Chondroid chordomas and low-grade chondrosarcomas of the craniospinal axis. An immunohistochemical analysis of 17 cases.
The classification of cartilaginous neoplasms of the craniospinal axis is controversial. Indeed, the very existence of chondroid chordomas has recently been questioned. In an effort to clarify the direction of differentiation of cartilaginous neoplasms of this region, 17 neoplasms obtained from 17 patients with cartilaginous tumors of the craniospinal axis were examined by immunohistochemistry with a panel of antibodies. The panel included antibodies to cytokeratin (CK), epithelial membrane antigen (EMA), vimentin (VIM), S-100 protein, carcinoembryonic antigen (CEA), and type II collagen. Areas with cartilaginous differentiation were present in all 17 neoplasms. These areas were characterized by a matrix of amorphous blue ground substance with lacunae that contained enlarged and slightly atypical cells. This cartilaginous matrix stained strongly for type II collagen. Thirteen of the 17 neoplasms had a biphasic growth pattern in which areas with conventional chordoma were admixed with areas with cartilaginous differentiation. The cells within the cartilaginous components of these 13 neoplasms stained for CK (10 of 12 cases), EMA (10 of 13 cases), VIM (12 of 12 cases), S-100 protein (seven of 12 cases), and CEA (two of nine cases). Similarly, the conventional chordoma components of these same 13 neoplasms stained for CK (12 of 12 cases), EMA (13 of 13 cases), VIM (12 of 12 cases), S-100 protein (nine of 12 cases), and CEA (two of nine cases). The hyaline-appearing areas between the cords and sheets of cells of the conventional chordoma components of these 13 tumors also stained with type II collagen. These 13 tumors with both neoplastic cartilage and conventional chordoma were classified as chondroid chordomas. One of the 17 cases was composed entirely of neoplastic cartilage; however, the cells within the matrix of the cartilage of this neoplasm stained with the epithelial markers (CK and EMA). Based on the presence of epithelial differentiation within this otherwise cartilaginous neoplasm, it was also classified as a chondroid chordoma. In contrast, the remaining three cases without histologic evidence of chordoma differentiation did not stain for CK or EMA, but they did stain for S-100 protein (three of three cases) and VIM (three of three cases). These three tumors were therefore classified as chondrosarcomas. For purposes of comparison, 19 conventional chordomas without cartilage and 29 peripheral chondrosarcomas were also stained. The 19 conventional chordomas stained in a pattern similar to the conventional chordoma components of the chondroid chordomas, whereas the 29 peripheral chondrosarcomas stained in a pattern similar to the three chondrosarcomas of the craniospinal axis.(ABSTRACT TRUNCATED AT 400 WORDS)


1550-nm nonablative laser resurfacing for facial surgical scars.
To investigate the efficacy of 1550-nm (Fraxel SR1500 RE:Store; Solta Medical, Hayward, California) nonablative laser treatment of facial surgical scars. In this prospective clinical study, a volunteer sample of 13 adults with Fitzpatrick skin types I to III and facial surgical scars with a postoperative duration longer than 6 months were enrolled. Subjects were treated once every 4 weeks for a total of 4 treatments. Initial settings for the 1550-nm nonablative laser were at energy level 40 mJ and treatment level 4 and were subsequently increased on each visit according to the patients' tolerance level. Using a previously validated Patient and Observer Scar Assessment Scale (POSAS), the study subject and an independent evaluator completed assessments of the scar at each visit. According to the Friedman test on ratings across all occasions after the first treatment to the last evaluation, there was a statistically significant improvement in the patient's assessment of the color, stiffness, thickness, and irregularity of the scar but not for pain or itching. For the observer's ratings, there was a statistically significant improvement in pigmentation, thickness, relief, and pliability but not for vascularization. Preliminary data suggest improved aesthetic results, demonstrating the potential use of fractional photothermolysis as a scar revision technique. Future studies with a longer follow-up period could elucidate the role of fractional photothermolysis in more permanent scar improvements.


Linkage, clinical features, and prognosis of autosomal dominant polycystic kidney disease types 1 and 2.
Linkage analysis was performed on 49 Catalan families with autosomal dominant polycystic kidney disease obtained via the Nephrology Department and related nephrology centers. A total of 336 subjects, 267 at risk for the disease, were investigated using three microsatellites linked to polycystic kidney disease Type 1 (PKD1) and three microsatellites linked to PKD2. All of the subjects underwent physical and sonographic examination. The results demonstrate locus heterogeneity, with 0.85 as the maximum likelihood for the proportion of families linked to PKD1. All of the remaining families were found to be linked to PKD2. Analysis of clinical data in the PKD1 group (N = 146) versus the PKD2 group (N = 20) showed a milder form of the disease in the latter, with a later age at diagnosis (27.4 versus 41.4 yr, P = 0.0002), later age of onset of ESRD (53.4 versus 72.7 yr, P < 0.0001), later age of diagnosis of hypertension (34.8 versus 49.7 yr, P = 0.001) and lower prevalence of hypertension at younger ages. Sonographic findings did not differ significantly between both groups. Although anticipation was observed in both groups, it did not affect the majority of families. No signs of imprinting were found in this study, and the only gender effect was an earlier age of onset of ESRD in men than in women (49.5 versus 53.1 yr in PKD1, P < 0.01 and 70.57 versus 73.6 yr in PKD2, P = 0.1). Molecular analysis of autosomal-dominant polycystic kidney disease allows presymptomatic diagnosis in individuals younger than age 30, and helps in establishing prognosis.


A prospective study of maternal preference for indomethacin prophylaxis versus symptomatic treatment of a patent ductus arteriosus in preterm infants.
The management of a patent ductus arteriosus in preterm infants continues to be debated among neonatologists due to the absence of concrete evidence that precisely weighs the long term outcomes of active, early intervention against a conservative approach. In the majority of institutions, parents are encouraged to play an active role in the complex, decision -making processes with regard to the care of their infants. The objective of this study is to elicit maternal preferences for indomethacin prophylaxis versus treatment of a patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants, utilizing a decision aid instrument (DAI). Healthy and high risk pregnant women at 23-28 weeks gestation, and mothers of admitted ELBW infants were enrolled. A computer based, validated DAI was utilized during interviews. The DAI first provides information about prematurity and concurrent morbidities with comprehensive facts of the pros and cons about prophylactic versus treatment options. It subsequently coaches participants how to select values and preferences based on their decisions. A 17-item questionnaire assessed and valued each short and long term morbidity of extreme prematurity and preferred choice for PDA management. Two hundred ninety nine subjects were enrolled; 75% were healthy women at 23-28 weeks gestation, 19% were high risk and 6% recently delivered an ELBW infant. Eighty-two percent preferred a prophylactic indomethacin strategy versus symptomatic treatment for the management of PDA. Across a spectrum of potential morbidities, the occurrence of severe intraventricular hemorrhage was viewed by mothers as the most un-wanted outcome irrespective of the two proposed options. In contrast to neonatal practitioners, mothers who used this particular DAI strongly endorsed prophylactic indomethacin versus a treatment intervention for the management of PDA in preterm infants.


Patient dose, image quality and radiographic techniques for common X ray examinations in two Greek hospitals and comparison with European guidelines.
The radiographic technique factors and the quality of each radiographic image for three common examinations (chest PA, pelvis AP and lumbar spine LAT) were compared with the European criteria and entrance surface dose (ESD) was measured for each radiograph in two Greek hospitals. The measurements were carried out using calibrated LiF thermoluminescence dosemeters. The patients were selected so that their weight was close to 70 +/- 10 kg and their height to 170 +/- 10 cm. Effective dose values were calculated using a PC-based Monte Carlo program. All four X ray rooms in the survey achieved mean doses well below the European reference doses. However the mean doses in the X ray rooms differed by a factor of about 3.


Glycoconjugate profiles of the lancelet (Branchiostoma lanceolatum) ovary: a lectin histochemical study by laser confocal microscopy.
The presence and the distribution of carbohydrate moieties in ripe lancelet (Branchiostoma lanceolatum) oocytes (mean diameter 130 microm) was studied by lectin histochemistry in combination with enzyme and chemical treatments. Binding sites for eight lectins with specificities towards different glycan moieties were studied on sections of the whole body of mature female lancelets. Only three of the lectins tested reacted positively. Concanavalin-A (ConA)-binding glycoconjugates were localized in the cytoplasm, namely in yolk granules, whereas Artocarpus integrifolia (AIA) and Ricinus communis (RCA) agglutinins bound strongly to extracellular coats of the oocyte identified as the jelly coat and vitelline layer. No other tissues of the lancelet body were found to be positive to any lectin tested, except gut enterocytes which reacted strongly with AIA. Reactivity to ConA was abolished by pretreatment of sections with N-glycosidase F but not by mild alkaline hydrolysis, confirming that the glycoconjugates were of the N-linked type. On the contrary, chemical removal of O-linked chains by mild alkaline hydrolysis abolished AIA and RCA reactivity but had no effect on ConA positivity.


Partial rigid-body dynamics in NPT, NPAT and NPgammaT ensembles for proteins and membranes.
A partial rigid-body method of molecular dynamics simulations for proteins and membranes is presented. In this method, the symplectic integrator for rigid bodies is combined with the equations of motion for the NPT ensemble. The standard NPT ensemble is extended to the membrane-specific ensembles, the NPAT (constant normal pressure and lateral surface area of membranes and constant temperature) and NPgammaT (constant normal pressure and lateral surface tension of membranes and constant temperature) ensembles. By more than 30-ns simulations of aqueous proteins and hydrated lipid bilayers, the results of the partial rigid-body method demonstrated excellent conservation of total energy and consistent behavior with the traditional constraint method in terms of structural distribution and fluctuation of proteins and lipids. The efficient implementation of the partial rigid-body method in parallel computation is presented, which is shown to work well in large-scale molecular dynamics simulations.


