Continuity of cannabis use and violent offending over the life course.
Although the association between cannabis use and violence has been reported in the literature, the precise nature of this relationship, especially the directionality of the association, is unclear. Young males from the Cambridge Study of Delinquent Development (n = 411) were followed up between the ages of 8 and 56 years to prospectively investigate the association between cannabis use and violence. A multi-wave (eight assessments, T1-T8) follow-up design was employed that allowed temporal sequencing of the variables of interest and the analysis of violent outcome measures obtained from two sources: (i) criminal records (violent conviction); and (ii) self-reports. A combination of analytic approaches allowing inferences as to the directionality of associations was employed, including multivariate logistic regression analysis, fixed-effects analysis and cross-lagged modelling. Multivariable logistic regression revealed that compared with never-users, continued exposure to cannabis (use at age 18, 32 and 48 years) was associated with a higher risk of subsequent violent behaviour, as indexed by convictions [odds ratio (OR) 7.1, 95% confidence interval (CI) 2.19-23.59] or self-reports (OR 8.9, 95% CI 2.37-46.21). This effect persisted after controlling for other putative risk factors for violence. In predicting violence, fixed-effects analysis and cross-lagged modelling further indicated that this effect could not be explained by other unobserved time-invariant factors. Furthermore, these analyses uncovered a bi-directional relationship between cannabis use and violence. Together, these results provide strong indication that cannabis use predicts subsequent violent offending, suggesting a possible causal effect, and provide empirical evidence that may have implications for public policy.


The expression of the transcription factor TAF1 is modified by the HPV16 E2 protein.
High-risk human papillomaviruses (e.g., HPV16 and 18) are associated with cervical cancer occurrence and development. The early viral gene E2 encodes a protein involved in several key processes in HPV biology, such as replication, genome segregation, and viral gene transcription. E2's presence also affects the expression of a variety of cellular genes involved in a wide range of biological processes, including cell cycle regulation and apoptosis, which are mediated by E2's interaction with cellular proteins. In this report, a lentiviral system was used to express the HPV16 E2 gene in the HPV-negative C-33A cell line for several weeks. E2 expression was measured by RT-qPCR and its biological activity was evaluated using a reporter gene. In HPV16 E2-positive cells, we observed a statistically significant increase in mRNA and protein levels of TAF1 and p27, a basal transcription factor and one of its target genes, respectively. To our knowledge, this is the first study showing that the viral protein HPV16 E2 upregulates TAF1 expression. This suggests that E2's expression promotes a transcriptionally-favorable cellular environment that allows HPV to successfully complete its replication cycle. Keywords: HPV16; E2 protein; transcription; TAF1 regulation.


Analysis of the GGGGCC Repeat Expansions of the C9orf72 Gene in SCA3/MJD Patients from China.
Neurodegenerative disorders are a heterogeneous group of chronic progressive diseases and have pathological mechanisms in common. A certain causative gene identified for a particular disease may be found to play roles in more than one neurodegenerative disorder. We analyzed the GGGGCC repeat expansions of C9orf72 gene in patients with SCA3/MJD from mainland China to determine whether the C9orf72 gene plays a role in the pathogenesis of SCA3/MJD. In our study, there were no pathogenic repeats (>30 repeats) detected in either the patients or controls. SCA3/MJD patients with intermediate/intermediate or short/intermediate genotype (short: <7 repeats; intermediate: 7-30 repeats) of the GGGGCC repeats had an earlier onset compared with those with short/short genotype. The presence of the intermediate allele of the GGGGCC repeats in the patients decreased the age at onset by nearly 3 years. Our study firstly demonstrate that the development of SCA3/MJD may involve some physiological functions of the C9orf72 gene and provide new evidence to the hypothesis that a specific mutation identified in one of the neurodegenerative disorders may be a modulator in this class of diseases.


Self-care among chronically ill African Americans: culture, health disparities, and health insurance status.
Little is known about the self-care practices of chronically ill African Americans or how lack of access to health care affects self-care. Results from a qualitative interview study of 167 African Americans who had one or more chronic illnesses found that self-care practices were culturally based, and the insured reported more extensive programs of self-care. Those who had some form of health insurance much more frequently reported the influence of physicians and health education programs in self-care regimens than did those who were uninsured. It is concluded that the cultural components of self-care have been underemphasized, and further, that the potential to maximize chronic illness management through self-care strategies is not realized for those who lack access to health care.


Prostaglandin biosynthesis in the rat lens.
Rat lens microsomal preparations possess the capability of converting exogenous arachidonic acid into prostaglandins (PG) E2 and F2 alpha. The low, yet measurable prostaglandin biosynthetic capacity of the lens microsomes was demonstrated by radioimmunoassay (RIA) and by separation of radiolabeled products after incubation with high specific activity U-14 [C]-arachidonic acid. Maximal formation of radioimmunoassayable PGE2 and PGF2 alpha was measured after a 15-min incubation at 37 degrees C with approximately 0.5 mg protein. Prostaglandin biosynthesis was inhibited by the nonsteroidal anti-inflammatory agents aspirin (IC50 = 52 microM) and indomethacin (IC50 = 20 microM). These results unequivocally demonstrate prostaglandin biosynthesis in rat lens.


Population pharmacokinetics for oral paclitaxel in patients with advanced/metastatic solid tumors.
Oraxol consists of an oral dosage form of the chemotherapeutic agent paclitaxel administered with a novel P-glycoprotein inhibitor encequidar methanesulfonate monohydrate (formerly named HM30181A), which allows oral treatment of cancers that would otherwise be treated with intravenous paclitaxel. Here we describe the population pharmacokinetics (popPK) analyses for oral paclitaxel in patients with advanced/metastatic solid tumors to characterize pharmacokinetic (PK) profiles and quantify sources of PK variability. The best fit popPK model for oral paclitaxel, based on data from seven clinical studies (197 patients with advanced/metastatic solid tumors), involves a linear two-compartment structural model containing first-order absorption with a short lag time and first-order elimination as well as a log additive error. In this popPK model, lower population estimates of central volume for Asian patients versus Caucasian patients did not translate into clinical meaningful differences in oral paclitaxel exposure. Age, sex, body weight or surface area, mild hepatic impairment, and mild to moderate renal impairment had no clinically meaningful effects on the systemic exposure of oral paclitaxel. Simulations were performed on clinical therapeutic dose (oral paclitaxel 205 mg/m2 once daily ×3 days per week) to predict exposure of oral paclitaxel and to support treatment benefits observed in a pivotal phase III trial.


[Correction of carbohydrate metabolism in animals in experimental autoimmune pancreatitis].
Autoimmune pancreatitis was simulated in experiment. For the carbohydrate metabolism disorders correction in animals with an acute pancreatitis the preparation was applied on which a patent of the Ukraine have been got.


Automated software analysis of corneal micrographs for peripheral neuropathy.
A relationship has been reported between the presence of peripheral neuropathy and the density and shape of corneal nerve fibers. Peripheral neuropathy is a debilitating condition that arises from many common health problems, and its presence is often confirmed with an invasive clinical test called intramuscular electromyography (EMG). In this study, the possibility of developing an alternative or adjunct test to EMG based on the appearance of nerve fibers in corneal micrographs was explored. Since corneal imaging is virtually noninvasive compared with EMG, such a test may be administered more liberally and frequently, before neuropathy symptoms occur. A software program that automatically traces nerve fibers in corneal micrographs and generates measures based on these traces was implemented. This software was applied to a database of images collected by confocal laser scanning corneal microscopy from diabetic subjects whose levels of neuropathy were measured with EMG and from healthy subjects. Trends in the nerve fiber density and various measures of shape were calculated and observed, to explore the possibility of using these measures as a clinical tool for corroborating symptoms, confirming an evaluation, or evaluating risk factors for developing neuropathy. Preliminary statistical trends show a potential for measuring and observing neuropathy severity or for providing an objective risk measure for a patient's ensuing condition. More work is needed in the development of the measures and in their testing to prove that the measures can be made repeatable in a clinical environment.


Phenotypic variation and identification of Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae) in China.
Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae) is an invasive mealybug that seriously damages cotton and other important crops. In previous studies in China, the presence of two submedian longitudinal lines of pigmented spots on the dorsum of adult females frequently has been used to identify this species. However, the present study records the occasional absence of pigmented spots in a sample from Guangxi province, China. Specimens without pigmented spots showed all the molecular and morphological characters that separate P. solenopsis from the similar species P. solani Ferris, especially the distribution of multilocular disc pores. In different geographic populations of P. solenopsis in China, mitochondrial COI and nuclear 28SrDNA genes are very similar (99.8-100%), indicating that they are conspecific. For COI, the genetic distance between P. solenopsis and P. solani is more than 3%. A map of the distribution of P. solenopsis in China is given. To help identify both pigmented and non-pigmented P. solenopsis accurately, an identification key to the 16 species of Phenacoccus found in China is provided. The key also identifies five potentially invasive Phenacoccus species not yet established in China, in case they get introduced there.


Cloning and expression of a gibberellin 2 beta,3 beta-hydroxylase cDNA from pumpkin endosperm.
A cDNA expression library in lambda MOSEIox derived from poly(A)+ RNA from pumpkin endosperm was screened immunologically with a polyclonal antibody raised against partially purified gibberellin (GA) 2 beta,3 beta-hydroxylase from pumpkin endosperm. A recombinant fusion protein encoded by a selected positive clone catalyzed 3 beta-hydroxylation of GA15, GA24, GA25, and GA17 and of GA12-aldehyde, GA12, GA9, and GA20, albeit less efficiently. The fusion protein also catalyzed 2 beta-hydroxylation of the C20 GAS GA25, GA13, and, as identified putatively, GA28. The full-length clone contains an open reading frame of 1041 nucleotides encoding 346 amino acid residues with a predicted molecular weight of 38,992 and pI of 7.2. Transcript levels of this gene and of the previously cloned GA 7-oxidase and 20-oxidase genes from pumpkin endosperm rose until day 2 after the start of imbibition of the mature seeds, but only at one-two hundredth to one-six thousandth of the level found in the endosperm, as determined by quantitative reverse transcriptase-polymerase chain reaction. In contrast, GA 7-oxidase, 20-oxidase, and 3 beta-hydroxylase enzyme activities were present in cell-free systems prepared from embryos of mature seeds and decreased after imbibition.


