and coronal planes with a phased array of four surface coils (multicoil) for signal reception. Four of these men also were imaged with fast spin-echo sequences and the body coil, and six of these men also were imaged with T2-weighted conventional spin echo sequences and the multicoil; image qualities achieved with these techniques were compared. The use of IV glucagon (42 of 71 studies) before fast spin-echo sequences was correlated with the subsequent presence or absence of peristaltic artifacts on MR images. MR images were analyzed for the presence or absence of prostatic cancer in the right and left sides of the gland and for evidence of spread either through the capsule, into the seminal vesicles, or to lymph nodes or bone. Findings at MR imaging were compared with results of radical prostatectomy (20), lymph node dissection without prostatectomy (seven), and biopsy (67). Image quality obtained with the combination of the fast spin-echo sequence with the multicoil was judged superior to that obtained with either the conventional spin-echo sequence with the multicoil or the fast spin-echo sequence with the body coil. Significant motion artifacts were noted in 45% of studies (13/29) performed without glucagon vs 7% of studies (3/42) performed with glucagon. In the 58 patients for whom information concerning the location of tumor in either the right or left side of the gland was obtained from biopsy (39) or surgery (19), MR images allowed cancer to be detected with 89% sensitivity and 77% specificity. Among the 20 patients undergoing prostatectomy and seven others undergoing lymph node dissection, MR imaging permitted high accuracies in predicting involvement of the seminal vesicles (100%), local transcapsular spread (85%), and involvement of pelvic lymph nodes (85%). Fast spin-echo imaging with a pelvic phased-array multicoil provides high-resolution images of the prostate that may obviate an endorectal coil for the detection, localization, and staging of prostatic carcinoma.


Transport in disordered media with spatially nonuniform fields.
The theoretical treatment of transport in a disordered system in the presence of a system-wide force field F(x) or spatially varying macroscopic velocity field v(x) is developed in the framework of continuous time random walk (CTRW). The physical basis of CTRW and related fractional derivative equations relies on a mapping of the aggregate of transition rates w(s,s'), between sites s and s', in the Master equation describing the system kinetics, onto a joint probability distribution function psi(s,t). This distribution is calculated from the ensemble average of a position-dependent functional of w(s,s'); the procedure is effective when the scale of heterogeneities is much smaller than the system size. However, statistical homogeneity does not hold in the presence of large heterogeneities, which control the macroscopic v(x), or in the case of an interaction of F(x) with the transition rates. The transport equation, incorporating large-scale heterogeneity, involves the use of a local ensemble average to obtain a position-dependent psi(s,t;x); this determines a memory function, M(t;x), which is convoluted with the advection-dispersion operator. A prototype transport equation for a system with statistical inhomogeneity is developed as an integrodifferential equation. It is solved numerically for particles migrating with a steady-state Darcy velocity v(x , determined for different permeability fields and boundary conditions. The nature of the solutions as a function of key transport parameters (e.g., a characteristic time tc) is explored, and solutions are also compared to those of the advection-dispersion equation for v(x) and to a laboratory experiment. This transport equation is in contrast to the fractional Fokker-Planck equation, which is based on a decoupling of F(x) or v(x) with the transition rates w(s,s'). Further, an analytic expression for the effect of a variance of the ensemble average on the solution of the CTRW transport equation is derived.


A role for metallothionein and zinc in spontaneous mutagenesis.
G12, a transgenic Chinese hamster V79 cell derivative which contains a single copy of the Escherichia coli gpt gene as a target for mutagenesis, has little constitutive metallothionein (MT) expression. It was transfected with a vector containing the mouse MT-I gene, and MT-I-overproducing lines were isolated. MT-I transfectants had lower spontaneous mutation frequencies compared with the G12 parental cell line. Mutagenesis by alkylating agents was unchanged. MT expression in G12 and MT transfectants could be modulated by exposure to Zn(II) or Cd(II). The spontaneous mutation frequencies in Zn(II)- and Cd(II)-treated cells was inversely related to MT expression. In G12 cells grown in concentrations of Zn(II) up to 12 microM, a significant dose-dependent increase in spontaneous mutagenesis was observed. At higher (but subtoxic) concentrations in which endogenous MT was induced, a dramatic decrease in spontaneous mutagenesis was observed. In contrast, MT-I transfectants exhibited much lower spontaneous mutagenesis after growth in all concentrations of Zn(II). These data demonstrate a possible role for MT in modulating spontaneous mutagenesis and point to a role for Zn(II) in contributing to spontaneous mutagenesis. Because there is variability in human MT expression, low MT expression might be a risk factor for cancer.


Rapid qualitative profiling of metabolites present in Fusarium solani, a rhizospheric fungus derived from Senna spectabilis, using GC/MS and UPLC-QTOF/MSE techniques assisted by UNIFI information system.
Fungi are an important source of natural products found in a variety of plant species. A wide range of methods for the detection of metabolites present in fungi have been reported in the literature. The search for methodologies that allow the rapid detection of compounds present in crude extracts is crucial to enable the metabolite annotation doing a qualitative analysis of the complex matrix. Mass spectrometry is an important ally when it comes to in silico detection of previously reported metabolites. In this work, the ethyl acetate extract of Fusarium solani was analyzed by gas chromatography coupled to mass spectrometry (GC/MS) after derivatization process. The ethyl acetate extract was also investigated by liquid chromatography coupled with high-resolution tandem mass spectrometry assisted by the UNIFI software system. A library containing previously reported metabolites from the Fusarium genus was added to the UNIFI platform. Simultaneously, the extract was analyzed through anticholinesterase and antifungal assays. The analysis of the derivatized extract by GC/MS led to the putative identification of five metabolites, and the investigation using Ultra-High Performance Liquid Chromatography - Quadrupole Time-of-Flight Mass Spectrometry (UPLC-QTOF) analysis in data-independent acquisition mode (mass spectrometry) led to the annotation of 15 compounds present in the built-in Fusarium library added to the UNIFI system. The Fusarium solani extract showed potential anticholinesterase and in vitro antifungal activity supported by the detection of bioactive metabolites.


Novel virtual screening approach for the discovery of human tyrosinase inhibitors.
Tyrosinase is the key enzyme involved in the human pigmentation process, as well as the undesired browning of fruits and vegetables. Compounds inhibiting tyrosinase catalytic activity are an important class of cosmetic and dermatological agents which show high potential as depigmentation agents used for skin lightening. The multi-step protocol employed for the identification of novel tyrosinase inhibitors incorporated the Shape Signatures computational algorithm for rapid screening of chemical libraries. This algorithm converts the size and shape of a molecule, as well its surface charge distribution and other bio-relevant properties, into compact histograms (signatures) that lend themselves to rapid comparison between molecules. Shape Signatures excels at scaffold hopping across different chemical families, which enables identification of new actives whose molecular structure is distinct from other known actives. Using this approach, we identified a novel class of depigmentation agents that demonstrated promise for skin lightening product development.


Leptin and mTOR: partners in metabolism and inflammation.
Leptin is both a hormone/cytokine that plays a major role in the regulation of feeding and energy expenditure. Beyond its central role in the hypothalamus, leptin modulates peripheral tissues' responses to growth and storage based on nutrient availability, and it regulates the innate and adaptive immune responses. mTOR (mammalian Target of Rapamycin) is a core component of intracellular signaling for cellular growth, mRNA translation, and metabolism. Here, we review recent findings on the cross talk between mTOR and leptin signaling. Important roles for mTOR on leptin signaling have been established both in hypothalamic centers to control food intake and in peripheral cells to regulate lipid metabolism and inflammation. Leptin directly activates resident macrophages to form ADRP-enriched lipid droplets and enhances eicosanoid production via a mechanism that is dependent on activation of the PI3K/mTOR pathway. Leptin-induced mTOR activation may have implications for obesity-related pathophysiological conditions such as diabetes, cardiovascular disease and cancer.


