High yields of small and flat adenomas with high-definition colonoscopes using either white light or narrow band imaging.
Detection of adenomas is an important goal of colonoscopy. Narrow band imaging (NBI) might highlight adenomas and lead to higher rates of adenoma detection. This was a randomized controlled trial of colonoscopy withdrawal in white light versus NBI in 434 patients aged 50 years or older with intact colons. All examinations were performed by a single experienced endoscopist with a known high detection rate of adenomas using high-definition, wide-angle (170 degrees field of view) colonoscopes. There was no difference in the percent of patients with >or=1 adenoma for the entire cohort in white light (67%) versus NBI (65%) (P = .61) or in the subset of 257 patients with indication screening (58% vs 57%; P = .91). Both the prevalences of adenomas and the numbers of adenomas per colonoscopy are the highest ever reported in colonoscopy studies. The high prevalence rates of adenomas were accounted for by detection of large numbers of adenomas, including flat adenomas, which were <or=5 mm. NBI did not result in better detection of adenomas by an endoscopist with a known high detection rate using white light. This result does not exclude a possible benefit of NBI in reducing variation between endoscopists in detection of adenomas. The very high adenoma detection rate in this study suggests that high definition should be directly tested for its effect on detection of adenomas.


Staff ownership would revolutionize patient safety - if we let it.
Healthcare has failed to make the same progress as other high-risk industries when it comes to creating safety - despite over a decade of research, education and implementation of safety systems in health services. Safe care is created by systems and standardization, and also by proactive, thinking staff working in partnership with consumers and each other; but the healthcare industry appears to struggle to reconcile these concepts. Even with our evolved knowledge of how human beings operate in organizations, and the best intentions, the dominant change paradigm in healthcare is still hierarchical, based on top-down policies implemented by managers and staff. Although the power spread in health services is being tested through generational change, we have a long way to go before proactivity and initiative at the front line are universally fostered and welcomed by healthcare managers and senior clinicians. "Front Line Ownership: Generating a Cure Mindset for Patient Safety," by Zimmerman et al., presents a persuasive example of how staff ownership of improving consumer safety is a powerful tool for change, one that deserves its place at the front line of safety and quality improvement methods.


Separate checkpoints regulate splenic plasma cell accumulation and IgG autoantibody production in Lyn-deficient mice.
Accumulation of plasma cells and autoantibodies against nuclear antigens characterize both human and murine lupus. Understanding how these processes are controlled may reveal novel therapeutic targets for this disease. Mice deficient in Lyn, a negative regulator of B and myeloid cell activity, develop lupus-like autoimmune disease. Here, we show that lyn(-) (/) (-) mice exhibit increased splenic plasmablasts and plasma cells and produce IgM against a wide range of self-antigens. Both events require Btk, a target of Lyn-dependent inhibitory pathways. A Btk-dependent increase in the expression of the plasma cell survival factor IL-6 by lyn(-) (/) (-) splenic myeloid cells was also observed. Surprisingly, IL-6 was not required for plasma cell accumulation or polyclonal IgM autoreactivity in lyn(-/-) mice. IL-6 was, however, necessary for the production of IgG autoantibodies, which we show are focused towards a limited set of nucleic acid-containing and glomerular autoantigens in lyn(-) (/) (-) mice. A similar uncoupling of plasma cell accumulation from IgG autoantibodies was seen in lyn(+/-) mice. Plasma cell accumulation and polyclonal IgM autoreactivity are therefore controlled separately from, and are insufficient for, the production of IgG against lupus-associated autoantigens. Regulators of either of these two checkpoints may be attractive therapeutic targets for lupus.


Charge Transport in 4 nm Molecular Wires with Interrupted Conjugation: Combined Experimental and Computational Evidence for Thermally Assisted Polaron Tunneling.
We report the synthesis, transport measurements, and electronic structure of conjugation-broken oligophenyleneimine (CB-OPI 6) molecular wires with lengths of ∼4 nm. The wires were grown from Au surfaces using stepwise aryl imine condensation reactions between 1,4-diaminobenzene and terephthalaldehyde (1,4-benzenedicarbaldehyde). Saturated spacers (conjugation breakers) were introduced into the molecular backbone by replacing the aromatic diamine with trans-1,4-diaminocyclohexane at specific steps during the growth processes. FT-IR and ellipsometry were used to follow the imination reactions on Au surfaces. Surface coverages (∼4 molecules/nm(2)) and electronic structures of the wires were determined by cyclic voltammetry and UV-vis spectroscopy, respectively. The current-voltage (I-V) characteristics of the wires were acquired using conducting probe atomic force microscopy (CP-AFM) in which an Au-coated AFM probe was brought into contact with the wires to form metal-molecule-metal junctions with contact areas of ∼50 nm(2). The low bias resistance increased with the number of saturated spacers, but was not sensitive to the position of the spacer within the wire. Temperature dependent measurements of resistance were consistent with a localized charge (polaron) hopping mechanism in all of the wires. Activation energies were in the range of 0.18-0.26 eV (4.2-6.0 kcal/mol) with the highest belonging to the fully conjugated OPI 6 wire and the lowest to the CB3,5-OPI 6 wire (the wire with two saturated spacers). For the two other wires with a single conjugation breaker, CB3-OPI 6 and CB5-OPI 6, activation energies of 0.20 eV (4.6 kcal/mol) and 0.21 eV (4.8 kcal/mol) were found, respectively. Computational studies using density functional theory confirmed the polaronic nature of charge carriers but predicted that the semiclassical activation energy of hopping should be higher for CB-OPI molecular wires than for the OPI 6 wire. To reconcile the experimental and computational results, we propose that the transport mechanism is thermally assisted polaron tunneling in the case of CB-OPI wires, which is consistent with their increased resistance.


Gallstone ileus 30 years after cholecystectomy and hepaticojejunostomy.
Gallstone ileus occurs when the small or large intestine is obstructed by a gallstone and is a rare occurrence in a post-cholecystectomy patient. Non-specific clinical symptoms and inconsistent imaging results often lead to a delay in diagnosis. Complex anatomy, such as a Roux-en-Y biliary-enteric anastomosis, can increase the risk of stone formation and further confound a potential case of gallstone ileus. Here, we present a rare case of gallstone ileus at the anastomosis site of a Roux-en-Y hepaticojejunostomy done 30 years prior for a common bile duct injury during a cholecystectomy. The possibility of negative CT findings, pattern of presentation on imaging as intussusception, and potential pathomechanism of gallstone formation in post-cholecystectomy patients are discussed. Through this case and review of similar cases, we emphasise the need for further study of post-cholecystectomy gallstone ileus and the importance of clinical suspicion during diagnosis.


Liver repopulation: a new concept of hepatocyte transplantation.
Hepatocyte transplantation has been recognized as an alternative strategy for organ transplantation because the supply of donor livers is limited. However, in conventional hepatocyte transplantation, only 1%-10% of the liver replaced with transplanted hepatocytes. Recently a novel concept termed "liver repopulation" has been established, where the whole recipient liver can be replaced by a small number of donor hepatocytes. To induce liver repopulation, growth advantage of the donor hepatocytes against the host liver seems to be required according to the data of previous studies. Additionally, various cell sources, including bone marrow cells and other stem cells, could potentially be used as donor cells for liver repopulation. In this article, we discuss recent progress and future perspectives of this emerging technology.


Photonic crystal nanobeam biosensors based on porous silicon.
Photonic crystal (PhC) nanobeams (NB) patterned on porous silicon (PSi) waveguide substrates are demonstrated for the specific, label-free detection of oligonucleotides. These photonic structures combine the large active sensing area intrinsic to PSi sensors with the high-quality (Q) factor and low-mode volume characteristic of compact resonant silicon-on-insulator (SOI) PhC NB devices. The PSi PhC NB can achieve a Q-factor near 9,000 and has an approximately 40-fold increased active sensing area for molecular attachment, compared to traditional SOI PhC NB sensors. The PSi PhC NB exhibits a resonance shift that is more than one order of magnitude larger than that of a similarly designed SOI PhC NB for the detection of small chemical molecules and 16-base peptide nucleic acids. The design and fabrication of PSi PhC NB sensors are compatible with CMOS processing, sensor arrays, and integration with lab-on-chip systems.


Comparison of the Efficacy and Tolerability of Dexketoprofen and Ketoprofen in the Treatment of Primary Dysmenorrhea.
Dexketoprofen, the pure S(+)-enantiomer of ketoprofen, is a promising new analgesic, but few clinical trials have yet examined its efficacy and tolerability. In this study, patients with a history of primary dysmenorrhea were treated with dexketoprofen doses of 12.5 and 25 mg, ketoprofen 50 mg, and placebo using a randomized, four-way crossover design. Efficacy analyses showed that dexketoprofen 12.5 and 25 mg and racemic ketoprofen 50 mg significantly reduced pain intensity compared with placebo from 1 h after dose to 4-6 h after dose. Interestingly, dexketoprofen at 12.5 mg was significantly superior to placebo at 30 min after dose. Mean pain relief scores also demonstrated that both doses of dexketoprofen and racemic ketoprofen were significantly superior to placebo at 1-6 h after the first dose. No indices of analgesic efficacy showed any significant differences between the two doses of dexketoprofen or between dexketoprofen and ketoprofen. After repeated dose administration, similar results were obtained. There were no significant effects of any treatment on activities of daily living, menstrual flow, or associated symptoms. Dexketoprofen was effective, well tolerated, and had no difference in the incidence of adverse events compared to ketoprofen or placebo.


Social information use is a process across time, space, and ecology, reaching heterospecifics.
Decision making can be facilitated by observing other individuals faced with the same or similar problem, and recent research suggests that this social information use is a widespread phenomenon. Implications of this are diverse and profound: for example, social information use may trigger cultural evolution, affect distribution and dispersal of populations, and involve intriguing cognitive traits. We emphasize here that social information use is a process consisting of the scenes of (1) event, (2) observation, (3) decision, and (4) consequence, where the initial event is a scene in such a process of another individual. This helps to construct a sound conceptual framework for measuring and studying social information use. Importantly, the potential value of social information is affected by the distance in time, space, and ecology between the initial observation and eventual consequence of a decision. Because negative interactions between individuals (such as direct and apparent competition) also depend on the distance between individuals along these dimensions, the potential value of information and the negative interactions may form a trade-off situation. Optimal solutions to this trade-off can result in adaptively extended social information use, where using information gathered some time ago, some distance away, and from ecologically different individuals is preferred. Conceivably, using information gathered from a heterospecific individual might often be optimal. Many recent studies demonstrate that social information use does occur between species, and the first review of published cases is provided here. Such interaction between species, especially in habitat selection, has important consequences for community ecology and conservation. Adaptively extended social information use may also be an important evolutionary force in guild formation. Complex coevolutionary patterns may result depending on the effect of information use on the provider of information.