Authors' response: the primacy of conscious decision making.
The target article sought to question the common belief that our decisions are often biased by unconscious influences. While many commentators offer additional support for this perspective, others question our theoretical assumptions, empirical evaluations, and methodological criteria. We rebut in particular the starting assumption that all decision making is unconscious, and that the onus should be on researchers to prove conscious influences. Further evidence is evaluated in relation to the core topics we reviewed (multiple-cue judgment, deliberation without attention, and decisions under uncertainty), as well as priming effects. We reiterate a key conclusion from the target article, namely, that it now seems to be generally accepted that awareness should be operationally defined as reportable knowledge, and that such knowledge can only be evaluated by careful and thorough probing. We call for future research to pay heed to the different ways in which awareness can intervene in decision making (as identified in our lens model analysis) and to employ suitable methodology in the assessment of awareness, including the requirements that awareness assessment must be reliable, relevant, immediate, and sensitive.


A double-blind phase II randomized controlled trial of an online cognitive bias modification for interpretation program with and without psychoeducation for people with chronic pain.
Cognitive bias modification for interpretation (CBM-I) is an effective intervention for anxiety, but there is only a single trial in people with chronic pain. The aim of this randomized controlled trial was to test CBM-I with and without psychoeducation for people with chronic pain. We randomized 288 participants to 4 groups comprising treatment (CBM-I vs placebo) with or without psychoeducation. One hundred and eighty-three participants (64%) completed 4, 15-minute training sessions over 2 weeks. The coprimary outcomes were pain interference and pain intensity. We also measured interpretation bias, fear of movement, catastrophizing, depression, anxiety, and stress. Participants with more psychopathology at baseline were more likely to dropout, as were those allocated to psychoeducation. Intention-to-treat analyses using linear mixed models regression were conducted. Training effects of CBM-I were found on interpretation bias, but not a near-transfer task. Cognitive bias modification of interpretation improved both primary outcomes compared with placebo. For pain interference, there was also a main effect favoring psychoeducation. The CBM-I group improved significantly more than placebo for fear of movement, but not catastrophizing, depression, or anxiety. Cognitive bias modification of interpretation reduced stress but only for those who also received psychoeducation. This trial shows that CBM-I has promise in the management of pain, but there was limited evidence that psychoeducation improved the efficacy of CBM-I. Cognitive bias modification of interpretation was administered entirely remotely and is highly scalable, but future research should focus on paradigms that lead to better engagement of people with chronic pain with CBM-I.


The right hemisphere is not unitary in its role in aphasia recovery.
Neurologists and aphasiologists have debated for over a century whether right hemisphere recruitment facilitates or impedes recovery from aphasia. Here we present a well-characterized patient with sequential left and right hemisphere strokes whose case substantially informs this debate. A 72-year-old woman with chronic nonfluent aphasia was enrolled in a trial of transcranial magnetic stimulation (TMS). She underwent 10 daily sessions of inhibitory TMS to the right pars triangularis. Brain activity was measured during picture naming using functional magnetic resonance imaging (fMRI) prior to TMS exposure and before and after TMS on the first day of treatment. Language and cognition were tested behaviorally three times prior to treatment, and at 2 and 6 months afterward. Inhibitory TMS to the right pars triangularis induced immediate improvement in naming, which was sustained 2 months later. fMRI confirmed a local reduction in activity at the TMS target, without expected increased activity in corresponding left hemisphere areas. Three months after TMS, the patient suffered a right hemisphere ischemic stroke, resulting in worsening of aphasia without other clinical deficits. Behavioral testing 3 months later confirmed that language function was impacted more than other cognitive domains. The paradoxical effects of inhibitory TMS and the stroke to the right hemisphere demonstrate that even within a single patient, involvement of some right hemisphere areas may support recovery, while others interfere. The behavioral evidence confirms that compensatory reorganization occurred within the right hemisphere after the original stroke. No support is found for interhemispheric inhibition, the theoretical framework on which most therapeutic brain stimulation protocols for aphasia are based.


Medicare claims analysis of agents used to manage dementia-related psychosis: a treatment pattern study.
Currently, no agents are approved in the USA to treat dementia-related psychosis. After failure of a nonpharmacologic approach to treatment, antipsychotics or divalproex is often prescribed. We characterized existing treatment patterns in patients with dementia-related psychosis. Medicare claims data from 2008 to 2016 were used to identify patients with dementia-related psychosis. The agents and associated dosages prescribed, time to first use, and patterns of use were evaluated for agents prescribed to treat dementia-related psychosis. In total, 49 509 patients were identified as having dementia-related psychosis. Over three-quarters (76.8%) received an antipsychotic or divalproex. The most prescribed first-line agents were quetiapine (30.5%), risperidone (19.5%), and divalproex (11.2%). More than 80% of patients received a low dose of an agent, and 65.5% switched or discontinued their first-line treatment during a mean follow-up period of 1.8 years. In the absence of US FDA-approved therapies to treat dementia-related psychosis, treatment after behavioral intervention involves frequent use of low-dose antipsychotics or divalproex. The high rate of treatment switching or discontinuation is consistent with current treatment guidelines and suggests a need for an improved, standardized pharmacological approach to treat dementia-related psychosis.


Individualism, acceptance and differentiation as attitude traits in the public's response to vaccination.
The attitude of the general public to vaccination was evaluated through a survey conducted on a representative sample of the Israeli population (n = 2,018), in which interviewees were requested to express their standpoints regarding five different vaccination programs. These included: pandemic influenza vaccination, seasonal influenza vaccination, travel vaccines, Human Papilloma Virus vaccine and childhood vaccinations. Analysis of the responses reveal three major attitude traits: a) acceptance, characterized by the opinion that targets should be vaccinated; b) individualism, characterized by the opinion that vaccination should be left to personal choice; and c) differentiation, characterized by the tendency to express different attitudes when addressing different vaccination programs. Interestingly, direct opposition to vaccination was found to be a minor attitude trait in this survey. Groups within the population could be defined according to their tendency to assume these different attitudes as Acceptors, Judicious-acceptors, Differentiators, Soft-individualists, and Hard-individualists. These groups expressed different standpoints on all five vaccination programs as well as on other health recommendations, such as screening for early detection of cancer. Attitude traits could be also correlated, to a certain extent, with actual compliance with vaccination programs. Interestingly, attitudes to vaccination were not correlated with social profiles related to income or education, although younger individuals exhibited higher degrees of individualism and differentiation. Taken together, all this is in accordance with the current social settings, underlining the individual's tendency for critical evaluation and self-stirring. This should be taken into consideration by health authorities involved in vaccination programs.


Socioeconomic differences in children's television viewing trajectory: A population-based prospective cohort study.
We aimed to evaluate the association between family socioeconomic status and repeatedly measured child television viewing time from early childhood to the school period. We analyzed data on 3,561 Dutch children from the Generation R Study, a population-based study in the Netherlands. Parent-reported television viewing time for children aged 2, 3, 4, 6 and 9 years were collected by questionnaires sent from April 2004 until January 2015. Odds ratios of watching television ≥1 hour/day at each age were calculated for children of mothers with low, mid-low, mid-high and high (reference group) education and children from low, middle and high (reference group) income households. A generalized logistic mixed model was used to assess the association between family socioeconomic status and child television viewing time trajectory. The percentage of children watching television ≥1 hour/day increased from age 2 to 9 years for all children (24.2%-85.0% for children of low-educated mothers; 4.7%-61.4% for children of high-educated mothers; 17.2%-74.9% for children from low income households; 6.2%-65.1% for children from high income households). Independent socioeconomic effect in child television viewing time was found for maternal educational level. The interaction between net household income and child age in longitudinal analyses was significant (p = 0.01), indicating that the television viewing time trajectories were different in household income subgroups. However the interaction between maternal educational level and child age was not significant (p = 0.19). Inverse socioeconomic gradients in child television viewing time were found from the preschool period to the late school period. The educational differences between the various educational subgroups remained stable with increasing age, but the differences between household income groups changed over time. Intervention developers and healthcare practitioners need to raise awareness among non-highly educated parents that the socioeconomic gradient in television viewing time has a tracking effect starting from preschool age.


Gender-specific correlates of sufficient physical activity among vulnerable children.
We aimed to identify the levels and types of physical activity (PA) by gender, and to determine correlates of sufficient PA on a theoretical basis of self-determination and social support; moreover, if significant correlates with sufficient PA would differ by gender among vulnerable children. Participants were 319 children enrolled in public welfare systems in Seoul, South Korea. Sufficient PA was defined as daily activity with moderate or vigorous intensity for 60 min. Self-determined motivation was assessed by autonomous and controlled forms; social support was assessed as two types: family and peer support. Questionnaires were self-reported by children and their parents. Of the participants, 20.4% achieved sufficient PA, specifically 15.0% for girls versus 27.3% for boys (P < .001). Girls were more likely to perform casual exercise types, while boys were more likely to perform sports types (P < .05 for all). The autonomous form of self-determined motivation, but not its controlled form, was significantly associated with sufficient PA in both girls (adjusted odds ratio [AOR] = 2.03, P = .028) and boys (AOR = 2.47, P = .007). Family support was not significantly associated in girls and boys; however, peer support was significantly associated only in boys (AOR = 3.72, P = .042). Of the children, girls were less likely to achieve sufficient PA and to perform sports than were boys. Self-determined motivation was a PA correlate uniformly in girls and boys; however, peer support was a PA correlate only in boys. Self-determined motivation-enhanced strategies should be integrated with peer support provided through gender-specific strategies when employing a PA intervention for vulnerable children.


Milk intake, height and body mass index in preschool children.
To evaluate links between the volume of milk consumed and weight and height status in children aged 4 and 5 years. We analysed data from 8950 children followed up as part of the Early Childhood Longitudinal Survey, Birth cohort, a nationally representative cohort of children. We used linear and logistic regression to assess associations of daily servings of milk intake at age 4 years with z-scores of body mass index (BMI), height and weight-for-height at 4 and 5 years, adjusted for sex, race/ethnicity, socioeconomic status and type of milk consumed. Among children who drank milk at age 4 years, higher milk consumption was associated with higher z-scores of BMI, height and weight-for-height at 4 years (all p<0.05). This corresponded to differences between children drinking <1 and ≥4 milk servings daily of approximately 1 cm in height and 0.15 kg in weight. By age 5 years, only the association with height remained significant (p<0.001). At 4 years, children drinking ≥3 servings of milk daily were more likely to be overweight/obese (BMI≥85th percentile) than those drinking 0.5-2 servings of milk daily (adjusted OR 1.16 (95% CI 1.02 to 1.32) p=0.02). In a cohort of children at age 4 years, the volume of milk consumed was associated with higher weight status and taller stature, while at 5 years, higher milk consumption continued to be associated with taller stature. Given higher odds of overweight/obesity with milk consumption ≥3 servings daily, this study supports current American Academy of Pediatrics recommendations that pre-school children consume two milk servings daily.