Prospective validation of neutrophil-to-lymphocyte ratio as a diagnostic and management adjunct in acute appendicitis.
No optimal biomarker exists that accurately diagnoses appendicitis or predicts severity, estimates post-operative complications or total length of hospital stay (LOS). To prospectively validate the utility of neutrophil-to-lymphocyte (NLR) ratio in predicting the severity of appendicitis, LOS, and 30-day complication rates. Patients who were admitted with a provisional diagnosis of acute appendicitis over a period of 18 months (Oct 2014-April 2016) were included. Patient demographics and blood results were prospectively collected. Details of imaging, operative intervention, severity of appendicitis, length of stay, and 30-days post admission complications were recorded. Recommended cut-off values of NLR and C-reactive protein for severity of appendicitis were determined using receiver operating characteristic analysis (ROC). These cut-off values were compared with C-reactive protein levels. Mann-Whitney test was performed to assess the correlations between LOS and 30-day complications to NLR. Four hundred fifty-three patients were included in the study; 55.2% (n = 245) were female with mean patient age of 23 years. Two-thirds (n = 281, 62.03%) underwent operative management. Histologically, appendicitis was confirmed in 214 (76%) patients. A NLR of >6.36 or CRP of >28 were statistically associated with complicated acute appendicitis, with a median of one extra hospital day (p < 0.0001). Mean NLR was statistically higher in patients with post-operative complications (14.42 vs. 7.29 for simple appendicitis group, p < 0.001). This confirms previous reports that NLR is a simple, readily available adjunct in predicting severity of appendicitis. Additionally, it can aid delineating severe appendicitis that should proceed to surgery without substantial delay.


Effects of the Nintendo Wii training on balance rehabilitation and quality of life of patients with Parkinson's disease: A systematic review and meta-analysis.
Randomized clinical trials (RCTs) used the Nintendo Wii (NW) in the treatment of Parkinson Disease, however, no meta-analysis was developed to determine the effects in these patients. To analyze RCTs that investigated the effects of NW versus traditional physiotherapy on balance rehabilitation and quality of life of patients with PD. Electronic research was conducted between December 2018 and January 2019 in the MEDLINE, PEDro, CENTRAL, LILACS and SciELO databases. The methodological quality was evaluated by the PEDro scale and the completeness of the description of the interventions by the TIDieR checklist. Weighted mean differences (WMD) and 95% confidence interval (CI) were calculated. Five studies were included and presented an average of 5.4 (1.5) on the PEDro scale and 6.7 (1.4) on the TIDieR. Compared to traditional physiotherapy, combined NW and traditional physiotherapy resulted in improvement in balance WMD 1.24 (95% CI: CI: 0.2 to 2.3 N = 72) and quality of life WMD- 8.9 (95% CI: -15.2 to -2.6 N = 56). combined NW and traditional physiotherapy was more effective on balance rehabilitation and quality of life of patients with PD, but the values demonstrated a poor methodological quality and a low level of completeness of the intervention descriptions.


Modification of a Braided Support Catheter into a Rapid Exchange System for Navigation of a Distal Protection Device through Significant Vascular Tortuosity.
Cerebral embolic protection devices (EPD) reduce the rate of periprocedural thromboembolic complications and are currently used in all carotid artery stenting (CAS) procedures. However, tortuous vascular anatomy of the internal carotid artery (ICA) may prevent navigation of distal EPDs, thereby leading to inadequate cerebral protection. We present a case in which significant tortuosity of the ICA distal to the stenotic lesion precluded navigation of currently available distal EPDs. During a CAS procedure, significant vascular tortuosity of the distal cervical ICA was noted which prevented navigation of currently available distal EPDs due to catheter kinking. In order to overcome this anatomic barrier, a novel rapid exchange catheter system (RECS) was created using a modified DAC 038 braided catheter through which a distal EPD and microguidewire were placed. This newly devised RECS allowed navigation of the distal EPD past the tortuous ICA bend and successful completion of the CAS procedure without periprocedural complications. We demonstrate that modification of currently available devices can, in select cases, effectively address cases of significant vascular tortuosity which limit the use of conventional distal EPDs.


Extrachromosomal genes: a powerful tool in gene targeting approaches.
Several studies, some of which have been updated during the recent workshop entitled Genome Medicine: Gene Therapy for the Millennium (Rome, 30 September-3 October 2001), have highlighted the usefulness of extrachromosomal or episomal genes in gene targeting strategies. Due to the selectable nature of antibiotic resistance and reporter genes, targeted correction of mutated versions of these extrachromosomal genes allows an accurate quantification of correction frequency. In addition, these model systems facilitate and speed up the optimization of critical parameters for the successful application of gene targeting approaches. In fact, type of cell line, gene delivery system, molar ratio of episomal target/therapeutic constructs, nature and design of therapeutic complexes and different recombinative proteins may be critical for the actual feasibility of each method. Although virus-based approaches are now being investigated as well, this article is focusing on the targeted correction of extrachromosomal genes by the use of small DNA fragments (SDF), chimeric RNA/DNA oligonucleotides (RDO) and triplex-forming oligonucleotides (TFO).


Inflammation and cardiovascular risk in dialysis patients.
Chronic inflammation, as evidenced by increased levels of C-reactive protein (CRP), predicts all-cause and cardiovascular mortality in hemodialysis patients in short-term studies. Whether CRP is also predictive in the long-term follow-up is unknown. We conducted a 4-year follow-up of a cross-sectional study in a cohort of 280 stable hemodialysis patients. CRP was determined once at the beginning of the study, and all-cause as well as cardiovascular mortality was monitored prospectively. During follow-up, 123 patients (43.9%) had died, mostly from cardiovascular events (58.5%) corresponding to an annual mortality rate of 11%. Overall mortality and cardiovascular mortality were significantly higher in patients with a CRP more than 8 mg/L (73% vs. 39% and 87% vs. 55%, respectively). Multivariate Cox regression analysis demonstrated that age, CRP, and preexisting cardiovascular disease were the most powerful predictors, but the presence of diabetes, albumin, and BMI also remained in the model. A single determination of CRP is a powerful indicator of all cause and cardiovascular death even after a follow-up period of 4 years in patients on hemodialysis treatment.


Circadian Variation of Migraine Attack Onset Affects fMRI Brain Response to Fearful Faces.
Previous studies suggested a circadian variation of migraine attack onset, although, with contradictory results - possibly because of the existence of migraine subgroups with different circadian attack onset peaks. Migraine is primarily a brain disorder, and if the diversity in daily distribution of migraine attack onset reflects an important aspect of migraine, it may also associate with interictal brain activity. Our goal was to assess brain activity differences in episodic migraine subgroups who were classified according to their typical circadian peak of attack onset. Two fMRI studies were conducted with migraine without aura patients (n = 31 in Study 1, n = 48 in Study 2). Among them, three subgroups emerged with typical Morning, Evening, and Varying start of attack onset. Whole brain activity was compared between the groups in an implicit emotional processing fMRI task, comparing fearful, sad, and happy facial stimuli to neutral ones. In both studies, significantly increased neural activation was detected to fearful (but not sad or happy) faces. In Study 1, the Evening start group showed increased activation compared to the Morning start group in regions involved in emotional, self-referential (left posterior cingulate gyrus, right precuneus), pain (including left middle cingulate, left postcentral, left supramarginal gyri, right Rolandic operculum) and sensory (including bilateral superior temporal gyrus, right Heschl's gyrus) processing. While in Study 2, the Morning start group showed increased activation compared to the Varying start group at a nominally significant level in regions with pain (right precentral gyrus, right supplementary motor area) and sensory processing (bilateral paracentral lobule) functions. Our fMRI studies suggest that different circadian attack onset peaks are associated with interictal brain activity differences indicating heterogeneity within migraine patients and alterations in sensitivity to threatening fearful stimuli. Circadian variation of migraine attack onset may be an important characteristic to address in future studies and migraine prophylaxis.