Nephrotoxic acute renal failure due to common drugs.
Antibiotics are the most common drugs implicated in clinical reports of drug-induced nephrotoxicity. The experimental basis for proposed mechanisms of acute renal failure in association with three groups of antibiotics--aminoglycoside, cephalosporin, and amphotericin B--are reviewed in detail. Proposed mechanisms of antibiotic-induced acute renal tubular necrosis involve either altering plasma membrane permeability or interference with cellular energy derived from mitochondria, For either aminoglycoside or cephalosporin antibiotics, cellular accumulation followed by interruption of mitochondrial respiration is the concept that has greatest support, although the possibility of an induced phospholipidosis involving intracellular lysosomes cannot be excluded. Altered renal tubular cell permeability due to the incorporation of amphotericin B into the pore structure of the plasma membrane is consistent with in vivo observation in either clinical or experimental examples of nephrotoxicity with this agent. The metal cis-platinum, used in treatment of neoplastic disease, has a clearly defined incidence of clinical nephrotoxicity with little insight as to cellular mechanisms. A possible mediation involving cis-platinum reducing the protein-bound sulfhydryl group of renal tissue has been proposed. With the ever increasing potency of modern pharmacologic agents come a rising risk of serious toxic side effects.


Congenital cardiac anomalies in calves.
Seven cases of congenital cardiac anomalies in calves were reviewed from the files of the Ohio Veterinary Diagnostic Laboratory. The collection of material occurred during a six-month period from June 1977 to January 1978. The major clinical signs were dyspnoea, failure to gain weight and sudden death in young animals. The cardiac defects included two patent ductus arteriosus, two anomalies of the coronary vessels, one persistent truncus arteriosus, one transposition of the aorta and pulmonary artery and one ventricular septal defect.


Nerve transfers for femoral nerve palsy: an updated approach and surgical technique.
Femoral nerve palsy results in significant impairment of lower extremity function due to the loss of quadriceps muscle function. The authors have previously described their techniques utilizing the anterior obturator and sartorius nerves for transfer in cases of femoral nerve palsy presenting within 1 year of injury. In the current study, the authors discuss their updated techniques, results, and approach to partial and complete femoral nerve palsies using femoral nerve decompression and nerve transfers. They conducted a retrospective review of patients with femoral nerve palsies treated with their technique at the Washington University School of Medicine in 2008-2019. Primary outcomes were active knee extension Medical Research Council (MRC) grades and visual analog scale (VAS) pain scores. Fourteen patients with femoral nerve palsy were treated with femoral nerve decompression and nerve transfer: 4 with end-to-end (ETE) nerve transfers, 6 with supercharged end-to-side (SETS) transfers, and 4 with ETE and SETS transfers, using the anterior branch of the obturator nerve, the sartorius branches, or a combination of both. The median preoperative knee extension MRC grade was 2 (range 0-3). The average preoperative VAS pain score was 5.2 (range 1-9). Postoperatively, all patients attained an MRC grade 4 or greater and subjectively noted improved strength and muscle bulk and more natural gait. The average postoperative pain score was 2.3 (range 0-6), a statistically significant improvement (p = 0.001). Until recently, few treatments were available for high femoral nerve palsy. A treatment strategy involving femoral nerve decompression and nerve transfers allows for meaningful functional recovery and pain relief in cases of partial and total femoral nerve palsy. An algorithm for the management of partial and complete femoral nerve palsies and a detailed description of surgical techniques are presented.


Treat-to-target in dermatology: A scoping review and International Eczema Council survey on the approach in atopic dermatitis.
Treat-to-target (T2T) is a pragmatic therapeutic strategy being gradually introduced into dermatology after adoption in several other clinical areas. Atopic dermatitis (AD), one of the most common inflammatory skin diseases, may also benefit from this structured and practical therapeutic approach. We aimed to evaluate existing data regarding the T2T approach in dermatology, with a specific focus on AD, as well as the views of International Eczema Council (IEC) members on the potential application of a T2T approach to AD management. To do so, we systematically searched for peer-reviewed publications on the T2T approach for any skin disease in the PubMed and Scopus databases up to February 2022 and conducted a survey among IEC members regarding various components to potentially include in a T2T approach in AD. We identified 21 relevant T2T-related reports in dermatology, of which 14 were related to psoriasis, five to AD, one for juvenile dermatomyositis and one for urticaria. In the IEC member survey, respondents proposed treatable traits (with itch, disease severity and sleep problems getting the highest scores), relevant comorbidities (with asthma being selected most commonly, followed by anxiety and depression in adults), recommended specialists that should define the approach in AD (dermatologists, allergists and primary care physicians were most commonly selected in adults), and applicable assessment tools (both physician- and patient-reported), in both adult and paediatric patients, for potential future utilization of the T2T approach in AD. In conclusion, while the T2T approach may become a useful tool to simplify therapeutic goals and AD management, its foundation in AD is only starting to build. A multidisciplinary approach, including a wide range of stakeholders, including patients, is needed to further define the essential components needed to utilize T2T in AD.


Effect of the Shaping Healthy Choices Program, a Multicomponent, School-Based Nutrition Intervention, on Physical Activity Intensity.
Physical activity has been shown to have a wide range of beneficial health effects, yet few youth meet the United States physical activity recommendation of 60 minutes of moderate-to-vigorous physical activity (MVPA) everyday. The objective of this study was to determine whether physical activity patterns improved in a subsample of fourth-graders participating in the multicomponent intervention, the Shaping Healthy Choices Program (SHCP). At pre- and post-intervention assessments, youth at the control and intervention schools wore a Polar Active monitor on their nondominant wrist 24 h/d for at least 2 consecutive days. Multiple linear regression was used to evaluate change in physical activity by adjusting for covariates and other potential confounders, including ethnicity/race, household income, and sex. Statistical significance was set at p < 0.05. Mean minutes of MVPA significantly increased at the intervention school (22.3 + 37.8; p = 0.01) and at the control school (29.1 + 49.5; p = 0.01). There were no significant differences in the change in MVPA between the schools. Youth at the intervention school significantly decreased mean minutes in sedentary activity compared to the controls (p = 0.02). Youth who participated in the SHCP decreased time spent in sedentary activity and increased very vigorous physical activity from pre- to post-intervention, while these changes were not observed at the control school. The overall small physical activity intensity pattern shift supports that physical activity is an important area to target within a multicomponent nutrition intervention aimed at preventing childhood obesity.


Evaluation of ultrasonically placed MTA and fracture resistance with intracanal composite resin in a model of apexification.
The purpose of this study was to evaluate whether intracoronal delivery of an apical barrier of mineral trioxide aggregate (MTA) placed ultrasonically, non-ultrasonically, or ultrasonically with the addition of an intracanal composite resin provided a better seal against bacterial leakage. A second purpose was to determine whether intracanal composite resin or gutta-percha and sealer placed against an apical barrier of MTA provided greater resistance to root fracture. In a standardized in vitro open apex model, MTA was placed as an apical barrier at a thickness of 4 mm, with and without ultrasonic vibration. The barriers were challenged with bacteria exposure within a leakage model, and fracture resistance was assessed with increasing forces applied via an Instron machine. After 45 days, the addition of ultrasonics significantly improved the MTA seal, compared with the non-ultrasonics treatment (Kruskal Wallis nonparametric ANOVA with Dunn multiple comparison test p < 0.05). Bacterial leakage occurred in 6 (33%) of 18 in the non-ultrasonic MTA group, 2 (11%) of 18 in the ultrasonic MTA group, and 1 (6%) of 18 in the ultrasonic MTA-composite group. There were no significant differences at 90 days. A 4-mm thickness of MTA followed with an intracanal composite resin demonstrated a significantly greater resistance to root fracture than MTA followed with gutta-percha and sealer (one-way ANOVA with Newman-Keuls multiple comparison test, p < 0.01). The MTA-gutta-percha group was not significantly different than the MTA unrestored positive control.


The Mental Status in Patients with Diabetes Mellitus Admitted to a Diabetes Clinic After Presenting in the Emergency Room: The Application of the SCL-90 Scale.
Diabetes mellitus (DM) is one of the most serious public health problems, involving increasing costs worldwide. The mental state of a person with DM is varied and ever-changing, such as stress, the pressure to always do everything by the book, sadness, anger, and even denial of the disease, all these are feelings patients with DM will experience throughout their life. The aim of our study was to assess the presence of mental and psychiatric disorders (anxiety, depressive states, paranoid ideation, phobia, obsessive-compulsive disorder) in a group of patients with DM after hospitalization in the Clinic for Diabetes, Nutrition, and Metabolic Diseases, for various exacerbations of the underlying condition, looking for possible correlations with other cardiovascular risk factors. Clinical and biological parameters, the presence of acute and chronic complications of the diabetic patients have been evaluated. To assess mental health, the symptom checklist (SCL)-90 questionnaire was conducted for all admitted patients. We observed that the number of patients with obsessive-compulsive disorders was relatively high (23.3%), while depression was present in 17.1% of the patients. Also, 10.6% of patients had hostility and 15.6% had delusional ideation. The presence of psychiatric disorders was associated with a higher age (62 vs. 46.5 years; p <0.001), a longer diabetes duration (11 vs. 9 years; p <0.001), higher fasting glycemia (188 vs. 132 mg/dL; p <0.001) and postprandial glycemia (212 vs. 152 mg/dL; p <0.001), and triglycerides (125 vs. 110 mg/dL; p <0.001). Patients with altered mental status have shown statistically significantly more altered clinical and biological parameters compared to those without these mental disorders. Patients with DM represent a psychologically vulnerable population, which is why they should undergo early and regular screening for both psychological and psychiatric conditions, especially at admission.


Electrodermal reactivity and its association to substance use disorders.
Poor electrodermal response modulation is associated with substance use disorders, but the specificity of the relationship has not been tested. To test this, 112 college students were assessed for psychiatric symptoms using structured interviews and for ability to modulate skin conductance responses to 2-s 92- or 110-dB white noise blasts that varied in temporal predictability. Twenty-eight good and 28 poor modulators were compared on symptoms of alcohol and illicit drug use disorders, personality disorders (antisocial, borderline, histrionic, and narcissistic), social and specific phobia, and depression. As expected, poor modulators had significantly more symptoms of substance use disorders than good modulators. Groups did not differ in symptoms of anxiety disorder, depression, or personality disorders marked by disinhibition. Poor electrodermal response modulation may reflect a biological risk factor for substance use disorders in particular.