Unlocking sexual issues. Counseling strategies for nurses.
Providing truly holistic care means that nurses must recognize that their clients are sexual beings and that they often suffer from sexual concerns and problems related to their past history and their current medical problems. In addition to helping clients move toward physical wellness, nurses should intervene with intrapersonal and interpersonal problems affecting client's sexual feelings and behaviors.


Assessment of infertility surgery by a pelvic scoring system.
A pelvic scoring and staging system previously reported was used to evaluate 77 major microsurgical procedures during a 3-year period. Pregnancy rates by clinical assessment groups were (a) surgery indicated for tubo-ovarian adhesions (SGY:F) = 50%; (b) surgery indicated with other pelvic pathology, such as adnexal masses or myoma (SGY:F/etc) = 23%; and (c) surgery questionably indicated (SGY:?) = 18%. Using the scoring system, pregnancy rates by stage were 75%, 41%, and 14% for Stages I, II, and III, respectively. The pregnancy rate was higher in the pure tubal factor group as compared with those with additional infertility factors. Pelvic scores and stages correlated well with clinical expectations. Life-table analysis of cumulative pregnancy rates showed that all subsequent pregnancies occurred within the 24 months following surgery. A significant correlation noted between pelvic scores and cumulative pregnancy rates illustrates the system's usefulness in predicting reproductive potential postoperatively. This method can be used to assist the surgeon in establishing a couple's prognosis and to compare results between surgeons or different surgical techniques.


Review of Value of CT Texture Analysis and Machine Learning in Differentiating Fat-Poor Renal Angiomyolipoma from Renal Cell Carcinoma.
The diagnosis of patients with suspected angiomyolipoma relies on the detection of abundant macroscopic intralesional fat, which is always of no use to differentiate fat-poor angiomyolipoma (fp-AML) from renal cell carcinoma and diagnosis of fp-AML excessively depends on individual experience. Texture analysis was proven to be a potentially useful biomarker for distinguishing between benign and malignant tumors because of its capability of providing objective and quantitative assessment of lesions by analyzing features that are not visible to the human eye. This review aimed to summarize the literature on the use of texture analysis to diagnose patients with fat-poor angiomyolipoma vs those with renal cell carcinoma and to evaluate its current application, limitations, and future challenges in order to avoid unnecessary surgical resection.


Mechanism of silver sulfadiazine action on burn wound infections.
The role of silver and sulfadiazine in the mechanism of action of silver sulfadiazine on burn wound infections was investigated. Silver, but not sulfadiazine, was bound by bacteria. Sulfadiazine did not act as an antibacterial agent in low concentrations, but exhibited specific synergism in combination with subinhibitory levels of silver sulfadiazine. The efficacy of silver sulfadiazine is thought to result from its slow and steady reactions with serum and other sodium chloride-containing body fluids, which permits the slow and sustained delivery of silver ions into the wound environs. In this circumstance, a relatively minute amount of sulfadiazine appears active.


The combination of antitumor drugs, exemestane and erlotinib, induced resistance mechanism in H358 and A549 non-small cell lung cancer (NSCLC) cell lines.
Abstract Context: Estrogens in non-small-cell lung cancer (NSCLC) are important, and their interaction with epidermal growth factor receptor (EGFR) might be crucial. Objective: This study investigates the effect of exemestane, an aromatase inhibitor, and erlotinib, an EGFR inhibitor, on human NSCLC cell lines; H23, H358 and A549. Materials and methods: A cell proliferation assay was used for measuring cell number, apoptosis assay for detecting apoptosis and necrosis and immunoblotting for beclin-1 and Bcl-2 proteins detection. An immunofluorescence assay was used for EGFR localization. A migration assay and zymography were used for cell motility and metalloproteinases (MMPs) expression, respectively. Results: Exemestane, erlotinib or their combination decreased cell proliferation and increased apoptosis. Exemestane's half maximal inhibitory concentration (IC50) was 50 μM for H23 and H358 cells and 20 μM for A549. The IC50 of erlotinib was 25 μM for all cell lines. Apoptosis increase induced by exemestane was 58.0 (H23), 186.3 (H358) and 34.7% (A549) and by erlotinib was 16.7 (H23), 65.3 (H358) and 66.3% (A549). A synergy effect was observed only in H23 cells. Noteworthy, the combination of exemestane and erlotinib decreased beclin-1 protein levels (32.3 ± 19.2%), an indicator of autophagy, in H23 cells. The combination of exemestane and erlotinib partially reversed the EGFR translocation to mitochondria and decreased MMP levels and migration. Discussion and conclusions: The benefit from a dual targeting of aromatase and EGFR seems to be regulated by NSCLC cell content. The diverse responses of cells to agents might be influenced by the dominance of certain molecular pathways.


Mycophenolate mofetil therapy in frequently relapsing steroid-dependent and steroid-resistant nephrotic syndrome of childhood: current status and future directions.
Clinicians are often faced with therapeutic dilemmas and challenges while treating children with frequently relapsing steroid-dependent nephrotic syndrome (SDNS) and steroid-resistant nephrotic syndrome (SRNS). In the past, children with SDNS have been treated with long-term alternate day steroids cyclophosphamide, cyclosporine (CSA), chlorambucil, levamisole, and azathioprine. The essential aim of these therapies is to maintain remission while limiting exposure to steroids. These medications have variable efficacy and undesirable toxicity profiles. Recently, mycophenolate mofetil (MMF) has emerged as a new therapeutic option for the management of SDNS in a few uncontrolled clinical trials. Preliminary data are encouraging. MMF was found to be useful in maintaining remission and has a steroid-sparing effect. Clearly, more data are needed to further characterize the safety and efficacy of MMF, define adequate length of treatment, and optimize drug exposure and monitoring. The management of SRNS is primarily aimed at decreasing proteinuria and inducing remission, if possible. By doing so, one would aim to preserve renal function. CSA therapy is known to be useful in this regard but has undesirable side effects, the most concerning being nephrotoxicity. MMF in combination with steroids and angiotensin-converting enzyme-inhibitor drugs is known to have some efficacy in the management of SRNS. These preliminary data have prompted the National Institutes of Health to sponsor a multicentric controlled trial to compare the safety and efficacy of MMF with that of CSA in the treatment of steroid-resistant focal segmental glomerulosclerosis (FSGS). If MMF therapy is found to be efficacious, it would help obviate the need for CSA and its associated nephrotoxicity. Clearly, MMF has emerged as an important new therapeutic option for the treatment of childhood nephrotic syndrome and FSGS. Further data are required to assess those conditions most likely to respond.


Reduced Recurrence of Primary IgA Nephropathy in Kidney Transplant Recipients Receiving Everolimus With Corticosteroid: A Retrospective, Single-Center Study of 135 Transplant Patients.
Long-term kidney allograft survival remains a major clinical challenge. Recurrent glomerulonephritis disease, including recurrence of IgA nephropathy (IgAN), is a significant barrier to long-term kidney allograft survival. We performed a retrospective, observational study to evaluate the role of everolimus (EVR) in the risk of recurrent IgAN. The study included data from 135 patients aged ≥16 years with biopsy-proven IgAN on native kidneys who underwent a kidney transplant (KT) between December 2002 and December 2018. Patients who underwent de novo KT received mycophenolate mofetil (MMF) (n = 107) or EVR (n = 28). The mean recipient age in the MMF and EVR groups was 44.9 ± 13.7 and 41.1 ± 10.1, respectively. The median (interquartile range) follow-up period was 90.9 (64.9-115.3) and 21.2 (11.4-30.6) months, respectively (< .0001). All patients received continuous corticosteroid and tacrolimus therapy. The death-censored graft survival rate after KT and the recurrence-free survival rate did not differ significantly between the groups. Univariate and multivariate Cox regression analyses identified EVR for de novo KT as an independent predictive factor for recurrence-free survival (P = .024). Our findings suggest that EVR-based regimens with tacrolimus and corticosteroid therapy for de novo KT reduce the recurrence of IgAN compared with MMF-based regimens with tacrolimus and corticosteroid therapy.


[Diaphragmatic cyst in children].
The experience of treatment of 4 children with nonparasitic diaphragmatic cyst was summarized. The informatic diagnostic methods are--ultrasonography of the thoracic and abdominal cavity organs, and in the cyst presence--sceletotopy in the hepatic segments projection, roentgenography, roentgenoscopy, pneumoperitoneum, pneumothorax. All the patients were operated on. The cyst had the right-sided localization, in 2 observations the mesothelial cyst was diagnosed, and in 2--the cystic teratoma of diaphragm.


Is local hypoperfusion the reason for transient neurological deficits after STA-MCA bypass for moyamoya disease?
Hyperperfusion is believed to be the cause of transient neurological events (TNEs) in patients with moyamoya disease (MMD) who have undergone an extracranial-to-intracranial (EC-IC) bypass between the superficial temporal artery (STA) and the middle cerebral artery (MCA). The objective of this study was to evaluate this possibility by analyzing cerebral blood flow (CBF) data obtained with thermal diffusion probes used at the authors' center. The authors examined postoperative cerebral perfusion in 31 patients with MMD who underwent a direct EC-IC STA-MCA bypass. A Hemedex Q500 flow probe was placed in the frontal lobe adjacent to the bypass and connected to a Bowman cerebral perfusion monitor, and CBF data were statistically analyzed using JMP 8.0.2 software. Seven patients experienced a TNE after surgery in the left hemisphere (that is, after left-sided surgery), manifesting as dysphasia approximately 24 hours postoperatively and which had improved by 48 hours. No TNEs were observed after right-sided surgeries. Operative and postoperative CBFs in the left side with the TNE were compared with those in the left side with no TNE and on the right side. A detailed analysis of 64,980 minute-by-minute flow observations showed that the initial postbypass CBF was higher on the left side where the TNEs occurred. This CBF increase was followed by a widely fluctuating pattern and a statistically significant and sharp drop in perfusion (p < 0.001, mean difference of CBF between groups, paired t-test) associated with a TNE not observed in the other 2 groups. On the basis of the authors' initial observations, an early-onset altered pattern of CBF was identified. These findings suggest local hypoperfusion as the cause of the TNEs. This hypoperfusion may originate from competing blood flows resulting from impaired cerebral autoregulation and a fluctuating flow in cerebral microcirculation.