Modulation of triple-helical stability and subsequent melanoma cellular responses by single-site substitution of fluoroproline derivatives.
Collagen is a multifunctional protein, serving as a structural scaffold and a modulator of cellular responses. Prior work has identified distinct regions from several collagen types that promote cell adhesion, spreading, migration, and signal transduction. One of these regions, alpha1(IV)1263-1277 from type IV collagen, mediates these responses via melanoma cell CD44-chondrotin sulfate proteoglycan receptors. In the study presented here, we have used a triple-helical model of alpha1(IV)1263-1277 to evaluate (a) conformational stability and (b) cellular responses based on single-site incorporation of trans-4-fluoro-L-proline (trans-Flp) or cis-4-fluoro-L-proline (cis-Flp) for trans-4-hydroxy-L-proline (trans-Hyp). The structural effects of cis-Flp and trans-Flp substitution were studied by circular dichroism and NMR spectroscopies. The peptide containing a single trans-Flp instead of trans-Hyp was slightly more thermally stable than the parent peptide (T(m) = 37 vs 34 degrees C), while the peptide containing cis-Flp was considerably less stable than the parent peptide (T(m) = 30 degrees C). Melanoma cell adhesion and spreading were examined under conditions where the trans-Hyp-, trans-Flp-, and cis-Flp-containing ligands were approximately 15, <10, and approximately 65% denatured, respectively. Adhesion to each of the three ligands was remarkably sensitive to the respective ligand conformation, with EC(50) values of approximately 2.5, approximately 0.35, and >5.0 microM for the trans-Hyp-, trans-Flp-, and cis-Flp-containing ligands, respectively. Melanoma cell spreading was quantitated over a ligand concentration range of 0.01-50 microM and, in a fashion similar to adhesion, was more extensive on the trans-Flp ligand than on the trans-Hyp ligand. Very low levels of spreading were observed with the cis-Flp-containing ligand at all concentrations tested. Melanoma cell adhesion to and spreading on the three ligands suggested the dramatic biological consequence of even subtle changes in relative triple-helical content. Such subtle changes may model those occurring in the basement membrane during the tumor cell invasion process, and thus provide mechanistic insight into this stage of metastasis.


Induction of protective immunity against malaria by priming-boosting immunization with recombinant cold-adapted influenza and modified vaccinia Ankara viruses expressing a CD8+-T-cell epitope derived from the circumsporozoite protein of Plasmodium yoelii.
We immunized mice with an attenuated (cold-adapted) influenza virus followed by an attenuated vaccinia virus (modified vaccinia virus Ankara), both expressing a CD8(+)-T-cell epitope derived from malaria sporozoites. This vaccination regimen elicited high levels of protection against malaria. This is the first time that the vaccine efficacy of a recombinant cold-adapted influenza virus vector expressing a foreign antigen has been evaluated.


Ultrabroadband metamaterial absorbers from ultraviolet to near-infrared based on multiple resonances for harvesting solar energy.
In this paper, a metal-dielectric metamaterial absorber is proposed to achieve ultrabroadband absorption at frequencies from ultraviolet to near-infrared. Based on finite element method solutions, the average absorption of the absorber is 97.75% from 382 nm to 1100 nm, with a maximum of 99.92%, resulting from multiple resonance coupling. The influences of geometric parameters and incident conditions on absorption are investigated. Broadband and narrowband absorption changes are realized by changing incident light polarization. Polarization-independent properties can be realized by changing the dielectric structure to centrosymmetric. The average absorption of the polarization-independent structure is 97.11% from 250 nm to 1115 nm, with a maximum of 99.98%. The proposed absorber structure has wide optical applications including solar energy harvesting and light-emitting devices.


Innate immunity and atherogenesis.
Atherosclerosis is recognized as the pathological basis of cardiovascular disease (CVD) and recent advances in basic science have shown that it should be considered as a chronic inflammatory process. Both elements of the innate and the adaptive immunity appear to be actively involved in atherogenesis. In fact, the potential role played by pattern-recognition receptors (Toll-like receptors and scavenger receptors), cytokines (such as IL-1, IL-6, TNFalpha), chemokines and pentraxines (such as CRP and PTX3) represents an emerging field of investigation in atherogenesis. In the near future we expect a better definition of the real biological and clinical impact on CVD of these mediators. On one side, they could become useful to complement traditional risk factors, in order to identify new categories of subjects prone to CVD development. On the other, they could become an additional potential target for therapeutic strategies.


Covid-19: virology, variants, and vaccines.
As of 25 January 2022, over 349 million individuals have received a confirmed diagnosis of covid-19, with over 5.59 million confirmed deaths associated with the SARS-CoV-2 virus. The covid-19 pandemic has prompted an extensive global effort to study the molecular evolution of the virus and develop vaccines to prevent its spread. Although rigorous determination of SARS-CoV-2 infectivity remains elusive, owing to the continuous evolution of the virus, steps have been made to understand its genome, structure, and emerging genetic mutations. The SARS-CoV-2 genome is composed of several open reading frames and structural proteins, including the spike protein, which is essential for entry into host cells. As of 25 January 2022, the World Health Organization has reported five variants of concern, two variants of interest, and three variants under monitoring. Additional sublineages have since been identified, and are being monitored. The mutations harboured in these variants confer an increased transmissibility, severity of disease, and escape from neutralising antibodies compared with the primary strain. The current vaccine strategy, including booster doses, provides protection from severe disease. As of 24 January 2022, 33 vaccines have been approved for use in 197 countries. In this review, we discuss the genetics, structure, and transmission methods of SARS-CoV-2 and its variants, highlighting how mutations provide enhanced abilities to spread and inflict disease. This review also outlines the vaccines currently in use around the world, providing evidence for every vaccine's immunogenicity and effectiveness.


AIG1 affects in vitro and in vivo virulence in clinical isolates of Entamoeba histolytica.
The disease state of amebiasis, caused by Entamoeba histolytica, varies from asymptomatic to severe manifestations that include dysentery and extraintestinal abscesses. The virulence factors of the pathogen, and host defense mechanisms, contribute to the outcomes of infection; however, the underlying genetic factors, which affect clinical outcomes, remain to be fully elucidated. To identify these genetic factors in E. histolytica, we used Illumina next-generation sequencing to conduct a comparative genomic analysis of two clinical isolates obtained from diarrheal and asymptomatic patients (strains KU50 and KU27, respectively). By mapping KU50 and KU27 reads to the genome of a reference HM-1:IMSS strain, we identified two genes (EHI_089440 and EHI_176590) that were absent in strain KU27. In KU27, a single AIG1 (avrRpt2-induced gene 1) family gene (EHI_176590) was found to be deleted, from a tandem array of three AIG1 genes, by homologous recombination between the two flanking genes. Overexpression of the EHI_176590 gene, in strain HM-1:IMSS cl6, resulted in increased formation of cell-surface protrusions and enhanced adhesion to human erythrocytes. The EHI_176590 gene was detected by PCR in 56% of stool samples from symptomatic patients infected with E. histolytica, but only in 15% of stool samples from asymptomatic individuals. This suggests that the presence of the EHI_176590 gene is correlated with the outcomes of infection. Taken together, these data strongly indicate that the AIG1 family protein plays a pivotal role in E. histolytica virulence via regulation of host cell adhesion. Our in-vivo experiments, using a hamster liver abscess model, showed that overexpression or gene silencing of EHI_176590 reduced and increased liver abscess formation, respectively. This suggests that the AIG1 genes may have contrasting roles in virulence depending on the genetic background of the parasite and host environment.


Effects of Nesting Material on Energy Homeostasis in BALB/cAnNCrl, C57BL/6NCrl, and Crl:CD1(ICR) Mice Housed at 20 °C.
Discrepancies exist between the preferred temperature range for mice (26 to 32 °C) and current recommendations (20 to 26 °C), which may alter metabolism and negatively affect studies using mice. Previous research indicates that nesting material can alleviate cold stress in mice; therefore, we sought to determine the effects of the amount of nesting material provided (0, 6, or 12 g) on heat energy loss and energy balance in 3 mouse strains housed at currently recommended temperatures during the daytime, a period of presumed inactivity. Groups of BALB/cAnNCrl, C57BL/6NCrl, and Crl:CD1(ICR) mice, balanced by strain and sex, were group-housed and provided 0, 6, or 12 g of nesting material. After a 3-d acclimation period, body weight was determined daily at 0800, food intake was determined at 0800 and 2000, and total heat production was evaluated from 0800 to 2000 on 4 consecutive days and used to calculate energy balance and the respiratory quotient. Although the amount of nesting material had no overall effect on food intake or heat production, mice provided 12 g of nesting material had greater weight gain than those given 0 or 6 g. This increase in body weight might have been due to improved energy balance, which was corroborated by an increased respiratory quotient in mice provided 12 g of nesting material. In summary, although heat production did not differ, providing 12 g of nesting material improved energy balance, likely leading to an increase in body weight during the 0800-2000 testing period.