Efficacy of gene-therapy based on adenovirus encoding granulocyte-macrophage colony-stimulating factor in drug-sensitive and drug-resistant experimental pulmonary tuberculosis.
Tuberculosis (TB), although a curable disease, remains a major cause of morbidity and mortality worldwide. It is necessary to develop a short-term therapy with reduced drug toxicity in order to improve adherence rate and control disease burden. Granulocyte-macrophage colony-stimulating factor (GM-CSF) may be a key cytokine in the treatment of pulmonary TB since it primes the activation and differentiation of myeloid and non-myeloid precursor cells, inducing the release of protective Th1 cytokines. In this work, we administrated by intratracheal route recombinant adenoviruses encoding GM-CSF (AdGM-CSF). This treatment produced significant bacterial elimination when administered in a single dose at 60 days of infection with drug sensitive or drug resistant Mtb strains in a murine model of progressive disease. Moreover, AdGM-CSF combined with primary antibiotics produced more rapid elimination of pulmonary bacterial burdens than conventional chemotherapy suggesting that this form of treatment could shorten the conventional treatment.


When the Mind Comes to Live Inside the Body: The Ontogeny of the Perceptual Control Clock.
In this editorial, we discuss the neurobiological processes underlying the early emergence of awareness that we term the "when" and "how" the mind comes to live inside the body. We describe an accumulative developmental process starting during embryonic life and continuing to fetal and postnatal development, of coupling of heart rate, body movements, and sleep states on the behavioral level with underlying mechanisms on the structural, functional, cellular, and molecular levels. A developmental perspective is proposed based on Perceptual Control Theory (PCT). This includes a developing sequence of modules starting from early sensing of neural intensities to early manifestation of human mindful capacities. We also address pharmacological treatments administered to preterm infants, which may interfere with this development, and highlight the need to consider this potential "side effect" of current pharmaceuticals when developing novel pharmacogenomic treatments.


Intronic DNA elements regulate androgen-dependent expression of the murine Nkx3.1 gene.
Nkx3.1 is a well-conserved homeobox gene that is involved in development, differentiation and maintenance of prostate epithelial cells. Nkx3.1 expression is induced by androgen in prostate epithelia and, as such, our interest is to understand the mechanism(s) for this androgen-dependent expression in normal epithelial cells. In this report, we show that the region of DNA sequence 2.7 kilobases in front of the mouse Nkx3.1 gene drives enhanced transcription in prostate epithelia cells; however, this segment was not capable of androgen-directed regulation. Among the multiple, potential androgen response elements (AREs) identified by scanning sequences near and within the gene, two sequences within the intron of the murine Nkx3.1 gene were demonstrated to confer androgen-dependent transcription in reporter gene transfection experiments. Each of the elements, termed ARE A and ARE B, contained a 6-base pair core sequence, TGTTCT, that has been described as an androgen receptor half-site binding sequence, separated by 498 base pairs of DNA. Both of the intronic half-sites bind activated androgen receptor from a variety of sources, albeit with different apparent affinities. This region of the Nkx3.1 gene demonstrates a high degree of conservation among diverse species and mutagenesis experiments demonstrated that both elements are required for androgen stimulation. Taken together, our study shows that androgen-dependent transcription of the mouse Nkx3.1 gene is conferred through a noncanonical element within the intron of the gene.


Intermediate-Term Outcomes for Men with Very Low/Low and Intermediate/High Risk Prostate Cancer Managed by Active Surveillance.
We compare intermediate term clinical outcomes among men with favorable risk and intermediate/high risk prostate cancer managed by active surveillance. A total of 635 men with localized prostate cancer have been on active surveillance since 2002 at a high volume academic hospital in the United States. Median followup is 50.5 months (IQR 31.1-80.3). Time to event analysis was performed for our clinical end points. Of the cohort 117 men (18.4%) had intermediate/high risk disease. Overall 5 and 10-year all cause survival was 98% and 94%, respectively. Cumulative metastasis-free survival at 5 and 10 years was 99% and 98%, respectively. To date no cancer specific deaths had been observed. Overall freedom from intervention was 61% and 49% at 5 and 10 years, respectively. Overall cumulative freedom from failure of active surveillance, defined as metastasis or biochemical failure after local therapy with curative intent, was 97% and 91% at 5 and 10 years, respectively. Of the men 21 (9.9%) experienced biochemical failure after deferred treatment and the 5-year progression-free probability was 92%. Compared to men with favorable risk disease those with intermediate/high risk cancer experienced no difference in metastases, surveillance failure or curative intervention. However, patients at higher risk were at significantly increased risk for all cause mortality, likely reflecting patient selection factors. These conclusions may be limited by the small number of events and the duration of our study. Patients with localized prostate cancer who are on active surveillance demonstrated a low rate of active surveillance failure, prostate cancer specific mortality and metastases regardless of baseline risk.


Functional expression of Kir2.x in human aortic endothelial cells: the dominant role of Kir2.2.
Inward rectifier K(+) channels (Kir) are a significant determinant of endothelial cell (EC) membrane potential, which plays an important role in endothelium-dependent vasodilatation. In the present study, several complementary strategies were applied to determine the Kir2 subunit composition of human aortic endothelial cells (HAECs). Expression levels of Kir2.1, Kir2.2, and Kir2.4 mRNA were similar, whereas Kir2.3 mRNA expression was significantly weaker. Western blot analysis showed clear Kir2.1 and Kir2.2 protein expression, but Kir2.3 protein was undetectable. Functional analysis of endothelial inward rectifier K(+) current (I(K)) demonstrated that 1) I(K) current sensitivity to Ba(2+) and pH were consistent with currents determined using Kir2.1 and Kir2.2 but not Kir2.3 and Kir2.4, and 2) unitary conductance distributions showed two prominent peaks corresponding to known unitary conductances of Kir2.1 and Kir2.2 channels with a ratio of approximately 4:6. When HAECs were transfected with dominant-negative (dn)Kir2.x mutants, endogenous current was reduced approximately 50% by dnKir2.1 and approximately 85% by dnKir2.2, whereas no significant effect was observed with dnKir2.3 or dnKir2.4. These studies suggest that Kir2.2 and Kir2.1 are primary determinants of endogenous K(+) conductance in HAECs under resting conditions and that Kir2.2 provides the dominant conductance in these cells.


Microglial interleukin-1β in the ipsilateral dorsal horn inhibits the development of mirror-image contralateral mechanical allodynia through astrocyte activation in a rat model of inflammatory pain.
Damage on one side of the body can also result in pain on the contralateral unaffected side, called mirror-image pain (MIP). Currently, the mechanisms responsible for the development of MIP are unknown. In this study, we investigated the involvement of spinal microglia and interleukin-1β (IL-1β) in the development of MIP using a peripheral inflammatory pain model. After unilateral carrageenan injection, mechanical allodynia (MA) in both hind paws and the expression levels of spinal Iba-1, IL-1β, and GFAP were evaluated. Ipsilateral MA was induced beginning at 3 hours after carrageenan injection, whereas contralateral MA showed a delayed onset occurring 5 days after injection. A single intrathecal (i.t.) injection of minocycline, a tetracycline derivative that displays selective inhibition of microglial activation, or an interleukin-1 receptor antagonist (IL-1ra) on the day of carrageenan injection caused an early temporary induction of contralateral MA, whereas repeated i.t. treatment with these drugs from days 0 to 3 resulted in a long-lasting contralateral MA, which was evident in its advanced development. We further showed that IL-1β was localized to microglia and that minocycline inhibited the carrageenan-induced increases in spinal Iba-1 and IL-1β expression. Conversely, minocycline or IL-1ra pretreatment increased GFAP expression as compared with that of control rats. However, i.t. pretreatment with fluorocitrate, an astrocyte inhibitor, restored minocycline- or IL-1ra-induced contralateral MA. These results suggest that spinal IL-1β derived from activated microglia temporarily suppresses astrocyte activation, which can ultimately prevent the development of contralateral MA under inflammatory conditions. These findings imply that microglial IL-1β plays an important role in regulating the induction of inflammatory MIP.


[Thyroid function after thyroidectomy for benign goiter. 200 cases explored by ultrasensitive TSH].
Based on a retrospective study of a series of 200 thyroidectomies for benign goitre and a mean follow up period of 12 Months, the authors analysed post-operative thyroid function and correlated it with the degree of surgical excision (47 unilateral lobectomies, 91 classical subtotal bilateral lobectomies and 62 extended bilateral subtotal lobectomies). After a presentation of the results in comparison with data from the literature, the timing and threshold for the institution of replacement therapy are examined and the need for prolonged clinical and laboratory monitoring is also stressed. In terms of changes in laboratory criteria only monitoring of spontaneous changes in US TSH allows opotherapy to be avoided or conversely to accurately define the conditions for institution of definitive replacement therapy. The justification of total thyroidectomy in the treatment of multihetoronodular goitres almost totally involving the glandular parenchyma is acknowledged.


Menstrual regulation in family planning services.
Menstrual regulation is a safe, effective, and economical method of fertility control. Its increased safety compared to first trimester abortion establishes menstrual regulation by vacuum aspiration for treatment of up to 14 days missed menstrual period as probably better medical practice than waiting to confirm the presence of a pregnancy. Because it is a postcontraceptive method, menstrual regulation has potential in family planning services both as a recruitment service and for the treatment of contraceptive failures. Its use as an only method of fertility control is being studied. The acceptance of this new family planning service will primarily depend on its availability, dissemination of information about the service, and the ability of women freely to avail themselves of the service without delay. Although long term effects of single and repeated use of menstrual regulation are not known, its immediate complications are few and it can be recommended as a useful addition to present fertility control methods in family planning programs.


INTERACT in VA Community Living Centers (CLCs): Training and Implementation Strategies.
Studies have shown that hospitalizations of nursing home (NH) residents lead to complications and poorer quality of life. The Interventions to Reduce Acute Care Transfers (INTERACT) Quality Improvement (QI) Program assists licensed NH staff in avoiding such hospitalizations. INTERACT aims to improve the management of acute changes in residents' conditions by providing tools to help staff recognize subtle changes in condition, improve communication, and implement QI strategies. INTERACT has been vetted by national clinical leaders and experts in long term care (LTC). Multiple NHs have implemented INTERACT and it has been adopted in Canada, the United Kingdom, and Singapore. QI initiatives involve adaptation to the organizational context in which it is being implemented. We report adaptation of the INTERACT QI program and implementation training into Veteran Affairs (VA) Community Living Centers (CLCs) (VA equivalent NH) and summarize the efforts to introduce and train nursing leadership to integrate the intervention into selected CLCs.