Predictors of preoperative anxiety among surgical patients in Jimma University Specialized Teaching Hospital, South Western Ethiopia.
Hospitalization and surgery are critical negative life events that lead to the experience of considerable anxiety in patients. Patients may perceive the day of surgery as the biggest and the most threatening day in their lives. There is paucity of information on predictors of anxiety in the current study area. The main objective of this study is to assess predictors of preoperative anxiety among patients scheduled for surgery in Jimma University Specialized Teaching Hospital. A facility based cross-sectional study was conducted using quantitative data collection technique in Jimma University Specialized Teaching Hospital from February 13 to April 13, 2012 on 239 patients scheduled for surgery. The data were collected by five trained diploma nurses using structured interviewer administered questionnaires that were prepared based on state trait anxiety inventory measurement scale. The quantitative data were entered into SPSS for windows version 16. 0 and descriptive, simple and multiple linear regression analyses were performed. A total of 239 patients were enrolled in the study with a response rate of 93.0%. Their mean age was 42.7 ± 1.8 years (range 16 to 85 years). Nearly over half 53.6% were females, while 48.1% illiterate, 72.4% Oromo and 56.5% were Muslim followers. Significant preoperative anxiety was seen in 70.3% patients. The most common factors that lead to anxiety were fear of death 38.1% and fear of unknown origin 24.3% and the most common strategy mentioned by patient in reducing anxiety were talking to other patient 79.8% and religious belief. In the present study, two third 70.3% of preoperative patients had anxiety. Factors which were positively correlated with anxiety were trait anxiety, single and divorced, time of operation and income. Factors which were shown to reduce anxiety were preoperative anxiety related information provision and afternoon operation. Health professionals working in the hospital should provide anxiety related information for patients.


Primary cancer cell culture: mammary-optimized vs conditional reprogramming.
The impact of different culture conditions on biology of primary cancer cells is not always addressed. Here, conditional reprogramming (CRC) was compared with mammary-optimized EpiCult-B (EpiC) for primary mammary epithelial cell isolation and propagation, allograft generation, and genome-wide transcriptional consequences using cancer and non-cancer mammary tissue from mice with different dosages of Brca1 and p53 Selective comparison to DMEM was included. Primary cultures were established with all three media, but CRC was most efficient for initial isolation (P<0.05). Allograft development was faster using cells grown in EpiC compared with CRC (P<0.05). Transcriptome comparison of paired CRC and EpiC cultures revealed 1700 differentially expressed genes by passage 20. CRC promoted Trp53 gene family upregulation and increased expression of epithelial differentiation genes, whereas EpiC elevated expression of epithelial-mesenchymal transition genes. Differences did not persist in allografts where both methods yielded allografts with relatively similar transcriptomes. Restricting passage (<7) reduced numbers of differentially expressed genes below 50. In conclusion, CRC was most efficient for initial cell isolation but EpiC was quicker for allograft generation. The extensive culture-specific gene expression patterns that emerged with longer passage could be limited by reducing passage number when both culture transcriptomes were equally similar to that of the primary tissue. Defining impact of culture condition and passage on the transcriptome of primary cells could assist experimental design and interpretation. For example, differences that appear with passage and culture condition are potentially exploitable for comparative studies targeting specific biological networks in different transcriptional environments.


Mania in adolescence.
The clinical features, treatment, and outcome of bipolar disorder in a consecutive series of 14 adolescent patients are described. Diagnostic confusion was common, although the clinical features were similar to those found in adult patients. Treatment response and short-term outcome seemed favorable. The findings are discussed in the light of current literature.


Synthesis of Amino Acids Bearing Halodifluoromethyl Moieties and Their Application to p53-Derived Peptides Binding to Mdm2/Mdm4.
Therapeutic peptides are a significant class of drugs in the treatment of a wide range of diseases. To enhance their properties, such as stability or binding affinity, they are usually chemically modified. This includes, among other techniques, cyclization of the peptide chain by bridging, modifications to the backbone, and incorporation of unnatural amino acids. One approach previously established, is the use of halogenated aromatic amino acids. In principle, they are thereby enabled to form halogen bonds (XB). In this study, we focus on the -R-CF2X moiety (R = O, NHCO; X = Cl, Br) as an uncommon halogen bond donor. These groups enable more spatial variability in protein-protein interactions. The chosen approach via Fmoc-protected building blocks allows for the incorporation of these modified amino acids in peptides using solid-phase peptide synthesis. Using a competitive fluorescence polarization assay to monitor binding to Mdm4, we demonstrate that a p53-derived peptide with Lys24Nle(εNHCOCF2X) exhibits an improved inhibition constant Ki compared to the unmodified peptide. Decreasing Ki values observed with the increasing XB capacity of the halogen atoms (F ≪ Cl < Br) indicates the formation of a halogen bond. By reducing the side chain length of Nle(εNHCOCF2X) to Abu(γNHCOCF2X) as control experiments and through quantum mechanical calculations, we suggest that the observed affinity enhancement is related to halogen bond-induced intramolecular stabilization of the α-helical binding mode of the peptide or a direct interaction with His54 in human Mdm4.


Intermediates generated during the reaction of reduced Rhodobacter sphaeroides cytochrome c oxidase with dioxygen.
Cytochrome oxidase is one of the functionally most intriguing redox-driven proton pumps. During the last decade our increased understanding of the system has greatly benefited from theoretical calculations and modeling in the framework of three-dimensional structures of cytochrome c oxidases from different species. Because these studies are based on results from experiments, it is important that any ambiguities in the conclusions extracted from these experiments are discussed and elucidated. In a recent study Szundi et al. (Szundi et al. Biochemistry 2012, 51, 9302) investigated the reaction of the reduced Rhodobacter sphaeroides cytochrome c oxidase with O2 and arrived at conclusions different from those derived from earlier investigations. In this short communication we compare these very recent data to those obtained from earlier studies and discuss the origin of the differences.


Specific induction of heat shock protein 90beta by high hydrostatic pressure.
In chondrocytes, a low-amplitude intermittent hydrostatic pressure induces production of extracellular matrix molecules, while high hydrostatic pressure inhibits it. High pressure increases cellular heat shock protein 70 level in a number of cell types on account of increased stabilisation of the heat shock protein 70 mRNA. In our experiments, only bovine primary chondrocytes, but not an immortalized chondrocytic cell line, could resist the induction of the stress response in the presence of continuous 30 MPa hydrostatic pressure. We have recently shown that protein synthesis is required for the stabilization. According to two-dimensional gel electrophoresis the synthesis of heat shock protein 90 was also increased in a chondrocytic cell line and in HeLa cells, and mass spectrometric analysis suggested that the induction was rather due to increase in heat shock protein 90beta than in heat shock protein 90alpha. The stress response was rather intense in HeLa cells, therefore, we investigated the effect of continuous 30 MPa hydrostatic pressure on the expression of the two heat shock protein 90 genes in HeLa cells using Northern and Western blot analyses. Heat shock protein 90beta mRNA level increased within 6 hours of exposure to 30 MPa hydrostatic pressure, while hsp90alpha level remained stable. At protein level there was a clear increase in the heat shock protein 90beta/heat shock protein 90alpha ratio, too. These results show a specific regulation of stress proteins in cells exposed to high hydrostatic pressure.


Characterisation of Walker 256 breast carcinoma cells from two tumour cell banks as assessed using two models of secondary brain tumours.
Metastatic brain tumours are a common end stage of breast cancer progression, with significant associated morbidity and high mortality. Walker 256 is a rat breast carcinoma cell line syngeneic to Wistar rats and commonly used to induce secondary brain tumours. Previously there has been the assumption that the same cancer cell line from different cell banks behave in a similar manner, although recent studies have suggested that cell lines may change their characteristics over time in vitro. In this study internal carotid artery injection and direct cerebral inoculation models of secondary brain tumours were used to determine the tumorigenicity of Walker 256 cells obtained from two cell banks, the American Type Culture Collection (ATCC), and the Cell Resource Centre for Medical Research at Tohoku University (CRCTU). Tumour incidence and volume, plus immunoreactivity to albumin, IBA1 and GFAP, were used as indicators of tumorigenicity and tumour interaction with the host brain microenvironment. CRCTU Walker 256 cells showed greater incidence, larger tumour volume, pronounced blood-brain barrier disruption and prominent glial response when compared to ATCC cell line. These findings indicate that immortalised cancer cell lines obtained from different cell banks may have diverse characteristics and behaviour in vivo.


[Evaluation of nutrition manner and nutritional status of girls during the period of adolescence, including girls who apply slimming diets].
The purpose of the research was the evaluation of nutrition methods and the nutrition status of girls in the age ranging between 15 and 16, who had body substance, height, waist measurements taken; and the BMI, WC, and WHtR indicators were calculated. Three day menus were also evaluated and an inquiry containing questionnaire concerning the manner of apply slimming diets. It has also been ascertained that 40.8% of fifteen year old and 31% of sixteen year old girls apply slimming diets. It was discovered that only in 76% of younger girls and in 71% of older girls the value of the BMI indicator was proper. The problem of accumulation of fat tissue (WC > or = 95 c) around the waist concerned 4% younger girls and 10% older. It was discovered that the values of WHtR > or = 90 c were almost 10% and 23% in the cases of younger and older girls, respectively. Analysis of nutrition of the girls showed low energy value of the diet, too low total protein level, too low of complex carbohydrates, minerals (K, Ca, Mg, Cu, Zn) and vitamins (A, E, B group) and also liquids shortage. The girls have been educated in the form of workshops in the matter concerning healthy nutrition.