Procedural Adaptations to Avoid Haemodynamic Instability During Catheter Ablation of Scar-related Ventricular Tachycardia.
Classically, catheter ablation for scar-related ventricular tachycardia (VT) relied upon activation and entrainment mapping of induced VT. Advances in post-MI therapies have led to VTs that are faster and haemodynamically less stable, because of more heterogeneous myocardial fibrosis patterns. The PAINESD score is one means of identifying patients at highest risk for haemodynamic decompensation during attempted VT induction, who may, therefore, benefit from alternative ablation strategies. One strategy is to use temporary mechanical circulatory support, although this warrants formal assessment of cost-effectiveness. A second strategy is to minimise or avoid VT induction altogether by employing a family of 'substrate'-based approaches aimed at identifying VT isthmuses during sinus or paced rhythm. Substrate mapping techniques are diverse, and focus on the timing, morphology and amplitude of local ventricular electrograms - sometimes aided by advanced non-invasive cardiac imaging modalities. In this review, the evolution of VT ablation over time is discussed, with an emphasis on procedural adaptations to the challenge of haemodynamic instability.


Schisandrin B inhibits LPS-induced inflammatory response in human umbilical vein endothelial cells by activating Nrf2.
Schisandrin B (SchB), an active ingredient extracted from Schisandra chinensis (Turcz.) Baill, has been known to have anti-oxidant and anti-inflammatory activities. In this study, we investigated the anti-inflammatory effects and mechanism of SchB in LPS-stimulated human umbilical vein endothelial cells (HUVECs). The effects of SchB on VCAM-1, ICAM-1, NF-κB and Nrf2 expression were detected by western blot analysis. The effects of SchB on TNF-α and IL-8 production were detected by ELISA. The results showed that SchB strongly suppressed the production of TNF-α and IL-8 in HUVECs stimulated with LPS. SchB also inhibited LPS-induced VCAM-1 and ICAM-1 expression. Furthermore, SchB blocked the activation of NF-κB induced by LPS. In addition, SchB increased the expression of Nrf2 and HO-1 in a concentration-dependent manner. And the inhibition of TNF-α and IL-8 production by SchB was blocked by transfection with Nrf2 siRNA. Our findings showed that SchB inhibited LPS-induced inflammation in HUVECs by activating Nrf2 signaling pathway.


Telepsychiatry in emergency consultations: a follow-up study of sixty patients.
The objective was to investigate how telepsychiatry works in the assessment of psychiatric emergency patients. Sixty consecutive patients referred to the acute open ward having their first psychiatric contact through the videolink with the psychiatrist on duty. Only minor technical problems occurred. The results suggest both acceptance and satisfaction on the part of patients and staff with new technology, instead of waiting for a consultation or traveling to see a psychiatrist in face-to-face meeting. Telepsychiatry seems to be suitable for the assessment of psychiatric emergency patients, and satisfactory for patients and staff alike.


Multi-Component Structure of Roland-Morris Disability Questionnaire (RDQ), a Lumbago-Specific QOL (Quality of Life) Measure.
Lumbago is one of the most prevalent symptoms in patients with osteoporotic vertebral fracture. Roland-Morris Disability Questionnaire (RDQ) is a quality of life (QOL) questionnaire targeted for evaluating lumbago. Although total score is the usual way of analysis, we have tried to make more use of it by subscale analysis. Forty-four osteoporotic patients were evaluated for their QOL using RDQ and SF-8; a widely accepted generic (non disease-specific) QOL questionnaire. Subscales and summary scores of SF-8 were significantly lower than Japanese norm. Patients with fracture had significantly lower scores including RDQ. Multiple regression analysis has shown that total score of RDQ was significantly contributed by bodily pain as well as other subscales of SF-8. Principal component analysis has revealed that RDQ consists of two components representing general, and mental or social aspect of lumbago. Defining the component structure and determining the procedure to obtain the subscales would make the most use of RDQ, and contribute to the better evaluation of patients with lumbago.


Colon cancer and the epidermal growth factor receptor: Current treatment paradigms, the importance of diet, and the role of chemoprevention.
Colorectal cancer represents the third most common and the second deadliest type of cancer for both men and women in the United States claiming over 50000 lives in 2014. The 5-year survival rate for patients diagnosed with metastatic colon and rectal cancer is < 15%. Early detection and more effective treatments are urgently needed to reduce morbidity and mortality of patients afflicted with this disease. Here we will review the risk factors and current treatment paradigms for colorectal cancer, with an emphasis on the role of chemoprevention as they relate to epidermal growth factor receptor (EGFR) blockade. We will discuss how various EGFR ligands are upregulated in the presence of Western diets high in saturated and N-6 polyunsaturated fats. We will also outline the various mechanisms of EGFR inhibition that are induced by naturally occurring chemopreventative agents such as ginseng, green tea, and curcumin. Finally, we will discuss the current role of targeted chemotherapy in colon cancer and outline the limitations of our current treatment options, describing mechanisms of resistance and escape.


The spacing effect, free recall, and two-process theory: a closer look.
Two experiments used procedures similar to those used by R. L. Greene (1989) to test the 2-process theory of the spacing effect and, in particular, the contextual-variability subtheory that applies to free-recall performance. Experiment 1 obtained a spacing effect in free recall following intentional learning but not following incidental learning, contrary to a previous result supporting the 2-process theory. Experiment 2 replicated the incidental-learning results when a slow presentation rate was used. However, with a faster presentation rate, a spacing effect was obtained, and performance exceeded that of the slow-presentation-rate condition at the longest lag. Neither the contextual-variability subtheory of 2-process theory nor an alternative deficient-processing hypothesis was able to account for all of the data.


Enantiomer-specific biomagnification of alpha-hexachlorocyclohexane and selected chiral chlordane-related compounds within an Arctic marine food web.
Concentrations of achiral and chiral organochlorine contaminants (OCs), including hexachlorocyclohexane isomers (HCH), chlordane congeners (cis- and trans-chlordane, cis- and trans-nonachlor, MC5, MC7, and U82), and related metabolites (oxychlordane [OXY] and heptachlor exo-epoxide [HEPX]), were quantified in seawater (100 L; n = 6) and biota from the coastal Beaufort-Chukchi Seas food web near Barrow (AK, USA). The biota included zooplankton (Calanus spp.; n = 5), fish species such as arctic cod (Boreogadus saida; n = 10), arctic char (Salvelinus alpinus; n = 3), and marine mammals including bowhead whales (Balaena mysticetus; liver: n = 23; blubber: n = 40), beluga whales (Delphinapterus leucas; blubber: n = 20), ringed seals (Phoca hispida; blubber: n = 20), and bearded seals (Erignathus barbatus; blubber: n = 7). The food web magnification factors (FWMFs) for HCHs and chlordane compounds ranged from 0.5 (gamma-HCH) to 6.5 (HEPX) and were expected based on known recalcitrance and biotransformation of OCs. The enantiomer fractions (EFs) of all chiral OCs were near racemic (EF = 0.50) in the seawater, zooplankton, and all fish analyzed. In contrast, the EFs for most OCs analyzed were nonracemic (EF # 0.50) in the marine mammals blubber (range: 0.09-0.79) because of enantiomer-specific biotransformation and (or) accumulation. However, EF values were not significantly correlated with isotopically determined trophic level. The EFs for all chiral OCs (except alpha-HCH) in bowhead whale liver closely approximated the values in zooplankton, suggesting that the accumulation of chiral OCs from prey into this cetacean is not enantiomer specific. However, the modification of EFs from bowhead liver to blubber suggests that this species has the ability to enantioselectively biotransform and accumulate several chiral OC compounds.