Validity Evidence for the LittlEARS Early Speech Production Questionnaire: An English-Speaking, Canadian Sample.
Purpose This study reports validity evidence for an English translation of the LittlEARS Early Speech Production Questionnaire (LEESPQ). The LEESPQ was designed to support early spoken language outcome monitoring in young children who are deaf/hard of hearing. Methods Data from 90 children with normal hearing, ages 0-18 months, are reported. Parents completed the LEESPQ in addition to a concurrent measure of spoken language development, the Receptive-Expressive Emergent Language Test-Third Edition. Normal hearing status and development were confirmed. Results Traditional scale analyses, in addition to item parameters, are reported. The LEESPQ was highly correlated with the Receptive-Expressive Emergent Language Test-Third Edition (r = .92) and age (r = .90) and had high internal consistency (Ω = 0.92). Common factor analysis revealed 2 underlying factors conceptually mapping onto items measuring vocal and symbolic development. A latent traits model was the best fit to the data, and item difficulty broadly conformed to theoretical expectations. Conclusions The present work demonstrates that the LEESPQ accurately captures early spoken language development in a typically developing group of young children. The LEESPQ holds promise as a clinically feasible, spoken language outcome monitoring tool. Future work to identify differences in performance characteristics between typically developing children and clinical populations is warranted.


Sympathetic skin response and R-R interval variation in rheumatoid arthritis. Two simple tests for the assessment of autonomic function.
Autonomic nervous system involvement with peripheral neuropathy is a well known complication of rheumatoid arthritis (RA). In the assessment of autonomic function of patients with rheumatoid arthritis, we performed sympathetic skin response (SSR) and R-R interval variation (RRIV) tests in 30 patients and in 30 normal controls. Of 30 patients, 5 had complaints of clinical dysautonomic symptoms. SSRs were abnormal in 6 of 30 patients, whereas 8 showed abnormal RRIVs during deep breathing. Nine of 30 patients also showed electrophysiologic evidence of peripheral neuropathy. All 5 of the patients with clinical dysautonomic symptoms showed abnormal SSR and RRIV test results. No patients with normal results on both tests had clinical dysautonomia. This study showed that there are frequent abnormalities in SSR and RRIV tests in patients with rheumatoid arthritis whether there is a clinical symptom of autonomic dysfunction or not.


Decrease of RBM4 indicates poor prognosis in patients with hepatocellular carcinoma after hepatectomy.
RNA-binding motif 4 (RBM4) has been reported to play an important role in many human tumors such as lung cancer, breast cancer, ovarian cancer and gastric cancer by regulating alternative splicing and messenger RNA (mRNA) translation. However, little is known about the role of RBM4 in the development of hepatocellular carcinoma (HCC). This study aimed to investigate the expression of RBM4 in HCC tissues. Expression of RBM4 was detected by immunohistochemistry in 95 cases of HCC. Correlations of RBM4 expression with the overall survival and disease-free survival of HCC were also studied. Patients with high RBM4 expression had better overall survival rate and disease-free survival rate than those with low RBM4 expression (P<0.001, P=0.007, respectively). RBM4 expression, together with tumor numbers, capsular formation, vascular invasion and Barcelona clinic liver cancer (BCLC) stage, was an independent prognostic factor for overall survival rate and disease-free survival rate of HCC. Our data implicate RBM4 as a novel prognostic marker and a potential therapeutic target for HCC.


Attributes of errors, facilitators, and barriers related to rate control of IV medications: a scoping review.
Intravenous (IV) medication is commonly administered and closely associated with patient safety. Although nurses dedicate considerable time and effort to rate the control of IV medications, many medication errors have been linked to the wrong rate of IV medication. Further, there is a lack of comprehensive studies examining the literature on rate control of IV medications. This study aimed to identify the attributes of errors, facilitators, and barriers related to rate control of IV medications by summarizing and synthesizing the existing literature. This scoping review was conducted using the framework proposed by Arksey and O'Malley and PRISMA-ScR. Overall, four databases-PubMed, Web of Science, EMBASE, and CINAHL-were employed to search for studies published in English before January 2023. We also manually searched reference lists, related journals, and Google Scholar. A total of 1211 studies were retrieved from the database searches and 23 studies were identified from manual searches, after which 22 studies were selected for the analysis. Among the nine project or experiment studies, two interventions were effective in decreasing errors related to rate control of IV medications. One of them was prospective, continuous incident reporting followed by prevention strategies, and the other encompassed six interventions to mitigate interruptions in medication verification and administration. Facilitators and barriers related to rate control of IV medications were classified as human, design, and system-related contributing factors. The sub-categories of human factors were classified as knowledge deficit, performance deficit, and incorrect dosage or infusion rate. The sub-category of design factor was device. The system-related contributing factors were classified as frequent interruptions and distractions, training, assignment or placement of healthcare providers (HCPs) or inexperienced personnel, policies and procedures, and communication systems between HCPs. Further research is needed to develop effective interventions to improve IV rate control. Considering the rapid growth of technology in medical settings, interventions and policy changes regarding education and the work environment are necessary. Additionally, each key group such as HCPs, healthcare administrators, and engineers specializing in IV medication infusion devices should perform its role and cooperate for appropriate IV rate control within a structured system.


Interventions to improve oncofertility knowledge and decision-making in patients with low health literacy: A systematic review.
To conduct a systematic review of interventions that improve knowledge, health and decision-related outcomes in cancer, fertility or the intersection of both among low health literacy (LHL) patients. Articles published from 2000 to March 2022 in English were identified through searching MEDLINE, PsycInfo, and Embase databases on 29/03/2022. Studies were independently screened against eligibility criteria and appraised for quality. A narrative synthesis of data was presented. Of 235 citations, 11 studies (2585 participants) investigating three categories were included: decision-support tools (n = 8), mobile health applications (n = 2) and communication tools (n = 1). No eligible study was identified for fertility or oncofertility. All interventions integrated multimedia or interactivity to supplement plain-language text. Decision aids and mobile health applications improved knowledge, reduced decisional conflict and increased clarity around cancer-related choices. Overall, findings favoured the use of online interventions tailored for LHL patients. There is a lack of data on LHL interventions in fertility and oncofertility. In cancer, LHL interventions improved knowledge and decision-making outcomes. The ideal intervention remains inconclusive. Lack of engagement with LHL needs in oncofertility and fertility settings have implications for informed treatment decision-making. In cancer, further research is required to ascertain most effective intervention format.


Uptake of hepatitis C treatment among people who inject drugs attending Needle and Syringe Programs in Australia, 1999-2011.
The majority of new and existing cases of hepatitis C virus (HCV) infection occur among people who inject drugs (PWID). Despite safe and efficacious HCV antiviral therapy, uptake remains low in this population. This study examined trends in HCV treatment uptake among a large national sample of PWID attending Australian Needle and Syringe Programs between 1999 and 2011. Annual cross-sectional sero-surveys conducted among PWID since 1995 involve completion of a self-administered questionnaire and provision of a dried blood spot for HCV antibody testing. Multivariate logistic regression identified variables independently associated with HCV treatment uptake among 9478 participants with both self-reported and serologically confirmed prior HCV infection. Between 1999 and 2011, the proportion currently receiving treatment increased from 1.1% to 2.1% (P < 0.001), while the proportion having ever received treatment increased from 3.4% to 8.6% (P < 0.001). Men were significantly more likely than women to have undertaken HCV treatment (P = 0.002). Among men, independent predictors of HCV treatment uptake were homosexual identity and older age; among women, independent predictors included homosexual identity and an incarceration history. Despite increases in HCV treatment among Australian PWID between 1999 and 2011, uptake remains low. Strategies are required to increase the proportion of PWID assessed and treated for HCV infection to address the increasing burden of disease. Specific approaches that target women may also be warranted. Continued surveillance of HCV treatment uptake among PWID will be important to monitor the roll-out of simple, safe and more effective HCV treatments expected to be available in the future.


Deterministic modelling for transmission of Human Papillomavirus 6/11: impact of vaccination.
This paper is devoted to assess the impact of quadrivalent human papillomavirus (HPV) vaccine on the prevalence of non-oncogenic HPV 6/11 types in French males and females. For this purpose, a non-linear dynamic model of heterosexual transmission for HPV 6/11 types infection is developed, which accounts for immunity due to vaccination, in particular. The vaccinated reproduction number Rv is derived using the approach described by Diekmann et al. (2010) called the next generation operator approach. The model proposed is analysed, with regard to existence and uniqueness of the solution, steady-state stability. Precisely, the stability of the model is investigated depending on the sign of Rv-1. Prevalence data are used to fit a numerical HPV model, so as to assess infection rates. Our approach suggests that 10 years after introducing vaccination, the prevalence of HPV 6/11 types in females will be halved and that in males will be reduced by one-quarter, assuming a sustained vaccine coverage of 30% among females. Using the formula, we derived for the vaccinated reproduction number, we show that the non-oncogenic HPV 6/11 types would be eradicated if vaccine coverage in females is kept above 12%.