Aspirin stimulates insulin and glucagon secretion and increases glucose tolerance in normal and diabetic subjects.
Normal subjects and patients with adult-onset diabetes received 10 gm. of aspirin in four days. On the fourth day, the fasting serum glucose and the glucose response to oral glucose were decreased in both groups. These changes were associated with increased levels of serum insulin and pancreatic glucagon, although the glucagon responses to oral glucose were unchanged. In the diabetic patients, aspirin therapy was followed by a decreased glucose response to I.V. glucose and by the appearance of an early insulin peak, which could not be demonstrated before treatment. Aspirin did not affect the I.V. glucose tolerance in normal subjects, although it did enhance the early insulin peak. A decrease in the fasting levels of free fatty acids was noted in both groups, whereas the fasting level of triglycerides decreased only in the diabetic patients. Cholesterolemia did not change in either group. A few preliminary observations indicate that, in normal subjects, ibuprofen and ketoprofen, two other presumed prostaglandin inhibitors, did not affect fasting glycemia, glucose tolerance, or the insulin response to glucose. No changes were noted after the administration of placebo.


Stereotactic radiosurgical treatment of cerebral arteriovenous malformations. Gamma Unit Radiosurgery Study Group.
To assess the role of clinical factors, size of lesion, site of involvement, and radiation dose in patients with cerebral arteriovenous malformations (AVMs) who underwent stereotactic radiosurgical treatment. We reviewed the results in 121 patients with cerebral AVMs treated with the Leksell "Gamma Knife" between January 1990 and December 1993 at the Mayo Clinic in Rochester, Minnesota. The following strict dose-volume protocol was used: AVMs 2.0 cm or smaller in diameter (volume, 4.2 cm3 or less) received 20 Gy to the margin of the nidus, those between 2.1 and 3.0 cm in diameter (4.3 to 14.1 cm3) received 18 Gy to the margin, and those that exceeded 3.0 cm in diameter (more than 14.1 cm3) received 16 Gy to the margin. Lesions that involved the brain stem received a radiosurgical dose of 18 Gy or less to the margin. Patients participated in regular follow-up clinical and imaging studies for up to 55 months. Follow-up cerebral angiography in 43 patients demonstrated total obliteration of the AVM nidus in 31 (72.1%), including 5 of 7 (71.4%) who had AVMs with a volume larger than 10 cm3. Clinical follow-up revealed that 111 patients (91.7%) had a stable or improved outcome, 3 had a nonfatal AVM hemorrhage, 2 suffered a fatal hemorrhage, and 2 died of causes not directly attributed to the AVM or radiosurgical treatment. Two patients had new or increased, nondisabling neurologic deficits as a result of treatment, and one patient had a temporary partial eyelid ptosis. Our findings suggest that previous theories about the relationship between AVM size and rate of obliteration after radiosurgical treatment may need revision. Our experience confirms that radiosurgical treatment for cerebral AVMs is safe and effective, even in cases for which the latency period before obliteration is longer than 2 years.


Molecular diagnostic tools for detection and differentiation of phytoplasmas based on chaperonin-60 reveal differences in host plant infection patterns.
Phytoplasmas ('Candidatus Phytoplasma' spp.) are insect-vectored bacteria that infect a wide variety of plants, including many agriculturally important species. The infections can cause devastating yield losses by inducing morphological changes that dramatically alter inflorescence development. Detection of phytoplasma infection typically utilizes sequences located within the 16S-23S rRNA-encoding locus, and these sequences are necessary for strain identification by currently accepted standards for phytoplasma classification. However, these methods can generate PCR products >1400 bp that are less divergent in sequence than protein-encoding genes, limiting strain resolution in certain cases. We describe a method for accessing the chaperonin-60 (cpn60) gene sequence from a diverse array of 'Ca.Phytoplasma' spp. Two degenerate primer sets were designed based on the known sequence diversity of cpn60 from 'Ca.Phytoplasma' spp. and used to amplify cpn60 gene fragments from various reference samples and infected plant tissues. Forty three cpn60 sequences were thereby determined. The cpn60 PCR-gel electrophoresis method was highly sensitive compared to 16S-23S-targeted PCR-gel electrophoresis. The topology of a phylogenetic tree generated using cpn60 sequences was congruent with that reported for 16S rRNA-encoding genes. The cpn60 sequences were used to design a hybridization array using oligonucleotide-coupled fluorescent microspheres, providing rapid diagnosis and typing of phytoplasma infections. The oligonucleotide-coupled fluorescent microsphere assay revealed samples that were infected simultaneously with two subtypes of phytoplasma. These tools were applied to show that two host plants, Brassica napus and Camelina sativa, displayed different phytoplasma infection patterns.


Recently recycled synaptic vesicles use multi-cytoskeletal transport and differential presynaptic capture probability to establish a retrograde net flux during ISVE in central neurons.
Presynapses locally recycle synaptic vesicles to efficiently communicate information. During use and recycling, proteins on the surface of synaptic vesicles break down and become less efficient. In order to maintain efficient presynaptic function and accommodate protein breakdown, new proteins are regularly produced in the soma and trafficked to presynaptic locations where they replace older protein-carrying vesicles. Maintaining a balance of new proteins and older proteins is thus essential for presynaptic maintenance and plasticity. While protein production and turnover have been extensively studied, it is still unclear how older synaptic vesicles are trafficked back to the soma for recycling in order to maintain balance. In the present study, we use a combination of fluorescence microscopy, hippocampal cell cultures, and computational analyses to determine the mechanisms that mediate older synaptic vesicle trafficking back to the soma. We show that synaptic vesicles, which have recently undergone exocytosis, can differentially utilize either the microtubule or the actin cytoskeleton networks. We show that axonally trafficked vesicles traveling with higher speeds utilize the microtubule network and are less likely to be captured by presynapses, while slower vesicles utilize the actin network and are more likely to be captured by presynapses. We also show that retrograde-driven vesicles are less likely to be captured by a neighboring presynapse than anterograde-driven vesicles. We show that the loss of synaptic vesicle with bound molecular motor myosin V is the mechanism that differentiates whether vesicles will utilize the microtubule or actin networks. Finally, we present a theoretical framework of how our experimentally observed retrograde vesicle trafficking bias maintains the balance with previously observed rates of new vesicle trafficking from the soma.


Commuting physical activity and risk of colon cancer in Shanghai, China.
Colon cancer incidence rates have been rapidly increasing in Shanghai, China, for reasons still unclear. Low physical activity is a known risk factor for colon cancer. The authors examined the effects of physical activity, particularly commuting physical activity, and its joint effects with body mass index on colon cancer risk in a population-based, case-control study. The study included 931 incident colon cancer patients and 1,552 randomly selected controls in Shanghai between 1990 and 1993. Colon cancer risk was significantly reduced among subjects with high commuting physical activity (odds ratio (OR) = 0.52, 95% confidence interval (CI): 0.27, 0.87 for men; OR = 0.56, 95% CI: 0.21, 0.91 for women), particularly among those who had high commuting physical activity for at least 35 years (OR = 0.34, 95% CI: 0.09, 0.76 for men; OR = 0.31, 95% CI: 0.07, 0.72 for women). Commuting physical activity significantly modified the risk conferred by high body mass index, with the highest risk observed among those at the highest quintile of body mass index and the lowest activity level (OR = 6.43, 95% CI: 1.82, 8.54 for men; OR = 7.42, 95% CI: 2.84, 10.01 for women). Our results suggest that regular and frequent physical activity over a long period of time protects from colon cancer and significantly modifies the body mass index-associated risk.


Integrins and other cell adhesion molecules.
Cell-cell and cell-substratum interactions are mediated through several different families of receptors. In addition to targeting cell adhesion to specific extracellular matrix proteins and ligands on adjacent cells, these receptors influence many diverse processes including cellular growth, differentiation, junction formation, and polarity. Several families of adhesion receptors have been identified. These include: 1) the integrins, heterodimeric molecules that function both as cell-substratum and cell-cell adhesion receptors; 2) the adhesion molecules of the immunoglobulin superfamily, which are involved in cell-cell adhesion and especially important during embryo-genesis, wound healing, and the inflammatory response; 3) the cadherins, developmentally regulated, calcium-dependent homophilic cell-cell adhesion proteins; 4) the LEC-CAMs, cell adhesion molecules with lectin-like domains that mediate white blood cell/endothelial cell adhesion; and 5) homing receptors that target lymphocytes to specific lymphoid tissue. In this review we summarize recent data describing the structure and function of some of these cell adhesion molecules (with special emphasis on the integrin family) and discuss the possible role of these molecules in development, inflammation, wound healing, coagulation, and tumor metastasis.


Relationships between the neuronal sodium/potassium pump and energy metabolism. Effects of K+, Na+, and adenosine triphosphate in isolated brain synaptosomes.
The relationships between Na/K pump activity and adenosine triphosphate (ATP) production were determined in isolated rat brain synaptosomes. The activity of the enzyme was modulated by altering [K+]e, [Na+]i, and [ATP]i while synaptosomal oxygen uptake and lactate production were measured simultaneously. KCl increased respiration and glycolysis with an apparent Km of about 1 mM which suggests that, at the [K+]e normally present in brain, 3.3-4 mM, the pump is near saturation with this cation. Depolarization with 6-40 mM KCl had negligible effect on ouabain-sensitive O2 uptake indicating that at the voltages involved the activity of the Na/K ATPase is largely independent of membrane potential. Increases in [Na+]i by addition of veratridine markedly enhanced glycoside-inhibitable respiration and lactate production. Calculations of the rates of ATP synthesis necessary to support the operation of the pump showed that greater than 90% of the energy was derived from oxidative phosphorylation. Consistent with this: (a) the ouabain-sensitive Rb/O2 ratio was close to 12 (i.e., Rb/ATP ratio of 2); (b) inhibition of mitochondrial ATP synthesis by Amytal resulted in a decrease in the glycoside-dependent rate of 86Rb uptake. Analyses of the mechanisms responsible for activation of the energy-producing pathways during enhanced Na and K movements indicate that glycolysis is predominantly stimulated by increase in activity of phosphofructokinase mediated via a rise in the concentrations of adenosine monophosphate [AMP] and inorganic phosphate [Pi] and a fall in the concentration of phosphocreatine [PCr]; the main moving force for the elevation in mitochondrial ATP generation is the decline in [ATP]/[ADP] [Pi] (or equivalent) and consequent readjustments in the ratio of the intramitochondrial pyridine nucleotides [( NAD]m/[NADH]m). Direct stimulation of pyruvate dehydrogenase by calcium appears to be of secondary importance. It is concluded that synaptosomal Na/K pump is fueled primarily by oxidative phosphorylation and that a fall in [ATP]/[ADP][Pi] is the chief factor responsible for increased energy production.


