Comparison of the microflora on organically and conventionally grown spring mix from a California processor.
Considerable speculation has occurred concerning the potential for higher numbers of foodborne pathogens on organically grown produce compared with produce not grown organically. The microflora composition of spring mix or mesclun, a mixture of multiple salad ingredients, grown either by organic or conventional means was determined. Unwashed or washed spring mix was obtained from a commercial California fresh-cut produce processor who does not use manure in their cultivation practices. Fifty-four samples of each type of product were supplied over a 4-month period. Analysis included enumeration of total mesophiles, psychrotrophs, coliforms, generic Escherichia coli, lactic acid bacteria, yeasts, and molds. In addition, spring mix was analyzed for the presence of Salmonella and Listeria monocytogenes. The mean populations of mesophilic and psychrotrophic bacteria, yeasts, molds, lactic acid bacteria, and coliforms on conventionally grown spring mix were not statistically different (P > 0.05) from respective mean populations on organically grown spring mix. The mean population of each microbial group was significantly higher on unwashed spring mix compared with the washed product. Of the 14 samples found to contain E. coli, eight were from nonwashed conventional spring mix, one was from washed conventional spring mix, and four were from nonwashed organic spring mix. Salmonella and L. monocytogenes were not detected in any of the samples analyzed.


Comet-FISH with strand-specific probes reveals transcription-coupled repair of 8-oxoGuanine in human cells.
Oxidized bases in DNA have been implicated in cancer, aging and neurodegenerative disease. We have developed an approach combining single-cell gel electrophoresis (comet) with fluorescence in situ hybridization (FISH) that enables the comparative quantification of low, physiologically relevant levels of DNA lesions in the respective strands of defined nucleotide sequences and in the genome overall. We have synthesized single-stranded probes targeting the termini of DNA segments of interest using a polymerase chain reaction-based method. These probes facilitate detection of damage at the single-molecule level, as the lesions are converted to DNA strand breaks by lesion-specific endonucleases or glycosylases. To validate our method, we have documented transcription-coupled repair of cyclobutane pyrimidine dimers in the ataxia telangiectasia-mutated (ATM) gene in human fibroblasts irradiated with 254 nm ultraviolet at 0.1 J/m2, a dose ∼100-fold lower than those typically used. The high specificity and sensitivity of our approach revealed that 7,8-dihydro-8-oxoguanine (8-oxoG) at an incidence of approximately three lesions per megabase is preferentially repaired in the transcribed strand of the ATM gene. We have also demonstrated that the hOGG1, XPA, CSB and UVSSA proteins, as well as actively elongating RNA polymerase II, are required for this process, suggesting cross-talk between DNA repair pathways.


Cortical Axons, Isolated in Channels, Display Activity-Dependent Signal Modulation as a Result of Targeted Stimulation.
Mammalian cortical axons are extremely thin processes that are difficult to study as a result of their small diameter: they are too narrow to patch while intact, and super-resolution microscopy is needed to resolve single axons. We present a method for studying axonal physiology by pairing a high-density microelectrode array with a microfluidic axonal isolation device, and use it to study activity-dependent modulation of axonal signal propagation evoked by stimulation near the soma. Up to three axonal branches from a single neuron, isolated in different channels, were recorded from simultaneously using 10-20 electrodes per channel. The axonal channels amplified spikes such that propagations of individual signals along tens of electrodes could easily be discerned with high signal to noise. Stimulation from 10 up to 160 Hz demonstrated similar qualitative results from all of the cells studied: extracellular action potential characteristics changed drastically in response to stimulation. Spike height decreased, spike width increased, and latency increased, as a result of reduced propagation velocity, as the number of stimulations and the stimulation frequencies increased. Quantitatively, the strength of these changes manifested itself differently in cells at different frequencies of stimulation. Some cells' signal fidelity fell to 80% already at 10 Hz, while others maintained 80% signal fidelity at 80 Hz. Differences in modulation by axonal branches of the same cell were also seen for different stimulation frequencies, starting at 10 Hz. Potassium ion concentration changes altered the behavior of the cells causing propagation failures at lower concentrations and improving signal fidelity at higher concentrations.


Prognostic factors associated with favourable functional outcome among adult patients requiring extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A systematic review and meta-analysis.
Extracorporeal cardiopulmonary resuscitation (ECPR), has demonstrated promise in the management of refractory out-of-hospital cardiac arrest (OHCA). However, evidence from observational studies and clinical trials are conflicting and the factors influencing outcome have not been well established. We conducted a systematic review and meta-analysis summarizing the association between pre-ECPR prognostic factors and likelihood of good functional outcome among adult patients requiring ECPR for OHCA. We searched Medline and Embase databases from inception to February 28, 2023 and screened studies with two independent reviewers. We performed meta-analyses of unadjusted and adjusted odds ratios, adjusted hazard ratios and mean differences separately. We assessed risk of bias using the QUIPS tool and certainty of evidence using the GRADE approach. We included 29 observational and randomized studies involving 7,397 patients. Factors with moderate or high certainty of association with increased survival with favourable functional outcome include pre-arrest patient factors, such as younger age (odds ratio (OR) 2.13, 95% CI 1.52 to 2.99) and female sex (OR 1.37, 95% CI 1.11 to 1.70), as well as intra-arrest factors, such as shockable rhythm (OR 2.79, 95% CI 2.04 to 3.80), witnessed arrest (OR 1.68 (95% CI 1.16 to 2.42), bystander CPR (OR 1.55, 95% CI 1.19 to 2.01), return of spontaneous circulation (OR 2.81, 95% CI 2.19 to 3.61) and shorter time to cannulation (OR 1.14, 95% CI 1.17 to 1.69 per 10 minutes). The findings of this review confirm several clinical concepts wellestablished in the cardiac arrest literature and their applicability to the patient for whom ECPR is considered - that is, the impact of pre-existing patient factors, the benefit of timely and effective CPR, as well as the prognostic importance of minimizing low-flow time. We advocate for the thoughtful consideration of these prognostic factors as part of a risk stratification framework when evaluating a patient's potential candidacy for ECPR.


Assessment of Public Hospital Governance in Romania: Lessons From 10 Case Studies.
The Government of Romania commissioned international technical assistance to help unpacking the causes of arrears in selected public hospitals. Emphases were placed on the governance-related determinants of the hospital performance in the context of the Romanian health system. The assessment was structured around a public hospital governance framework examining 4 dimensions: institutional arrangements, financing arrangements, accountability arrangements and correspondence between responsibility and decision-making capacity. The framework was operationalized using a 2-pronged approach: (i) a policy review of broader health system governance arrangements influencing hospital performance; and (ii) a series of 10 casestudies of public hospitals experiencing financial hardship. Data were collected during 2016-2017 through key informant interviews with central authorities and hospital management teams, exhaustive semi-structured questionnaires filled in by hospitals, as well as the review of documentary sources where feasible. Overall, the governance landscape of Romanian public hospitals includes a large number of seemingly modern legislative provisions and management instruments. Over the past 30 years substantial efforts have been made to put in place standardised hospital classification, hospital governance structures, management and service purchasing contracts with key performance indicators, modern reimbursement mechanisms based on diagnosis-related groups (DRGs), and regulatory requirements for accountability, including internal and external audit. Nevertheless, their application appears to have been challenging for a range of reasons, pointing to the misalignment between the responsibility and decisionmaking capacity given to hospitals in a questionably conducive context. Incoherent policy design, outdated and often disjointed regulatory frameworks, and cumbersome administrative procedures limit managerial autonomy and obstruct efficiency gains. In a context of chronic insufficient funding, misaligned incentives, and overly rigid service procurement processes, hospitals seem to struggle to adjust service baskets to the population's health needs or to overcoming financial hardship. External challenges, combined with the limited strategic, operational, and financial management capacity within hospitals, make it difficult to exhibit good financial and general performance. Existing governance arrangements for Romanian public hospitals appear conducive to poor financial performance. The suggested framework for hospital governance assessment has proved a powerful tool for identifying system and hospital-specific challenges contributing to sub-optimal hospital performance.


Nutritional regulation of IGF-I and IGFBPs.
IGF-I concentrations in serum are decreased in states of chronic undernutrition or when food intake is restricted. A variety of mechanisms including decreased GH receptor binding, post-receptor resistance to GH, and reduced steady-state mRNA for IGF-I contribute to this decrease. In addition, dietary manipulation causes profound alterations in the IGF binding proteins, including reduced IGFBP-3, the principal serum carrier of IGF-I. Under some adverse nutritional conditions IGFBP-1 and IGFBP-2 are increased. Concomitant with changes in IGFBPs, IGF-I volume of distribution is increased and clearance is hastened. It seems likely that nutrition related changes in IGFBPs contribute significantly to alterations in IGF-I concentration and actions.


Microcomputers and phylogenetic analysis.
The programs discussed above show how microcomputers have added to the arsenal of systematic biologists. This is a rapidly developing field, and there are no doubt major changes on the horizon. Swofford is working on a new version of PAUP that will have some of the interactive features of MacClade (and will not require a math coprocessor) and there are efforts under way to make PAUP available on Macintosh. PHYLIP has undergone a steady evolution since its release, and Felsenstein has plans to continue that policy. A microcomputer descendant of the large mainframe program PHYSYS, authored by James S. Farris, is supposed to be forthcoming before the end of the year. Just as this review was being completed, J. Rohlf and R. Sokal of the State University of New York at Stony Brook unveiled a beta-test microcomputer version of their phenetic program package, NT-SYS. Inasmuch as it was not in release form and does not include algorithms specifically designed to do phylogenetic analysis, it has not been included here (although some phenetic techniques, such as UPGMA, produce results similar to parsimony trees under certain assumptions).


Deciding to opt out of childhood vaccination mandates.
We explore the attitudes and beliefs of parents who consciously choose not to vaccinate their children and the ways in which these parents process information on the pros and cons of vaccines. In-depth, semistructured interviews were conducted. The study population consisted of 25 parents who do not vaccinate their children, identified through snowball and targeted sampling. Participants were asked about their processes and actions when choosing not to vaccinate their children. Interviews were taped and transcribed, and the content was analyzed for emergent themes. Two predominant themes emerged in our data: a desire to collect information on vaccines and trust issues with the medical community. Evidence of sophisticated data collection and information processing was a repeated theme in the interview data. Simultaneously, while participants placed a high value on scientific knowledge, they also expressed high levels of distrust of the medical community. The challenge for public health is to balance scientific data with popular epidemiology and to maintain legitimacy. Understanding the differences in lay versus expert knowledge has implications for crafting health messages. How experts frame knowledge for consumption has an important impact on this group and their decision-making processes.