Surgical decompression of painful diabetic peripheral neuropathy: the role of pain distribution.
To investigate the effect of surgical decompression on painful diabetic peripheral neuropathy (DPN) patients and discuss the role which pain distribution and characterization play in the management of painful DPN as well as the underlying mechanism involved. A total of 306 patients with painful diabetic lower-extremity neuropathy were treated with Dellon surgical nerve decompression in our department. Clinical evaluation including Visual analogue scale (VAS), Brief Pain Inventory Short Form for diabetic peripheral neuropathy (BPI-DPN) questionnaire, two-point discrimination (2-PD), nerve conduction velocity (NCV) and high-resolution ultrasonography (cross-sectional area, CSA) were performed in all cases preoperatively, and at 6 month intervals for 2 years post-decompression. The patients who underwent surgery were retrospectively assigned into two subgroups (focal and diffuse pain) according to the distribution of the diabetic neuropathic pain. The control group included 92 painful DPN patients without surgery. The levels of VAS, scores in BPI-DPN, 2-PD, NCV results and CSA were all improved in surgical group when compared to the control group (P<0.05). More improvement of VAS, scores in BPI-DPN and CSA was observed in focal pain group than that in diffuse group (P<0.05). Efficacy of decompression of multiple lower-extremity peripheral nerves in patients with painful diabetic neuropathy was confirmed in this study. While both focal and diffuse group could benefit from surgical decompression, pain relief and morphological restoration could be better achieved in focal group.


Phantom stock dividend plan.
The Phantom Stock Dividend Plan is a method of sharing net profits with staff in the same way a stock holder in a company receives periodic dividends. The purposes of the plan are to reward the staff for creative talents and recommendations for improvements; to involve the staff in the concept of being partially responsible for increased profitability of the practice; to encourage long-term employment; and to base increases in staff remuneration on profits rather than simply on seniority. An example of the plan is presented which can be modified to fit different practice situations.


[The functional activity and count of the natural killer cells in patients with recently diagnosed diabetes mellitus types I and II].
Eight patients with type I diabetes mellitus (D-I), seven patients with type II diabetes mellitus (D-11) and 8 healthy donors were examined. The disease standing did not exceed 1 year since the moment of the diagnosis establishment. The patients with D-I manifested activation of natural killers (NK) as compared to their activity in the donors and patients with D-II (76.05 +/- 6.5%, 52.33 +/- 9.55% and 55.39 +/- 10.63%, respectively, p less than 0.01) in the presence of the attenuated response of NK to interleukin-2 and alpha-interferon, determined by NK prestimulation. The amount of NK (CD16-positive) in D-I was significantly less than in the donors and patients with D-II. The high activity of NK in D-I correlated with an increase of receptor expression for transferrin on the mononuclear cells of peripheral blood. At the same time 5 out of the 8 patients with D-I and 2 patients with D-II out of the 7 demonstrated the rise of serum alpha-interferon (in the titer 1:40 and over). Activation of NK and the rise of serum interferon may be due to viral etiology of the disease and may play a role in the autoimmune process in patients suffering from D-I.


Bladder Injury During Cesarean Delivery.
Cesarean section is the most common surgery performed in the United States with over 30% of deliveries occurring via this route. This number is likely to increase given decreasing rates of vaginal birth after cesarean section (VBAC) and primary cesarean delivery on maternal request, which carries the inherent risk for intraoperative complications. Urologic injury is the most common injury at the time of either obstetric or gynecologic surgery, with the bladder being the most frequent organ damaged. Risk factors for bladder injury during cesarean section include previous cesarean delivery, adhesions, emergent cesarean delivery, and cesarean section performed at the time of the second stage of labor. Fortunately, most bladder injuries are recognized at the time of surgery, which is important, as quick recognition and repair are associated with a significant reduction in patient mortality. Although cesarean delivery is a cornerstone of obstetrics, there is a paucity of data in the literature either supporting or refuting specific techniques that are performed today. There is evidence to support double-layer closure of the hysterotomy, the routine use of adhesive barriers, and performing a Pfannenstiel skin incision versus a vertical midline subumbilical incision to decrease the risk for bladder injury during cesarean section. There is also no evidence that supports the creation of a bladder flap, although routinely performed during cesarean section, as a method to reduce the risk of bladder injury. Finally, more research is needed to determine if indwelling catheterization, exteriorization of the uterus, and methods to extend hysterotomy incision lead to bladder injury.


Pathways in Skeletal Muscle: Protein Signaling and Insulin Sensitivity after Exercise Training and Weight Loss Interventions in Middle-Aged and Older Adults.
Aging and obesity contribute to insulin resistance with skeletal muscle being critically important for maintaining whole-body glucose homeostasis. Both exercise and weight loss are lifestyle interventions that can affect glucose metabolism. The purpose of this study was to examine the effects of a six-month trial of aerobic exercise training or weight loss on signaling pathways in skeletal muscle in the basal condition and during hyperinsulinemia during a glucose clamp in middle-aged and older adults. Overweight and obese men and women aged 50-70 years were randomly allocated and completed six months of either weight loss (WL) (n = 18) or 3x/week aerobic exercise training (AEX) (n = 17). WL resulted in 10% weight loss and AEX increased maximal oxygen consumption (VO2max) (both p < 0.001). Insulin sensitivity (hyperinsulinemic-euglycemic 80 mU·m-2·min-1 clamp) increased in WL and AEX (both p < 0.01). In vivo insulin stimulation increased phosphorylation/total protein ratio (P/T) of protein kinase B (Akt), glycogen synthase kinase 3 beta (GSK-β3), 70 kDa ribosomal protein S6 kinase (p70S6k), insulin receptor substrate 1 (IRS-1), and insulin receptor (IR) expression (all p < 0.05) but not P/T extracellular regulated kinase ½ (ERK1/2), c-jun N-terminal kinases (JNK), p38 mitogen-activated protein kinases (p38), or insulin-like growth factor 1 receptor (IGF-1R). There were differences between WL and AEX in the change in basal Akt P/T (p = 0.05), GSK-3β P/T ratio (p < 0.01), p70S6k (p < 0.001), ERK1/2 (p = 0.01) P/T ratio but not p38, JNK, IRS-1, and IGF-1R P/T ratios. There was a difference between WL and AEX in the insulin stimulation changes in GSK3 which increased more after WL than AEX (p < 0.05). In the total group, changes in M were associated with changes in basal total GSK-3β and basal total p70Sk as well as insulin stimulation of total p70Sk. Protein signaling in skeletal muscle provides insight as to mechanisms for improvements in insulin sensitivity in aging and obesity.


Characterization of nucleolar SUMO isopeptidases unveils a general p53-independent checkpoint of impaired ribosome biogenesis.
Ribosome biogenesis is a multi-step process, in which a network of trans-acting factors ensures the coordinated assembly of pre-ribosomal particles in order to generate functional ribosomes. Ribosome biogenesis is tightly coordinated with cell proliferation and its perturbation activates a p53-dependent cell-cycle checkpoint. How p53-independent signalling networks connect impaired ribosome biogenesis to the cell-cycle machinery has remained largely enigmatic. We demonstrate that inactivation of the nucleolar SUMO isopeptidases SENP3 and SENP5 disturbs distinct steps of 40S and 60S ribosomal subunit assembly pathways, thereby triggering the canonical p53-dependent impaired ribosome biogenesis checkpoint. However, inactivation of SENP3 or SENP5 also induces a p53-independent checkpoint that converges on the specific downregulation of the key cell-cycle regulator CDK6. We further reveal that impaired ribosome biogenesis generally triggers the downregulation of CDK6, independent of the cellular p53 status. Altogether, these data define the role of SUMO signalling in ribosome biogenesis and unveil a p53-independent checkpoint of impaired ribosome biogenesis.


The constant threat of terrorism: stress levels and coping strategies amongst university students of Karachi.
To assess the levels of stress in the face of terrorism and the adopted coping strategies, amongst the student population of universities in Karachi. A descriptive, cross sectional study was conducted on undergraduate students from four universities of Karachi. Self-administered questionnaires were filled out by 291 students. Pearson Chi-Square test was used to assess associations between stress levels and different variables at a level of significance of 0.05%. A total of 65.8% of the students had mild stress levels, 91.5% of university students were exposed to terrorism through television, while only 26.5% students reported personal exposure to terrorism. 67.4% students were forbidden by their parents to go out (p = 0.002). Most of those who had self exposure to an attack were the ones whose parents forbade them from going out (p = 0.00). Most commonly used coping strategy was increased faith in religion. Irritability was the most common stress symptom. A majority of students studying in universities of Karachi had mild stress levels due to the constant threat of terrorism whereas a minority had severe stress levels. Possible reasons for resilience and only mild stress levels could be the history of Karachi's internal conflicts and its prolonged duration of being exposed to terrorism. These students who are positive for stress need to be targeted for counseling either through the media or through their universities. More extensive research is needed in this area.


The apolipoprotein(a) component of lipoprotein(a) mediates binding to laminin: contribution to selective retention of lipoprotein(a) in atherosclerotic lesions.
Lipoprotein(a) [Lp(a)] entrapment by vascular extracellular matrix may be important in atherogenesis. We sought to determine whether laminin, a major component of the basal membrane, may contribute to Lp(a) retention in the arterial wall. First, immunohistochemistry experiments were performed to examine the relative distribution of Lp(a) and laminin in human carotid artery specimens. There was a high degree of co-localization of Lp(a) and laminin in atherosclerotic specimens, but not in non-atherosclerotic sections. We then studied the binding interaction between Lp(a) and laminin in vitro. ELISA experiments showed that native Lp(a) particles and 17K and 12K recombinant apolipoprotein(a) [r-apo(a)] variants interacted strongly with laminin whereas LDL, apoB-100, and the truncated KIV(6-P), KIV(8-P), and KIV(9-P) r-apo(a) variants did not. Overall, the ELISA data demonstrated that Lp(a) binding to laminin is mediated by apo(a) and a combination of the lysine analogue epsilon-aminocaproic acid and salt effectively decreases apo(a) binding to laminin. Secondary binding analyses with 125I-labeled r-apo(a) revealed equilibrium dissociation constants (K(d)) of 180 and 360 nM for the 17K and 12K variants binding to laminin, respectively. Such similar K(d) values between these two r-apo(a) variants suggest that isoform size does not appear to influence apo(a) binding to laminin. In summary, our data suggest that laminin may bind to apo(a) in the atherosclerotic intima, thus contributing to the selective retention of Lp(a) in this milieu.