[Effects of early estrogen replacement therapy on bone stability of ovariectomized rats. A biomechanical and radiologic study of the tibial plateau].
Postmenopausal osteoporosis leads to a significant increase in bone fragility. In this study we used the rat tibia plateau fracture model to investigate the efficiency of estrogen replacement therapy (ERT) to mitigate the post-ovariectomy decrease in fracture load. A total of 73 virgin Sprague Dawley rats had been ovariectomized and 26 animals underwent sham operation. The ovariectomized animals were either untreated (n = 35) or treated with estrogen injections (10 micrograms/kg per day 3 days a week until sacrifice), starting treatment at either 0, 5, 8, or 13 days post surgery. Before starting ERT and at 50 days post surgery, the trabecular structure of the right proximal tibial metaphysis of each animal was imaged non-invasively using high resolution X-ray topography. The animals were then sacrificed and the right knee from each animal was harvested and mounted into a servo-hydraulic materials testing system so that the distal femoral condyle could be forced into the proximal tibial plateau until fracture occurred. The failure load (F) of the ovariectomized group without estrogen administration was significantly less than that for the sham group. The mean stiffness (K) of the ovariectomized group was 22 percent less than that of the sham group, though this difference did not reach statistical significance. Across all groups, the failure load and stiffness were significantly correlated with the trabecular bone volume. Our data suggest that prompt ERT can increase the fracture load and stiffness of trabecular bone by allowing bone formation to continue in previously activated bone remodeling units while suppressing the production of new remodeling units. This may be the mechanism by which estrogen and other antiresorptive agents increase bone mass, and thereby reduce the risk of osteoporotic fractures in postmenopausal women.


Impact of azithromycin administration for trachoma control on the carriage of antibiotic-resistant Streptococcus pneumoniae.
Community distribution of azithromycin has an important role to play in trachoma control. Previous studies have suggested that this may increase the prevalence of macrolide-resistant Streptococcus pneumoniae. S. pneumoniae was isolated from children under 7 years of age in Rombo District, northern Tanzania, before and 2 and 6 months after community-wide administration of azithromycin. Overall carriage rates were 11, 12, and 7%, respectively. Only one macrolide-resistant isolate carrying the mef gene was obtained 6 months after azithromycin administration. This contrasted with cotrimoxazole and penicillin resistance, both of which were common (cotrimoxazole resistance, 42, 43, and 47%, and penicillin resistance, 21, 17, and 16% at baseline, 2 months, and 6 months, respectively). There was a significant association between cotrimoxazole and penicillin resistance (P < 0.0001, Fisher's exact). These data suggest that in communities where macrolide resistance is rare, azithromycin distribution for trachoma control is unlikely to increase the prevalence of resistant organisms.


New drug targets in inflammation: efforts to expand the anti-inflammatory armoury.
Inflammation is a beneficial host response to challenge by foreign bodies or to tissue injury. When this normal physiological process (which is designed to restore normal tissue structure and function), becomes dysregulated, it can become harmful and destructive leading to inflammatory diseases that are a major burden on humanity. Despite some notable successes, there are still major unmet medical needs in the treatment of inflammatory diseases and the development of new anti-inflammatory drugs features prominently in the research portfolios of most pharmaceutical and biotech companies. New insights into inflammatory processes and new anti-inflammatory drug targets were the subjects of a Focus Topic organized for the Life Sciences 2007 meeting in Glasgow (July 2007). The speakers from this meeting were invited to generate reviews on the basis of their presentations and these reviews contribute to this themed issue and are summarized in this short article.


The Prevalence and Predicting Factors of Pulmonary Thromboembolism in Patients with Exacerbated Chronic Obstructive Pulmonary Disease.
The risk of pulmonary thromboembolism (PTE) in patients with exacerbated chronic obstructive pulmonary disease (e-COPD) is higher than in non-COPD states. This study aimed to evaluate the prevalence and the parameters that are critical for finding the incidence of PTE in patients with e-COPD. This cross-sectional study was performed on 68 consecutive patients with the e-COPD, referred to the Pulmonary Disease Department at the Shariati Hospital in Tehran between 2013 and 2014. In addition to collecting data on the history of disease and physical examination, arterial blood sampling, spirometry, electrocardiography and echocardiography were performed for all patients. All patients underwent the computed the tomography pulmonary angiography (CT-PA) as a method of choice for diagnosing PTE. Out of 68 cases (7.4%), five were had CT angiography findings suggesting PTE. These patients were all male and had a higher mean age (79 vs. 65 years), lower mean systolic blood pressure (88.36 vs. 118.33 mmHg), and a higher mean heart rate (133.12 vs 90.33 beats/min), compared to e-COPD patients without PTE. Arterial blood gas analysis in patients with PTE demonstrated a lower HC03 (2.33 vs. 9.44 mEq/l) and PC02 (44.35 vs. 51.43 mmHg) levels. The mean LVEF was lower in patients with PTE (34.14 ±4.49% vs. 46.94 ± 8.27%). The prevalence of PTE in our series of patients with e-COPD was 7.4%. According to the study results, male gender, advanced age, hypotension, tachycardia, and respiratory alkalosis are factors indicating possible PTE among patients with e-COPD.


Studies on fusobacteria associated with periodontal diseases.
The physiological and metabolic characteristics of representative isolates of the various subspecies of Fusobacterium nucleatum were investigated by growing them in continuous culture in chemically-defined, media. Behaving almost identically, these organisms were found to obtain energy from the fermentation of simple carbohydrates such as glucose or fructose or from the fermentation of certain amino acids, free or in the form of small peptides. The latter can be attacked by aminopeptidase activity which was shown to be essential for the growth of the organism in an environment lacking fermentable carbohydrate and free amino acids but replete with small peptides. This metabolic versatility may explain the presence of F. nucleatum in both supra- and sub-gingival dental plaque and why it is often found together with organisms such as Porphyromonas gingivalis which display powerful endopeptidase activities. Using the technique of allozyme electrophoresis, the current subspeciation of F. nucleatum was shown to be of doubtful validity and evidence, based upon physiological and metabolic properties, for differences in pathogenicity between isolates was not detected. While this organism is a member of various bacterial consortia associated with periodontal diseases, its contribution to the disease process remains unclear.


Ligation, inhibition, and activation of cytochrome c oxidase by fatty acids.
Free fatty acids bind to beef heart cytochrome c oxidase and induce spectral shifts similar to those obtained with high spin ligands. Oleic (18:1(n-9)) and linoleic (18:2(n-6)) acids induce substantial blue shifts of the Soret peak of oxidized enzyme. Small saturated fatty acids (< 15 carbon atoms) shift the Soret peak to the red, and longer chain acids induce smaller blue shifts. Formate-induced spectral shifts are modified by short chain fatty acids but are unaffected by longer chain fatty acids for which effects are additive with those of formate. Inhibition by formate is partially relieved by all fatty acids tested. Palmitic and linoleic acids increase turnover at low cytochrome c levels and decrease the K(m) for cytochrome c at high cytochrome c levels. Oleic acid protects the enzyme against acid denaturation during turnover. Bovine serum albumin produces a red shift in the oxidase Soret peak and inhibits turnover of the isolated enzyme. Oleic acid and serum albumin modify the electron paramagnetic resonance spectrum of oxidized oxidase, oleic acid shifting the g = 3 (cytochrome a) peak towards low field and albumin towards higher field strengths. The oxidase may possess at least two fatty acid binding sites at one of which cytochrome c binding is modulated and at another spectral changes may be induced. One site is close enough to the binuclear centre to interact allosterically with ligand binding at that centre.


Cost effectiveness of a pharmacy-only refill program in a large urban HIV/AIDS clinic in Uganda.
HIV/AIDS clinics in Uganda and other low-income countries face increasing numbers of patients and workforce shortages. We performed a cost-effectiveness analysis comparing a Pharmacy-only Refill Program (PRP), a form of task-shifting, to the Standard of Care (SOC) at a large HIV/AIDS clinic in Uganda, the Infectious Diseases Institute (IDI). The PRP was started to reduce workforce shortages and optimize patient care by substituting pharmacy visits for SOC involving monthly physician visits for accessing antiretroviral medicines. We used a retrospective cohort analysis to compare the effectiveness of the PRP compared to SOC. Effectiveness was defined as Favorable Immune Response (FIR), measured as having a CD4 lymphocyte count of over 500 cells/µl at follow-up. We used multivariate logistic regression to assess the difference in FIR between patients in the PRP and SOC. We incorporated estimates of effectiveness into an incremental cost-effectiveness analysis performed from a limited societal perspective. We estimated costs from previous studies at IDI and conducted univariate and probabilistic sensitivity analyses. We identified 829 patients, 578 in the PRP and 251 in SOC. After 12.8 months (PRP) and 15.1 months (SOC) of follow-up, 18.9% of patients had a FIR, 18.6% in the PRP and 19.6% in SOC. There was a non-significant 9% decrease in the odds of having a FIR for PRP compared to SOC after adjusting for other variables (OR 0.93, 95% CI 0.55-1.58). The PRP was less costly than the SOC (US$ 520 vs. 655 annually, respectively). The incremental cost-effectiveness ratio comparing PRP to SOC was US$ 13,500 per FIR. PRP remained cost-effective at univariate and probabilistic sensitivity analysis. The PRP is more cost-effective than the standard of care. Similar task-shifting programs might help large HIV/AIDS clinics in Uganda and other low-income countries to cope with increasing numbers of patients seeking care.


Recurrent Clostridium difficile infection is associated with increased mortality.
Clostridium difficile infections (CDI) are associated with decreased survival, and up to 30% of CDI patients may experience a recurrence. Data on the impact of recurrent CDI on mortality are scarce. The purpose of this study was to determine whether recurrent CDI was independently associated with decreased 6-month survival compared with patients with CDI who did not develop a recurrence. We performed a retrospective cohort study at an academic, urban, tertiary care hospital. Data were collected from the electronic medical record and chart review. CDI patients were followed for 180 days from the end of their index hospital discharge or end of index CDI antibiotic treatment, whichever was later, to determine mortality. Kaplan-Meier analysis was used to compare patient mortality by recurrent CDI status. Cox proportional hazards models were used to determine independent risk factors for death within 180 days. In all, 3958 patients aged ≥ 18 years who developed an initial CDI episode from 2003 to 2009, including 421 patients with recurrent CDI, were included in the study. Thirty-six per cent of persons with recurrent CDI died within 180 days, compared with 26% of persons without CDI recurrence (log-rank p <0.001). Recurrent CDI was associated with significantly higher hazards of death within 180 days, adjusting for demographics, comorbidities and medications received during the index CDI hospitalization (hazard ratio 1.33; 95% CI 1.12-1.58). Recurrent CDI is associated with significantly increased risk of death within 6 months after completion of their initial CDI treatment compared with CDI patients who do not develop a recurrence.