Responses of blood pressure and lactate levels to various aquatic exercise movements in postmenopausal women.
Middle-aged and elderly women represent the main attending group in head-out aquatic exercise (HOAE). Blood pressure (BP) significantly increases both during water immersion and aquatic walking. Based on risk concerns, it is important to evaluate BP responses in postmenopausal women doing HOAE. The aim of this study was to determine BP, lactate levels, and rating of perceived exertion (RPE) changes associated with performing 3 different movements at 3 levels of exercise intensity in water. Twelve postmenopausal women (59.9±0.6 years old) participated in 3 aquatic trials involving running (RU), rocking (RO), and scissor kicks (SK) on separate days. Systolic BP, mean arterial pressure (MAP), lactate levels, RPE, and motion cadence were measured at rest; upon reaching 50%, 65%, and 80% of heart rate reserve for 6 minutes; and 10 and 30 minutes after exercise. Under similar RPE responses at 3 levels of intensity, SK resulted in higher systolic BP, MAP, and lactate levels than RO at 10 minutes after exercise (P<0.05) and the lowest motion cadence (P<0.05). RO resulted in the lowest MAP and diastolic BP responses during exercise (P<0.05). RU resulted in lower responses of lactate levels at high exercise intensity (P<0.05). RO resulted in lower diastolic BP and MAP responses compared with RU and SK during exercise. These findings suggest that RO movement in aquatic exercises is more suitable for people at high risk for cardiovascular disease.


[The Hospital, patients, health and territories Act and the recentralisation of the social and long term care sector].
Hypothesis: The 2009 Hospital, Patients, Health and Territories Act crystallises a central government attempt to regain control over the social and long term care sector, which involves the utilisation of policy instruments borrowed from the hospital sector: capped budgets, agreements on targets and resources, competitive tendering or quasi-market mechanisms involving hospitals and services, etc. This paper is therefore based on the hypothesis of a recentralisation and healthicization of the social and long term care sector, with a key role for the regional health authorities. Method and data: 27 semi-structured interviews were conducted with actors operating within and outside the regional health agencies and thereafter analysed using Alceste. The aim was to describe and to analyse the positioning of the RHAs in relation to key actors of the social and long-term care sector in 2 regions in 2011. Results: Key issues for public organisations include the style of planning and knowhow transfer, while the professionals were chiefly concerned with the intensity of the ambulatory turn and needs analysis methodology. The compromises forged were related to types of democratic legitimacy, namely representative or participatory democracy. Conclusion: There is little evidence to support the initial hypothesis, namely the existence of a link between the creation of RHAs and a recentralisation of health policy between 2009 and 2013. One may rather suggest that a reconfiguration of the activities and resources of the actors operating at the centre (RHAs and conseils départementaux) and at the periphery (territorial units of the RHAs and third sector umbrella organisations) has occurred.


The transcription factor Gli3 promotes B cell development in fetal liver through repression of Shh.
Before birth, B cells develop in the fetal liver (FL). In this study, we show that Gli3 activity in the FL stroma is required for B cell development. In the Gli3-deficient FL, B cell development was reduced at multiple stages, whereas the Sonic hedgehog (Hh [Shh])-deficient FL showed increased B cell development, and Gli3 functioned to repress Shh transcription. Use of a transgenic Hh-reporter mouse showed that Shh signals directly to developing B cells and that Hh pathway activation was increased in developing B cells from Gli3-deficient FLs. RNA sequencing confirmed that Hh-mediated transcription is increased in B-lineage cells from Gli3-deficient FL and showed that these cells expressed reduced levels of B-lineage transcription factors and B cell receptor (BCR)/pre-BCR-signaling genes. Expression of the master regulators of B cell development Ebf1 and Pax5 was reduced in developing B cells from Gli3-deficient FL but increased in Shh-deficient FL, and in vitro Shh treatment or neutralization reduced or increased their expression, respectively.


A Comparison of Mixed Dentition Dental Development in Cleft Patients Treated With and Without the Latham-type Appliance.
The purpose of this study was to retrospectively evaluate the Latham-type appliance's effect on the development and eruption of posterior teeth during the mixed dentition stage before palatal expansion and secondary alveolar bone graft(s). The charts of complete cleft lip and palate (CLP) patients treated with and without the Latham-type appliance were screened using the following inclusion criteria: nonsyndromic; CLP; and available panoramic radiographs and clinical photographs in the mixed dentition prior to palatal expansion and secondary alveolar bone grafts. Surgical repair for Latham-type appliance patients followed the Latham-Millard protocol. The differences in outcomes were analyzed using Fisher's exact tests. The sample consisted of 65 patients treated with the appliance (Latham group) and 36 subjects who were not (non-Latham group). Similar incidences were found between the non-Latham group and the Latham group for maxillary second premolar agenesis (11 percent versus 10 percent) and enamel defects in the maxillary arch (17 percent versus 14 percent). The incidence of ectopic permanent maxillary first molars was higher in the Latham group than in the non-Latham group (28 percent versus one percent, P=0.01). A higher incidence of ectopic permanent maxillary first molars was found in patients treated with the Latham-type appliance.


Quantitative immunoelectrophoretic analysis of the plasma proteins in the sol phase of sputum from patients with chronic bronchitis.
An analysis of the plasma proteins in the sol phase of sputum was carried out using quantitative cross immunoelectrophoresis. The average concentrations of nine plasma proteins were estimated in the sol phase of sputum specimens from 30 patients with chronic bronchitis and the values were compared with the concentrations of these proteins in saliva and serum specimens from the same group of patients. The results showed that alpha(1) antichymotrypsin and IgA concentrations were higher in the sol phase of sputum than would be expected if their presence were due entirely to passive transudation.


BioMAJ: a flexible framework for databanks synchronization and processing.
Large- and medium-scale computational molecular biology projects require accurate bioinformatics software and numerous heterogeneous biological databanks, which are distributed around the world. BioMAJ provides a flexible, robust, fully automated environment for managing such massive amounts of data. The JAVA application enables automation of the data update cycle process and supervision of the locally mirrored data repository. We have developed workflows that handle some of the most commonly used bioinformatics databases. A set of scripts is also available for post-synchronization data treatment consisting of indexation or format conversion (for NCBI blast, SRS, EMBOSS, GCG, etc.). BioMAJ can be easily extended by personal homemade processing scripts. Source history can be kept via html reports containing statements of locally managed databanks. http://biomaj.genouest.org. BioMAJ is free open software. It is freely available under the CECILL version 2 license.


Addressing myths about end-of-life care: research into the use of acute care hospitals over the last five years of life.
Despite very little confirming evidence, one of the most pervasive beliefs about dying is that terminally ill people receive a great deal of health care in the last few days, weeks, or months of life. A secondary analysis of 1992/93 through 1996/97 Alberta inpatient hospital abstracts data was undertaken to explore and describe hospital use over the five years before death by all Albertans who died in acute care hospital beds during the 1996/97 year (n = 7,429). There were four key findings: (1) hospital use varied, but was most often low, (2) the last hospital stay was infrequently resource intensive, (3) age, gender, and illness did not distinguish use, and (4) most ultra-high users were rural residents, with the majority of care episodes taking place in small, rural hospitals.


Environmental stress increases out-group aggression and intergroup conflict in humans.
Peaceful coexistence and trade among human groups can be fragile and intergroup relations frequently transition to violent exchange and conflict. Here we specify how exogenous changes in groups' environment and ensuing carrying-capacity stress can increase individual participation in intergroup conflict, and out-group aggression in particular. In two intergroup contest experiments, individuals could contribute private resources to out-group aggression (versus in-group defense). Environmental unpredictability, induced by making non-invested resources subject to risk of destruction (versus not), created psychological stress and increased participation in and coordination of out-group attacks. Archival analyses of interstate conflicts showed, likewise, that sovereign states engage in revisionist warfare more when their pre-conflict economic and climatic environment were more volatile and unpredictable. Given that participation in conflict is wasteful, environmental unpredictability not only made groups more often victorious but also less wealthy. Macro-level changes in the natural and economic environment can be a root cause of out-group aggression and turn benign intergroup relations violent. This article is part of the theme issue 'Intergroup conflict across taxa'.