A new, structurally nonredundant, diverse data set of protein-protein interfaces and its implications.
Here, we present a diverse, structurally nonredundant data set of two-chain protein-protein interfaces derived from the PDB. Using a sequence order-independent structural comparison algorithm and hierarchical clustering, 3799 interface clusters are obtained. These yield 103 clusters with at least five nonhomologous members. We divide the clusters into three types. In Type I clusters, the global structures of the chains from which the interfaces are derived are also similar. This cluster type is expected because, in general, related proteins associate in similar ways. In Type II, the interfaces are similar; however, remarkably, the overall structures and functions of the chains are different. The functional spectrum is broad, from enzymes/inhibitors to immunoglobulins and toxins. The fact that structurally different monomers associate in similar ways, suggests "good" binding architectures. This observation extends a paradigm in protein science: It has been well known that proteins with similar structures may have different functions. Here, we show that it extends to interfaces. In Type III clusters, only one side of the interface is similar across the cluster. This structurally nonredundant data set provides rich data for studies of protein-protein interactions and recognition, cellular networks and drug design. In particular, it may be useful in addressing the difficult question of what are the favorable ways for proteins to interact. (The data set is available at http://protein3d.ncifcrf.gov/~keskino/ and http://home.ku.edu.tr/~okeskin/INTERFACE/INTERFACES.html.)


Oleic acid in Angus and Hanwoo (Korean native cattle) fat reduced the fatty acid synthase activity in rat adipose tissues.
This study aimed to determine the blood lipid profiles, fatty acid composition, and lipogenic enzyme activities in rat adipose tissues as affected by the Angus beef fat (ABF) and Hanwoo beef fat (HBF) containing high oleic acid (OA) content. We assigned 60 Sprague Dawley rats with a mean bodyweight of 249 ± 3.04 g to three groups (n = 20 each) to receive diets containing 7% coconut oil (CON), 7% ABF, or 7% HBF. The OA content was highest in the HBF (45.23%) followed by ABF (39.51%) and CON (6.10%). The final body weight of the HBF-fed group was significantly increased, probably due to increased feed intake, indicating the palatability of the diet. The HBF and ABF significantly increased high-density lipoprotein cholesterol (HDL-C), decreased triglyceride (TG) and total cholesterol (TC) levels, and also tended to attenuate glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels in the bloodstream of the rats compared to CON. As compared to CON, lauric, myristic, and palmitic acids were significantly lower, and those of OA and α-linolenic acid (ALA) were significantly higher in the adipose tissues of HBF and ABF-fed groups. The HBF and ABF also reduced lipogenesis as induced by depleted fatty acid synthase (FAS) activity in rat adipose tissues. Nevertheless, between the two fats, HBF showed high feed intake due to its high palatability but reduced lipogenic enzyme activity, specifically that of FAS, and increased HDL-C, decreased TC and TG levels in the bloodstream, reduced saturated fatty acids (SFA), and increased oleic and ALA contents in rat adipose tissues indicating that HBF consumption does not pose significant risks of cardiovascular disease.


Mutations in the MRPS28 gene encoding the small mitoribosomal subunit protein bS1m in a patient with intrauterine growth retardation, craniofacial dysmorphism and multisystemic involvement.
Mitochondria contain a dedicated translation system, which is responsible for the intramitochondrial synthesis of 13 mitochondrial DNA (mtDNA)-encoded polypeptides essential for the biogenesis of oxidative phosphorylation (OXPHOS) complexes I and III-V. Mutations in nuclear genes encoding factors involved in mitochondrial translation result in isolated or multiple OXPHOS deficiencies and mitochondrial disease. Here, we report the identification of disease-causing variants in the MRPS28 gene, encoding the small mitoribosomal subunit (mtSSU) protein bS1m in a patient with intrauterine growth retardation, craniofacial dysmorphism and developmental delay. Whole exome sequencing helped identify a seemingly homozygous missense variant NM_014018.2:c.356A>G, p.(Lys119Arg) which affected a highly conserved lysine residue. The variant was present in the mother in a heterozygous state, but not in the father who likely carried a large deletion spanning exon 2 and parts of introns 1 and 2 that could account for the apparent homozygosity of the patient. Polymerase chain reaction (PCR) amplification and Sanger sequencing of MRPS28 cDNA from patient fibroblasts revealed the presence of a truncated MRPS28 transcript, which lacked exon 2. Molecular and biochemical characterization of patient fibroblasts revealed a decrease in the abundance of the bS1m protein, decreased abundance of assembled mtSSU and inhibited mitochondrial translation. Consequently, OXPHOS biogenesis and cellular respiration were compromised in these cells. Expression of wild-type MRPS28 restored mitoribosomal assembly, mitochondrial translation and OXPHOS biogenesis, thereby demonstrating the deleterious nature of the identified MRPS28 variants. Thus, MRPS28 joins the increasing number of nuclear genes encoding mitoribosomal structural proteins linked to mitochondrial disease.


Lung cancer in US women: a contemporary epidemic.
Lung cancer is the leading cause of cancer death in US women and is responsible for as many deaths as breast cancer and all gynecological cancers combined. Most lung cancer is caused by cigarette smoke. Despite all that is known about the devastating effects of cigarettes, one quarter of women in the United States continue to smoke. Women are targeted in tobacco advertising, and teenage girls are often drawn to cigarette smoking under a variety of social pressures. Following the increase in smoking, the death rate from lung cancer in US women rose 600% from 1930 to 1997. Women may be more susceptible than men to the carcinogenic properties of cigarette smoke. In addition, differences in the biology of lung cancer exist between the 2 sexes with higher levels of DNA adduct formation, increased CYP1A1 expression, decreased DNA repair capacity, and increased incidence of K-ras gene mutations in women. The novel estrogen receptor beta has also been detected in lung tumors and suggests that estrogen signaling may have a biological role in tumorigenesis. Given these differences and given the enormous toll this disease has on US women, undertaking sex-specific research in lung cancer is crucial. Finally, disseminating information about this epidemic may prevent a similar epidemic in other parts of the world where women are just now becoming addicted to tobacco.


Chronic, low-level exposure to diisopropylfluorophosphate causes protracted impairment of spatial navigation learning.
Chronic, low-level exposure to cholinesterase inhibitor organophosphate (OP) insecticides or chemical warfare agents produces abnormalities in CNS acetylcholine (ACh) function, and in humans, may be associated with impaired cognitive function as well after withdrawal from such exposure. The purpose of the present study was to identify the severity of impairment in spatial learning of rats following protracted withdrawal from chronic, low-level exposure to the OP agent diisopropylfluorophosphate (DFP). Assessment of spatial learning began either 3 or 17 days after completion of a 14-day DFP treatment regimen (50, 250, or 500 micrograms/kg). During the 14-day treatment regimen, spontaneous activity and olfactory behaviors were suppressed, effects which subsided with repeated exposure to the 250 micrograms/kg dose regimen. In contrast, both behaviors were stimulated by exposure to the 50 micrograms/kg dose regimen, as was body weight gain. Performance of the spatial test of working memory was impaired for up to 21 days after withdrawal from treatment with a 250 micrograms/kg dose of DFP. AChE activity in the frontal cortex and hippocampus was suppressed to 42.58% and 50.35% of control levels, respectively, 3 days after completion of the DFP (250 micrograms/kg) treatment regimen. By 7 days after withdrawal from treatment, AChE activity in the cortex and hippocampus had recovered to 81.87% and 64.61% of control levels, respectively. These levels represent increases in activity of 39.29% and 14.26% in these regions, as compared to AChE activity in 3 days after DFP withdrawal. By 21 days after withdrawal from treatment, AChE in both brain regions had recovered to levels similar to those of controls. Chronic, low-level OP exposure, therefore, produces protracted impairment of working memory after drug withdrawal that is not associated with continued suppression of AChE activity. This impairment may, however, be associated with a decreased rate of AChE recovery in the hippocampus, relative to the cortex. This decreased rate of enzyme recovery may contribute to hippocampal toxicity underlying protracted impairment of working memory.


Phenotypic similarity for rare disease: Ciliopathy diagnoses and subtyping.
Rare diseases are often hard and long to be diagnosed precisely, and most of them lack approved treatment. For some complex rare diseases, precision medicine approach is further required to stratify patients into homogeneous subgroups based on the clinical, biological or molecular features. In such situation, deep phenotyping of these patients and comparing their profiles based on subjacent similarities are thus essential to help fast and precise diagnoses and better understanding of pathophysiological processes in order to develop therapeutic solutions. In this article, we developed a new pipeline of using deep phenotyping to define patient similarity and applied it to ciliopathies, a group of rare and severe diseases caused by ciliary dysfunction. As a French national reference center for rare and undiagnosed diseases, the Necker-Enfants Malades Hospital (Necker Children's Hospital) hosts the Imagine Institute, a research institute focusing on genetic diseases. The clinical data warehouse contains on one hand EHR data, and on the other hand, clinical research data. The similarity metrics were computed on both data sources, and were evaluated with two tasks: diagnoses with EHRs and subtyping with ciliopathy specific research data. We obtained a precision of 0.767 in the top 30 most similar patients with diagnosed ciliopathies. Subtyping ciliopathy patients with phenotypic similarity showed concordances with expert knowledge. Similarity metrics applied to rare disease offer new perspectives in a translational context that may help to recruit patients for research, reduce the length of the diagnostic journey, and better understand the mechanisms of the disease.