Quinacrine, a PLA2 inhibitor, alleviates LPS-induced acute kidney injury in rats: Involvement of TLR4/NF-κB/TNF α-mediated signaling.
Acute Kidney Injury (AKI) is a major factor in sepsis-related mortality and may occur due to lipopolysaccharide (LPS), an endotoxin produced by gram-negative bacteria that triggers a systemic acute inflammatory response. Quinacrine's (QC) renoprotective properties in sepsis and the underlying mechanism, however, are still not fully understood. This study was done to investigate the anti-inflammatory, antioxidative, and anti-apoptotic effects of QC, a phospholipase A2 (PLA2) inhibitor, against LPS-induced AKI. Rats were randomly divided into five groups: control group, QC30 group, LPS group, LPS+QC 10 group, and LPS+QC 30 group. The rats were administered intraperitoneally QC (10 and 30 mg/kg) for 3 days (once a day) prior to injection of LPS (3 mg/kg). Six hours after the LPS injection, the histopathological changes, oxidative stress, inflammation, and apoptosis in the collected kidney tissues were detected by hematoxylin and eosin staining, enzyme-linked immunosorbent assay (ELISA), real-time PCR (RT-PCR), and immunohistochemistry staining, respectively. QC pretreatment could successfully attenuate LPS-induced AKI, as evidenced by a decrease in tissue histopathological injury. Meanwhile, QC alleviated LPS-induced kidney oxidative stress; it reduced MDA levels and increased levels of SOD, CAT, GPX, and GSH. LPS-induced elevations in kidney TLR4, NF-κB, TNF-α, IL-1β, IL-6, PLA2, caspase 3, and Bax contents were significantly attenuated in QC-treated groups. Our findings revealed a significant effect of QC: protecting against LPS-induced AKI through inhibition of PLA2 and decreasing inflammation, oxidative stress, and apoptosis. To treat LPS-induced AKI, QC may be an effective substance with an excellent protection profile.


Characteristics and Pharmacological Regulation of Epithelial Na+ Channel (ENaC) and Epithelial Na+ Transport.
Epithelial Na+ transport participates in control of various body functions and conditions: e.g., homeostasis of body fluid content influencing blood pressure, control of amounts of fluids covering the apical surface of alveolar epithelial cells at appropriate levels for normal gas exchange, and prevention of bacterial/viral infection. Epithelial Na+ transport via the transcellular pathway is mediated by the entry step of Na+ across the apical membrane via Epithelial Na+ Channel (ENaC) located at the apical membrane, and the extrusion step of Na+ across the basolateral membrane via the Na+,K+-ATPase located at the basolateral membrane. The rate-limiting step of the epithelial Na+ transport via the transcellular pathway is generally recognized to be the entry step of Na+ across the apical membrane via ENaC. Thus, up-/down-regulation of ENaC essentially participates in regulatory systems of blood pressure and normal gas exchange. Amount of ENaC-mediated Na+ transport is determined by the number of ENaCs located at the apical membrane, activity (open probability) of individual ENaC located at the apical membrane, single channel conductance of ENaC located at the apical membrane, and driving force for the Na+ entry via ENaCs across the apical membrane. In the present review article, I discuss the characteristics of ENaC and how these factors are regulated.


Local recurrence of disease after unplanned excisions of high-grade soft tissue sarcomas.
Unplanned excisions of soft tissue sarcomas occur with alarming frequency and result in high rates of residual disease, potentially affecting patient prognosis. To determine if unplanned excisions and residual disease status at tumor bed excision increased local recurrence rates and predicted disease-specific patient survival, we retrospectively reviewed 203 consecutive patients with high-grade soft tissue sarcomas treated operatively and followed for at least 2 years (mean, 4.8 years) or until patient death. Among the 64 patients (32%) who had undergone previous unplanned excisions, six had gross residual disease and 40 of the remaining 58 (69%) had microscopic residual disease in the tumor bed. We observed subsequent local recurrence in nine of the 139 patients (6%) after planned excision compared with 22 patients (34%) after unplanned excision. More patients with unplanned excisions who underwent limb salvage procedures required flap coverage and/or skin grafting with their definitive resection (30% versus 5%). In the unplanned excision cohort, residual disease status at tumor bed excision predicted increased rates of local recurrence and decreased disease-specific survival. Unplanned excisions of high-grade soft tissue sarcomas resulted in increased rates of local recurrence but not disease-specific survival. Residual disease at reexcision predicted the likelihood of local recurrence. Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.


Clinical evaluation of amikacin in treatment of infections due to gram-negative aerobic bacilli.
The efficacy and safety of amikacin were evaluated in 42 patients with infections presumed to be due to gram-negative rods. The dosage of 7.5 mg of amikacin/kg every 12 hr was administered intramuscularly to 32 patients and intravenously to seven patients; three patients with renal impairment were given a modified regimen. The duration of treatment was three to 51 days (mean, 9.6 days). Of 19 patients with acute pyelonephritis, five had positive blood culture results. Ten patients had chronic urinary infection, and isolates of Pseudomonas aeruginosa from four of these patients acquired resistance to amikacin during therapy. Of seven patients with gram-negative bacteremia from sources other than the urinary tract, four showed satisfactory and three had less than optimal responses to therapy with amikacin. Two patients with chronic osteomyelitis or soft tissue infection improved but subsequently relapsed. Two patients with acute febrile illness, in whom the etiologic agent was unidentified, recovered. Serial audiograms revealed no change in 26 of 27 patients; one had a significant deterioration in hearing. A transient rise in the level of serum creatinine was noted in three patients. Serial tests of liver function revealed no abnormalities.


The thermal behaviour and structural stability of nesquehonite, MgCO3.3H2O, evaluated by in situ laboratory parallel-beam X-ray powder diffraction: New constraints on CO2 sequestration within minerals.
In order to gauge the appropriateness of CO(2) reaction with Mg chloride solutions as a process for storing carbon dioxide, the thermal behaviour and structural stability of its solid product, nesquehonite (MgCO(3).3H(2)O), were investigated in situ using real-time laboratory parallel-beam X-ray powder diffraction. The results suggest that the nesquehonite structure remains substantially unaffected up to 373 K, with the exception of a markedly anisotropic thermal expansion acting mainly along the c axis. In the 371-390 K range, the loss of one water molecule results in the nucleation of a phase of probable composition MgCO(3).2H(2)O, which is characterized by significant structural disorder. At higher temperatures (423-483 K), both magnesite and MgO.2MgCO(3) coexist. Finally, at 603 K, periclase nucleation starts and the disappearance of carbonate phases is completed at 683 K. Consequently, the structural stability of nesquehonite at high temperatures suggests that it will remain stable under the temperature conditions that prevail at the Earth's surface. These results will help (a) to set constraints on the temperature conditions under which nesquehonite may be safely stored and (b) to develop CO(2) sequestration via the synthesis of nesquehonite for industrial application.


Evaluation of the pathologic results of prostate biopsies in terms of age, Gleason score and PSA level: our experience and review of the literature.
To evaluate the pathologic and clinic results of our large series of transrectal prostate biopsies in relation to Gleason score, age and PSA level. We reviewed the pathologic results of transrectal prostate biopsies performed because of high PSA levels and abnormal digital rectal examination findings between January 2008 and February 2012. The pathologic result of 835 prostate biopsies was benign in 82.2% and malign in 17.8%. Furthermore in 3.7% high grade PIN (Prostatic Intraepitelial Neoplasia) or ASAP (Atypical Small Acinar Proliferation) was shown. In the interval of total PSA values between 4 and 10 ng/dl, that is thw so-called grey zone, cancer detection rate was 12.4%. There was a significant relationship between cancer detection and cancer stage at all high levels of PSA also in the grey zone. The most common Gleason score observed was 3 + 3 wirh a rate of 7.4% whereas the second most commonly observed scare was 3 + 4 with a rate of 2.5%. In the patients with abnormal digital rectal examination findings but normal PSA levels according to age the cancer detection rate was 8.7%, in patients with only high PSA levels the rate was 41.2% and in the patients with both high PSA levels and abnormal digital rectal examination findings. the rate was 49.3%. Our study underlines the relationship between age, PSA level and pathologic stage of prostate cancer and also the importance of digital rectal examination.


Universal health coverage: necessary but not sufficient.
In this article, we highlight key considerations for better addressing sexual and reproductive health and rights issues within universal health coverage (UHC), particularly in the context of the post-2015 sustainable development agenda. We look at UHC as a health, development and health care financing issue, and its history. We discuss its limitations as currently understood from a human rights perspective, and show why structural barriers to health and the legal and policy environment, which are essential to health (particularly to sexual and reproductive health and rights), require critical consideration in current discussions about health in the post-2015 development framework and must be taken into account above and beyond UHC in any future health goal. As a result, we suggest that UHC alone will not result in universal access to sexual and reproductive health, and certainly not to sexual and reproductive rights. Instead, it should be considered as a means to achieving broader health and development goals. A goal such as seeking to reach the highest attainable standard of health or maximizing healthy lives that is informed by a rights-based approach should be the aspiration for the post-2015 development agenda.


Growth hormone-binding protein directly depends on serum leptin levels in adults with different nutritional status.
The aim of this work was to assess the relationship between GH-binding protein (GHBP) and leptin. Both peptides are nutritionally regulated, but the recent implication of a role for leptin in the GH axis requires further study. To avoid the sexual dimorphism in leptin values, we performed leptin standardization according to gender (SD score-leptin). The relationship between SD score-leptin and GHBP was studied in 128 adults with different nutritional status [8 groups according to body mass index (BMI)], ranging from severely underweight anorexia nervosa to highly morbid obesity. Both GHBP and SD score-leptin significantly increased according to BMI within the range from 18-27 kg/m2, whereas no significant differences were found among underweight groups (BMI, < 18 kg/m2) or among obesity grades (BMI, > 27 kg/m2). We found a strong correlation between GHBP and SD score-leptin (r = 0.8; P < 0.0001). Multiple regression analysis revealed SD score-leptin to be a significant determinant of GHBP, accounting for 64% of the variation, whereas BMI did not contribute further to explaining changes in GHBP. This suggests a physiological pathway involving both GHBP (the soluble fraction of GH receptor) and leptin. Thus, we might speculate that leptin could be the signal that induces the related nutritional changes observed in GHBP/GH receptor expression.