[Efficiency and mechanisms of antihypoxic effect of ATP in newborn rats].
Effect of ATP (administered at the doses of 20 mg and 100 mg per kg of body mass) on sensitivity of 5-7 days old rats to acute hypoxia as well as content of 2,3-DPH and ATP in erythrocytes were studied. ATP exhibited the most effective antihypoxic influence at a dose of 100 mg/kg. After administration of ATP a dissimilar increase in content of 2,3-DPH and ATP was observed in erythrocytes of newborn rats maintained under conditions of normal atmospheric pressure. At the hypoxic step of compensated metabolic acidosis of blood the increase in content of 2,3-DPH, caused by the ATP administration, was combined with a less distinct alterations in acid-alkaline balance (SB, BE). Under conditions of decompensated metabolic acidosis preadministration of ATP did not prevent the pH dependent decrease in 2,3-DPH content in erythrocytes but slightly increased the ATP content. The alterations in content of 2,3-DPH and ATP, which occurred in erythrocytes apparently due to the effect of products of ATP dephosphorylation and which improved the oxygen transport by hemoglobin under conditions of oxygen deficiency, might be responsible for the positive influence of ATP on the stability of newborn rats to acute hypoxia.


Subband anticrossing and the spin Hall effect in quantum wires.
We report on numerical simulations of the intrinsic spin Hall effect in semiconductor quantum wires as a function of the Rashba spin-orbit coupling strength, the electron density, and the width of the wire. We find that the strength of the spin Hall effect does not depend monotonically on these parameters, but instead exhibits a local maximum. This behavior is explained by considering the dispersion relation of the electrons in the wire, which is characterized by the anticrossing of adjacent subbands. These results lead to a simple estimate of the optimal wire width for spin Hall transport experiments, and simulations indicate that this optimal width is independent of disorder. The anticrossing of adjacent subbands is related to a quantum phase transition in momentum space, and is accompanied by an enhancement of the Berry curvature and subsequently in the magnitude of the spin Hall effect.


Is plastic ingestion in birds as toxic as we think? Insights from a plastic feeding experiment.
Plastic pollution is a modern tragedy of the commons, with hundreds of species affected by society's waste. Birds in particular mistake plastic for prey, and millions of wild birds carry small plastic loads in their stomach and are exposed to potential toxicological effects. It is currently unknown how severely the toxicological and endocrine disrupting chemicals in plastic affect avian development, reproduction and endocrine function. To address this question, we conducted multi-generational plastic feeding experiments to test the toxicological consequences of plastic ingestion at environmentally relevant loads in Japanese quail, Coturnix japonica, investigating parental and two filial generations. Contrary to expectations, we found no evidence of lasting toxicological effects on mortality, adult body weight, organ histology, hormone levels, fertility, hatch rates and eggshell strength in birds experimentally fed plastic. However, we found plastic ingestion causes higher frequencies of male reproductive cysts and minor delays in chick growth and sexual maturity, though without affecting ultimate survival or reproductive output. We report that although plastic ingestion causes detectable endocrine effects in our model species, our lack of finding mortality, morbidity and adverse reproductive outcomes may challenge the common hypothesis of severe toxicological harm and population-level effects when environmentally relevant loads of plastic are ingested.


Processed pseudogenes of human endogenous retroviruses generated by LINEs: their integration, stability, and distribution.
We report here the presence of numerous processed pseudogenes derived from the W family of endogenous retroviruses in the human genome. These pseudogenes are structurally colinear with the retroviral mRNA followed by a poly(A) tail. Our analysis of insertion sites of HERV-W processed pseudogenes shows a strong preference for the insertion motif of long interspersed nuclear element (LINE) retrotransposons. The genomic distribution, stability during evolution, and frequent truncations at the 5' end resemble those of the pseudogenes generated by LINEs. We therefore suggest that HERV-W processed pseudogenes arose by multiple and independent LINE-mediated retrotransposition of retroviral mRNA. These data document that the majority of HERV-W copies are actually nontranscribed promoterless pseudogenes. The current search for HERV-Ws associated with several human diseases should concentrate on a small subset of transcriptionally competent elements.


The evolution and investigation of native coronary arteries in patients after coronary stent implantation: a study by 320-detector CT angiography.
To study the role of 320-detector coronary computed tomography angiography (CTA) in assessing native coronary arteries in patients treated with coronary stents. 123 patients with coronary stenting received both CTA and conventional coronary angiography (CCA) within 1 day. The clinical parameters, coronary calcium scoring, CTA and CCA were analyzed to determine the prevalence of significant stenosis of native coronary arteries (SSNCA), the predictive value of CTA and the factors correlating with SSNCA and newly developed SSNCA after stenting (NDSSNCAS), with CCA as the standard of reference, using both vessel-based analysis (VBA) and patient-based analysis (PBA). Both the source and the reconstructed images were analyzed by CTA. All native coronary arteries were interpretable independent of cardiac motion. CTA showed a sensitivity/specificity of 93.5%/97.3% and 92.5%/92.5% in diagnosing SSNCA in VBA and PBA, respectively. The significant factors related to SSNCA were higher calcium scores (P = 0.003), a higher serum glucose level (P = 0.048), a greater number of vessels without previous stent placement (P = 0.003) and fewer stents implanted within the vessels (P = 0.003). The risk factors showed no significant correlation from PBA on SSNCA or from NDSSNCAS on either VBA or PBA. CTA demonstrates excellent correlation with CCA. The prevalence of SSNCA is significantly correlated with the presence of higher calcium scores in the arteries, a higher serum glucose level, a greater number of vessels without previous stent placement and fewer stents implanted within the vessels; PBA on SSNCA and NDSSNCAS on both VBA and PBA showed no significance.


Identification and expression analysis of cytokinin metabolic genes in soybean under normal and drought conditions in relation to cytokinin levels.
Cytokinins (CKs) mediate cellular responses to drought stress and targeted control of CK metabolism can be used to develop drought-tolerant plants. Aiming to manipulate CK levels to improve drought tolerance of soybean cultivars through genetic engineering of CK metabolic genes, we surveyed the soybean genome and identified 14 CK biosynthetic (isopentenyltransferase, GmIPT) and 17 CK degradative (CK dehydrogenase, GmCKX) genes. Comparative analyses of GmIPTs and GmCKXs with Arabidopsis counterparts revealed their similar architecture. The average numbers of abiotic stress-inducible cis-elements per promoter were 0.4 and 1.2 for GmIPT and GmCKX genes, respectively, suggesting that upregulation of GmCKXs, thereby reduction of CK levels, maybe the major events under abiotic stresses. Indeed, the expression of 12 GmCKX genes was upregulated by dehydration in R2 roots. Overall, the expressions of soybean CK metabolic genes in various tissues at various stages were highly responsive to drought. CK contents in various organs at the reproductive (R2) stage were also determined under well-watered and drought stress conditions. Although tRNA-type GmIPT genes were highly expressed in soybean, cis-zeatin and its derivatives were found at low concentrations. Moreover, reduction of total CK content in R2 leaves under drought was attributable to the decrease in dihydrozeatin levels, suggesting a role of this molecule in regulating soybean's responses to drought stress. Our systematic analysis of the GmIPT and GmCKX families has provided an insight into CK metabolism in soybean under drought stress and a solid foundation for in-depth characterization and future development of improved drought-tolerant soybean cultivars by manipulation of CK levels via biotechnological approach.


Autoradiographic determination of brain pH following middle cerebral artery occlusion in the rat.
A method of quantitative autoradiography using 14C-labelled 5,5-dimethyl-2, 4-oxazolidinedione 14C-DMO to evaluate the local changes in brain pH after ischemia is described. In normal control rats the calculated tissue pH values in gray matter were slightly lower than those in white matter, and there was no significant difference in the calculated pH among the various structures in cortical and subcortical gray matter. Four hours after a left middle cerebral artery (MCA) occlusion, marked reductions in 14C-DMO concentrations were demonstrated in the anterior two-thirds of the cerebral cortex and in the lateral part of the caudate nucleus indicating tissue acidosis in these areas. Although several assumptions are required for the calculation of pH in brain tissue, this method would appear very useful in the investigation of the altered metabolic state in ischemic brain.


Food safety informatics: a public health imperative.
To date, little has been written about the implementation of utilizing food safety informatics as a technological tool to protect consumers, in real-time, against foodborne illnesses. Food safety outbreaks have become a major public health problem, causing an estimated 48 million illnesses, 128,000 hospitalizations, and 3,000 deaths in the U.S. each year. Yet, government inspectors/regulators that monitor foodservice operations struggle with how to collect, organize, and analyze data; implement, monitor, and enforce safe food systems. Currently, standardized technologies have not been implemented to efficiently establish "near-in-time" or "just-in-time" electronic awareness to enhance early detection of public health threats regarding food safety. To address the potential impact of collection, organization and analyses of data in a foodservice operation, a wireless food safety informatics (FSI) tool was pilot tested at a university student foodservice center. The technological platform in this test collected data every six minutes over a 24 hour period, across two primary domains: time and temperatures within freezers, walk-in refrigerators and dry storage areas. The results of this pilot study briefly illustrated how technology can assist in food safety surveillance and monitoring by efficiently detecting food safety abnormalities related to time and temperatures so that efficient and proper response in "real time" can be addressed to prevent potential foodborne illnesses.


Activation of Xenopus MyoD transcription by members of the MEF2 protein family.
Members of the MEF2 family of DNA binding proteins interact with a set of AT-rich sequences commonly found in the promoters and enhancers of muscle-specific genes. We have shown that a MEF2 binding site precisely overlaps the TFIID binding site (TATA box) in the Xenopus MyoDa (XMyoDa) promoter and appears to play an important role in muscle-specific activity of this promoter. To further investigate the potential role of MEF2 in the regulation of XMyoDa transcription, we have analyzed the appearance of factors that interact with the XMyoDa TATA/MEF2 site during early amphibian development. Proteins that bind specifically to this site were present at low levels during early development and increased in abundance during gastrulation and neurulation. Two related cDNAs were isolated that encode proteins that recognize the XMyoDa TATA motif. Both proteins are highly homologous to each other, belong to the MADS (MCM1 agamous deficiens SRF) protein family, and are most highly related to the mammalian MEF2A gene products. Xenopus MEF2A (XMEF2A) transcripts accumulated preferentially in forming somites after the appearance of XMyoD transcripts. Ectopic expression of XMEF2A and other members of the MEF2 gene family activated transcription of a reporter gene controlled by the XMyoDa promoter. Transcriptional activation of the XMyoDa promoter required only the conserved DNA binding domain of XMEF2A and was independent of a domain necessary for activity when this factor was bound to multiple upstream sites. These results suggest that the XMyoDa promoter can be activated by binding of MEF2 to the XMyoDa TATA motif and indicate that MEF2-dependent transcriptional activation occurs by different mechanisms depending on the location of the MEF2 binding site. We suggest that XMEF2 expression in myogenic cells contributes to the activation and stabilization of XMyoDa transcription during muscle cell differentiation.