Use of Cortical Strut Allograft After Extended Trochanteric Osteotomy in Revision Total Hip Arthroplasty.
Cortical strut allografts restore bone stock and improve postoperative clinical scores after revision total hip arthroplasty (THA). However, use of a cortical strut allograft is implicated in delayed healing of an extended trochanteric osteotomy (ETO). To date, there are no reports directly comparing ETO with or without cortical strut allografts. We reviewed prospectively gathered data on 50 revision THAs performed from 2004-2014 using an ETO. We compared the demographic, radiological, and clinical outcome of patients with (16 hips) and without (34 hips) cortical strut allograft after an ETO. There were no significant differences in Western Ontario McMaster Universities Osteoarthritis Index or Harris Hip Score between the ETOs with and without a cortical strut allograft. Fifteen of the ETOs (94%) with a cortical strut allograft and 31 of the ETOs (91%) without a cortical strut allograft were in situ at final follow-up (P = 1.000). A higher proportion hips with cortical strut allograft (100%, 16 patients) had preoperative Paprosky grade bone loss more than IIIA compared to those without allograft (29%, 10 patients) (P < .001). There were no differences in femoral stem subsidence (P = .207), alignment (P = .934), or migration of the osteotomized fragment (P = .171). Fourteen of the ETOs (88%) in patients with cortical strut allograft united compared to 34 ETOs (100%) in patients without allograft (P = .095). Our study shows that the use of cortical strut allograft during revision THA with ETO does not reduce the rate of union, radiological or clinical outcomes.


catena-Poly[[[di-aqua-bis-(seleno-cyanato-κN)iron(II)]-μ-1,2-bis-(pyridin-4-yl)ethane-κ(2) N:N'] 1,2-bis-(pyridin-4-yl)ethane disolvate dihydrate].
The title compound, {[Fe(NCSe)2(C12H12N2)(H2O)2]·2C12H12N2·2H2O} n , was obtained by the reaction of iron(II) sulfate hepta-hydrate and potassium seleno-cyanate with 1,2-bis-(pyridin-4-yl)ethane (bpa) in water. The Fe(II) cation is coordinated by two N-bonded seleno-cyanate anions, two water mol-ecules and two 1,2-bis-(pyridin-4-yl)ethane (bpa) ligands in a slightly distorted octa-hedral geometry. In addition, two non-coordinating bpa mol-ecules and two water mol-ecules are present. The Fe(II) cation is located on a center of inversion while the coordinating bpa ligand is located on a twofold rotation axis. The Fe(II) cations are linked by the bpa ligands into chains along the b-axis direction, which are further connected into layers perpedicular to the c axis by O-H⋯N and O-H⋯O hydrogen bonds to the non-coordin-ating bpa and the water mol-ecules. The crystal studied was twinned by pseudo-merohedry (180° rotation along c*; contribution of the minor twin component 3.7%).


Analysing nystagmus waveforms: a computational framework.
We present a new computational approach to analyse nystagmus waveforms. Our framework is designed to fully characterise the state of the nystagmus, aid clinical diagnosis and to quantify the dynamical changes in the oscillations over time. Both linear and nonlinear analyses of time series were used to determine the regularity and complexity of a specific homogenous phenotype of nystagmus. Two-dimensional binocular eye movement recordings were carried out on 5 adult subjects who exhibited a unilateral, uniplanar, vertical nystagmus secondary to a monocular late-onset severe visual loss in the oscillating eye (the Heimann-Bielschowsky Phenomenon). The non-affected eye held a central gaze in both horizontal and vertical planes (± 10 min. of arc). All affected eyes exhibited vertical oscillations, with mean amplitudes and frequencies ranging from 2.0°-4.0° to 0.25-1.5 Hz, respectively. Unstable periodic orbit analysis revealed only 1 subject exhibited a periodic oscillation. The remaining subjects were found to display quasiperiodic (n = 1) and nonperiodic (n = 3) oscillations. Phase space reconstruction allowed attractor identification and the computation of a time series complexity measure-the permutation entropy. The entropy measure was found to be able to distinguish between a periodic oscillation associated with a limit cycle attractor, a quasiperiodic oscillation associated with a torus attractor and nonperiodic oscillations associated with higher-dimensional attractors. Importantly, the permutation entropy was able to rank the oscillations, thereby providing an objective index of nystagmus complexity (range 0.15-0.21) that could not be obtained via unstable periodic orbit analysis or attractor identification alone. These results suggest that our framework provides a comprehensive methodology for characterising nystagmus, aiding differential diagnosis and also permitting investigation of the waveforms over time, thereby facilitating the quantification of future therapeutic managements. In addition, permutation entropy could provide an additional tool for future oculomotor modelling.


Different influences on lexical priming for integrative, thematic, and taxonomic relations.
Word pairs may be integrative (i.e., combination of two concepts into one meaningful entity; e.g., fruit-cake), thematically related (i.e., connected in time and place; e.g., party-cake), and/or taxonomically related (i.e., shared features and category co-members; e.g., muffin-cake). Using participant ratings and computational measures, we demonstrated distinct patterns across measures of similarity and co-occurrence, and familiarity for each relational construct in two different item sets. In a standard lexical decision task (LDT) with various delays between prime and target presentation (SOAs), target RTs and priming magnitudes were consistent across the three relations for both item sets. However, across the SOAs, there were distinct patterns among the three relations on some of the underlying measures influencing target word recognition (LSA, Google, and BEAGLE). These distinct patterns suggest different mechanisms of lexical priming and further demonstrate that integrative relations are distinct from thematic and taxonomic relations.


Genomic diversity is similar between Atlantic Forest restorations and natural remnants for the native tree Casearia sylvestris Sw.
The primary focus of tropical forest restoration has been the recovery of forest structure and tree taxonomic diversity, with limited attention given to genetic conservation. Populations reintroduced through restoration plantings may have low genetic diversity and be genetically structured due to founder effects and genetic drift, which limit the potential of restoration to recover ecologically resilient plant communities. Here, we studied the genetic diversity, genetic structure and differentiation using single nucleotide polymorphisms (SNP) markers between restored and natural populations of the native tree Casearia sylvestris in the Atlantic Forest of Brazil. We sampled leaves from approximately 24 adult individuals in each of the study sites: two restoration plantations (27 and 62 years old) and two forest remnants. We prepared and sequenced a genotyping-by-sequencing library, SNP markers were identified de novo using Stacks pipeline, and genetic parameters and structure analyses were then estimated for populations. The sequencing step was successful for 80 sampled individuals. Neutral genetic diversity was similar among restored and natural populations (AR = 1.72 ± 0.005; HO = 0.135 ± 0.005; HE = 0.167 ± 0.005; FIS = 0.16 ± 0.022), which were not genetically structured by population subdivision. In spite of this absence of genetic structure by population we found genetic structure within populations but even so there is not spatial genetic structure in any population studied. Less than 1% of the neutral alleles were exclusive to a population. In general, contrary to our expectations, restoration plantations were then effective for conserving tree genetic diversity in human-modified tropical landscapes. Furthermore, we demonstrate that genotyping-by-sequencing can be a useful tool in restoration genetics.


Associations between relationship status and day-to-day health behaviors and weight among diverse young adults.
Previous research has shown strong positive associations between physical and psychological health outcomes and being in a committed relationship, such as marriage; however, little research has investigated whether being in a committed relationship is protective for day-to-day health behaviors such as dietary patterns and physical activity. This research examined associations between relationship status and day-to-day health behaviors (e.g., dietary intake, physical activity) and weight status among a diverse cohort of young adults. This cross-sectional study used data from Project EAT-III, a 10-year longitudinal population-based study (N = 1,853) of Midwest young adults. Young adult participants had an average age of 25.3 years, and were 45% male and 55% female. Participants were socioeconomically and racially/ethnically diverse, including 48.4% White, 18.6% African American, 5.9% Hispanic, 19.6% Asian, 3.3% Native American, and 4.2% mixed or other race/ethnicity. Results indicated that married men were more likely to be overweight/obese (body mass index ≥ 25) compared with single/casually dating and committed dating/engaged men. Married women were more likely to eat breakfast ≥5 times per week compared with women in other relationship categories. No differences were observed in other health behaviors by relationship status. There were no significant interactions by race/ethnicity. Relationship status seems largely unrelated to young adults' participation in physical activity and dietary behaviors. However, findings suggest that being married may be a risk factor for overweight/obesity in young adult men and may be a protective factor for health-related behaviors associated with overweight/obesity such as breakfast intake for young adult women.


Multiple pathways inhibit NHEJ at telomeres.
The nonhomologous end-joining (NHEJ) repair pathway is inhibited at telomeres, preventing chromosome fusion. In budding yeast Saccharomyces cerevisiae, the Rap1 protein directly binds the telomere sequences and is required for NHEJ inhibition. Here we show that the Rap1 C-terminal domain establishes two parallel inhibitory pathways through the proteins Rif2 and Sir4. In addition, the central domain of Rap1 inhibits NHEJ independently of Rif2 and Sir4. Thus, Rap1 establishes several independent pathways to prevent telomere fusions. We discuss a possible mechanism that would explain Rif2 multifunctionality at telomeres and the recent evolutionary origin of Rif2 from an origin recognition complex (ORC) subunit.


Role of osteopontin in the pathogenesis of bleomycin-induced pulmonary fibrosis.
Pulmonary fibrosis is initiated by migration, adhesion, and proliferation of fibroblasts. Osteopontin (OPN) is one of the cytokines produced by activated macrophages and mediates various functions, including cell attachment and migration, by interacting with alphav integrin. In this study, we have investigated the role of OPN in the pathogenesis of pulmonary fibrosis. We developed a mouse model for pulmonary fibrosis by intratracheal instillation of bleomycin (BLM). OPN was strongly expressed in alveolar macrophages accumulating in the fibrotic area of the lung. OPN messenger RNA (mRNA) in the lung was notably induced by BLM instillation, and the development of the fibrotic process was associated with an increase in the expression of OPN mRNA and protein. In vitro, recombinant OPN enhanced migration, adhesion, and platelet-derived growth factor (PDGF)-mediated DNA synthesis of murine fibroblast cell line NIH3T3. These effects of OPN on fibroblasts were significantly suppressed by addition of antimouse alphav integrin monoclonal antibody (RMV-7). Furthermore, treatment of mice with RMV-7 repressed the extent of pulmonary fibrosis in this model. Conclusively, these data suggest that OPN produced by alveolar macrophages functions as a fibrogenic cytokine that promotes migration, adhesion, and proliferation of fibroblasts in the development of BLM-induced pulmonary fibrosis.