The thermally induced metal-semiconducting phase transition of samarium monosulfide (SmS) thin films.
High quality phase pure samarium monosulfide (SmS) thin films were prepared by electron beam evaporation using a samarium metal source in a H(2)S atmosphere. The optical properties (reflection, transmission, absorption) of the films in the semiconducting and metallic phase were analysed from the UV to the mid-IR and explained in terms of the electronic structure of SmS. In this paper it will be shown that metallic SmS thin films exhibit an apparently continuous thermally induced metallic to semiconducting phase transition when studied optically. Temperature dependent x-ray diffraction measurements, however, indicate that the metallic to semiconductor phase transition is in fact first order at a single grain level. The apparently continuous optical behaviour is therefore due to the polycrystalline nature of the films.


Breastfeeding Initiation in Mothers with Repeat Cesarean Section: The Impact of Marital Status.
Approximately 90% of mothers with a primary C-section have a subsequent C-section. To date, research has demonstrated that primary C-sections are associated with breastfeeding noninitiation. However, it is unknown if this association persists after the primary C-section. Furthermore, literature has shown a differing relationship between breastfeeding initiations by marital status. Due to the high proportion of women who give birth while unmarried, investigating differences by marital status will add a significant contribution to breastfeeding literature. This study investigates the association between repeat C-section and breastfeeding initiation within marital status groups using a nationally representative cross-sectional survey. Data from the 2004 to 2011 Pregnancy Risk Assessment Monitoring System were analyzed. The sample was restricted to women with a previous singleton live birth who had C-section and whose infant was alive at the time of interview (N = 34,854). Multiple logistic regression analyses were conducted to obtain crude and adjusted odds ratio (AOR) and 95% confidence intervals (CIs). After adjusting for potential confounders, married women who had a repeat C-section were 2.2 times (AOR = 2.16, 95% CI = 1.69-2.77) more likely to never breastfeed compared to women with vaginal birth after caesarean section (VBAC). Similarly, the odds of breastfeeding noninitiation were 76% (AOR = 1.76, 95% CI = 1.47-2.12) higher among women with a repeat C-section compared to women with VBAC. No significant associations were exhibited among nonmarried women. Enhanced educational programs and counseling support may be needed to help families cope with delivery challenges and resulting stressors that may reduce their desire to initiate breastfeeding in the postpartum period.


Kif3a controls murine nephron number via GLI3 repressor, cell survival, and gene expression in a lineage-specific manner.
The primary cilium is required during early embryo patterning, epithelial tubulogenesis, and growth factor-dependent signal transduction. The requirement for primary cilia during renal epithelial-mesenchymal tissue interactions that give rise to nephrons is undefined. Here, we used Cre-mediated recombination to generate mice with Kif3a deficiency targeted to the ureteric and/or metanephric mesenchyme cell lineages in the embryonic kidney. Gradual loss of primary cilia in either lineage leads to a phenotype of reduced nephron number. Remarkably, in addition to cyst formation, loss of primary cilia in the ureteric epithelial cell leads to decreased expression of Wnt11 and Ret and reduced ureteric branching. Constitutive expression of GLI3 repressor (Gli3(Δ699/+) ) rescues these abnormalities. In embryonic metanephric mesenchyme cells, Kif3a deficiency limits survival of nephrogenic progenitor cells and expression of genes required for nephron formation. Together, our data demonstrate that Kif3a controls nephron number via distinct cell lineage-specific mechanisms.


The effect of subglottic secretion drainage on the incidence of ventilator associated pneumonia.
Ventilator-Associated Pneumonia (VAP) is an undesired side effect of mechanical ventilation in intensive care units (ICUs). We evaluated whether endotracheal tubes with subglottic secretion drainage (SSD) would reduce the incidence of VAP among patients undergoing mechanical ventilation in an ICU. The analysis of medical records of patients undergoing mechanical ventilation exceeding 48 h who were hospitalised in ICUs between 2007 and 2014 led to separating two groups of patients: those in whom no subglottic drainage was applied (NSSD) (records dating from 2007-2010) and those whose treatment involved endotracheal tubes with subglottic secretion drainage (SSD) (records dating from 2011-2014). Analysis of 1807 patients hospitalised in ICUs (804 NSSD patients and 1003 SSD patients). A difference was found in the frequency of VAP incidence between the groups (P<0.001). In the NSSD group as many as 84 cases were reported (incidence: 10.7%), and in the SSD group - 43 cases (incidence: 5.2%). The odds ratio (OR) and relative risk (RR) was 2.5. The probability of VAP was significantly higher in the NSSD group. The risk factors of VAP incidence (P<0.001) included the correlation between reintubation (R=0.271), tracheostomy (R=0.309) and bronchoscopy (R=0.316). Use of endotracheal tubes with subglottic secretion drainage in patients in the ICU on mechanical ventilation significantly reduced the incidence of VAP.


Nicotine, cotinine, and β-nicotyrine inhibit NNK-induced DNA-strand break in the hepatic cell line HepaRG.
Recent in vitro work using purified enzymes demonstrated that nicotine and/or a nicotine metabolite could inhibit CYPs (CYP2A6, 2A13, 2E1) involved in the metabolism of the genotoxic tobacco nitrosamine NNK. This observation raises the possibility of nicotine interaction with the mechanism of NNK bioactivation. Therefore, we hypothesized that nicotine or a nicotine metabolite such as cotinine might contribute to the inhibition of NNK-induced DNA strand breaks by interfering with CYP enzymes. The effect of nicotine and cotinine on DNA strand breaks was evaluated using the COMET assay in CYP competent HepaRG cells incubated with bioactive CYP-dependent NNK and CYP-independent NNKOAc (4-(acetoxymethylnitrosoamino)-1-(3-pyridyl)-1-butanone). We report a dose-dependent reduction in DNA damage in hepatic-derived cell lines in the presence of nicotine and cotinine. Those results are discussed in the context of the in vitro model selected.


Different CSF protein profiles in amyotrophic lateral sclerosis and frontotemporal dementia with C9orf72 hexanucleotide repeat expansion.
The hexanucleotide repeat expansion in the C9orf72 gene is the most common mutation associated with amyotrophic lateral sclerosis (C9-ALS) and frontotemporal dementia (C9-FTD). Until now, it is unknown which factors define whether C9orf72 mutation carriers develop ALS or FTD. Our aim was to identify protein biomarker candidates in the cerebrospinal fluid (CSF) which differentiate between C9-ALS and C9-FTD and might be indicative for the outcome of the mutation. We compared the CSF proteome of 16 C9-ALS and 8 C9-FTD patients and 11 asymptomatic C9orf72 mutation carriers (CAR) by isobaric tags for relative and absolute quantitation. Eleven biomarker candidates were selected from the pool of differentially regulated proteins for further validation by multiple reaction monitoring and single-molecule array in a larger cohort (n=156). In total, 2095 CSF proteins were identified and 236 proteins were significantly different in C9-ALS versus C9-FTD including neurofilament medium polypeptide (NEFM) and chitotriosidase-1 (CHIT1). Eight candidates were successfully validated including significantly increased ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) levels in C9-ALS compared with C9-FTD and controls and decreased neuronal pentraxin receptor (NPTXR) levels in C9-FTD versus CAR. This study presents a deep proteomic CSF analysis of C9-ALS versus C9-FTD patients. As a proof of concept, we observed higher NEFM and CHIT1 CSF levels in C9-ALS. In addition, we also show clear upregulation of UCHL1 in C9-ALS and downregulation of NPTXR in C9-FTD. Significant differences in UCHL1 CSF levels may explain diverging ubiquitination and autophagy processes and NPTXR levels might reflect different synapses organisation processes.


Cyanobacterial bloom-associated lipopolysaccharides induce pro-inflammatory processes in keratinocytes in vitro.
Our previous studies have shown that CyanoHAB LPS (lipopolysaccharides) and LPS from cyanobacterial cultures induce pro-inflammatory effects on intestinal epithelial and immune cells in vitro. To expand our understanding, we investigated their impact on human keratinocytes, which are targeted during water recreational activities. LPS samples were isolated from CyanoHAB biomasses dominated by Microcystis, Aphanizomenon, Planktothrix, and Dolichospermum, or from axenic cultures of these genera. We identified two CyanoHAB biomasses containing a high proportion of Gram-negative bacteria, including potentially pathogenic genera. These biomasses showed the highest induction of interleukin (IL) 8, IL-6, C-C motif chemokine ligand (CCL) 2 (also known as MCP-1), and CCL20 production by HaCaT cells. Interestingly, all CyanoHAB-derived LPS and LPS from axenic cultures (except for Microcystis) accelerated cell proliferation and migration. Our findings highlight the role of G- bacteria composition and LPS structural disparities in influencing these effects, with implications for skin health during recreational activities.


Oxidative stress-induced dysregulation of arteriolar wall shear stress and blood pressure in hyperhomocysteinemia is prevented by chronic vitamin C treatment.
We aimed to test the hypothesis that an enhanced level of reactive oxygen species (ROS) is primarily responsible for the impairment of nitric oxide (NO)-mediated regulation of arteriolar wall shear stress (WSS) in hyperhomocysteinemia (HHcy). Thus flow/WSS-induced dilations of pressurized gracilis muscle arterioles (basal diameter: approximately 170 microm) isolated from control (serum Hcy: 6 +/- 1 microM), methionine diet-induced HHcy rats (4 wk, serum Hcy: 30 +/- 6 microM), and HHcy rats treated with vitamin C, a known antioxidant (4 wk, 150 mg. kg body wt-1.day-1; serum Hcy: 32 +/- 10 microM), were investigated. In vessels of HHcy rats, increases in intraluminal flow/WSS-induced dilations were converted to constrictions. Constrictions were unaffected by inhibition of NO synthesis by N omega-nitro-L-arginine methyl ester (L-NAME). Vitamin C treatment of HHcy rats reversed the WSS-induced arteriolar constrictions to L-NAME-sensitive dilations but did not affect control responses. Similar changes in responses were obtained for the calcium ionophore A-23187. In addition, diastolic and mean arterial blood pressure and serum 8-isoprostane levels (a marker of in vivo oxidative stress) were significantly elevated in rats with HHcy, changes that were normalized by vitamin C treatment. Taken together, our data show that in chronic HHcy long-term vitamin C treatment, by decreasing oxidative stress in vivo, enhanced NO bioavailability, restored the regulation of shear stress in arterioles, and normalized systemic blood pressure. Thus our study provides evidence that oxidative stress is an important in vivo mechanism that is primarily responsible for the development of endothelial dysregulation of WSS in HHcy.