NMR study of the complexes between a synthetic peptide derived from the B subunit of cholera toxin and three monoclonal antibodies against it.
The contact interactions between a synthetic peptide and three different anti-peptide monoclonal antibodies have been studied by nuclear magnetic resonance (NMR). The synthetic peptide is CTP3 (residues 50-64 of the B subunit of cholera toxin) suggested as a possible epitope for synthetic vaccine against cholera. The hybridoma cell lines TE33 and TE32 derived after immunization with CTP3 produce antibodies cross-reactive with the native toxin. The cell line TE34 produces anti-CTP3 antibodies that do not bind the toxin. Selective deuteriation of the antibodies has been used to simplify the proton NMR spectra and to assign resonances to specific types of amino acids. The difference spectra between the proton NMR spectrum of the peptide-Fab complex and that of Fab indicate that the combining site structures of TE32 and TE33 are very similar but differ considerably from the combining site structure of TE34. By magnetization transfer experiments with selectively deuteriated Fab fragment of the antibody, we have found that in TE32 and TE33 the histidine residue of the peptide is buried in a hydrophobic pocket of the antibody combining site, formed by a tryptophan and two tyrosine residues. The hydrophobic nature of the pocket is further demonstrated by the lack of any pH titration effect on the chemical shift of the C4H of the bound peptide histidine. In contrast, for TE34 we have found only one tyrosine residue in contact with the histidine of the peptide.(ABSTRACT TRUNCATED AT 250 WORDS)


Chalmers J. Lyons memorial lecture: Metal implants and the mandibular staple bone plate.
To briefly summarize our results, two of the five three-pin staples (40%) have survived and have functioned well for more than six years. Four of the five four-pin staples (80%) have survived five years or longer and are functioning well. Twenty-four of the 25 seven-pin staples (96%) are functioning well, some for a period of 4-1/2 years; a few in this group have been used a little less than a year. Our total percentage of survival with good function is 30 of 35, or 86%, which includes our pilot study of the three- and four-pin staples. A more significant statistic, however, might be those patients with staples who we feel have been free of any significant trouble; these are 27 of 35, or 77%. All of our patients have been subjected to peer review examination and grading by members of the oral surgery staff at Sinai Hospital. They were examined and graded according to three criteria. The first was clinical appearance which included firmness of the staple and clinical appearance of the gingiva (Fig 16). The second was radiographic evidence of bone loss along the transosteal pins and retentive pins (Fig 17). The third category was patient evaluation of improved function and stability of the lower denture (Fig 18). The peer review group used marks A, B, C, D, as excellent, good, fair, and failure. Four points were assigned to A, 3 points to B, 2 points to C, and 1 point to D, so that the grade averages for all three categories were as follows: clinical appearance, 3.6; radiographic appearance, 3.5; and patient evaluation, 3.9. The conclusion of the review group was that the mandibular staple was functioning well and that it was clinically useful. I have presented an overview of some of the characteristics of metallic implants that make them implantable devices, and some of the qualities of the host tissues that will allow placement of foreign material. We do not yet understand all of the factors that make alloplastic materials biocompatible or some of the reasons for rejection by the host. We need continued research in animal models to study new devices and new materials that might permit biologic attachments of the host to implant. We also need controlled clinical studies with peer review to establish reliability of those devices that are clinically useful. The mandibular staple has had an initial clinical trial that seems very promising and is worthy of continued clinical study and clinical application.


Digitalgia paresthetica with digital neuropathy in rheumatoid arthritis.
Two cases demonstrate the digital neuropathy of rheumatoid arthritis with hyperpathia. This phenomenon occurs in types II and IV, but the paresthetic character has not been emphasized previously.


Non-linearity of the collagen triple helix in solution and implications for collagen function.
Collagen adopts a characteristic supercoiled triple helical conformation which requires a repeating (Xaa-Yaa-Gly)n sequence. Despite the abundance of collagen, a combined experimental and atomistic modelling approach has not so far quantitated the degree of flexibility seen experimentally in the solution structures of collagen triple helices. To address this question, we report an experimental study on the flexibility of varying lengths of collagen triple helical peptides, composed of six, eight, ten and twelve repeats of the most stable Pro-Hyp-Gly (POG) units. In addition, one unblocked peptide, (POG)10unblocked, was compared with the blocked (POG)10 as a control for the significance of end effects. Complementary analytical ultracentrifugation and synchrotron small angle X-ray scattering data showed that the conformations of the longer triple helical peptides were not well explained by a linear structure derived from crystallography. To interpret these data, molecular dynamics simulations were used to generate 50 000 physically realistic collagen structures for each of the helices. These structures were fitted against their respective scattering data to reveal the best fitting structures from this large ensemble of possible helix structures. This curve fitting confirmed a small degree of non-linearity to exist in these best fit triple helices, with the degree of bending approximated as 4-17° from linearity. Our results open the way for further studies of other collagen triple helices with different sequences and stabilities in order to clarify the role of molecular rigidity and flexibility in collagen extracellular and immune function and disease.


Pre-emptive renal transplantation: optimum treatment for end-stage renal disease?
Renal transplantation (RT) prior to having dialysis or pre-emptive renal transplantation (PRT) has been controversial because of the paucity of clinical evidence to clarify the benefits and risks of PRT. The recent emergence of evidences from major transplant centres in the United Kingdom and United States have confirmed the survival advantages for both renal allografts and RT recipients. Hence an increasing number of transplant centres are adopting the practice of PRT. This article discusses the advantages and disadvantages of PRT and highlights the clinical evidences in support of PRT.


Cross-sectional assessment of haemostatic profile and hepatic dysfunction in Fontan patients.
Fontan-associated liver disease is accompanied by a hypercoagulable state. While hepatic dysfunction in Fontan patients is common, its relationship with haemostatic changes and clinical outcomes in this patient population remains unclear. To correlate liver dysfunction and haemostatic profiles with clinical outcomes in the Fontan population. Patients were enrolled in a multicentre, cross-sectional study in Australia and New Zealand. Hepatic structure and function were assessed using serum-based calculations (Fibrotest and model for end-stage liver disease excluding international normalised ratio scores). Haemostatic profiles were assessed by Thrombin Generation. Platelet function was assessed via Platelet Factor 4 (PF4) and P-selectin (P-SEL). Clinical outcomes were obtained from the Australian and New Zealand Fontan Registry. Seventy-three patients participated in the study (mean age 18.9±8.5 years with a mean of 13.5±6.9 years post-Fontan). The Endogenous Thrombin Potential (ETP) for patients who suffered thrombotic events (TE) (1366.4±66.2 nM/min) was higher compared with patients with major bleeding events (1011.1±138.4 nM/min) (p=0.03). Except for a negative correlation between Fibrotest-score and PF4 (p=0.045), PF4 and P-SEL concentrations did not correlate with markers of hepatic dysfunction or structural abnormality. Increased ETP is associated with TE during clinical follow-up after Fontan. This study reinforces that hepatic dysfunction may contribute to the derangement of coagulation factors, impacting the individual risk of haemostatic complications for the Fontan population.


Determinants of malnutrition in Senegal: individual, household, community variables, and their interaction.
The relationship between poverty and nutrition is a two-sided one: on the one hand, economic growth (which is generally associated with an eradication of poverty) leads to reduced malnutrition. On the other hand, nutrition is one of the key ingredients for human capital formation, which in turn represents one of the fundamental factors of growth. There are numerous studies that show the correlates of malnutrition using both household- and community-level variables. However, few of these studies allow for the potential endogeneity of community infrastructure or indicate their interplay with characteristics of the mother. The current study considers the socio-economic determinants of child malnutrition and investigates how programs compensate for the increased risks facing young mothers and their children or substitute for a low social status of the mother in the household. The empirical results show that children of mothers giving birth at a young age are disadvantaged in terms of their anthropometric status. Interaction effects of the presence of a non-governmental organization (NGO) or a health post in the village with characteristics of the mother stress the important role played by these institutions in helping disadvantaged mothers overcome their difficulties. These findings have implications for efficient program design and represent a further step towards gaining an improved understanding of the complex determinants of child (mal)nutrition.


Abortion and Ectogenesis: Moral Compromise.
The contemporary philosophical literature on abortion primarily revolves around three seemingly intractable debates, concerning the (1) moral status of the fetus, (2) scope of women's rights and (3) moral relevance of the killing/letting die distinction. The possibility of ectogenesis-technology that would allow a fetus to develop outside of a gestational mother's womb-presents a unique opportunity for moral compromise. Here, I argue those opposed to abortion have a prima facie moral obligation to pursue ectogenesis technology and provide ectogenesis for disconnected fetuses as part of a moral compromise.


Physiological and behavioural adjustment of a wild rodent to laboratory conditions.
Wild animals are brought to captivity for different reasons, for example to be kept in zoos and rehabilitation centres, but also for basic research. Such animals usually undergo a process of adjustment to captive conditions. While this adjustment occurs on the behavioural and the physiological level, those are usually studied separately. The aim of this study was to assess both the physiological and behavioural responses of wild wood mice, Apodemus sylvaticus, while adjusting to laboratory conditions. Over the course of four weeks, we measured in wild-caught mice brought to the laboratory faecal corticosterone metabolites and body mass as physiological parameters, stereotypic behaviour and nest-quality, as welfare-linked behavioural parameters, and four personality measures as additional behavioural parameters. The results of our study indicate that mice exhibited an adjustment in both behaviour and physiology over time in the laboratory. While the hormonal stress response decreased significantly, body mass and the proportion of stereotypic behaviours showed a tendency to increase over time. The slight increase of stereotypic behaviours, although not statistically significant, suggests the development of repetitive and non-functional behaviours as a response to laboratory conditions. However, we suggest that those behaviours might have been used by animals as a coping strategy to decrease the physiological stress response. Other behavioural parameters measured, such as boldness and nestbuilding behaviour were stable over time. The information obtained in the present study hints at a complex interplay between behavioural and physiological adjustments of wild animals to laboratory conditions, which should be considered when intending to use wild animals in experimental research.