A facile and reversible method to decrease the copy number of the ColE1-related cloning vectors commonly used in Escherichia coli.
We report a technique which uses the cointegrate intermediate of transposon Tn1000 transposition as a means to lower the copy number of ColE1-type plasmids. The transposition of Tn1000 from one replicon to another is considered a two-step process. In the first step, the transposon-encoded TnpA protein mediates fusion of the two replicons to produce a cointegrate. In the second step, the cointegrate is resolved by site-specific recombination between the two transposon copies to yield the final transposition products: the target replicon with an integrated transposon plus the regenerated donor replicon. Using in vitro techniques, the DNA sequence of the Tn1000 transposon was altered so that cointegrate formation occurs but resolution by the site-specific recombination pathway is blocked. When this transposon was resident on an F factor-derived plasmid, a cointegrate was formed between a multicopy ColE1-type target plasmid and the conjugative F plasmid. Conjugational transfer of this cointegrate into a polA strain resulted in a stable cointegrate in which replication from the ColE1 plasmid origin was inhibited and replication proceeded only from the single-copy F factor replication origin. We assayed isogenic strains which harbored plasmids encoding chloramphenicol acetyltransferase to measure the copy number of such F factor-ColE1-type cointegrate plasmids and found that the copy number was decreased to the level of single-copy chromosomal elements. This method was used to study the effect of copy number on the expression of the fabA gene (which encodes the key fatty acid-biosynthetic enzyme beta-hydroxydecanoylthioester dehydrase) by the regulatory protein encoded by the fadR gene.


Evaluation of the association between arsenic and diabetes: a National Toxicology Program workshop review.
Diabetes affects an estimated 346 million persons globally, and total deaths from diabetes are projected to increase > 50% in the next decade. Understanding the role of environmental chemicals in the development or progression of diabetes is an emerging issue in environmental health. In 2011, the National Toxicology Program (NTP) organized a workshop to assess the literature for evidence of associations between certain chemicals, including inorganic arsenic, and diabetes and/or obesity to help develop a focused research agenda. This review is derived from discussions at that workshop. Our objectives were to assess the consistency, strength/weaknesses, and biological plausibility of findings in the scientific literature regarding arsenic and diabetes and to identify data gaps and areas for future evaluation or research. The extent of the existing literature was insufficient to consider obesity as an outcome. Studies related to arsenic and diabetes or obesity were identified through PubMed and supplemented with relevant studies identified by reviewing the reference lists in the primary literature or review articles. Existing human data provide limited to sufficient support for an association between arsenic and diabetes in populations with relatively high exposure levels (≥ 150 µg arsenic/L in drinking water). The evidence is insufficient to conclude that arsenic is associated with diabetes in lower exposure (< 150 µg arsenic/L drinking water), although recent studies with better measures of outcome and exposure support an association. The animal literature as a whole was inconclusive; however, studies using better measures of diabetes-relevant end points support a link between arsenic and diabetes.


Decreased birth weight and attainment of postnatal catch-up growth in offspring of rats exposed to cigarette smoke during gestation.
Pregnant rats were exposed to cigarette smoke daily for a 2-hour period throughout gestation and the body weights of offspring were monitored for 5 weeks postnatally. The average birth weight of the cigarette smoke exposed pups was significantly smaller compared to both pair-fed and ad libitum control groups. However, the body weights of the pups exposed to smoke were no longer significantly different from those in the pair-fed and ad libitum control groups at weeks 1 and 2 after birth, respectively. This study indicates that fetal growth retardation caused by exposure to cigarette smoke during pregnancy does not persist after birth.


[The role of a health information system as an aid in making regional public health decisions. Experience in Botswana (Southern Africa)].
Decision-making procedures within a health system vary according to the administrative and political organisation of each country. All health levels have, daily or irregularly, decisions to make. To provide reliable, objective and understandable information to decision makers is a difficult, expensive and sometimes misleading exercise. Basic data can be gathered through surveys or institutional routine. Through a concrete example within a Primary Health Care context, the possibilities and the advantages of the utilisation of routinely collected information, regionally processed, are described with the positive interactions within the whole health system. Validation, processing, relativization of the results and their use in supervision, epidemiological and performance surveillance are discussed, emphasizing the privileged aspect of Botswana.


The Use of Physiologically Based Pharmacokinetic Analyses-in Biopharmaceutics Applications -Regulatory and Industry Perspectives.
The use of physiologically based pharmacokinetic (PBPK) modeling to support the drug product quality attributes, also known as physiologically based biopharmaceutics modeling (PBBM) is an evolving field and the interest in using PBBM is increasing. The US-FDA has emphasized on the use of patient centric quality standards and clinically relevant drug product specifications over the years. Establishing an in vitro in vivo link is an important step towards achieving the goal of patient centric quality standard. Such a link can aid in constructing a bioequivalence safe space and establishing clinically relevant drug product specifications. PBBM is an important tool to construct a safe space which can be used during the drug product development and lifecycle management. There are several advantages of using the PBBM approach, though there are also a few challenges, both with in vitro methods and in vivo understanding of drug absorption and disposition, that preclude using this approach and therefore further improvements are needed. In this review we have provided an overview of experience gained so far and the current perspective from regulatory and industry point of view. Collaboration between scientists from regulatory, industry and academic fields can further help to advance this field and deliver on promises that PBBM can offer towards establishing patient centric quality standards.


Biofilm modelling on the contact lenses and comparison of the in vitro activities of multipurpose lens solutions and antibiotics.
During the contact lens (CL) usage, microbial adhesion and biofilm formation are crucial threats for eye health due to the development of mature biofilms on CL surfaces associated with serious eye infections such as keratitis. For CL related eye infections, multi drug resistant Pseudomonas aeruginosa or Staphylococcus aureus (especially MRSA) and Candida albicans are the most common infectious bacteria and yeast, respectively. In this study, CL biofilm models were created by comparing them to reveal the differences on specific conditions. Then the anti-biofilm activities of some commercially available multipurpose CL solutions (MPSs) and antibiotic eye drops against mature biofilms of S. aureus, P. aeruginosa, and C. albicans standard and clinical strains were determined by the time killing curve (TKC) method at 6, 24 and 48 h. According to the biofilm formation models, the optimal biofilms occurred in a mixture of bovine serum albumin (20% v/v) and lysozyme (2 g/L) diluted in PBS at 37 °C for 24 h, without shaking. When we compared the CL types under the same conditions, the strongest biofilms according to their cell density, were formed on Pure Vision ≥ Softens 38 > Acuve 2 ∼ Softens Toric CLs. When we compared the used CLs with the new ones, a significant increase at the density of biofilms on the used CLs was observed. The most active MPS against P. aeruginosa and S. aureus biofilms at 24 h was Opti-Free followed by Bio-True and Renu according to the TKC analyses. In addition, the most active MPS against C. albicans was Renu followed by Opti-Free and Bio-True at 48 h. None of the MPSs showed 3 Log bactericidal/fungicidal activity, except for Opti-Free against S. aureus and P. aeruginosa biofilms during 6 h contact time. Moreover, all studied antibiotic eye drops were active against S. aureus and P. aeruginosa biofilms on CLs at 6 h and 24 h either directly or as 1/10 concentration, respectively. According to the results of the study, anti-biofilm activities of MPSs have changed depending on the chemical ingredients and contact times of MPSs, the type of infectious agent, and especially the CL type and usage time.


Astrocytic hamartoma in tuberous sclerosis mimicking necrotizing retinochoroiditis.
A pale, elevated peripapillary lesion discovered in a young child with no family history of phakomatoses, grew larger, caused vitreous hemorrhage and underwent necrosis. Secondary inflammation developed in the eye, finally producing rubeosis irides with elevated intraocular pressure and a blind, painful eye which required enucleation. Clinically, the lesion was variably diagnosed and treated as toxoplasmosis and toxocara canis. These diagnoses were made despite low titres, a negative ELISA test and a normal eosinophil count. On histopathologic examination, a diagnosis of toxocara canis was entertained, although no remnants of the organism could be found in serial sections. Years later, when a family history of tuberous sclerosis became apparent, a diagnosis of astrocytic hamartoma of the retina with secondary hemorrhage and inflammation was made on the basis of re-examination of the pathologic specimen and special stains.


Prediction of survival by tumor area on endosonography after definitive chemoradiotherapy for locally advanced squamous cell carcinoma of the esophagus.
Definitive chemoradiotherapy (CRT) is a reasonable approach for patients with locally advanced esophageal cancer who are not surgical candidates. This study was performed to investigate whether endosonography (EUS) assessment of tumor area response is a useful prognostic marker in patients with squamous cell carcinoma (SCC) of the esophagus who receive definitive CRT. A total of 33 patients who received definitive CRT for locally advanced esophageal SCC were enrolled. The maximal transverse cross-sectional area of the tumor was measured before and after definitive therapy. EUS response was defined as a ≥50% reduction of the tumor area after definitive CRT. Based on EUS evaluation, there were 20 nonresponders (60.6%) and 13 responders (39.4%). The median progression-free survival (PFS) was significantly longer in EUS responders than EUS nonresponders (p = 0.005). However, there was no statistical significance in overall survival according to EUS response (p = 0.120). During multivariate analysis, EUS response to definitive CRT was the only significant factor associated with PFS (p = 0.045), whereas EUS response to definitive CRT was not associated with overall survival (p = 0.221). A reduction of the maximal cross-sectional tumor area measured by EUS correlates with a superior prognosis in patients with locally advanced SCC of the esophagus after definitive CRT.