Preparation and Functional Properties of Synbiotic Yogurt Fermented with Lactobacillus brevis PML1 Derived from a Fermented Cereal-Dairy Product.
Nowadays, production of functional foods has become very essential. Inulin is one of the most functional hydrocolloid compounds used in such products. In the present study, the production of a synbiotic yogurt containing 1, 2.5, and 5% (w/v) inulin has been investigated. The yogurt was fermented with Lactobacillus brevis PML1 derived from Tarkhineh, an Iranian cereal-dairy fermented food. Furthermore, the physicochemical properties, antioxidant activity, sensory attributes, and microbial viability properties were investigated on the 0th, 7th, and 14th days of storage after fermentation. The viable cells of L. brevis PML1 reached 108 CFU/g, and the product resisted to simulated digestive juices. Moreover, the synbiotic yogurt impressively increased the production of antimicrobial compounds and had the most profound antimicrobial effect on S. typhimurium. The physiochemical properties were in the normal range, and the fat content of the synbiotic yogurt was reduced remarkably. The antioxidant capacity of the fermented yogurt was significantly increased (p < 0.05), which was equal to those of DPPH (69.18 ± 1.00%) and BHA (89.16 ± 2.00%). The viability of L. brevis PML1 was increased during storage. Sensory analysis showed that there were significant differences in terms of the impressive parameters between the samples and the control (p < 0.05). Addition of 2.5% inulin not only improved the physical properties but also retained the viability of the probiotic after 14 days of storage, in addition to the viability of L. brevis with a viability count above 6 log CFU/g in the yogurt. Therefore, a novel synbiotic product containing L. brevis PML1, which can exert the desired properties, can be used as a suitable carrier for the delivery of the probiotic strain, exerting its beneficial health effects.


Neural correlates of prior expectations of motion in the lateral intraparietal and middle temporal areas.
Successful decision making involves combining observations of the external world with prior knowledge. Recent studies suggest that neural activity in macaque lateral intraparietal area (LIP) provides a useful window into this process. This study examines how rapidly changing prior knowledge about an upcoming sensory stimulus influences the computations that convert sensory signals into plans for action. Two monkeys performed a cued direction discrimination task, in which an arrow cue presented at the start of each trial communicated the prior probability of the direction of stimulus motion. We hypothesized that the cue would either shift the initial level of LIP activity before sensory evidence arrived, or it would scale sensory responses according to the prior probability of each stimulus, manifesting as a change in slope of LIP firing rates. Neural recordings demonstrated a clear shift in the activity level of LIP neurons following the arrow cue, which persisted into the presentation of the motion stimulus. No significant change in slope of responses was observed, suggesting that sensory gain was not strongly modulated. To confirm the latter observation, middle temporal area (MT) neurons were recorded during a version of the cued direction discrimination task, and we found no change in MT responses resulting from the presentation of the directional cue. These results suggest that information about an immediately upcoming stimulus does not scale the sensory response, but rather changes the amount of evidence that must be accumulated to reach a decision in areas that are involved in planning action.


[Function tests of the lower small intestine with 75selenium-labeled homotaurocholic acid in Crohn disease and resections of the small intestine].
Faecal excretion of bile acids was investigated using 75Se-homotaurocholic acid (75SeHCAT) in a total of 75 patients: 9 with irritable colon, 58 with Crohn's disease and 8 with small-bowel resection due to various indications but without Crohn's disease. Bile acid malabsorption, taken as a pathological bile acid retention of less than 19%, was found present in 43 patients with diseased terminal ileum or with more than 20 cm resection of this organ, except in one case (12 cm). On the other hand a normal bile acid retention (21 to 27%) was found in 29 of 72 patients (including 9 patients with irritable colon) who showed either no radiologically detectable lesion of the ileum (n = 21) or changes involving an extension of up to 30 cm (inflammation or resection) in the terminal ileum (n = 8), with the exception of one case (50 cm). Three patients had a raised bile acid excretion contrary to clinical expectation: they had colitis Crohn without radiologically detectable involvement of the small intestine. Thus using the 75SeHCAT-retention test it seems possible to recognize functional disorders in diseased segments of the bowel before the appearance of radiologically detectable changes. 75SeHCAT is a suitable substance for investigations on the function of the lower small intestine.


The Occipital Artery-Based Fascial Flap for Ear Reconstruction.
The temporoparietal fascia flap is frequently used in ear reconstruction. When the temporoparietal fascia flap is unavailable, options for primary or secondary salvage reconstruction are limited. In these patients, an inferiorly based occipital artery fascia transpositional flap is a good alternative for soft-tissue coverage over a framework. This article describes the use of the occipital artery fascia flap for ear reconstruction in conjunction with a porous polyethylene framework. The authors included all patients who underwent occipital artery fascia flap surgery with a porous polyethylene framework for ear reconstruction performed by the first author from 1992 to 2017. A total of 83 patients received an occipital artery fascia flap: 24 for primary microtia reconstruction and 59 for revision or salvage of unsatisfactory results. All had contraindications for temporoparietal fascia flap use: prior use, flap injury from previous surgery, trauma, inappropriate flap location, or inadequate flap perfusion. Twelve patients (14 percent) developed occipital artery fascia flap complications (infection or necrosis) and underwent further revision to achieve satisfactory results. Given the paucity of reported techniques for large-scale auricular salvage/revision, the authors offer a versatile option that remains available when other conventional flaps are unavailable. The occipital artery fascia flap may be used with either alloplastic or autologous frameworks. Therapeutic, IV.


Weighing obligations to home care workers and Medicaid recipients.
In June 2016, a US Department of Labor rule extending minimum wage and overtime pay protections to home care workers such as certified nursing assistants and home health aides survived its final legal challenge and became effective. However, Medicaid officials in certain states reported that during the intervening decades when these protections were not in place, their states had developed a range of innovative services and programs providing home care to people with disabilities-services and programs that would be at risk if workers were newly owed minimum wage and overtime pay. In this article, we examine whether the Department of Labor was right to extend these wage protections to home care workers even at the risk of a reduction in these home care services to people with disabilities. We argue that it was right to do so. Home care workers are entitled to these protections, and, although it is permissible under certain conditions for government to infringe workers' occupational rights and entitlements, these conditions are not satisfied in this case.


Interpersonal subtypes and change of interpersonal problems in the treatment of patients with generalized anxiety disorder: a pilot study.
Interpersonal problems are highly relevant to the treatment of generalized anxiety disorder (GAD) patients. Previous studies using the Inventory of Interpersonal Problems identified several interpersonal subtypes in GAD patients. In this study, we wanted to replicate earlier findings of interpersonal subtypes in GAD. We investigated whether these interpersonal subtypes are characterized by different types of interpersonal problems and different levels of interpersonal distress, and we further examined whether they differed with regard to improvement of interpersonal problems after short-term treatment. This study is based on results from a randomized controlled trial that investigated short-term treatments in GAD outpatients. For secondary analysis, interpersonal subtypes were identified by cluster analysis and Inventory of Interpersonal Problems profiles were calculated for both the total sample (N = 52) and the interpersonal subtypes using the Structural Summary Method for Circumplex Data. This study confirmed previous results demonstrating the existence of interpersonal subtypes in GAD. Four interpersonal subtypes were identified: Overly Nurturant, Intrusive, Socially Avoidant, and Nonassertive. Short-term treatment significantly improved interpersonal problems (d = 0.46) within the total GAD sample. Interestingly, the effect sizes of the four clusters differed considerably (d = 0.19-1.24) and the clusters displayed different changes in the two circumplex axes Dominance and Nurturance. Our study indicates that change of interpersonal problems needs to be specifically analyzed, even within homogenous diagnostic groups.


Preclinical Alzheimer Disease and the Electronic Health Record: Balancing Confidentiality and Care.
Because information technologies are increasingly used to improve clinical research and care, personal health information (PHI) has wider dissemination than ever before. The 21st Century Cures Act in the United States now requires patient access to many components of the electronic health record (EHR). Although these changes promise to enhance communication and information sharing, they also bring higher risks of unwanted disclosure, both within and outside of health systems. Having preclinical Alzheimer disease (AD), where biological markers of AD are identified before the onset of any symptoms, is sensitive PHI. Because of the melding of ideas between preclinical and "clinical" (symptomatic) AD, unwanted disclosure of preclinical AD status can lead to personal harms of stigma, discrimination, and changes to insurability. At present, preclinical AD is identified mainly in research settings, although the consensus criteria for a clinical diagnosis may soon be established. There is not yet adequate legal protection for the growing number of individuals with preclinical AD. Some PHI generated in preclinical AD trials has clinical significance, necessitating urgent evaluations and longitudinal monitoring in care settings. AD researchers are obligated to both respect the confidentiality of participants' sensitive PHI and facilitate providers' access to necessary information, often requiring disclosure of preclinical AD status. The AD research community must continue to develop ethical, participant-centered practices related to confidentiality and disclosure, with attention to sensitive information in the EHR. These practices will be essential for translation into the clinic and across health systems and society at large.


Value of incisional negative pressure wound therapy in orthopaedic surgery.
Soft tissue and wound treatment after orthopaedic interventions (especially after trauma) is still an enormously challenging situation for every surgeon. Since development of negative pressure wound therapy (NPWT), new indications have been consistently added to the original field of application. Recently, NPWT has been applied directly over high-risk closed surgical incisions. Review of the literature indicates that this therapy has shown positive effects on incisions after total ankle replacement or calcaneal fractures, preventing haematoma and wound dehiscence. In those cases reduced swelling, decreased pain and healing time of the wound were seen. Additionally, NPWT applied on incisions after acetabular fractures showed a decreased rate of infection and wound healing problems compared with published infection rates. Even after total hip arthroplasty, incisional NPWT reduced incidence of postoperative seroma and improved wound healing. In patients with tibial plateau, pilon or calcaneus fractures requiring surgical stabilisation after blunt trauma, reduced risk of developing acute and chronic wound dehiscence and infection was observed when using incisional NPWT. To conclude, incisional NPWT can help to reduce risk of delayed wound healing and infection after severe trauma and orthopaedic interventions.