Correlations Between Objective Behavioral Features Collected From Mobile and Wearable Devices and Depressive Mood Symptoms in Patients With Affective Disorders: Systematic Review.
Several studies have recently reported on the correlation between objective behavioral features collected via mobile and wearable devices and depressive mood symptoms in patients with affective disorders (unipolar and bipolar disorders). However, individual studies have reported on different and sometimes contradicting results, and no quantitative systematic review of the correlation between objective behavioral features and depressive mood symptoms has been published. The objectives of this systematic review were to (1) provide an overview of the correlations between objective behavioral features and depressive mood symptoms reported in the literature and (2) investigate the strength and statistical significance of these correlations across studies. The answers to these questions could potentially help identify which objective features have shown most promising results across studies. We conducted a systematic review of the scientific literature, reported according to the preferred reporting items for systematic reviews and meta-analyses guidelines. IEEE Xplore, ACM Digital Library, Web of Sciences, PsychINFO, PubMed, DBLP computer science bibliography, HTA, DARE, Scopus, and Science Direct were searched and supplemented by hand examination of reference lists. The search ended on April 27, 2017, and was limited to studies published between 2007 and 2017. A total of 46 studies were eligible for the review. These studies identified and investigated 85 unique objective behavioral features, covering 17 various sensor data inputs. These features were divided into 7 categories. Several features were found to have statistically significant and consistent correlation directionality with mood assessment (eg, the amount of home stay, sleep duration, and vigorous activity), while others showed directionality discrepancies across the studies (eg, amount of text messages [short message service] sent, time spent between locations, and frequency of mobile phone screen activity). Several studies showed consistent and statistically significant correlations between objective behavioral features collected via mobile and wearable devices and depressive mood symptoms. Hence, continuous and everyday monitoring of behavioral aspects in affective disorders could be a promising supplementary objective measure for estimating depressive mood symptoms. However, the evidence is limited by methodological issues in individual studies and by a lack of standardization of (1) the collected objective features, (2) the mood assessment methodology, and (3) the statistical methods applied. Therefore, consistency in data collection and analysis in future studies is needed, making replication studies as well as meta-analyses possible.


Maintenance of own health after acute hospitalization - older people's experiences and perspectives on physical activity and nutrition.
Studies indicate that prefrail and frail older people would like to exercise, but support from healthcare professionals is required. Knowledge regarding health maintenance in prefrail or frail older people in terms of physical training and nutrition after hospitalization is scarce. To explore the perspectives and experiences of prefrail and frail older people concerning physical training and nutrition one and four weeks after an acute medical hospitalization. Repeated individual semi-structured interviews with ten prefrail and frail older people were conducted. An inductive-deductive thematic analysis was performed. Previous experiences with healthcare affected the views of the participants on training, nutrition, and health. Although the participants' knowledge about physical training was limited, they were positive about participating in training and obtaining knowledge about their condition. However, their positive intentions were not successfully achieved within four weeks. Despite positive intentions, appointments at the hospital, musculoskeletal pain, and other limitations hindered the intended training. Furthermore, changing nutritional habits seemed difficult. The participants were positive toward participating in training and interested in knowledge addressing their condition. Nutritional habits were considered as a personal matter and difficult to change, as they had year long habits about when and how they ate. These findings indicate that a lack of dialogue about training and nutrition may contribute to lower health literacy in frail older people and may therefore affect the maintenance of health after an acute hospitalization. This suggests that physiotherapists should ensure that follow-up is discussed and planned in detail with patients before discharge.


Effect of phytohemagglutinin-stimulated human lymphocytes on isolated rat atria. Participation of lipoxygenase products of arachidonic acid metabolism.
The effect of phytohemagglutinin (PHA) stimulated human lymphocytes on the contractile activity of isolated rat atria was studied. Increased isometric developed tension (IDT) and higher frequency of contractions (FC) were observed shortly after contact of PHA-activated lymphocytes with spontaneously beating rat atria. Since pre-exposure of the lymphocytes to PHA was not necessary and the pharmacologic effects were demonstrated immediately after addition of the lectin, division of the effector cells as a requisite for their action was excluded. Experiments performed with the antibiotic crystallized from Streptomyces chartreusenis, Ca2+-ionophore A-23187, yielded similar effects. Lymphocyte fractionation studies showed that T-lymphocyte-rich and T-lymphocyte-depleted cell fractions had opposite effects on IDT and FC. The inotropic and chronotropic effects were not modified by (-)-propranolol or antihistaminics. Inhibitor of the synthesis of prostaglandins enhanced the action of PHA-activated lymphocytes but inhibitors of the lipoxygenase pathway: 5,8,11,14-eicosatetraynoic acid (ETYA) and nordihydroguaiaretic acid (NDGA) prevented the increment of IDT and FC. Also, FPL55712, an antagonist of SRS-A abolished the positive inotropic and chronotropic effects of PHA-activated lymphocytes on rat atria. Therefore, a central role for SRS-A in this reaction is suggested.


Pediatric Asthma Care Assessment for the Emergency Department.
In the United States alone, approximately 6.2 million children have asthma. Managing the care of pediatric patients presenting in the emergency department with asthma requires clinicians to access multiple locations within the electronic health record. This wealth of information makes it vital to develop methods for sifting through the clutter to information that is relevant to the specific task to be completed. Unfortunately, current information displays have not been developed to maximize provider efficiency when integrating information across a number of disparate locations. Using proven data display theories, we aimed to create a consolidated acute pediatric asthma display to aid in the patient's care with the goal of improving the efficiency and consistency by which they are treated - ultimately reducing the length of stay, complications, and morbidity in these patients.


Evaluation of a polyvalent enzyme-linked immunosorbent assay incorporating a recombinant p44 antigen for diagnosis of granulocytic ehrlichiosis in dogs and horses.
To develop and evaluate a polyvalent ELISA incorporating a highly specific recombinant antigen (p44) for diagnosis of granulocytic ehrlichiosis in dogs and horses. 32 dogs and 43 horses. Results of the ELISA were compared with results of indirect fluorescent antibody (IFA) staining and western immunoblotting incorporating whole-cell antigen. For the canine and equine samples, percentages of samples with positive IFA staining, western immunoblotting, and ELISA results were similar. For 29 (91 %) canine samples and 30 (70%) equine samples, results of IFA staining, western immunoblotting, and the ELISA were in complete agreement. Results of the ELISA for 3 canine serum samples known to contain antibodies to Ehrlichia canis and 12 equine serum samples known to contain antibodies to E risticii were negative. Results of the present study suggest that a polyvalent ELISA incorporating a recombinant p44 antigen is suitable for detecting antibodies to E equi in dogs and horses.


The rough endoplasmic reticulum-resident FK506-binding protein FKBP65 is a molecular chaperone that interacts with collagens.
The rough endoplasmic reticulum-resident FK-506-binding protein FKBP65 can be isolated from chick embryos on a gelatin-Sepharose column, indicating some involvement in the biosynthesis of procollagens. The peptidylprolyl cis-trans-isomerase activity of FKBP65 was previously shown to have only marginal effects on the rate of triple helix formation (Zeng, B., MacDonald, J. R., Bann, J. G., Beck, K., Gambee, J. E., Boswell, B. A., and Bächinger, H. P. (1998) Biochem. J. 330, 109-114). Here we show that FKBP65 is a monomer in solution and acts as a chaperone molecule when tested with two classic chaperone assays: FKBP65 inhibits the thermal aggregation of citrate synthase and is active in the denatured rhodanese refolding and aggregation assay. The chaperone activity is comparable to that of protein-disulfide isomerase, a well characterized chaperone. FKBP65 delays the in vitro fibril formation of type I collagen, indicating that FKBP65 is also able to interact with triple helical collagen, and acts as a collagen chaperone.


Climate change rapidly warms and acidifies Australian estuaries.
Climate change is impacting ecosystems worldwide. Estuaries are diverse and important aquatic ecosystems; and yet until now we have lacked information on the response of estuaries to climate change. Here we present data from a twelve-year monitoring program, involving 6200 observations of 166 estuaries along >1100 kilometres of the Australian coastline encompassing all estuary morphologies. Estuary temperatures increased by 2.16 °C on average over 12 years, at a rate of 0.2 °C year-1, with waters acidifying at a rate of 0.09 pH units and freshening at 0.086 PSU year-1. The response of estuaries to climate change is dependent on their morphology. Lagoons and rivers are warming and acidifying at the fastest rate because of shallow average depths and limited oceanic exchange. The changes measured are an order of magnitude faster than predicted by global ocean and atmospheric models, indicating that existing global models may not be useful to predict change in estuaries.


Sleep deprivation causes behavioral, synaptic, and membrane excitability alterations in hippocampal neurons.
Although the function of sleep remains elusive, several lines of evidence suggest that sleep has an important role in learning and memory. In light of the available data and with the prevalence of sleep deprivation (SD), we sought to determine the effect of SD on neuronal functioning. We found that the exposure of rats to 72 hr of primarily rapid eye movement SD impaired their subsequent performance on a hippocampus-dependent spatial learning task but had no effect on an amygdala-dependent learning task. To determine the underlying cellular level mechanisms of this hippocampal deficit, we examined the impact of SD on several fundamental aspects of membrane excitability and synaptic physiology in hippocampal CA1 pyramidal neurons and dentate gyrus granule cells. We found that neuronal excitability was severely reduced in CA1 neurons but not in granule cells and that the production of long-term potentiation of synaptic strength was inhibited in both areas. Using multiple SD methods we further attempted to differentiate the effects of sleep deprivation from those associated with the nonspecific stress induced by the sleep deprivation methods. Together these data suggest that failure to acquire adequate sleep produces several molecular and cellular level alterations that profoundly inhibit hippocampal functioning.