Efficacy of LY333328 against experimental methicillin-resistant Staphylococcus aureus endocarditis.
The in vivo efficacy of LY333328, a new glycopeptide antibiotic, was compared with that of vancomycin by using the rabbit model of left-sided methicillin-resistant Staphylococcus aureus endocarditis. Animals received LY333328 or vancomycin (25 mg/kg of body weight every 24 or 8 h, respectively) for 4 days. These drugs were equally effective in clearing bacteremia and in reducing bacterial counts in vegetations and tissues. We conclude that in this model, LY333328 was microbiologically effective and may be a therapeutic alternative to vancomycin.


The expression of 1-deoxy-D-xylulose synthase and geraniol-10-hydroxylase or anthranilate synthase increases terpenoid indole alkaloid accumulation in Catharanthus roseus hairy roots.
The terpenoid indole alkaloid (TIA) pathway in Catharanthus roseus produces two important anticancer drugs, vinblastine and vincristine, in very low yields. This study focuses on overexpressing several key genes in the upper part of the TIA pathway in order to increase flux toward downstream metabolites within hairy root cultures. Specifically, we constructed hairy root lines with inducible overexpression of 1-deoxy-D-xylulose synthase (DXS) or geraniol-10-hydroxylase (G10H). We also constructed hairy root lines with inducible expression of DXS and anthranilate synthase α subunit (ASA) or DXS and G10H. DXS overexpression resulted in a significant increase in ajmalicine by 67%, serpentine by 26% and lochnericine by 49% and a significant decrease in tabersonine by 66% and hörhammericine by 54%. Co-overexpression of DXS and G10H caused a significant increase in ajmalicine by 16%, lochnericine by 31% and tabersonine by 13%. Likewise, DXS and ASA overexpression displayed a significant increase in hörhammericine by 30%, lochnericine by 27% and tabersonine by 34%. These results point to the need for overexpressing multiple genes within the pathway to increase the flux toward vinblastine and vincristine.


GENETIC VARIABILITY, QUEEN NUMBER, AND POLYANDRY IN SOCIAL HYMENOPTERA.
Several hypotheses have been put forward to explain the adaptive significance of interspecific variation in mating frequencies by eusocial hymenopteran queens. Four of these hypotheses assert that polyandry is advantageous to queens because of the resultant increase in genetic variability within colonies (referred to as the "GV" hypotheses). Here we compare the frequency of polyandry between monogynous (single-queen) and polygynous (multiple-queen) ant species to test the hypotheses that (1) multiple mating functions primarily to increase intracolonial genetic variability, and (2) mating has costs (such as increased energetic losses or risk of predation or venereal disease). If one of the GV hypotheses is true and mating is costly, the frequency of polyandry should be lower in polygynous species (in which the presence of multiple queens results in low relatedness among workers) than in monogynous species. As predicted by the GV hypotheses, polyandry is less common among polygynous than among monogynous species. Furthermore, it seems that the causal relationship underlying this association is that the number of matings by queens depends on the number of queens present in the colony (rather than the number of queens being influenced by the number of matings), which also supports the GV hypotheses together with the assumption that mating has costs.


A Brief Educational Intervention Improves Medication Safety Knowledge in Grandparents of Young Children.
Increasing grandparent-grandchild interactions have not been targeted as a potential contributing factor to the recent surge in pediatric poisonings. We hypothesized that in grandparents with a young grandchild, a single educational intervention based on the PROTECT "Up & Away" campaign will improve safe medication knowledge and storage at follow-up from baseline. This prospective cohort study validated the educational intervention and survey via cognitive debriefing followed by evaluation of the educational intervention in increasing safe medication storage. Participants had to read and speak English and have annual contact with one grandchild ≤ 5-years-old. Participants were recruited from a convenience sample of employees in a regional healthcare system. They completed a pre-intervention survey querying baseline demographics, poisoning prevention knowledge, and medication storage, followed by the educational intervention and post-intervention survey. Participants completed a delayed post-intervention survey 50-90 days later assessing medication storage and poisoning prevention knowledge. Storage sites were classified as safe or unsafe a priori; a panel classified handwritten responses. 120 participants were enrolled; 95 (79%) completed the delayed post-intervention survey. Participants were predominantly female (93%) and white (76%); 50% had a clinical degree. Participants averaged 1.9 grandchildren. Initially, 23% of participants reported safe medication storage; this improved to 48% after the intervention (OR 6.4; 95% CI = 2.5-21.0). 78% of participants made at least one improvement in their medication storage after the intervention even if they did not meet all criteria for safe storage. Participants also demonstrated retention of poisoning prevention knowledge. This brief educational intervention improved safe medication storage and poisoning prevention knowledge in grandparents of young children; further evaluation of this intervention is warranted.


Metastatic pulmonary intimal sarcoma presenting as cauda equina syndrome: first report of a case.
Case report and clinical discussion. To describe a rare case of metastatic pulmonary intimal sarcoma presenting as cauda equine syndrome. Pulmonary artery sarcoma is a rare tumor, frequently misdiagnosed as pulmonary embolism, and although it is highly aggressive, metastasis to bone is very rare. In our case, the tumor metastasised to the vertebral column, which lead the patient to present with cauda equine-type symptoms. We report the clinical and imaging features in a 38-year-old female presenting with back pain and weakness of the legs. Although initially misdiagnosed as a primary bone tumor of the vertebral column and a concurrent pulmonary embolism, the final diagnosis of pulmonary artery sarcoma with spinal metastasis, presenting as cauda equina syndrome was made. At surgery, the mass was excised with the pulmonary valve and replaced with a homograft. The histology demonstrated an undifferentiated intimal sarcoma of the pulmonary artery. When stable enough the patient underwent a posterior L4-S1 decompression laminectomy after which she regained the power in the legs. The histology also showed a metastatic undifferentiated intimal sarcoma likely to have come from the pulmonary artery. The patient went on to receive a more formal vertebrectomy, front and back repair, and radiotherapy. Her 1-year follow-up computed tomography (CT) chest showed evidence of further metastases. To our knowledge, this is the first case of metastatic pulmonary intimal sarcoma presenting as cauda equine syndrome described in the literature.


The prevalence of endometrial cancer in pre- and postmenopausal Chinese women.
The incidence of endometrial cancer depends in part on the ethnicity and geographical area in which the woman resides. Menopause status is a well-known risk factor for endometrial cancer and most cases occur after menopause. It is, however, less clear how the menopause status is associated with endometrial cancer including its subtypes in Chinese women. Data on 1,746 women with endometrial cancer including age at diagnosis, age at menopause, and tumor histology from two large obstetrical and gynecological hospitals in China were analyzed. The median age of women at diagnosis was 50 years. Fifty-eight percent of women were diagnosed after menopause. Fifty-six percent of women with type 1 and 69% with type 2 were diagnosed after menopause. In addition, in both pre- and postmenopausal women, there was no difference in the age at diagnosis between type 1 (46 vs 46 y) and type 2 endometrial cancer (53 vs 52 y). Our data demonstrate that although both type 1 and type 2 endometrial cancers are more likely to occur in Chinese women after menopause than before, the total prevalence of endometrial cancer is lower in our study population than in previous reports from white women (80%). The age at diagnosis did not differ between type 1 and type 2 endometrial cancers regardless of the menopause status in our study population. Our results caution clinicians to be more aware of the importance of abnormal uterine bleeding in premenopausal Chinese women.