[Study on quality of gossypol recrystalized from chloroform].
In this paper, the chemical properties of gossypol recrystalized from chloroform are described. Samples were dried at different temperatures at reduced pressure, and stored under room temperature for different times. They were identified and determined by melting point, thin layer chromatography, UV spectrophotometry, IR spectrophotometry, thermo-gravimetric analysis, X-ray diffraction, elementary analysis and also for the content of gossypol. The results of these tests proved gossypol to be solvated with chloroform at low temperature. This phenomenon decreased gradually with increase of drying temperature or storage time, and the content of gossypol increased accordingly. The presence of chloroform in the crystal interferes with the purity of gossypol. Thus, it is necessary to identify the presence of chloroform with oxygen flask ombustion-mercurimetry beforehand.


Mutual dilution of infection by an introduced parasite in native and invasive stream fishes across Hawaii.
The presence of introduced hosts can increase or decrease infections of co-introduced parasites in native species of conservation concern. In this study, we compared parasite abundance, intensity, and prevalence between native Awaous stamineus and introduced poeciliid fishes by a co-introduced nematode parasite (Camallanus cotti) in 42 watersheds across the Hawaiian Islands. We found that parasite abundance, intensity and prevalence were greater in native than introduced hosts. Parasite abundance, intensity and prevalence within A. stamineus varied between years, which largely reflected a transient spike in infection in three remote watersheds on Molokai. At each site we measured host factors (length, density of native host, density of introduced host) and environmental factors (per cent agricultural and urban land use, water chemistry, watershed area and precipitation) hypothesized to influence C. cotti abundance, intensity and prevalence. Factors associated with parasitism differed between native and introduced hosts. Notably, parasitism of native hosts was higher in streams with lower water quality, whereas parasitism of introduced hosts was lower in streams with lower water quality. We also found that parasite burdens were lower in both native and introduced hosts when coincident. Evidence of a mutual dilution effect indicates that introduced hosts can ameliorate parasitism of native fishes by co-introduced parasites, which raises questions about the value of remediation actions, such as the removal of introduced hosts, in stemming the rise of infectious disease in species of conservation concern.


Improvement of skin barrier function in atopic dermatitis patients with a new moisturizer containing a ceramide precursor.
Atopic dermatitis (AD) is characterized by barrier abnormalities, including insufficient ceramides in the stratum corneum (SC). To measure the effects of a new moisturizer (CRM) containing a ceramide precursor in improving skin barrier function in patients with controlled atopic dermatitis. In this randomized, intra-individual comparison, investigator-blinded study, CRM was applied to the test area of one lower leg for 27 days (the other leg remained as untreated control). Evaluations at baseline and day 28 included transepidermal water loss (TEWL), skin hydration by corneometry, dryness severity, Raman spectroscopy, and collection of adverse events. After 4 weeks of treatment, results showed a significantly greater reduction of TEWL and clinical dryness scores, and increased skin hydration (all p < 01) in the CRM-treated than untreated area. A significantly higher level of ceramide (p < 05) and a trend toward increased water content was observed with Raman in the SC for CRM than for the control. There were no related AEs. Skin barrier function and hydration were significantly improved after CRM treatment.


At the Interface Between Paradigms: English Mental Capacity Law and the CRPD.
The United Nations Convention on the Rights of Persons with Disabilities (CRPD) is rightly seen as a break from the past in mental capacity law. At the same time, implementation will occur in the specific existing legal and administrative contexts of each State. This article uses English mental capacity law to explore these issues. The English Mental Capacity Act 2005 (MCA) can be considered the best of the "old" paradigm. The article argues that there are continuities between it and a CRPD-compliant approach. These continuities should be built upon. Further, the implementation of the MCA is still in recent memory. The lessons of that implementation will have considerable application to moves toward CRPD compliance. CRPD compliance is not just about specialist stator guardianship régimes. It is also about a myriad of law, currently capacity based, located in specific legal areas such as contract, wills and succession, and criminal law. Reform in these areas will involve not just disability law, but successful integration into those other legal areas, a matter requiring the involvement of those knowledgeable in those other areas. Since change in these areas will involve the removal of disability as a gateway criterion, they will affect the public as a whole, and the thus, determination of the degree and sort of intervention that the broader public will consider appropriate.


Insulin binding of acute lymphocytic leukemia cells.
Because of differences in insulin binding of cultured lymphoic cell lines, T- and B-cell surface receptor and 125I-insulin binding studies were performed on the bone marrow and peripheral blood leukocytes of 13 children with active acute lymphocytec leukemia. Based on surface receptors, nine patients had null-cell disease and four had T-cell disease. The mean per cent insulin binding of the bone marrow cells from the null-cell patients was 10.0% +/- 8.1 and from the T-cell patients was 0.18% +/- 0.13. The mean insulin binding of the cell suspensions of the peripheral blood from the null-cell patients was 7.3% +/- 7.5 and 0.07% +/- 0.06 from the T-cell patients. Displacement studies with nonradioactive insulin indicated that null leukemic cells bore specific binding sites. These results indicated that there may be metabolic as well as surface membrane heterogeneity among the acute lymphocytic leukemias of childhood.


Neuronal damage in the rat retina after chronic stress.
Long-term exposure to escapable foot shock has been used to determine if chronic stress influences neuronal cell death in the retina of albino and pigmented rats. Histopathologic and morphometric approaches analyzed changes in photoreceptors and neurons of the bipolar and ganglion cell layers of the retina. Albino Fischer rats when exposed to chronic stress for 4-8 h daily for 1 week to 6 months, developed severe retinal damage, as compared to unstressed control retinas, with reduction in photoreceptor and bipolar neurons, particularly in the superior central retina. The damage was observed in male and female rats, but males appeared to be more susceptible to the influence of stress than female animals. Ganglion cells were unaffected. Photoreceptor destruction did not occur in Long-Evans pigmented rats under identical experimental conditions. The results suggest that: input of the sensory stimulus, light, to the retina of stressed rats augmented neuronal damage and might be required for its initiation; and hormones and/or neurotransmitters associated with long-term chronic stress might be related to increased neuronal cell death in the mammalian retina.


Microarray expression analysis reveals genetic pathways implicated in C621 synphilin-1-mediated toxicity.
Synphilin-1 has been linked to Parkinson's disease (PD) based on its role as an alpha-synuclein (PARK1) and Parkin (PARK2) interacting protein and its presence in lewy bodies in brains of PD patients. We recently identified a R621C mutation in the synphilin-1 gene in German PD patients. Functional analyses revealed that mutant synphilin-1 increases cellular stress, however, the involved molecular signalling pathways are currently unknown. Using microarray based gene expression analysis of dopaminergic SH-SY5Y cells overexpressing wild type or R621C mutant synphilin-1 we investigated differentially regulated genes and signalling networks using the Ingenuity Pathways Analysis tool. We show specific effects of C621 mutant synphilin-1 on gene expression that correlate with its role as a susceptibility factor in PD. The most significantly regulated signalling network was defined by the tumor growth factor beta 1 (TGF-beta1) suggesting an involvement of synphilin-1 in TGF-beta mediated signalling pathways modulating the cellular stress response.


The Sinorhizobium fredii HH103 lipopolysaccharide is not only relevant at early soybean nodulation stages but also for symbiosome stability in mature nodules.
In this work we have characterised the Sinorhizobium fredii HH103 greA lpsB lpsCDE genetic region and analysed for the first time the symbiotic performance of Sinorhizobium fredii lps mutants on soybean. The organization of the S. fredii HH103 greA, lpsB, and lpsCDE genes was equal to that of Sinorhizobium meliloti 1021. S. fredii HH103 greA, lpsB, and lpsE mutant derivatives produced altered LPS profiles that were characteristic of the gene mutated. In addition, S. fredii HH103 greA mutants showed a reduction in bacterial mobility and an increase of auto-agglutination in liquid cultures. RT-PCR and qPCR experiments demonstrated that the HH103 greA gene has a positive effect on the transcription of lpsB. Soybean plants inoculated with HH103 greA, lpsB or lpsE mutants formed numerous ineffective pseudonodules and showed severe symptoms of nitrogen starvation. However, HH103 greA and lps mutants were also able to induce the formation of a reduced number of soybean nodules of normal external morphology, allowing the possibility of studying the importance of bacterial LPS in later stages of the S. fredii HH103-soybean symbiosis. The infected cells of these nodules showed signs of early termination of symbiosis and lytical clearance of bacteroids. These cells also had very thick walls and accumulation of phenolic-like compounds, pointing to induced defense reactions. Our results show the importance of bacterial LPS in later stages of the S. fredii HH103-soybean symbiosis and their role in preventing host cell defense reactions. S. fredii HH103 lpsB mutants also showed reduced nodulation with Vigna unguiculata, although the symbiotic impairment was less pronounced than in soybean.


From forest to field: perennial fruit crop domestication.
Archaeological and genetic analyses of seed-propagated annual crops have greatly advanced our understanding of plant domestication and evolution. Comparatively little is known about perennial plant domestication, a relevant topic for understanding how genes and genomes evolve in long-lived species, and how perennials respond to selection pressures operating on a relatively short time scale. Here, we focus on long-lived perennial crops (mainly trees and other woody plants) grown for their fruits. We reviewed (1) the basic biology of long-lived perennials, setting the stage for perennial domestication by considering how these species evolve in nature; (2) the suite of morphological features associated with perennial fruit crops undergoing domestication; (3) the origins and evolution of domesticated perennials grown for their fruits; and (4) the genetic basis of domestication in perennial fruit crops. Long-lived perennials have lengthy juvenile phases, extensive outcrossing, widespread hybridization, and limited population structure. Under domestication, these features, combined with clonal propagation, multiple origins, and ongoing crop-wild gene flow, contribute to mild domestication bottlenecks in perennial fruit crops. Morphological changes under domestication have many parallels to annual crops, but with key differences for mating system evolution and mode of reproduction. Quantitative trait loci associated with domestication traits in perennials are mainly of minor effect and may not be stable across years. Future studies that take advantage of genomic approaches and consider demographic history will elucidate the genetics of agriculturally and ecologically important traits in perennial fruit crops and their wild relatives.