"…or else I close my ears" How women with obesity want to be approached and treated regarding gestational weight management: A qualitative interview study.
The importance of helping pregnant women maintain a healthy lifestyle and prevent excessive gestational weight gain is well recognized, but pregnant women do not always perceive communication about body weight as respectful or helpful. Furthermore, fear of inducing shame or guilt can prohibit some midwives from talking about body weight, especially if the woman has obesity. We aimed to explore what women of reproductive age with obesity regard to be the most important and relevant aspects when discussing gestational weight management. Qualitative interview study using focus groups and individual semi-structured interviews with 17 women of reproductive age (19-39 y) with obesity. Thematic analysis was used to analyze the data. We identified three themes: 1) Importance of obtaining vital medical information; 2) A wish to feel understood and treated with respect; 3) Midwives' approach is crucial in sensitive key situations, which include bringing up the subject of body weight, weighing, providing weight-related information, coaching lifestyle modification, dealing with emotional reactions and ending a conversation. A majority of the interviewed women wished to receive information about risks about obesity and gestational weight gain, and recommendations on weight management. However, the risk of midwives offending someone by raising the topic may be increased if the pregnant woman believe that gestational weight gain is uncontrollable by the individual. Also, several situations during maternity care meetings can be stigmatizing and make women less receptive to advice or support. Women suggest that a good working alliance is likely to be achieved if midwives have knowledge about the causes of obesity, take interest in the patients' background, have a non-judgmental approach and refrain from giving unsolicited advice.


[Treatment of vaginismus with EMDR: a report of two cases].
Vaginismus is a type of sexual dysfunction in which spasm of the vaginal musculature prevents penetrative intercourse. The main diagnostic criterion is the presence of recurrent or persistent involuntary spasm of the musculature of the outer third of the vagina that interferes with sexual intercourse. In many cases associated pain or the fear of pain may contribute to its persistence. Herein we report 2 patients that presented with vaginismus that developed secondary to childhood sexual trauma, which was treated with the Eye Movement Desensitization and Reprocessing (EMDR) technique. EMDR is a non-pharmacologic treatment for psychological trauma. Randomized controlled trials with posttraumatic stress disorder patients and with victims of sexual abuse have shown that EMDR is effective. The standard 8-phase EMDR protocol was used in both of the presented cases. Following 3 sessions of EMDR, the patients exhibited a substantial reduction in self-reported and clinician-rated anxiety, and a reduction in the credibility of dysfunctional beliefs concerning sexual intercourse. These findings support the notion that EMDR could be an effective treatment alternative for patients with vaginismus of traumatic etiology.


Regulation of thymus PCNA expression is altered in radiation-sensitive wasted mice.
Mice bearing the autosomal recessive mutation 'wasted' (wst/wst) express a disease syndrome characterized by neurologic dysfunction, immunodeficiency, and increased sensitivity to the killing effects of ionizing radiation relative to normal littermates (wst/-) and to parental control mice (BCF1, BALB/c, and C57BL/6). Many of these abnormalities, evident as early as 21 days of age, have been localized to thymic tissues and T-lymphocyte populations. Comparison of two-dimensional gel electrophoresis patterns of proteins from wst/wst and control mouse thymus revealed that an acidic protein with a molecular mass of approximately 30 kDa was consistently expressed at lower levels in wasted mice than in controls. Microsequencing of this protein revealed a sequence of 19 N-terminal amino acids identical to the sequence of murine proliferating cell nuclear antigen (PCNA). Northern blot analyses of PCNA expression in thymus and spleen demonstrated lower accumulation of PCNA-specific transcripts in wasted mice compared with that in controls. Because PCNA expression is associated with cell cycle progression, the percentages of thymic and splenic cells in each stage of the cell cycle were examined; there were no differences in the cell stage distribution of lymphocytes freshly isolated from wasted mice compared with littermate or parental controls. After activation with concanavalin A, however, splenocytes from wst/wst mice showed a lower percentage of cells in S phase compared with that in controls. Southern blots with PCNA probes showed that the PCNA loci from the wasted mice and their normal littermates have the same restriction maps. While differences in polymerase chain reaction (PCR) priming were obtained, these could be attributed to strain-specific differences in mouse PCNA pseudogenes. These results suggest the presence of an alteration in the pathway leading to PCNA expression in radiation-sensitive tissues of wasted mice.


Developmental up-regulation of vesicular glutamate transporter-1 promotes neocortical presynaptic terminal development.
Presynaptic terminal formation is a complex process that requires assembly of proteins responsible for synaptic transmission at sites of axo-dendritic contact. Accumulation of presynaptic proteins at developing terminals is facilitated by glutamate receptor activation. Glutamate is loaded into synaptic vesicles for release via the vesicular glutamate transporters VGLUT1 and VGLUT2. During postnatal development there is a switch from predominantly VGLUT2 expression to high VGLUT1 and low VGLUT2, raising the question of whether the developmental increase in VGLUT1 is important for presynaptic development. Here, we addressed this question using confocal microscopy and quantitative immunocytochemistry in primary cultures of rat neocortical neurons. First, in order to understand the extent to which the developmental switch from VGLUT2 to VGLUT1 occurs through an increase in VGLUT1 at individual presynaptic terminals or through addition of VGLUT1-positive presynaptic terminals, we examined the spatio-temporal dynamics of VGLUT1 and VGLUT2 expression. Between 5 and 12 days in culture, the percentage of presynaptic terminals that expressed VGLUT1 increased during synapse formation, as did expression of VGLUT1 at individual terminals. A subset of VGLUT1-positive terminals also expressed VGLUT2, which decreased at these terminals. At individual terminals, the increase in VGLUT1 correlated with greater accumulation of other synaptic vesicle proteins, such as synapsin and synaptophysin. When the developmental increase in VGLUT1 was prevented using VGLUT1-shRNA, the density of presynaptic terminals and accumulation of synapsin and synaptophysin at terminals were decreased. Since VGLUT1 knock-down was limited to a small number of neurons, the observed effects were cell-autonomous and independent of changes in overall network activity. These results demonstrate that up-regulation of VGLUT1 is important for development of presynaptic terminals in the cortex.


The 1980 and 1984 U.S. elections and the New Deal. An alternative interpretation.
This article has three sections. The first discusses the hegemonic interpretations of the 1980 and 1984 U.S. elections that are being reproduced on both sides of the political spectrum and that are presented as justification of current federal health and social policies. This section presents evidence that questions those hegemonic interpretations. Section II presents an alternative explanation of current political realities rooted in the class practices of the current federal administration and the Republican Party and in the abandonment by the opposition party--the Democratic Party--of the class practices of the New Deal. It discusses the reasons for that situation and analyzes its consequence for social policy. Section III presents evidence that questions the ideological arguments that are put forward by the Right (and are uncritically accepted by large sectors of the Left) and that sustain current federal economic and social policies. This section concludes with a discussion of alternative policies, stressing the need to rediscover class practices and its implication in health and social policy.


Hyperreactivity of coronary vasculature in platelet-perfused hearts from diabetic rats.
Coronary vascular responsiveness to platelet-produced eicosanoids was examined in isolated perfused hearts of alloxan-diabetic rats. Coronary perfusion pressure was increased in isolated hearts of control and diabetic rats on perfusion with platelets and arachidonic acid (AA). However, the increase in perfusion pressure was approximately twofold higher in hearts of diabetic rats when compared with those isolated from control rats. This was associated with increased thromboxane B2 (TxB2) and prostaglandin F2 alpha (PGF2 alpha) production that was comparable in platelet-perfused hearts of control and diabetic animals. Ibuprofen, a cyclooxygenase inhibitor, blocked the increase in perfusion pressure and TxB2 and PGF2 alpha production by greater than 90% in both control and diabetic hearts perfused with platelets and AA. Dazoxiben, a thromboxane synthetase inhibitor, blocked the increase in perfusion pressure by 50%, totally inhibited TxB2 production, but increased PGF2 alpha production by 60% in both groups of platelet-perfused hearts. Increased levels of PGF2 alpha and possibly other constrictor eicosanoids (e.g., leukotriene D4) may account for the partial constriction observed in platelet-perfused hearts with dazoxiben. Results of the present study suggest that vascular reactivity to vasoconstrictor eicosanoids is increased in hearts of diabetic animals.


Primary Thromboprophylaxis in Pancreatic Cancer Patients: Why Clinical Practice Guidelines Should Be Implemented.
Exocrine pancreatic ductal adenocarcinoma, simply referred to as pancreatic cancer (PC) has the worst prognosis of any malignancy. Despite recent advances in the use of adjuvant chemotherapy in PC, the prognosis remains poor, with fewer than 8% of patients being alive at 5 years after diagnosis. The prevalence of PC has steadily increased over the past decades, and it is projected to become the second-leading cause of cancer-related death by 2030. In this context, optimizing and integrating supportive care is important to improve quality of life and survival. Venous thromboembolism (VTE) is a common but preventable complication in PC patients. VTE occurs in one out of five PC patients and is associated with significantly reduced progression-free survival and overall survival. The appropriate use of primary thromboprophylaxis can drastically and safely reduce the rates of VTE in PC patients as shown from subgroup analysis of non-PC targeted placebo-controlled randomized trials of cancer patients and from two dedicated controlled randomized trials in locally advanced PC patients receiving chemotherapy. Therefore, primary thromboprophylaxis with a Grade 1B evidence level is recommended in locally advanced PC patients receiving chemotherapy by the International Initiative on Cancer and Thrombosis clinical practice guidelines since 2013. However, its use and potential significant clinical benefit continues to be underrecognized worldwide. This narrative review aims to summarize the main recent advances in the field including on the use of individualized risk assessment models to stratify the risk of VTE in each patient with individual available treatment options.


Patient expectations for recovery after elective surgery: a common-sense model approach.
Patient perceptions of the causes of preoperative symptoms, expected impact of surgery on symptoms and anticipated timeline of recovery are likely to affect the risk of readmission following elective surgical procedures. However, these perceptions have not been studied. A qualitative study was designed to explore these perceptions, using the common-sense model of self-regulation (CSM) as the conceptual framework. CSM is grounded in illness representations, describing how patients make sense of changes in physical well-being (e.g. symptoms) and develop and assess management plans. It also establishes a broader framework for examining patients' a priori expectations and timelines for outcomes based on comparisons to prior experiences and underlying self-prototypes, or "Self as Anchor". A convenience sample of 14 patients aged 56-81 who underwent elective surgery was recruited. Semi-structured interviews informed by the CSM were completed on the day of discharge. Content analysis with deductive coding was used, and emerging themes were fit to components of the CSM, including the five domains of Illness Representations-identity, cause, timeline, control, and consequences. Two additional themes, outlook (toward the health care system, providers and recovery efforts), and motivation (external or internal for recovering), relate to self-prototypes, expectations for outcomes, and search for coherence. Misattribution of symptoms, unrealistic expectations for outcomes (e.g. expecting complete resolution of symptoms unrelated to the surgical procedure) and timelines for recovery (unrealistically short), and the (baseline) "normal healthy self" as distinct from the (temporarily) "sick self" were recurrent themes. Findings suggest that patient perceptions and the actual recovery process may be misaligned. The results underscore the importance of assessing patients' perceptions and expectations, actively engaging patients in their own healthcare, and providing adequate support during the transition to home.