Effect of Intravenous Iron Supplementation on Iron Stores in Non-Anemic Iron-Deficient Patients with Hereditary Hemorrhagic Telangiectasia.
In hereditary hemorrhagic telangiectasia (HHT), frequent episodes of nasal and gastrointestinal bleeding commonly lead to iron-deficiency with or without anemia. In the retrospective study presented here we assessed the iron stores, as determined by analysis of plasma ferritin, during oral and intravenous iron supplementation, respectively, in a population of iron-deficient non-anemic HHT patients who were inadequately iron-repleted by oral supplementation. A switch from oral to intravenous iron supplementation was associated with a significant increase in ferritin in this patient population.


Identification of a 3-deoxy-D-manno-octulosonic acid biosynthetic operon in Moraxella catarrhalis and analysis of a KdsA-deficient isogenic mutant.
Lipooligosaccharide (LOS), a predominant surface-exposed component of the outer membrane, has been implicated as a virulence factor in the pathogenesis of Moraxella catarrhalis infections. However, the critical steps involved in the biosynthesis and assembly of M. catarrhalis LOS currently remain undefined. In this study, we used random transposon mutagenesis to identify a 3-deoxy-D-manno-octulosonic acid (KDO) biosynthetic operon in M. catarrhalis with the gene order pyrG-kdsA-eno. The lipid A-KDO molecule serves as the acceptor onto which a variety of glycosyl transferases sequentially add the core and branch oligosaccharide extensions for the LOS molecule. KdsA, the KDO-8-phosphate synthase, catalyzes the first step of KDO biosynthesis and is an essential enzyme in gram-negative enteric bacteria for maintenance of bacterial viability. We report the construction of an isogenic M. catarrhalis kdsA mutant in strain 7169 by allelic exchange. Our data indicate that an LOS molecule consisting only of lipid A and lacking KDO glycosylation is sufficient to sustain M. catarrhalis survival in vitro. In addition, comparative growth and susceptibility assays were performed to assess the sensitivity of 7169kdsA11 compared to that of the parental strain. The results of these studies demonstrate that the native LOS molecule is an important factor in maintaining the integrity of the outer membrane and suggest that LOS is a critical component involved in the ability of M. catarrhalis to resist the bactericidal activity of human sera.


Two food-assisted maternal and child health nutrition programs helped mitigate the impact of economic hardship on child stunting in Haiti.
Rigorous evaluations of food-assisted maternal and child health and nutrition programs are stymied by the ethics of randomizing recipients to a control treatment. Using nonexperimental matching methods, we evaluated the effect of 2 such programs on child linear growth in Haiti. The 2 well-implemented programs offered the same services (food assistance, behavior change communication, and preventive health services) to pregnant and lactating women and young children. They differed in that one (the preventive program) used blanket targeting of all children 6-23 mo, whereas the other (the recuperative program) targeted underweight (weight-for-age Z score < -2) children 6-59 mo, as traditionally done. We estimated program effects on height-for-age Z scores (HAZ) and stunting (HAZ < -2) by comparing outcomes of children in program areas with matched children from comparable populations in the Haiti Demographic and Health Survey. Children 12-41 mo in the preventive and recuperative program areas had lower prevalence of stunting than those in the matched control group [16 percentage points (pp) lower in preventive and 11 pp in recuperative]. Children in the 2 program areas also were more likely than those in the matched control group to be breast-fed up to 24 mo (25 pp higher in preventive, 22 in recuperative) and children 12 mo and older were more likely to have received the recommended full schedule of vaccinations (32 pp higher in preventive, 31 in recuperative). Both programs improved targeted behaviors and protected child growth in a time of deteriorating economic circumstances.


Promoting Community Pharmacy Practice for Chronic Obstructive Pulmonary Disease (COPD) Management: A Systematic Review and Logic Model.
This study aimed 1) to identify and analyse the professional services provided by community pharmacists for chronic obstructive pulmonary disease (COPD) management; and 2) to develop a logic model for community pharmacy practice for COPD management. A systematic review with a logic model was applied. English-language databases (PubMed, Web of Science, Embase, and Scopus) and a Chinese database (CNKI) were searched for articles published between January 2009 and June 2019. Studies concerning pharmacists and COPD were identified to screen for studies that focused on professional services provided at a community pharmacy level. Evidence on economic, clinical, and humanistic outcomes of interventions was summarized. Twenty-five articles were included in this study. Four categories of COPD-related interventions by community pharmacists were identified: 1) primary prevention; 2) early detection; 3) therapy management; and 4) long-term health management. The most common outputs examined were improvement in inhaler technique, medication adherence, and rate of smoking cessation. The clinical (improved quality of life, reduced frequency and severity of symptoms and exacerbation), humanistic (patient satisfaction), and economic (overall healthcare costs) outcomes were tested for some interventions through clinical studies. Contextual factors concerning pharmacists, healthcare providers, patients, facilities, clinic context, and socio-economic aspects were also identified. Studies in the literature have proposed and examined different components of professional services provided by community pharmacists for COPD management. However, relationships among outcomes, comprehensive professional services of community pharmacists, and contextual factors have not been systematically tested. More well-designed, rigorous studies with more sensitive and specific outcomes measures need to be conducted to assess the effect of community pharmacy practice for COPD management.


Results of the Lecompte procedure in malposition of the great arteries and pulmonary obstruction.
Assessment of the Lecompte procedure, our repair method of choice in malposition of the great arteries with pulmonary stenosis. A retrospective analysis of 42 patients (median age at operation, 1.4 years) operated on between 1986 and 1999 for various forms of great artery malposition, ventricular septal defect, and pulmonary stenosis. Relevant associated findings included the insertion of a tricuspid papillary muscle on the conal septum (nine patients), absence of conal septum (six patients), hypoplasia of a side pulmonary artery (four patients), and hypoplasia of the right ventricle (one patient). A preliminary systemico-pulmonary shunt was created in 28 patients and a cavo-pulmonary anastomosis in one patient. At operation, the conal septum (whenever present) was resected (36 patients), the pulmonary bifurcation was usually translocated over the ascending aorta (37 patients), and the main pulmonary artery was enlarged with a patch of pericardium. A monocusp valve was fashioned within the patch in 40 patients. The follow-up information was complete in 32 patients and ranged from 0.4 to 14 years (mean, 5.4+/-3.2 years). The survival rate at 5 years was 92+/-5%. Three patients died post-operatively (mortality, 7%) and none during follow-up. The freedom from reoperation was 86+/-8 and 51+/-22% at 5 and 10 years, respectively. Six patients were reoperated, all for a pulmonary stenosis. Calcification of the monocusp patch was present in all. Pulmonary stenosis developed in three further patients: one underwent percutaneous dilatation and two are awaiting surgery. No procedural factors thought to have a potential correlation with the development of right ventricular outflow tract stenosis could be individualized on univariate analysis. The Lecompte procedure, which allows early repair of these defects, provides overall good results. The need to reoperate on the right or left ventricular outflow tract seems reduced in comparison with the Rastelli operation, the other alternative.


A novel chromatin insulator regulates the chicken folate receptor gene from the influence of nearby constitutive heterochromatin and the β-globin locus.
The three-dimensional architecture of genomes provides new insights about genome organization and function, but many aspects remain unsolved at the local genomic scale. Here we investigate the regulation of two erythroid-specific loci, a folate receptor gene (FOLR1) and the β-globin gene cluster, which are separated by 16kb of constitutive heterochromatin. We found that in early erythroid differentiation the FOLR1 gene presents a permissive chromatin configuration that allows its expression. Once the transition to the next differentiation state occurs, the heterochromatin spreads into the FOLR1 domain, concomitant with the dissociation of CTCF from a novel binding site, thereby resulting in irreversible silencing of the FOLR1 gene. We demonstrate that the sequences surrounding the CTCF-binding site possess classical insulator properties in vitro and in vivo. In contrast, the chicken cHS4 β-globin insulator present on the other side of the heterochromatic segment is in a constitutive open chromatin configuration, with CTCF constantly bound from the early stages of erythroid differentiation. Therefore, this study demonstrates that the 16kb of constitutive heterochromatin contributes to silencing of the FOLR1 gene during erythroid differentiation.


A Toolkit for High Resolution Imaging of Cell Division and Phytohormone Signaling in Legume Roots and Root Nodules.
Legume plants benefit from a nitrogen-fixing symbiosis in association with rhizobia hosted in specialized root nodules. Formation of root nodules is initiated by de novo organogenesis and coordinated infection of these developing lateral root organs by rhizobia. Both bacterial infection and nodule organogenesis involve cell cycle activation and regulation by auxin and cytokinin is tightly integrated in the process. To characterize the hormone dynamics and cell division patterns with cellular resolution during nodulation, sensitive and specific sensors suited for imaging of multicellular tissues are required. Here we report a modular toolkit, optimized in the model legume Lotus japonicus, for use in legume roots and root nodules. This toolkit includes synthetic transcriptional reporters for auxin and cytokinin, auxin accumulation sensors and cell cycle progression markers optimized for fluorescent and bright field microscopy. The developed vectors allow for efficient one-step assembly of multiple units using the GoldenGate cloning system. Applied together with a fluorescence-compatible clearing approach, these reporters improve imaging depth and facilitate fluorescence examination in legume roots. We additionally evaluate the utility of the dynamic gravitropic root response in altering the timing and location of auxin accumulation and nodule emergence. We show that alteration of auxin distribution in roots allows for preferential nodule emergence at the outer side of the bend corresponding to a region of high auxin signaling capacity. The presented tools and procedures open new possibilities for comparative mutant studies and for developing a more comprehensive understanding of legume-rhizobia interactions.


Assessment of Potential Risk Factors for the Development of Persistent Postural-Perceptual Dizziness: A Case-Control Pilot Study.
Objectives: (1) To assess whether neuroticism, state anxiety, and body vigilance are higher in patients with persistent postural-perceptual dizziness (PPPD) compared to a recovered vestibular patient group and a non-dizzy patient group; (2) To gather pilot data on illness perceptions of patients with PPPD. Materials and Methods: 15 cases with PPPD and two control groups: (1) recovered vestibular patients (n = 12) and (2) non-dizzy patients (no previous vestibular insult, n = 12). Main outcome measures: Scores from the Big Five Inventory (BFI) of personality traits, Generalized Anxiety Disorder - 7 (GAD-7) scale, Body Vigilance Scale (BVS), Dizziness Handicap Inventory (DHI), modified Vertigo Symptom Scale (VSS) and Brief Illness Perception Questionnaire (BIPQ). Results: Compared to non-dizzy patients, PPPD cases had higher neuroticism (p = 0.02), higher introversion (p = 0.008), lower conscientiousness (p = 0.03) and higher anxiety (p = 0.02). There were no differences between PPPD cases and recovered vestibular patients in BFI and GAD-7. PPPD cases had higher body vigilance to dizziness than both control groups and their illness perceptions indicated higher levels of threat than recovered vestibular patients. Conclusion: PPPD patients showed statistically significant differences to non-dizzy patients, but not recovered vestibular controls in areas such as neuroticism and anxiety. Body vigilance was increased in PPPD patients when compared with both recovered vestibular and non-dizzy patient groups. PPPD patients also exhibited elements of negative illness perception suggesting that this may be the key element driving the development of PPPD. Large scale studies focusing on this area in the early stages following vestibular insult are needed.