Late-onset right ventricular failure in patients with preoperative small left ventricle after implantation of continuous flow left ventricular assist device.
The continuous flow (CF) left ventricular assist device (LVAD) has replaced the pulsatile flow (PF) LVAD because of its advantages of better patient survival and higher quality of life. However, "late-onset right ventricular failure (RVF)" after CF LVAD implantation has emerged as an increasing concern, but little is known about the mechanism. We retrospectively analyzed the 3-month hemodynamic and echocardiographic data from 38 consecutive patients who had received CF LVADs, and from 22 patients who had received PF LVADs. Late-onset RVF was defined as persistent right ventricular stroke work index (RVSWI) <4.0g/m(2) at any rotation speed and after saline infusion test at 5 weeks after implantation of CF LVAD. Patients with late-onset RVF had significantly impaired exercise tolerance indicated by shorter 6-min walking distance and lower peak VO2, and worsened tricuspid regurgitation, together with enlargement of the RV under CF LVAD treatment (all P<0.05). Univariable analyses demonstrated that preoperative smaller LV diastolic diameter (LVDd) was the risk factor for late-onset RVF with a cutoff value of 64mm calculated by ROC analysis (area under curve, 0.925). In contrast, there was no correlation between preoperative LVDd and postoperative RVSWI in the PF LVAD group, though their preoperative background was worse than that of the CF group. In the setting of preoperative small LVDd, CF LVAD may cause late-onset RVF by leftward shift of the interventricular septum. (Circ J 2014; 78: 625-633).


Lutzomyia longipalpis: an update on this sand fly vector.
Lutzomyia longipalpis is the most important vector of Leishmania infantum, the etiological agent of visceral leishmaniasis (VL) in the New World. It is a permissive vector susceptible to infection with several Leishmania species. One of the advantages that favors the study of this sand fly is the possibility of colonization in the laboratory. For this reason, several researchers around the world use this species as a model for different subjects including biology, insecticides testing, host-parasite interaction, physiology, genetics, proteomics, molecular biology, and saliva among others. In 2003, we published our first review (Soares & Turco 2003) on this vector covering several aspects of Lu. longipalpis. This current review summarizes what has been published between 2003-2020. During this period, modern approaches were incorporated following the development of more advanced and sensitive techniques to assess this sand fly.


Effects of in-vitro fertilization, culture, freezing and transfer on the ability of mouse embryos to implant and survive.
The survival after transfer of frozen-thawed mouse blastocysts obtained from culture of in-vitro fertilized oocytes or 1- and 2-cell ova was compared. About 10% of transferred embryos developed to term in each group and there was no difference between embryos fertilized in vitro or in vivo. In addition to embryonic loss due to transfer, in-vitro cultivation and freezing reduced the proportion of fetuses considered viable at Day 15 of pregnancy (29.8 versus 50.7% and 26.3 versus 50.7% respectively). When used together these procedures had an additive effect on fetal wastage (18.4 versus 50.7%). In-vitro culture also entailed a significant increase of resorbing implantation sites (10.2 versus 4.3%). The re-expansion rate after freezing and thawing of blastocysts grown in vitro was paradoxically greater than that of blastocysts grown in vivo (85.8 versus 54.6%).


Effects of 27.12 MHz Radio Frequency on the Rapid and Uniform Tempering of Cylindrical Frozen Pork Loin (Longissimus thoracis et lumborum).
Quality characteristics of frozen cylindrical pork loin were evaluated following different tempering methods: 27.12 MHz curved-electrode radio frequency (RF) at 1000 and 1500 W, and forced-air convection (FC) or water immersion (WI) at 4°C and 20°C. The developed RF tempering system with the newly designed curved-electrode achieved relatively uniform tempering compared to a parallel-plate RF system. FC tempering at 4°C was the most time-consuming process, whereas 1500 W RF was the shortest. Pork sample drip loss, water holding capacity, color, and microbiological quality declined after WI tempering at 20°C. Conversely, RF tempering yielded minimal sample changes in drip loss, microstructure, color, and total aerobic bacteria counts, along with relatively uniform internal sample temperature distributions compared to those of the other tempering treatments. These results indicate that curved-electrode RF tempering could be used to provide rapid defrosting with minimal quality deterioration of cylindrical frozen meat block products.


Hormones and hormone receptors in the etiology of breast cancer.
Many epidemiologic features of breast cancer suggest that endogenous hormones are of importance in the genesis of this disease. Endocrinologic studies based on total levels of various hormones in serum and urine have provided etiologic clues, but have failed to yield a clear understanding of the hormonal aberrations that promote the development of breast cancer. One reason for this is probably that neither urinary hormones, nor total levels of serum hormones accurately reflect biologically active levels to which the cells of origin are exposed. Levels of hormones unbound to serum sex binding globulin may be of more etiologic relevance, and future studies utilizing measurements of such hormone fractions may provide new information of etiologic importance. Some risk factors for breast cancer, especially age at birth of first child, may influence risk by altering the susceptibility of mammary ductal epithelial cells to estrogens or other endogenous hormones by altering the level of hormone receptor proteins in these cells. Additional studies to identify the determinants of hormone receptors in the breast are needed to test this hypothesis.


Predictive Modeling of Estrogen Receptor Binding Agents Using Advanced Cheminformatics Tools and Massive Public Data.
Estrogen receptors (ERα) are a critical target for drug design as well as a potential source of toxicity when activated unintentionally. Thus, evaluating potential ERα binding agents is critical in both drug discovery and chemical toxicity areas. Using computational tools, e.g., Quantitative Structure-Activity Relationship (QSAR) models, can predict potential ERα binding agents before chemical synthesis. The purpose of this project was to develop enhanced predictive models of ERα binding agents by utilizing advanced cheminformatics tools that can integrate publicly available bioassay data. The initial ERα binding agent data set, consisting of 446 binders and 8307 non-binders, was obtained from the Tox21 Challenge project organized by the NIH Chemical Genomics Center (NCGC). After removing the duplicates and inorganic compounds, this data set was used to create a training set (259 binders and 259 non-binders). This training set was used to develop QSAR models using chemical descriptors. The resulting models were then used to predict the binding activity of 264 external compounds, which were available to us after the models were developed. The cross-validation results of training set [Correct Classification Rate (CCR) = 0.72] were much higher than the external predictivity of the unknown compounds (CCR = 0.59). To improve the conventional QSAR models, all compounds in the training set were used to search PubChem and generate a profile of their biological responses across thousands of bioassays. The most important bioassays were prioritized to generate a similarity index that was used to calculate the biosimilarity score between each two compounds. The nearest neighbors for each compound within the set were then identified and its ERα binding potential was predicted by its nearest neighbors in the training set. The hybrid model performance (CCR = 0.94 for cross validation; CCR = 0.68 for external prediction) showed significant improvement over the original QSAR models, particularly for the activity cliffs that induce prediction errors. The results of this study indicate that the response profile of chemicals from public data provides useful information for modeling and evaluation purposes. The public big data resources should be considered along with chemical structure information when predicting new compounds, such as unknown ERα binding agents.


[Application of a paste composed of sodium bicarbonate, sodium chloride and hydrogen peroxide in treating of active periodontal pockets].
Close relationship existing between dentobacterial plaque and chronic inflammatory periodontal disease, as well as effectiveness of conservative treatments used to eliminate chronic gingivitis, is wordly known. However, several years ago, chronic destructive periodontal disease was only solved by surgical techniques, most of them bloody and of doubtful solution for some periodontal problems; for such reasons, a study was carried out in order to learn about the role played by a medicament formed with sodium bicarbonate, sodium chloride and hydrogen peroxide, deeply applied as a paste into active periodontal pockets, after an exquisite open radicular planing. Results obtained point out that the use of this procedure effective in the therapy of chronic inflammatory periodontal disease.


Methodology for Evidence Synthesis and Development of Comprehensive Evidence-Based Guidelines for Interventional Techniques in Chronic Spinal Pain.
The re-engineered definition of clinical guidelines in 2011 from the IOM (Institute of Medicine) states, "clinical practice guidelines are statements that include recommendations intended to optimize patient care that is informed by a systematic review of evidence and an assessment of the benefit and harms of alternative care options." The revised definition distinguishes between the term "clinical practice guideline" and other forms of clinical guidance derived from widely disparate development processes, such as consensus statements, expert advice, and appropriate use criteria. To assess the literature and develop methodology for evidence synthesis and development of comprehensive evidence-based guidelines for interventional techniques in chronic spinal pain. A systematic review of the literature including methodology of guideline development encompassing GRADE approach for guidance on evidence synthesis with recommendations. Some of the many factors described in 2011 continue as of 2020 and impede the development of clinical practice guidelines. These impediments include biases due to a variety of conflicts and confluence of interest, inappropriate and poor methodological quality, poor writing and ambiguous presentation, projecting a view that these are not applicable to individual patients or too restrictive with the elimination of clinician autonomy, and overzealous and inappropriate recommendations, either positive, negative, or non-committal. Thus, ideally, a knowledgeable, multidisciplinary panel of experts with true lack of bias and confluence of interest must develop guidelines based on a systematic review of the existing evidence. This manuscript describes evidence synthesis from observational studies, various types of randomized controlled trials (RCTs), and, finally, methodological and reporting quality of systematic reviews. The manuscript also describes various methods utilized in the assessment of the quality of observational studies, diagnostic accuracy studies, RCTs, and systematic reviews. Paucity of publications with appropriate evidence synthesis methodology in reference to interventional techniques. This review described comprehensive evidence synthesis derived from systematic reviews, including methodologic quality and bias measurement. The manuscript described various methods utilized in the assessment of the quality of the systematic reviews, RCTs, diagnostic accuracy studies, and observational studies.


[Raman spectroscopic study of human serum albumin interacting with 3-picolylamine].
Raman spectra of human serum albumin (HSA) and HSA-3-picolylamine complex were obtained. The spectra indicate the configuration and structural transformations of HSA. The results show that the secondary structure is main alpha-helix, and the binding of 3-picolylamine doesn't change the secondary structure. However, the binding changes the configuration of disulfide bonds, transforms a single tryptophan residue from exposed tryptophan residues to hydrophobic environment, and alters the microenvironment of tyrosine.