Effect of soil texture on surfactant-based remediation of hydrophobic organic-contaminated soil.
Surfactants may be used in remediation of subsoil and aquifer contaminated with hydrophobic compounds. The objectives of this study were to examine the effect of soil texture on hydrophobic organic contaminant (HOC; toluene, or 1,2,4-trichlorobenzene [TCB]) removal from six soils and to evaluate the optimal composition of soil texture for maximum HOC removal using aqueous surfactant solution. Selected surfactants were 4% (vol/vol) sodium diphenyl oxide disulfonate (DOSL) and 4% (wt/vol) sodium lauryl sulfate (LS). Toluene and TCB were selected as the lighter-than-water nonaqueous phase liquid (LNAPL) and denser-than-water nonaqueous phase liquid (DNAPL) model substances, respectively. Soil types used for this study were Ottawa sand and five Iowa soils (Fruitfield, Keomah, Crippin, Webster, and Galvar). The greatest recovery of toluene and TCB in batch tests was 73% and 84%, respectively, which was obtained with DOSL surfactant in Ottawa sand. The toluene removal of 95% in column tests has been achieved in the Ottawa sand and three Iowa soils (Fruitfield, Keomah, Crippin) with DOSL after effluent volume of 3750 ml (about 32 pore volume) passed. TCB removal of 98% in column tests has been achieved in Ottawa sand and three Iowa soils (Fruitfield, Keomah, Crippin) with DOSL after effluent volume of 2500 ml (about 21 pore volume) passed. These results were related with soil texture (clay content 30%), clay mineralogy (kaolinite and smectite), as a function of transported pore volume.


Thoracic reconstruction with the omentum: indications, complications, and results.
This study provides a retrospective analysis of 60 patients who underwent thoracic reconstruction with the omentum. Patients were identified by searching several databases to determine demographics, indications for surgery, operative technique, and postoperative course, including donor and recipient site morbidity. From January 1975 to May 2000, the authors harvested and transferred the omentum successfully (57 pedicled, 3 free) in 60 patients (mean age, 60 years; age range, 21-86 years) for sternal wound infections (N = 34), chest wall resections (N = 17), pectus deformities (N = 2), intrathoracic defects (N = 4), and breast reconstruction (N = 3). The omentum was used as a primary flap in 39 patients and as a salvage flap in 21 patients. Average operative time was 3.9 hours and average hospital stay was 34.3 days. Partial flap loss occurred in 7 patients, with no total flap failures. Morbidity included six abdominal wound infections and seven epigastric hernias. Mortality was 11.7%. The omentum can be harvested safely and used reliably to reconstruct varying thoracic wounds and defects. Specific indications from this series include osteoradionecrosis, chest wall tumors, massive sternal wounds, and refractory mediastinitis. Hultman CS, Culbertson JH, Jones GE, et al. Thoracic reconstruction with the omentum: indications, complications, and results.


Seasonal and interannual variability of climate and vegetation indices across the Amazon.
Drought exerts a strong influence on tropical forest metabolism, carbon stocks, and ultimately the flux of carbon to the atmosphere. Satellite-based studies have suggested that Amazon forests green up during droughts because of increased sunlight, whereas field studies have reported increased tree mortality during severe droughts. In an effort to reconcile these apparently conflicting findings, we conducted an analysis of climate data, field measurements, and improved satellite-based measures of forest photosynthetic activity. Wet-season precipitation and plant-available water (PAW) decreased over the Amazon Basin from 1996-2005, and photosynthetically active radiation (PAR) and air dryness (expressed as vapor pressure deficit, VPD) increased from 2002-2005. Using improved enhanced vegetation index (EVI) measurements (2000-2008), we show that gross primary productivity (expressed as EVI) declined with VPD and PAW in regions of sparse canopy cover across a wide range of environments for each year of the study. In densely forested areas, no climatic variable adequately explained the Basin-wide interannual variability of EVI. Based on a site-specific study, we show that monthly EVI was relatively insensitive to leaf area index (LAI) but correlated positively with leaf flushing and PAR measured in the field. These findings suggest that production of new leaves, even when unaccompanied by associated changes in LAI, could play an important role in Basin-wide interannual EVI variability. Because EVI variability was greatest in regions of lower PAW, we hypothesize that drought could increase EVI by synchronizing leaf flushing via its effects on leaf bud development.


[THE DEVELOPMENT OF MOBILE APPLICATION OF PATIENT FOR IMPLEMENTATION OF REMOTE MONITORING].
The article considers issues of necessity of development and implementation of mobile application of patient within the framework of automated system of remote monitoring of human health indicators as a mean of increasing quality of medical care of patients.


The alteration of apoptosis-related genes in female pelvic supportive tissues with regard to menopausal status.
We aimed to compare the expression levels of anti-apoptotic and proapoptotic genes in the parametrium, sacrouterine and round ligaments with respect to menopausal status in women presenting without any indication of pelvic organ prolapse (POP). We hypothesized that apoptosis related gene expressions in female pelvic tissues may be altered during menopause. The study groups consisted of pre-menopausal (n = 10) and menopausal (n = 10) females who did not have POP symptoms. Three different types of tissue samples (Parametrium, Round Ligament and Sacrouterine Ligament) were obtained and RNA was isolated from these tissues. After purifying and quantifying RNA samples, qPCR was used to determine the expression levels of anti-apoptotic and pro-apoptotic genes. BCL-2 gene expression levels were significantly lower in all the tissues of menopausal patients compared to those of premenopausal patients. In comparison to premenopausal patients, the sacrouterine ligament tissue BAD expression level was significantly high (p = 0.035), and the BCL-2/BAD ratio was significantly lower in menopausal patients (p = 0.006). Apoptosis-related protein levels change during menopause; pro-apoptotic gene expressions decrease and anti-apoptotic gene expressions increase. The significant alteration of BCL-2 and BAD expression in sacrouterine ligament with respect to menopausal status was observed and this suggested that when compared to other pelvic tissues, the sacrouterine ligament, which plays a crucial role for genital organs in restoring normal pelvic anatomy and providing support, could be affected more by menopause.


Sequence haplotypes revealed by sequence-tagged site fine mapping of the Ror1 gene in the centromeric region of barley chromosome 1H.
We describe the development of polymerase chain reaction-based, sequence-tagged site (STS) markers for fine mapping of the barley (Hordeum vulgare) Ror1 gene required for broad-spectrum resistance to powdery mildew (Blumeria graminis f. sp. hordei). After locating Ror1 to the centromeric region of barley chromosome 1H using a combined amplified fragment length polymorphism/restriction fragment-length polymorphism (RFLP) approach, sequences of RFLP probes from this chromosome region of barley and corresponding genome regions from the related grass species oat (Avena spp.), wheat, and Triticum monococcum were used to develop STS markers. Primers based on the RFLP probe sequences were used to polymerase chain reaction-amplify and directly sequence homologous DNA stretches from each of four parents that were used for mapping. Over 28,000 bp from 22 markers were compared. In addition to one insertion/deletion of at least 2.0 kb, 79 small unique sequence polymorphisms were observed, including 65 single nucleotide substitutions, two dinucleotide substitutions, 11 insertion/deletions, and one 5-bp/10-bp exchange. The frequency of polymorphism between any two barley lines ranged from 0.9 to 3.0 kb, and was greatest for comparisons involving an Ethiopian landrace. Haplotype structure was observed in the marker sequences over distances of several hundred basepairs. Polymorphisms in 16 STSs were used to generate genetic markers, scored by restriction enzyme digestion or by direct sequencing. Over 2,300 segregants from three populations were used in Ror1 linkage analysis, mapping Ror1 to a 0.2- to 0.5-cM marker interval. We discuss the implications of sequence haplotypes and STS markers for the generation of high-density maps in cereals.


Breast Cancer Early Detection: An Academic-Community Partnership in the Philippines.
A high proportion of patients with breast cancer in the Philippines present at an advanced stage and have a rapid, unfavorable outcome. Providing breast cancer education and early detection to this population is important to help reduce this health disparity. This article describes the impact of a train-the-trainer program, with mission groups traveling to the Philippines to promote female residents' breast cancer awareness, knowledge, and intent for future screening.


Dimethyl sulphoxide reduction with reduced sulphur compounds as electron donors by anoxygenic phototrophic bacteria.
The marine purple non-sulphur bacterium Rhodovulum euryhalinum strain DSM 4868 reduced dimethyl sulphoxide (DMSO) to dimethyl sulphide (DMS) chemotrophically with sulphide as electron donor. The oxidation of sulphide was correlated with the formation of polysulphides. R. euryhalinum reduced DMSO phototrophically with sulphide as well, but the amount of DMSO reduced in relation to sulphide oxidized was lower. The marine green sulphur bacterium Chlorobium vibrioforme strain DSM 8327 reduced DMSO to DMS phototrophically with sulphide and thiosulphate as electron donors. The extent of DMSO reduction was much less in the dark. Eight strains of purple sulphur bacteria - marine, brackish water and freshwater isolates - and another marine green sulphur bacterium showed a very weak capacity for DMSO reduction with sulphide or thiosulphate as electron donors in the light and dark, respectively.


Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice.
Increasing evidence point to the relevance of intestinal disfunction and changes in the microbiome composition during chronic liver disease. More specifically, recent studies have highlighted that cholestatic diseases associate with a reduction in the microbiome diversity in patients. Still, the dynamics of the changes in the microbiome composition observed, as well as their implication in contributing to the pathogenesis of this disease remain largely undefined. Hence, experimental mouse models resembling the human pathogenesis are crucial to move forward our understanding on the mechanisms underpinning cholestatic disease and to enable the development of effective therapeutics. Our results show that the bile duct ligation (BDL) experimental model of cholestasis leads to rapid and significant changes in the microbiome diversity, with more than 100 OTUs being significantly different in faecal samples obtained from WT mice at 3 days and 7 days after BDL when compared to control animals. Changes in the microbial composition in mice after BDL included the enrichment of Akkermansia, Prevotella, Bacteroides and unclassified Ruminococcaceae in parallel with a drastic reduction of the presence of Faecalibacterium prausnitzii. In conclusion, our results support that bile duct ligation induces changes in the microbiome that partly resemble the gut microbial changes observed during human cholestatic disease.