Osteoporosis: an evolutionary perspective.
Increased life expectancy has led to an overall aging of the population and greater numbers of elderly people. Therefore, the number of people with osteoporosis has increased substantially, accompanied with an epidemic of hip fractures. Osteoporosis is an age-related systemic condition that naturally occurs, among mammals, only in humans. Osteoporosis is known to be highly heritable. However, assuming a genetic determinant for this post-reproductive disease to be transmitted from one generation to the next is counter-intuitive, based on the principles of human evolution, I will attempt to provide an explanation of the phenomenon from the point of view of evolution, selection, and changed environment in humans, which contributed to human longevity, while on other hand, contribute to diseases of civilization, including osteoporosis. There is a need to delve into evolution of human species in search for adaptive patterns to a specific environment that humans are operating in the last couple of millennia, to clarify whether "good" and "bad" genes exist, and how to find and correct them. The answer to the above questions will help us to identify causes of the current epidemic of osteoporosis and to pin-point a tailored treatment.


[Acetylsalicylic acid resistance--clinical diagnosis with unclear mechanism].
A review on the subject of aspirin resistance and its role in vascular diseases is presented. Although the clinical diagnosis of aspirin resistance is frequently made, little is known about its biochemical background. Only a few follow-up studies, with varying design, have dealt with the possible association between an aspirin resistant phenotype and clinical outcome in patients with atherothrombosis. However, it was recently shown that ibuprofen acts as a competitive inhibitor in the blockage of COX-1. This pharmacodynamic interaction results in secondary aspirin resistance, which may have clinical significance in patients taking both medicines. With the complex nature of vascular diseases in mind, it is not surprising that aspirin used as a single preventive strategy fails in many cases. At present, there is no clear evidence that treatment failure is associated with a particular aspirin resistant phenotype.


Hypothesis: the significance of Winterbottom's sign.
Swollen glands in the neck in African sleeping sickness is usually considered to be a sign of peripheral trypanosomiasis without cerebral involvement. Experimental evidence of connection between these glands and the ventricles of the brain is reviewed. The evidence suggests that Winterbottom's sign may indicate also a cerebral infection. It also suggests that trypanosomes may enter the brain via the lymphatic system.


Radio science with voyager 2 at saturn: atmosphere and ionosphere and the masses of mimas, tethys, and iapetus.
Voyager 2 radio occultation measurements of Saturn's atmosphere probed to the 1.2-bar pressure level, where the temperature was 143 +/- 6 K and the lapse rate apparently equaled the dry adiabatic value of 0.85 K per kilometer. The tropopause at both mid-latitude occultation locations (36.5 degrees N and 31 degrees S) was at a pressure level of about 70 millibars and a temperature of approximately 82 K. The stratospheric structures were very similar with the temperature rising to about 140 K at the 1-millibar pressure level. The peak electron concentrations sensed were 1.7 x 10(4) and 0.64 x 10(4) per cubic centimeter in the predawn (31 degrees S) and late afternoon (36.5 degrees N) locations. The topside plasma scale heights were about 1000 kilometers for the late afternoon profile, and 260 kilometers for the lower portions and 1100 kilometers for the upper portions of the topside predawn ionosphere. Radio measurements of the masses of Tethys and Iapetus yield (7.55 +/- 0.90) x 10(20) and (18.8 +/- 1.2) x 10(20) kilograms respectively; the Tethys-Mimas resonance theory then provides a derived mass for Afimas of (0.455 +/- 0.054) x 10(20) kilograms. These values for Tethys and Mimas represent major increases from previously accepted ground-based values, and appear to reverse a suggested trend of increasing satellite density with orbital radius in the Saturnian system. Current results suggest the opposite trend, in which the intermediate-sized satellites of Saturn may represent several classes of objects that differ with respect to the relative amounts of water, ammonia, and methane ices incorporated at different temperatures during formation. The anomalously low density of lapetus might then be explained as resulting from a large hydrocarbon content, and its unusually dark surface markings as another manifestation of this same material.


[Von Meyenburg complexes in the liver: not metastases].
A 74-year-old woman underwent a laparotomy for a rectal carcinoma. Multiple lesions of the liver were discovered as incidental findings. Histopathology revealed that these were Von Meyenburg complexes (VMCs). VMCs, also called biliary hamartomas, are rare and benign malformations of the bile ducts. The lesions present as diffuse greyish-white to greyish-yellow or black nodules of the liver, which on gross inspection and in radiological examinations strongly resemble liver metastases. VMCs are mostly asymptomatic and therefore often an incidental finding at laparotomy or post-mortem examination. The prevalence of VMC is age dependent and is 5.6% in adult patients at post-mortem examination. VMCs are sometimes associated with cholangiocarcinoma. Diagnostic imaging of VMC is difficult and of little specificity. Intraoperative frozen section analysis to differentiate between malignant and benign lesions has a sensitivity of 97% and a specificity of 99%. The benign nature of VMCs means that they do not require treatment. The patient underwent total mesorectal excision and follow-up after 3, 7 and 9 months did not reveal any indications of recurrent colorectal cancer or metastases.


Utilizing Different Diffusion Mechanisms for Thin Film Fluorescence-Based Detection and Discrimination of Illicit Drug Vapors.
Film-based fluorescence sensors have been demonstrated to be powerful tools for real-time detection of trace chemical vapors. While explosive vapor detection via fluorescence quenching has been widely explored, fluorescence-based real-time detection and identification of illicit drug vapors remains a challenge. Here, we report two perylene diimide-based sensing materials, P1 and P2, incorporating 2,2-dihexyloctanyl chains and 4-[tris(4-{tert-butyl}phenyl)methyl]phenyl moieties at the imide positions, respectively. Quartz crystal microbalance with in situ photoluminescence measurements showed that N-methylphenethylamine, a simulant of methamphetamine (MA), diffused into films of P1 and P2 via Fickian and case-II mechanisms, respectively. The difference in the analyte diffusion mechanism led to P2 showing significantly faster luminescence quenching but slower luminescence recovery compared to P1. Finally, the different diffusion mechanisms were used as the basis for developing a simple sensor array based on P1 and P2 that could selectively detect free-base illicit drugs (MA, cocaine, and tetrahydrocannabinol) from potential interferants (organic amines, alcohol, and cosmetics) within 40 s.


[Intestine morphology and microbiocenosis changes in critically ill patients in neurosurgery].
In recent years, the effect of critical conditions on intestine and the role of such changes in maintenance and progression of systemic disorders are of particular attention. This issue is relevant in critically ill neurosurgical patients too. Intestine morphology and microbiome changes in these patients represent a wide field for researches in intensive care and prevention of secondary damage to other organs and systems. This review ensures a current approach to the problem of intestine morphology and microbiome changes in critically ill neurosurgical patients. We reviewed the data from clinical studies and experiments reproducing a critical condition in animals. Most publications are indexed in the PubMed, e-library, Google Scholar databases. We also analyzed the data from NEJM, JAMA, Lancet, Critical Care and other issues. The manuscript contains an overview of 44 foreign and 13 domestic references; over 50% of researches were published within the past 5 years. Searching depth was over 50 years.


Why do women's attitudes toward mammography change over time? Implications for physician-patient communication.
The present study examines women's decision making about mammography over a 1-year period, using "decisional balance," a summary of women's positive and negative perceptions about mammography derived from the Transtheoretical Model (TTM). Data were from a survey of women ages 50-74 years who completed both the baseline and 1-year follow-up telephone surveys (n = 1144) for an intervention study to increase the use of mammography screening. A shift toward less favorable perceptions about mammography was related to being a smoker and not having a recent clinical breast examination and Pap test. Change in women's attitudes toward mammography was also related to four dimensions of a woman's information environment. Women who rated the opinions of a physician as somewhat or not important, those who reported that at least one family member or friend discouraged them from having a mammogram, and women who felt they lacked enough people in their social network with whom they could discuss health concerns were less likely to express favorable attitudes about mammography over 1 year. In contrast, women who consistently communicated the value of mammography to others expressed more favorable views of screening over the study period. Interventions designed to promote breast cancer screening must recognize that a woman not only reacts to mammography information provided by significant others in her social network but may proactively reach out to others as an advocate of breast cancer screening, thus reinforcing or changing others' opinions or behavior as well as her own.


A randomised double-blind trial of minimal bolus doses of oxytocin for elective caesarean section under spinal anaesthesia: Optimal or not?
Oxytocin administration regimens are arbitrary and highly subjective. Hence, it is essential to reinvestigate the appropriate dose for effective uterine contraction with minimal bleeding and adverse effects. To determine the optimal dose of bolus oxytocin for uterine contractions for elective caesarean section under spinal anaesthesia. Ninety term mothers (37 to 41 weeks) undergoing caesarean section electively under spinal anaesthesia were considered for the trial and divided into three groups to receive oxytocin bolus of one, two or three units. The uterine tone was assessed at 2 min after oxytocin administration. Intraoperative blood loss, mean arterial pressure, heart rate and possible side effects were also compared. Paired t-test, Kruskal-Wallis test, Chi-square test and analysis of variance (ANOVA) test with Scheffe multiple comparisons were used as inferential statistics. Adequate uterine contraction was seen in 66% of participants who received one unit of oxytocin, and in 83.3% of participants who received two units of oxytocin. All those who received three units of oxytocin had an adequate uterine contraction. Blood loss was inversely related to the bolus dose of oxytocin. Lower bolus oxytocin doses of one and two units were inadequate for uterine contraction at elective caeserean section, while three units appeared to be effective in terms of adequate uterine contraction, reduced blood loss and stable haemodynamic system and absent side effects.