Chronic exposure to low doses of pharmaceuticals disturbs the hepatic expression of circadian genes in lean and obese mice.
Drinking water can be contaminated with pharmaceuticals. However, it is uncertain whether this contamination can be harmful for the liver, especially during obesity. Hence, the goal of our study was to determine whether chronic exposure to low doses of pharmaceuticals could have deleterious effects on livers of lean and obese mice. To this end, lean and ob/ob male mice were treated for 4 months with a mixture of 11 drugs provided in drinking water at concentrations ranging from 10 to 10⁶ ng/l. At the end of the treatment, some liver and plasma abnormalities were observed in ob/ob mice treated with the cocktail containing 10⁶ ng/l of each drug. For this dosage, a gene expression analysis by microarray showed altered expression of circadian genes (e.g. Bmal1, Dbp, Cry1) in lean and obese mice. RT-qPCR analyses carried out in all groups of animals confirmed that expression of 8 different circadian genes was modified in a dose-dependent manner. For some genes, a significant modification was observed for dosages as low as 10²-10³ ng/l. Drug mixture and obesity presented an additive effect on circadian gene expression. These data were validated in an independent study performed in female mice. Thus, our study showed that chronic exposure to trace pharmaceuticals disturbed hepatic expression of circadian genes, particularly in obese mice. Because some of the 11 drugs can be found in drinking water at such concentrations (e.g. acetaminophen, carbamazepine, ibuprofen) our data could be relevant in environmental toxicology, especially for obese individuals exposed to these contaminants.


Trends in use of complementary and alternative medicine by US adults: 1997-2002.
Complementary and alternative medicine (CAM) use by US adults increased substantially between 1990 and 1997, yet little is known about more recent trends. Compare CAM therapy use by US adults in 2002 and 1997. Comparison of two national surveys of CAM use by US adults: (1) the Alternative Health/Complementary and Alternative Medicine supplement to the 2002 National Health Interview Survey (NHIS, N = 31,044) and (2) a 1997 national survey (N = 2055), each containing questions about 15 common CAM therapies. Prevalence, sociodemographic correlates, and insurance coverage of CAM use. The most commonly used CAM modalities in 2002 were herbal therapy (18.6%, representing over 38 million US adults) followed by relaxation techniques (14.2%, representing 29 million US adults) and chiropractic (7.4%, representing 15 million US adults). Among CAM users, 41% used two or more CAM therapies during the prior year. Factors associated with highest rates of CAM use were ages 40-64, female gender, non-black/non-Hispanic race, and annual income of dollar 65,000 or higher. Overall CAM use for the 15 therapies common to both surveys was similar between 1997 and 2002 (36.5%, vs. 35.0%, respectively, each representing about 72 million US adults). The greatest relative increase in CAM use between 1997 and 2002 was seen for herbal medicine (12.1% vs.18.6%, respectively), and yoga (3.7% vs. 5.1%, respectively),while the largest relative decrease occurred for chiropractic (9.9% to 7.4%, respectively). The prevalence of CAM use has remained stable from 1997 to 2002. Over one in three respondents used CAM in the past year, representing about 72 million US adults.


Rapid host-plant adaptation in the herbivorous spider mite Tetranychus urticae occurs at low cost.
The herbivorous spider mite Tetranychus urticae is a generalist world crop pest. Early evidence for host races, its fully sequenced genome resolved to the chromosome level, and the development of other molecular tools in this species suggest that this arthropod can be a good model to address host plant adaptation and early stages of speciation. Here, we evaluate this possibility by reviewing recent studies of host-plant adaptation in T. urticae. We find that evidence for costs of adaptation are relatively scarce and that studies involving molecular-genetics and genomics are mostly disconnected from those with phenotypic tests. Still, with the ongoing development of genetic and genomic tools for this species, T. urticae is becoming an attractive model to understand the molecular basis of host-plant adaptation.


Finding confidence and inner trust as a parent: experiences of group-based compassion-focused therapy for the parents of adolescents with mental health problems.
Purpose: Compassion-focused therapy (CFT) can alleviate the stress and challenges faced by the parents of adolescents with mental health (MH) problems. Although CFT interventions have shown promising results, few studies have examined its effectiveness in adolescent psychiatric settings. Therefore, this study examined the participant experiences of group-based CFT for the parents of adolescents with MH problems.Methods: The reflective lifeworld research (RLR) approach was used to conduct in-depth interviews with eleven parents, focusing on participant experiences of group-based CFT. Meaning-oriented data analysis was undertaken.Results: The essential meaning of the phenomenon of participating in group-based CFT was understood as finding confidence and inner trust as a parent, characterized by an understanding of one's own needs, which provided parents with the confidence to support their children. The phenomenon is further explicated with its three constituents: (a) taking care of oneself and one's child; (b) being open and sharing experiences; and (c) acceptance and hope for the future.Conclusions: The CFT intervention enabled parents to find their agency and strengthened their relationships with their children. The findings underscore the need to acknowledge the supportive role parents play in the recovery of children who receive psychiatric care.


The X-ray structure of the PurR-guanine-purF operator complex reveals the contributions of complementary electrostatic surfaces and a water-mediated hydrogen bond to corepressor specificity and binding affinity.
The purine repressor, PurR, is the master regulatory protein of de novo purine nucleotide biosynthesis in Escherichia coli. This dimeric transcription factor is activated to bind to cognate DNA operator sites by initially binding either of its physiologically relevant, high affinity corepressors, hypoxanthine (Kd = 9.3 microM) or guanine (Kd = 1.5 microM). Here, we report the 2.5-A crystal structure of the PurR-guanine-purF operator ternary complex and complete the atomic description of 6-oxopurine-induced repression by PurR. As anticipated, the structure of the PurR-guanine-purF operator complex is isomorphous to the PurR-hypoxanthine-purF operator complex, and their protein-DNA and protein-corepressor interactions are nearly identical. The former finding confirms the use of an identical allosteric DNA-binding mechanism whereby corepressor binding 40 A from the DNA-binding domain juxtaposes the hinge regions of each monomer, thus favoring the formation and insertion of the critical minor groove-binding hinge helices. Strikingly, the higher binding affinity of guanine for PurR and the ability of PurR to discriminate against 2-oxopurines do not result from direct protein-ligand interactions, but rather from a water-mediated contact with the exocyclic N-2 of guanine, which dictates the presence of a donor group on the corepressor, and the better electrostatic complementarity of the guanine base and the corepressor-binding pocket.


Native state of natural proteins optimizes local entropy.
The differing ability of polypeptide conformations to act as the native state of proteins has long been rationalized in terms of differing kinetic accessibility or thermodynamic stability. Building on the successful applications of physical concepts and sampling algorithms recently introduced in the study of disordered systems, in particular artificial neural networks, we quantitatively explore how well a quantity known as the local entropy describes the native state of model proteins. In lattice models and all-atom representations of proteins, we are able to efficiently sample high local entropy states and to provide a proof of concept of enhanced stability and folding rate. Our methods are based on simple and general statistical-mechanics arguments, and thus we expect that they are of very general use.


Long-path measurement of atmospheric NO2 with an obstruction flashlight and a charge-coupled-device spectrometer.
A novel method of differential optical absorption spectroscopy (DOAS) is proposed and demonstrated to monitor the concentration of atmospheric pollutant gas. In contrast to conventional DOAS measurements with continuous light sources, the present method relies on white flashlights such as aviation obstruction lights that are generally installed on tall constructions. A simple detection system is devised by means of a telescope and a compact CCD spectrometer. A path length of 5.5 km allows us to measure atmospheric NO2 concentration with a detection limit of approximately 1 part per billion. We also discuss the possibility of deriving the aerosol optical thickness through the horizontal atmosphere from this pulsed DOAS measurement.


Communication discrepancies between physicians and hospitalized patients.
Hospital surveys indicate lack of patient awareness of diagnoses and treatments, yet physicians report they effectively communicate with patients. Gaps in understanding and communication could result in decreased quality of care. We sought to assess patient knowledge and perspectives of inpatient care and determine differences from physician assessments. Two validated questionnaires assessed the experiences of inpatients treated by house staff from October 10, 2008, through June 23, 2009. We surveyed corresponding internal medicine resident and attending physicians, asking them to report on their care of hospitalized patients and their understanding of their patients' perspectives on the care received. Eighty-nine patients and 43 physicians participated. Although 73% of patients thought there was 1 main physician, 18% correctly named that physician, compared with 67% of physicians who thought patients knew their names (P<.001). Most physicians (77%) believed patients knew their diagnosis; however, 57% of patients did (P<.001). A total of 58% of patients thought that physicians always explained things in a comprehensible way, compared with 21% of physicians who stated they always provided explanations of some kind (P<.001). Two-thirds of patients reported receiving a new medication in the hospital, yet 90% noted never being told of any adverse effects of these medications. Nearly all physicians (98%) stated that they at least sometimes discussed their patients' fears and anxieties, compared with 54% of patients who said their physicians never did this (P=.001). Significant differences exist between patients' and physicians' impressions about patient knowledge and inpatient care received. Steps to improve patient-physician communication should be identified and implemented.


Distinct structural domains in the planarian brain defined by the expression of evolutionarily conserved homeobox genes.
Homeobox genes such as orthodenticle in Drosophila and its mouse homologues, Otx1 and Otx2, are known to be essential for rostral brain development. To investigate the molecular basis of brain evolution, we searched for otd/Otx-related homeobox genes in the planarian Dugesia japonica, and identified two genes, DjotxA and B, whose expression appears to be restricted to the cephalic ganglion (brain). DjotxA was expressed more medially, in the region containing the termini of the visual axons, and in the visual cells, suggesting involvement in establishment of the visual system. DjotxB was expressed in a discrete region just lateral to the DjotxA-positive domain, but not in the more lateral branch structures, which in turn are characterized by the expression of Djotp, a planarian homeobox gene related to mouse Orthopedia (Otp). In transverse sections of planarians, DjotxA and B expression were observed only at the anterior ends of the stumps, corresponding to the regional pattern of the regenerating brain. Our findings suggest that the planarian brain is composed of structurally distinct and functionally diverse domains which are defined by the discrete expression of the three evolutionarily conserved homeobox genes.