[Colonoscopy, the primary tool for colonic screening].
Through an overview of the colonic screening methods, the authors study colonoscopy with high emphasis. Taking into consideration its high sensitivity and specificity in the detection of colorectal carcinomas and adenomas, as well as the possibility of adenoma removal through examination, colonoscopy is recommended to be applied as the primary colonic screening within the scope of a national screening program.


Covalent linkage of nanodiamond-paclitaxel for drug delivery and cancer therapy.
A nanoparticle-conjugated cancer drug provides a novel strategy for cancer therapy. In this study, we manipulated nanodiamond (ND), a carbon nanomaterial, to covalently link paclitaxel for cancer drug delivery and therapy. Paclitaxel was bound to the surface of 3-5 nm sized ND through a succession of chemical modifications. The ND-paclitaxel conjugation was measured by atomic force microscope and nuclear magnetic resonance spectroscopy, and confirmed with infrared spectroscopy by the detection of deuterated paclitaxel. Treatment with 0.1-50 microg ml(-1) ND-paclitaxel for 48 h significantly reduced the cell viability in the A549 human lung carcinoma cells. ND-paclitaxel induced both mitotic arrest and apoptosis in A549 cells. However, ND alone or denatured ND-paclitaxel (after treatment with strong alkaline solution, 1 M NaOH) did not induce the damage effects on A549 cells. ND-paclitaxel was taken into lung cancer cells in a concentration-dependent manner using flow cytometer analysis. The ND-paclitaxel particles were located in the microtubules and cytoplasm of A549 cells observed by confocal microscopy. Furthermore, ND-paclitaxel markedly blocked the tumor growth and formation of lung cancer cells in xenograft SCID mice. Together, we provide a functional covalent conjugation of ND-paclitaxel, which can be delivered into lung carcinoma cells and preserves the anticancer activities on the induction of mitotic blockage, apoptosis and anti-tumorigenesis.


COVID-19-Related Knowledge and Practices of Cancer Patients and Their Anxiety and Depression During the Early Surge Phase of the Pandemic: A Cross-sectional Online Survey.
We aimed to investigate the coronavirus disease 2019 (COVID-19)-related knowledge and practices of cancer patients and to assess their anxiety- and depression-related to COVID-19 during the early surge phase of the pandemic. An online questionnaire survey of cancer patients was conducted from February 10-29, 2020. Knowledge and practices related to COVID-19 were assessed using a custom-made questionnaire. The Hospital Anxiety and Depression Scale was used to assess the presence of anxiety and depression, with scores beyond 7 indicating anxiety or depressive disorder. Univariate and multiple linear regression analyses were used to identify the high-risk groups according to the level of knowledge, practices, anxiety, and depression scores. A total of 341 patients were included. The rate of lower level of knowledge and practices was 49.9% and 18.8%, respectively. Education level of junior high school degree or lower showed a significant association with lower knowledge score (β: -3.503; P < 0.001) and lower practices score (β: -2.210; P < 0.001) compared to the education level of college degree and above. The prevalence of anxiety and depression among the respondents was 17.6% and 23.2%, respectively. A higher depression score was associated with older age, marital status of the widowed, and lower level of education, knowledge score, and practices score (P < 0.05). Targeted COVID-19-related education interventions are required for cancer patients with a lower level of knowledge to help improve their practices. Interventions are also required to address the anxiety and depression of cancer patients.


Chemical sensing by nonequilibrium cooperative receptors.
Cooperativity arising from local interactions in equilibrium receptor systems provides gain, but does not increase sensory performance, as measured by the signal-to-noise ratio (SNR) due to a fundamental tradeoff between gain and intrinsic noise. Here we allow sensing to be a nonequilibrium process and show that energy dissipation cannot circumvent the fundamental tradeoff, so that the SNR is still optimal for independent receptors. For systems requiring high gain, nonequilibrium 2D-coupled receptors maximize the SNR, revealing a new design principle for biological sensors.


An ecological analysis of child sexual abuse disclosure: considerations for child and adolescent mental health.
Research continues to indicate a concerning number of children and youth, between 60-80%, withhold disclosure until adulthood suggesting that many children endure prolonged victimization or never receive necessary intervention. The study aim was to qualitatively identify factors that impede or promote child sexual abuse (CSA) disclosure. Using a phenomenological design, forty adult survivors of CSA were interviewed about their disclosure experiences to provide retrospective accounts of their childhood and adolescent abuse experiences, disclosure attempts, and meaning-making of these experiences. Findings show that disclosure is multiply determined by a complex interplay of factors related to child characteristics, family environment, community influences, and cultural and societal attitudes. An ecological analysis is offered to understand these complexities. Unless barriers to disclosure are eradicated, negative effects of CSA can persist manifesting in serious mental health issues. Practitioners can expect to work with children, adolescents and adults who have withheld disclosure or attempted to tell over time having experienced a wide range of responses. Multi-level intervention is recommended at the individual, community and macro-levels. Future investigations should focus on how to identify and measure the impact of community and macro level factors on disclosure, aspects that have received much less attention.


Effect of sulfate on methanogenic communities that degrade unsaturated and saturated long-chain fatty acids (LCFA).
Anaerobic bacteria involved in the degradation of long-chain fatty acids (LCFA), in the presence of sulfate as electron acceptor, were studied by combined cultivation-dependent and molecular techniques. The bacterial diversity in four mesophilic sulfate-reducing enrichment cultures, growing on oleate (C(18:1), unsaturated LCFA) or palmitate (C(16:0), saturated LCFA), was studied by denaturing gradient gel electrophoresis (DGGE) profiling of polymerase chain reaction (PCR)-amplified 16S rRNA gene fragments. These enrichment cultures were started using methanogenic inocula in order to assess the competition between methanogenic communities and sulfate-reducing bacteria. Phylogenetic affiliation of rRNA gene sequences corresponding to predominant DGGE bands demonstrated that members of the Syntrophomonadaceae, together with sulfate reducers mainly belonging to the Desulfovibrionales and Syntrophobacteraceae groups, were present in the sulfate-reducing enrichment cultures. Subculturing of LCFA-degrading methanogenic cultures in the presence of sulfate resulted in the inhibition of methanogenesis and, after several transfers, archaea could no longer be detected by real-time PCR. Competition for hydrogen and acetate was therefore won by sulfate reducers, but acetogenic syntrophic bacteria were the only known LCFA-degrading organisms present after subculturing with sulfate. Principal component analysis of the DGGE profiles from methanogenic and sulfate-reducing oleate- and palmitate-enrichment cultures showed a greater influence of the substrate than the presence or absence of sulfate, indicating that the bacterial communities degrading LCFA in the absence/presence of sulfate are rather stable.


[Hypotensive and anti-ischemic efficiency of estulic in course treatment of myocardial infarction complicated by essential hypertension].
To assess hypotensive and antiischemic activity of estulik (Sandos, Switzerland) in patients with myocardial infarction (MI) complicated by essential hypertension (EH). 23 MI patients with moderate EH (diastolic blood pressure up to 110 mm Hg) and 25 patients with manifest EH (diastolic blood pressure 115-120 mm Hg) of group 1 and 2, respectively, have received single doses and a 10-day course of estulik in a dose 0.5-1.0 mg/day. Hemodynamic and antiischemic activities were evaluated at echocardiography, coupled veloergometry, Holter monitoring, myocardial scintigraphy, polarography. In 31% of the patients selective coronarography was made. Clinical condition and hemodynamics of group 1 patients have improved by 30-40%, microcirculation has improved by 25-35%. In group 2 patients the drug was found ineffective. Estulik is a drug of choice in moderate EH with manifest angina pectoris.


Genetic risk factors for colorectal cancer in multiethnic Indonesians.
Colorectal cancer is a common cancer in Indonesia, yet it has been understudied in this resource-constrained setting. We conducted a genome-wide association study focused on evaluation and preliminary discovery of colorectal cancer risk factors in Indonesians. We administered detailed questionnaires and collecting blood samples from 162 colorectal cancer cases throughout Makassar, Indonesia. We also established a control set of 193 healthy individuals frequency matched by age, sex, and ethnicity. A genome-wide association analysis was performed on 84 cases and 89 controls passing quality control. We evaluated known colorectal cancer genetic variants using logistic regression and established a genome-wide polygenic risk model using a Bayesian variable selection technique. We replicate associations for rs9497673, rs6936461 and rs7758229 on chromosome 6; rs11255841 on chromosome 10; and rs4779584, rs11632715, and rs73376930 on chromosome 15. Polygenic modeling identified 10 SNP associated with colorectal cancer risk. This work helps characterize the relationship between variants in the SCL22A3, SCG5, GREM1, and STXBP5-AS1 genes and colorectal cancer in a diverse Indonesian population. With further biobanking and international research collaborations, variants specific to colorectal cancer risk in Indonesians will be identified.


[Notifiable and non-notifiable infectious diseases in the federal republic of germany (author's transl)].
Owing to the growing density of population, urbanization, and the use of all kinds of publicly accessible facilities, the interruption of the infection chain for air-borne diseases proves particularly inadequate if no efficient prophylactic inoculations are available to combat viral infections or if no efficient chemotherapeutical measures can be adopted against bacterial infections. Equally problematic is the struggle against salmonellosis associated with the mechanized mass production and distribution of foodstuffs as well as the forms of infectious hospitalism, especially hepatitis B, which are favoured by the technical advances in the medical field. Venereal diseases prove highly resistant because the human patterns of sexual behaviour are difficult to influence. Thus the infectious diseases caused by deficient hygiene have virtually disappeared in our country, while those diseases survive or occur which are capable of profiting from the sociological changes and the technical progress of civilisation. On the whole, the mortality rate has drastically dropped while morbidity has remained more or less the same (with, however, a change in the spectrum of the infectious diseases); this is due mainly to mass inoculation and specific therapy.