Monoclonal antibody-aided characterization of cellular p220 in uninfected and poliovirus-infected HeLa cells: subcellular distribution and identification of conformers.
A monoclonal antibody directed against the Mr-220,000 subunit (p220) of the mRNA cap-binding complex has been prepared and used to analyze the sucrose gradient sedimentation and subcellular location of p220 and its poliovirus-induced cleavage products. The antibody reacted with p220 on immunoblots of cell lysates from uninfected cells, but only with several smaller polypeptides, the p220 cleavage products, in cell lysates from poliovirus-infected cells. The sedimentation of p220 antigens from uninfected or infected cells was analyzed by immunoblot and by enzyme-linked immunosorbent assay (ELISA) of sucrose gradient fractions. The results indicate that antibody reactivity was partially influenced by antigen conformation. Major forms of intact p220 and cleaved p220 were identified by immunoblot, and these had similar sedimentation properties. ELISA analysis of the same gradient fractions detected only uncleaved p220; p220 cleavage products were not recognized. Furthermore, the antibody recognized two forms of native uncleaved p220, one of which appeared to bind antibody with greater affinity. This result suggested the existence of conformational variants of p220. The differential reactivity of the antibody for cleaved versus uncleaved p220 served as a useful control during indirect immunofluorescence analysis to determine the subcellular distribution of p220 antigens. The distribution of p220 in uninfected cells was mainly cytoplasmic, but some nuclear antigens were also apparent. After poliovirus infection only the nuclear pattern remained. Disappearance of the cytoplasmic pattern confirmed the inability of the antibody to react with native p220 cleavage products. The cytoplasmic pattern also disappeared after human rhinovirus 14 infection, but not after mengovirus infection, results which correlated with the ability of human rhinovirus 14 and the inability of mengovirus to induce the cleavage of p220. The results demonstrate that p220 is not likely to be associated with the cytoskeleton and hint at the possibility of a partially nuclear location.


Rapid fluorescence quenching of S2-xanthione by 3,3-diethylpentane in perfluorohydrocarbons.
Rapid fluorescence quenching of S2-xanthione by 3,3-diethylpentane has been studied in three perfluorohydrocarbons of different viscosities. The donor fluorescence decay in the presence of a quencher was fitted using the Smoluchowski-Collins-Kimball (SCK) model. The molecular parameters, R (the sum of the molecular radii), D (the sum of diffusion coefficients), and the specific rate constant of the process, kappa, were determined. The values of parameter D for all systems studied differed from the sum of the macroscopic diffusion coefficients Dx measured independently. This behavior is explained by the dependence of the molecular diffusion coefficient (as determined from the SCK model) on the distance traveled by the donor and quencher molecules during the excited donor lifetime.


Modulation of prefrontal cortex with anodal tDCS prevents post-exercise facilitation interference during dual task.
In this study we aimed to investigate whether transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (DLPFC) reduces interference effects of a dual task (DT) on post-exercise facilitation (PEF) of the motor evoked potentials. Anodal tDCS reversed the DT interference on PEF after a non-fatiguing isometric contraction. We conclude that anodal DLPFC tDCS improves the ability to allocate attentional resources and modulates plastic adaptations across brain systems.


[Histologic subtyping and prognosis of thymoma: a study of 108 cases].
To study the prognostic and clinical relevance of histologic subtyping of thymoma according to the World Health Organization (WHO) classification. The clinicopathologic features of 108 patients with thymoma removed surgically were retrospectively reviewed. The histologic diagnosis of the tumors was made on the basis of 2004 WHO classification by two experienced pathologists. The correlation between Masaoka tumor stage, WHO histologic subtype, completeness of resection, presence of myasthenia gravis, other clinical parameters (including age, gender and tumor size) and survival was studied. According to WHO classification, there were 7 cases (6.5%) of type A thymoma, 19 cases (17.6%) of type AB thymoma, 23 cases (21.3%) of type B1 thymoma, 19 cases (17.6%) of type B2 thymoma, 27 cases (25.0%) of type B3 thymoma and 13 cases (12.0%) of type C thymoma. According to Masaoka tumor staging, 36 cases (33.3%) were in stage I, 34 cases (31.5%) in stage II, 27 cases (25.0%) in stage III and 11 cases (10.2%) in stage IV(a). The association between histologic subtype and Masaoka tumor stage was statistically significant (P = 0.000). The 5-year survival rates of type A, AB, B1, B2 and B3 thymoma cases were 100%, 100%, 93%, 83% and 43%, respectively; while the 10-year survival rates were 100%, 100%, 81%, 70% and 33%, respectively. The median survival time of type C thymoma was 62.5 months. Type B2 and B3 thymoma cases had an intermediate prognostic ranking in comparison with type C thymoma and other groups (P = 0.000). The 5-year survival rates of tumors in stage I, II and III were 100%, 77% and 54%, respectively; while the 10-year survival rates were 100%, 70% and 27%, respectively. The median survival time of patients in stage IV(a) was 14.0 months. Masaoka tumor stage was highly significant in predicting survival of patients (P = 0.000). On multivariate analysis, Masaoka tumor stage was an independent predictive factor for survival (P = 0.027). On the other hand, the WHO subtype (type A to B1 versus type B2 to B3 versus type C) and completeness of resection could predict the tumor-related survival. The Masaoka tumor stage is the single most important prognostic factor of thymoma. The WHO histologic subtype and completeness of resection affect mainly the post-operative survival. The classification of thymoma may also reflect the clinical behavior of the tumor. Type A, AB and B1 thymomas belong to the low-risk group, while type B2 and B3 thymomas have an intermediate prognostic ranking. Type C thymoma carries the worst prognosis.


Endoscopic Bronchial Occlusion with Silicon Spigots for the Treatment of an Alveolar-pleural Fistula during Anti-tuberculosis Therapy for Tuberculous Empyema.
A prolonged air leak caused by pulmonary tuberculosis is difficult to treat, and little is known about optimal treatment strategies. We herein report the case of a 60-year-old man who demonstrated tuberculous empyema with a fistula. An air leak from a tuberculous cavity in his left upper lobe persisted for approximately 4 months; surgical repair could not be performed due to a poor physical status and undernourishment. However, the air leak was successfully treated with endobronchial occlusion using two silicone spigots in left B3b and B4, without any adverse effects or aggravation of the infection.


Anti-OX40 stimulation in vivo enhances CD8+ memory T cell survival and significantly increases recall responses.
There is growing evidence that engagement of OX40 (CD134), a member of the TNF receptor superfamily, can directly stimulate antigen-specific CD8+ T cells. It has been shown that CD8+ T cells express OX40 following activation, but the response of antigen-specific CD8+ T cells to OX40 stimulation has not been fully characterized. We utilized an antigen-specific transgenic CD8+ T cell model (OT-I) to determine if OX40 engagement can boost the generation of antigen-specific CD8+ T cell memory. Our results demonstrate that enhanced OX40 costimulation, via an agonist anti-OX40 antibody, increases CD25 and phospho-Akt expression on the antigen-specific CD8+ T cells and significantly increases the generation of long-lived antigen-specific CD8+ memory T cells. The increased numbers of memory CD8+ T cells generated via anti-OX40 treatment still required the presence of CD4+ T cells for their long-term maintenance in vivo. In addition, anti-OX40 costimulation greatly enhanced antigen-specific CD8+ T cell recall responses. These data show that OX40 engagement in vivo increases the number of antigen-specific CD8+ memory T cells surviving after antigen challenge and has implications for the development of more potent vaccines against pathogens and cancer.


Long-range correlations in amplitude variability of HF and LF components of heart rate variability.
For the assessment of autonomic nervous system activity based on heart rate variability (HRV) analysis, characteristics of high-frequency (HF; 0.15 to 0.4 Hz) and low-frequency (LF; 0.04 to 0.15 Hz) components have been widely employed. HF and LF band powers quantified by power spectral analysis have most commonly been used in the conventional studies; the physiological significance of these measures has also been extensively studied. However, nonlinear characteristics of HF and LF components have not been well established. In this paper, we investigated nonlinear properties of HF and LF components in 122 healthy subjects and 108 patients with congestive heart failure (CHF). By analyzing bandpass-filtered time series of HRV corresponding to HF and LF components, it is shown that amplitude variability of HF and LF components displays long-range correlation, which cannot be explained by linear HRV properties. Compared with the age-matched healthy control group, the CHF patients showed significantly decreased long range correlation of HF component amplitude variability. These findings suggest that nonlinear properties of HF and LF components provides some complementary information on HRV dynamics.