Evaluation of the role of incentive structure on student participation and performance in active learning strategies: A comparison of case-based and team-based learning.
Student participation is important for the success of active learning strategies, but participation is often linked to the level of preparation. At our institution, we use two types of active learning activities, a modified case-based learning exercise called active learning groups (ALG) and team-based learning (TBL). These strategies have different assessment and incentive structures for participation. Non-cognitive skills are assessed in ALG using a subjective five-point Likert scale. In TBL, assessment of individual student preparation is based on a multiple choice quiz conducted at the beginning of each session. We studied first-year medical student participation and performance in ALG and TBL as well as performance on course final examinations. Student performance in TBL, but not in ALG, was strongly correlated with final examination scores. Additionally, in students who performed in the upper 33rd percentile on the final examination, there was a positive correlation between final examination performance and participation in TBL and ALG. This correlation was not seen in students who performed in the lower 33rd percentile on the final examinations. Our results suggest that assessments of medical knowledge during active learning exercises could supplement non-cognitive assessments and could be good predictors of performance on summative examinations.


Pathogenesis of paralytic ileus: intestinal manipulation opens a transient pathway between the intestinal lumen and the leukocytic infiltrate of the jejunal muscularis.
To investigate the existence of a pathway between intraluminal products and the muscularis leukocytic infiltrate. Mild intestinal manipulation or lipopolysaccharide initiates an intense inflammatory response within the intestinal muscularis, resulting in paralytic ileus. A major potential morbidity factor in ileus is luminal bacterial overgrowth. ACI rats were subjected to small bowel manipulation, after which fluorescent carboxylated or paramagnetic microspheres were administered into the gut lumen. Animals were killed between 0 and 24 hours; unoperated rats served as controls. Intestinal manipulation led to an early transient transference of microspheres from the intestinal lumen into mesenteric lymph that was not observed in unmanipulated controls. A time- dependent, significant increase in microsphere-laden phagocytes was observed within the intestinal muscularis. Immunohistochemistry and electron microscopy of the intestinal muscularis identified the phagocytes as extravasating ED1+ monocytes. Interruption of the lymphatics abolished the accumulation of microsphere-laden monocytes within the muscularis, although a significant monocytic recruitment could still be observed within the intestinal muscularis. These data show that intestinal manipulation leads to a transient increase in mucosal permeability and that the extraintestinal endocytotic uptake of transferred particles by circulating monocytes precedes their infiltration into the gut wall. The transference of luminal bacterial products may follow a similar route and time course as the microspheres. The authors hypothesize that endogenous bacterial products act synergistically with the inflammatory response within the postsurgical intestinal muscularis, leading to an exacerbation of postoperative ileus.


Choice of injury scoring system in low- and middle-income countries: Lessons from Mumbai.
Injury is a major cause of morbidity and mortality in low- and middle-income countries. Effective trauma surveillance is imperative to guide research and quality improvement interventions, so an accurate metric for quantifying injury severity is crucial. The objectives of this study are (1) to assess the feasibility of calculating five injury scoring systems--ISS (injury severity score), RTS (revised trauma score), KTS (Kampala trauma score), MGAP (mechanism, GCS (Glasgow coma score), age, pressure) and GAP (GCS, age, pressure)--with data from a trauma registry in a lower middle-income country and (2) to determine which of these scoring systems most accurately predicts in-hospital mortality in this setting. This is a retrospective analysis of data from an institutional trauma registry in Mumbai, India. Values for each score were calculated when sufficient data were available. Logistic regression was used to compare the correlation between each score and in-hospital mortality. There were sufficient data recorded to calculate ISS in 73% of patients, RTS in 35%, KTS in 35%, MGAP in 88% and GAP in 92%. ISS was the weakest predictor of in-hospital mortality, while RTS, KTS, MGAP and GAP scores all correlated well with in-hospital mortality (area under ROC (receiver operating characteristic) curve 0.69 for ISS, 0.85 for RTS, 0.86 for KTS, 0.84 for MGAP, 0.85 for GAP). Respiratory rate measurements, missing in 63% of patients, were a major barrier to calculating RTS and KTS. Given the realities of medical practice in low- and middle-income countries, it is reasonable to modify the approach to characterising injury severity to favour simplified injury scoring systems that accurately predict in-hospital mortality despite limitations in trauma registry datasets.


'Imagine if I gave up smoking ...': a qualitative exploration of Aboriginal participants' perspectives of a self-management pilot training intervention.
This paper reports on a pilot qualitative study investigating Aboriginal participants' perspectives of the Flinders Living Well Smoke Free (LWSF) 'training intervention'. Health workers nationally have been trained in this program, which offers a self-management approach to reducing smoking among Aboriginal clients. A component of the training involves Aboriginal clients volunteering their time in a mock care-planning session providing the health workers with an opportunity to practise their newly acquired skills. During this simulation, the volunteer clients receive one condensed session of the LWSF intervention imitating how the training will be implemented when the health workers have completed the training. For the purpose of this study, 10 Aboriginal clients who had been volunteers in the mock care-planning process, underwent a semi-structured interview at seven sites in Australia, including mainstream health services, Aboriginal community controlled health services and remote Aboriginal communities. The study aimed to gauge their perspectives of the training intervention they experienced. Early indications suggest that Aboriginal volunteer clients responded positively to the process, with many reporting substantial health behaviour change or plans to make changes since taking part in this mock care-planning exercise. Enablers of the intervention are discussed along with factors to be considered in the training program.


Gray matter atrophy distinguishes between Parkinson disease motor subtypes.
To assess differences in gray matter (GM) atrophy between 2 Parkinson disease (PD) subtypes: the tremor dominant (TD) subtype and the postural instability gait difficulty (PIGD) subtype. Patients were classified as belonging to the predominately PIGD (n = 30) or predominately TD (n = 29) subtype. Voxel-based morphometry was used to compare GM in these 2 subtypes and to evaluate correlations between predefined regions of interest and the degree of symptoms. In the regions where GM atrophy was associated with symptoms, the relationship between GM volumes and functional connectivity was examined. GM was reduced in the predominately PIGD group, compared with the predominately TD group, in areas that involve motor, cognitive, limbic, and associative functions (p < 0.05, false discovery rate corrected). Lower GM volumes in the pre-supplementary motor area (SMA) and in the primary motor area were associated with increased severity of PIGD symptoms (r = -0.42, p < 0.001; r = -0.38, p < 0.003, respectively). Higher GM volumes within the pre-SMA were associated with stronger functional connectivity between the pre-SMA and the putamen (r = 0.415, p < 0.025) in the patients with predominately PIGD. In patients with PD, PIGD symptoms are apparently associated with GM atrophy in motor-related regions and decreased functional connectivity. GM degeneration and a related decrease in spontaneous coactivation between cortical and subcortical motor-planning areas may partially account for the unique clinical characteristics of a subset of patients with PD.


The additive and synergistic antimicrobial effects of select frankincense and myrrh oils--a combination from the pharaonic pharmacopoeia.
The in vitro antimicrobial activity of three essential oil samples of frankincense (Boswellia rivae, Boswellia neglecta and Boswellia papyrifera) and two essential oil samples of myrrh and sweet myrrh (Commiphora guidotti and Commiphora myrrha), collected from different regions of Ethiopia, was investigated independently and in combination to determine their anti-infective properties. The microdilution minimum inhibitory concentration (MIC) assay was performed, whereby it was noted that generally Cryptococcus neoformans (MIC values in the range of 0·8-1·4 mg ml(-1)) and Pseudomonas aeruginosa (MIC values in the range of 0·5-1·3 mg ml(-1)) often appeared to be the most susceptible micro-organisms against oils of both Boswellia and Commiphora spp. When assayed in various combinations, the frankincense and myrrh oils displayed synergistic, additive and noninteractive properties, with no antagonism noted. When investigating different ratio combinations against Bacillus cereus, the most favourable combination was between B. papyrifera and C. myrrha. The composition of the oils was determined by gas chromatography coupled to mass spectrometry (GC-MS) to document the specific chemotypes used in the study, and the chemical profiles were found to be congruent with previously reported data. The majority of interactions identified synergistic and additive effects, with strong synergism noted between B. papyrifera and C. myrrha. Frankincense and myrrh essential oils have been used in combination since 1500 bc; however, no antimicrobial investigations have been undertaken to confirm their effect in combination. This study validates the enhanced efficacy when used in combination against a selection of pathogens.


AAV5-Factor VIII Gene Transfer in Severe Hemophilia A.
Patients with hemophilia A rely on exogenous factor VIII to prevent bleeding in joints, soft tissue, and the central nervous system. Although successful gene transfer has been reported in patients with hemophilia B, the large size of the factor VIII coding region has precluded improved outcomes with gene therapy in patients with hemophilia A. We infused a single intravenous dose of a codon-optimized adeno-associated virus serotype 5 (AAV5) vector encoding a B-domain-deleted human factor VIII (AAV5-hFVIII-SQ) in nine men with severe hemophilia A. Participants were enrolled sequentially into one of three dose cohorts (low dose [one participant], intermediate dose [one participant], and high dose [seven participants]) and were followed through 52 weeks. Factor VIII activity levels remained at 3 IU or less per deciliter in the recipients of the low or intermediate dose. In the high-dose cohort, the factor VIII activity level was more than 5 IU per deciliter between weeks 2 and 9 after gene transfer in all seven participants, and the level in six participants increased to a normal value (>50 IU per deciliter) that was maintained at 1 year after receipt of the dose. In the high-dose cohort, the median annualized bleeding rate among participants who had previously received prophylactic therapy decreased from 16 events before the study to 1 event after gene transfer, and factor VIII use for participant-reported bleeding ceased in all the participants in this cohort by week 22. The primary adverse event was an elevation in the serum alanine aminotransferase level to 1.5 times the upper limit of the normal range or less. Progression of preexisting chronic arthropathy in one participant was the only serious adverse event. No neutralizing antibodies to factor VIII were detected. The infusion of AAV5-hFVIII-SQ was associated with the sustained normalization of factor VIII activity level over a period of 1 year in six of seven participants who received a high dose, with stabilization of hemostasis and a profound reduction in factor VIII use in all seven participants. In this small study, no safety events were noted, but no safety conclusions can be drawn. (Funded by BioMarin Pharmaceutical; ClinicalTrials.gov number, NCT02576795 ; EudraCT number, 2014-003880-38 .).