Study protocol for a process evaluation of a cluster randomised controlled trial to reduce potentially inappropriate prescribing and polypharmacy in patients with multimorbidity in Irish primary care (SPPiRE).
Background: Multimorbidity (the presence of two or more chronic conditions) is associated with poorer health outcomes, particularly for patients with significant polypharmacy (≥15 medications), due to the higher risk of adverse events and drug interactions. The SPPiRE study will assess the effectiveness of a complex intervention to support general practitioners (GPs) to reduce potentially inappropriate prescribing and consider deprescribing in older people with multimorbidity and significant polypharmacy. The aim of the SPPiRE process evaluation is to understand how and why the intervention is effective or ineffective and to explore the potential for system wide implementation of the intervention using the Medical Research Council general themes of context, implementation and mechanism of impact. Methods: The SPPiRE study is a clustered randomised controlled trial (RCT), aiming to recruit 55 general practices and 400 patients (≥65 years) on ≥15 medications throughout the Republic of Ireland. This mixed-methods process evaluation of the SPPiRE study will integrate both quantitative and qualitative data. Quantitative data will be collected on use of the intervention elements and from GP questionnaires. Qualitative data will be collected from semi-structured telephone interviews with all intervention GPs and a purposeful sample of patients from intervention practices. The topic guide will explore barriers and facilitators to participation and implementation of the intervention. Quantitative data will be analysed using descriptive statistics. Interviews will be transcribed and analysed using thematic analysis. Quantitative and qualitative data will be then be integrated. Discussion: The SPPiRE cluster RCT will provide evidence regarding the effectiveness and practicability of delivering a structured medication review in reducing polypharmacy and potentially inappropriate prescribing for patients with multimorbidity. This process evaluation will provide information on how the intervention was implemented, how it was or was not effective and the potential for a system wide implementation. Trial registration: ISRCTN 12752680, registration: 20/10/2016.


Randomized, Double-Blind, Placebo-Controlled Acute Comparator Trials of Lisdexamfetamine and Extended-Release Methylphenidate in Adolescents With Attention-Deficit/Hyperactivity Disorder.
Psychostimulants are considered first-line pharmacotherapy for youth with attention-deficit/hyperactivity disorder (ADHD), but questions remain regarding the comparative efficacy of amphetamine- and methylphenidate-based agents. Our objective was to describe two acute randomized, double-blind, placebo-controlled, head-to-head studies of lisdexamfetamine dimesylate (LDX) and osmotic-release oral system methylphenidate (OROS-MPH) in adolescents with ADHD. Adolescents (13-17 years) diagnosed with ADHD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria were enrolled in an 8-week flexible-dose study [LDX 30-70 mg/day (n = 186 randomized); OROS-MPH 18-72 mg/day (n = 185 randomized); placebo (n = 93 randomized)] or a 6-week forced-dose study [LDX 70 mg/day (n = 219 randomized); OROS-MPH 72 mg/day (n = 220 randomized); placebo (n = 110 randomized)]. Attention-Deficit/Hyperactivity Disorder Rating Scale IV (ADHD-RS-IV) total score changes from baseline (primary endpoint) at week 8 (flexible-dose study) or week 6 (forced-dose study) were assessed with mixed-effects models for repeated measures. Secondary endpoints included improvement on the dichotomized Clinical Global Impressions-Improvement scale (CGI-I; key secondary endpoint) and changes from baseline on the ADHD-RS-IV subscales. Safety assessments included treatment-emergent adverse events (TEAEs) and vital signs. Least squares (LS) mean ± standard error of the mean (SEM) ADHD-RS-IV total score changes from baseline to end of treatment were -17.0 ± 1.03 with placebo, -25.4 ± 0.74 with LDX, and -22.1 ± 0.73 with OROS-MPH in the forced-dose study and -13.4 ± 1.19 with placebo, -25.6 ± 0.82 with LDX, and -23.5 ± 0.80 with OROS-MPH in the flexible-dose study. LS mean ± SEM treatment difference for the change from baseline significantly favored LDX over OROS-MPH in the forced-dose [-3.4 ± 1.04, p = 0.0013, effect size (ES) -0.33] but not the flexible-dose (-2.1 ± 1.15, p = 0.0717, ES -0.20) study. The percentage of improved participants on the dichotomized CGI-I at end of treatment was significantly greater with LDX than with OROS-MPH in the forced-dose study (81.4 vs. 71.3%, p = 0.0188) but not the flexible-dose study (LDX 83.1%, OROS-MPH 81.0%, p = 0.6165). The LS mean ± SEM treatment differences for change from baseline on the ADHD-RS-IV hyperactivity/impulsivity and inattentiveness subscales nominally favored LDX in the forced-dose study (hyperactivity/impulsivity subscale -1.3 ± 0.49, nominal p = 0.0081, ES -0.27; inattentiveness subscale -2.0 ± 0.63, nominal p = 0.0013, ES -0.33), but there were no significant differences between active treatments in the flexible-dose study. In both studies, LDX and OROS-MPH were superior to placebo for all efficacy-related endpoints (all nominal p < 0.0001; ES range -0.43 to -1.16). The overall frequency of TEAEs for LDX and OROS-MPH, respectively, were 66.5 and 58.9% in the forced-dose study and 83.2 and 82.1% in the flexible-dose study. TEAEs occurring in ≥ 5% of participants that were also reported at two or more times the rate of placebo were decreased appetite, decreased weight, insomnia, initial insomnia, dry mouth, and nasopharyngitis (LDX and OROS-MPH), irritability and dizziness (LDX only), and increased heart rate (OROS-MPH only) in the forced-dose study and decreased appetite, decreased weight, insomnia, and dizziness (LDX and OROS-MPH) and dry mouth and upper abdominal pain (LDX only) in the flexible-dose study. Mean ± standard deviation (SD) increases from baseline in vital signs (systolic and diastolic blood pressure, pulse) were observed in the forced-dose study [LDX 1.6 ± 9.65 and 3.3 ± 8.11 mmHg, 6.7 ± 12.78 beats per minute (bpm); OROS-MPH 2.6 ± 10.15 and 3.3 ± 9.13 mmHg, 7.6 ± 12.47 bpm] and the flexible-dose study (LDX 2.4 ± 9.46 and 2.8 ± 8.41 mmHg, 4.7 ± 11.82 bpm; OROS-MPH 0.4 ± 9.90 and 2.2 ± 8.64 mmHg, 6.0 ± 10.52 bpm) at the last on-treatment assessment. LDX was superior to OROS-MPH in adolescents with ADHD in the forced-dose but not the flexible-dose study. Safety and tolerability for both medications was consistent with previous studies. These findings underscore the robust acute efficacy of both psychostimulant classes in treating adolescents with ADHD. CLINICALTRIALS. NCT01552915 and NCT01552902.


Development and implementation of nonpharmacologic protocols for the management of patients with Alzheimer's disease and their families in a multiracial primary care setting.
Most patients and families with dementia are cared for in primary care clinics. These clinics are seldom designed to provide the necessary comprehensive care. The purpose of this article is to describe nonpharmacologic protocols for the management of patients with Alzheimer's disease and their families that are administered as part of a multifaceted care-management intervention program in a multiracial primary care clinic. The nonpharmacologic component for the integrated program of collaborative care was developed based on a literature review and previous clinical experience. The care is coordinated by a geriatric nurse practitioner who meets with patients, families, and the primary care physicians. The nonpharmacologic protocols included general educational guidelines about Alzheimer's disease. Specific protocols to treat the common behavioral disturbances associated with Alzheimer's disease also were developed. A major component of the intervention is a monthly psychoeducational support group for caregivers. The intervention has been well accepted by patients, families, and physicians. Approximately one-half of the treatment group has participated in the support group regularly. The integration of behavioral interventions and team care within the primary care environment has been successful.


Use of sliding transphyseal flexible intramedullary nailing in pediatric osteogenesis imperfecta patients.
In our country, the sliding Flexible Intramedullary Nailing is used alone or in combination with Ilizarov frame in children with osteogenesis imperfecta. The study assesses the results of sliding intramedullary nailing in deformity correction in severe types of osteogenesis imperfecta. We retrospectively reviewed 17 consecutive cases (mean age 5.2 y.o.) of types III, IV and VII of osteogenesis imperfecta. In group I (9 patients) the transphyseal FIN was performed using titanium nails. Sliding flexible intramedullary nailing was associated with Ilizarov frame in group II in 8 children. Patients in group I had overall complication rate of 88.9%: proximal nail migration (3), early secondary torsional displacement (4), non-telescoping (12), angular deformity (2), delayed or non-union (2). The reoperation rate was 100%. In group II we observed complications in 6 patients: nail migration (2), bowing of femur (2), non-telescoping (3). The reoperation rate was 87.5%. Flexible intramedullary nailing allows realignment and good functional outcomes. Its major disadvantage is an important complication rate and related reoperation rate. The use of Ilizarov frame provides additional stability and allows early weight-bearing.


A matched-pair comparison of intensity-modulated radiation therapy with cetuximab versus intensity-modulated radiation therapy with platinum-based chemotherapy for locally advanced head neck cancer.
We retrospectively compared the efficacy of intensity-modulated radiotherapy (IMRT) and cetuximab (IMRT/cetuximab) versus IMRT and platinum-based chemotherapy (IMRT/platinum) for locally advanced head neck squamous cell carcinoma (LAHNSCC). Thirty-one IMRT/cetuximab patients were matched 1:2 with 62 IMRT/platinum patients according to primary site and clinical stage. The primary endpoint was locoregional recurrence (LRR), and secondary endpoints included distant metastasis (DM), cause-specific survival (CSS), and overall survival (OS). Because of inherent selection bias, the IMRT/cetuximab cohort was significantly older and with a higher Charlson Comorbidity Index. IMRT/cetuximab and IMRT/platinum did not have significantly different LRR and DM (33 vs. 23 % at 2 years, P = 0.22; 17 vs. 11 % at 2 years, P = 0.40; respectively). IMRT/cetuximab had significantly worse CSS and OS (67 vs. 84 %, P = 0.04; 58 vs. 83 %, P = 0.001; respectively). However, for the subset of elderly patients ≥65 years old, there is no difference between the two cohorts for all endpoints (all P = NS). IMRT/platinum should remain the preferred choice of chemoradiotherapy for LAHNSCC, but IMRT/cetuximab may be a reasonable alternative for elderly patients.