Automated 3-dimensional elastic registration of whole-body PET and CT from separate or combined scanners.
Registration and fusion of whole-body functional PET and anatomic CT is significant for accurate differentiation of viable tumors from benign masses, radiotherapy planning and monitoring treatment response, and cancer staging. Whole-body PET and CT acquired on separate scanners are misregistered because of differences in patient positions and orientations, couch shapes, and breathing protocols. Although a combined PET/CT scanner removes many of these misalignments, breathing-related nonrigid mismatches still persist. We have developed a new, fully automated normalized mutual information-based 3-dimensional elastic image registration technique that can accurately align whole-body PET and CT images acquired on stand-alone scanners as well as a combined PET/CT scanner. The algorithm morphs the PET image to align spatially with the CT image by generating an elastic transformation field by interpolating quaternions and translations from multiple 6-parameter rigid-body registrations, each obtained for hierarchically subdivided image subvolumes. Fifteen whole-body (spanning thorax and abdomen) PET/CT image pairs acquired separately and 5 image pairs acquired on a combined scanner were registered. The cases were selected on the basis of the availability of both CT and PET images, without any other screening criteria, such as a specific clinical condition or prognosis. A rigorous quantitative validation was performed by evaluating algorithm performance in the context of variability among 3 clinical experts in the identification of up to 32 homologous anatomic landmarks. The average execution time was 75 and 45 min for images acquired using separate scanners and combined scanner, respectively. Visual inspection indicated improved matching of homologous structures in all cases. The mean registration accuracy (5.5 and 5.9 mm for images from separate scanners and combined scanner, respectively) was found comparable to the mean interexpert difference in landmark identification (5.6 +/- 2.4 and 6.6 +/- 3.4 mm, respectively). The variability in landmark identification did not show statistically significant changes on replacing any expert by the algorithm. We have presented a new and automated elastic registration algorithm to correct for nonrigid misalignments in whole-body PET/CT images as well as improve the "mechanical" registration of a combined PET/CT scanner. The algorithm performance was on par with the average opinion of 3 experts.


Bright Optical Eigenmode of 1 nm^{3} Mode Volume.
We report on the discovery and rationale to devise bright single optical eigenmodes that feature quantum-optical mode volumes of about 1 nm^{3}. Our findings rely on the development and application of a quasinormal mode theory that self-consistently treats fields and electron nonlocality, spill-out, and Landau damping around atomistic protrusions on a metallic nanoantenna. By outpacing Landau damping with radiation via properly designed antenna modes, the extremely localized modes become bright with radiation efficiencies reaching 30% and could provide up to 4×10^{7} times intensity enhancement.


Multisocietal European consensus on the terminology, diagnosis, and management of patients with synchronous colorectal cancer and liver metastases: an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE.
Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases, with a focus on terminology, diagnosis, and management. This project was a multiorganizational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis, and management. Statements were refined during an online Delphi process, and those with 70 per cent agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising 12 key statements. Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term 'early metachronous metastases' applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour, the term 'late metachronous metastases' applies to those detected after 12 months. 'Disappearing metastases' applies to lesions that are no longer detectable on MRI after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards, and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways, including systemic chemotherapy, synchronous surgery, and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases.


Too Much Sitting: A Serious 21st Century Health Risk.
While weekly moderate-to-vigorous physical activity (MVPA) is considered a well-established key determinant for regulating weight and reducing risks of obesity and associated noncommunicable diseases, MVPA alone may not be enough to offset excessive sitting time. This integrative literature review aims to advance the discussion about sedentary behavior as a significant independent health risk for obesity and associated noncommunicable diseases, to increase awareness, to synthesize important evidence on sedentary behavior and a number of negative health outcomes, and to present the application of a whole-day approach to physical activity as a feasible strategy to promote health.


Determining the 3-substituted Coumarins inhibitory potential against the HslV protease of E. coli.
The growing bacterial resistance towards classical antibiotics demands the development of novel approaches for the effective treatment of potentially fatal bacterial infections in humans. Proteostasis is crucial for the survival of every living cell, as several important physiological functions depend on well-regulated proteostasis. Within bacteria, the regulation of proteostasis relies on AAA+ (Adenosine 5'-triphosphatases associated with diverse cellular activities), ATPases, such as the HslVU complex (heat shock locus gene products U and V), along with other proteases. The HslVU protease/chaperon complex is thought to be the progenitor of the eukaryotic proteasome that regulates proteostasis mostly in prokaryotes. This study aimed to determine the inhibitory potential of 3-substituted coumarin derivatives against Escherichia coli heat shock locus V (HslV) protease. In this study, twenty-three derivatives of 3-substituted coumarin were assessed for their inhibitory potential against E. coli HslV protease using both in-vitro and in-silico techniques. Among all the tested compounds, US-I-64, US-I-66, US-I-67, and US-I-68 displayed notable inhibitory potential against the HslV protease, showing IC50 (half maximal inhibitory concentration) values ranging from 0.2 to 0.73 μM. Additionally, the inhibitory potential of these compounds against the eukaryotic proteasome was also evaluated using a separate in-silico study. It was found that these compounds did not bind with the proteasomal active site, suggesting no apparent side effects of these lead molecules. These identified HslV protease inhibitors can be used for the development of novel and safer anti-bacterial drugs.


Amphotericin B and its delivery by liposomal and lipid formulations.
In recent years, new formulations of the original amphotericin B preparation (Fungizone) have been devised in order to overcome toxicity problems that frequently occur. These preparations represent an improved method of drug delivery, with an increased therapeutic index and a decrease in toxicity to mammalian cell membranes. The new formulations have different physico-chemical characteristics and differ in pharmacokinetic parameters. Their effects must be compared with conventional amphotericin B to ascertain potential roles in future antifungal therapy.


[Nosocomial infections in rooming-in system: results of a two-year study].
Nosocomial infections of 1356 mothers and their newborn have been analyzed and compared in three different regimens for postnatal care of newborn (rooming-in service, mixed service and central newborn nursery). The average nosocomial infection rate of mothers was significantly lower in the rooming-in service as compared to the newborn nursery. Most common nosocomial infections of mothers were urinary tract infections, endometritis, wound infection, enteritis and mastitis; in newborn enteritis, oral candida infections, panaritium, conjunctivitis and staphylococcus skin infections. Staphylococcal infection of newborn were higher in the newborn nursery as compared to the rooming-in service. Epidermic nosocomial infections (e.g. enteritis, candida infections) occurred more often in the newborn nursery as compared to the mixed system and rooming-in service. There was an increased risk of cross infections from mothers with wound infection, endometritis and mastitis to their children.


Compliance with universal precautions and needle handling and disposal practices among emergency department staff at two community hospitals.
To describe rates of needle disposal and barrier use within the emergency departments at two privately owned community hospitals in two suburbs of Minneapolis, a study was conducted. This study consisted of direct observation of a cohort of emergency department personnel providing patient care followed by a self-administered survey of the same personnel. From June through August 1990, seven specially trained registered nurses observed emergency department personnel for a total of 400 hours. The observers documented the appropriate rates of use of gowns, goggles, masks, and gloves. Observers also noted methods of needle disposal and frequency of needle recapping. After observation, surveys that included items requesting estimates of rates of use for each barrier, as well as estimates of the rates and methods of needle recapping and disposal, were distributed. For each observed and corresponding self-reported behavior, 95% confidence intervals were calculated and compared. A total of 1,822 procedures were recorded. Gloves were observed to be used when appropriate 67.2% of the time, followed by goggles (50.7%), masks (16.0%), and gowns (15.3%). Self-reported barrier rates were slightly higher in all cases except for goggle use. About one third (34.4%) of the needles were recapped; 78.1% of these were recapped two-handed. Previous studies have documented low universal precautions compliance rates at urban teaching hospitals. Our data indicate less than optimal levels of compliance also at community hospitals, and show that personnel are less than fully aware of their own noncompliance.