Given and chosen: youth-led research on family-supported conversations about sexuality.
The Youth Leadership Council supported by the Illinois Caucus for Adolescent Health completed a Community-Based Participatory Research study to assess the perceived barriers and benefits to conversations about sex and sexuality between youth and their given and chosen families. This mixed-methods research project defines given families as the family youths are born into or live at home with, and chosen families as those youths choose to surround themselves with such as friends or mentors. The Youth Leadership Council found that youths discuss sex and sexuality with both given and chosen families, but a majority felt that they received only "somewhat accurate" information. This project builds on current and past research by allowing youths to disclose their gender identity and sexual orientation, which showed a clear need for more education around asexual identities especially within given family settings. As a Community Based Participatory Research study, pragmatic next steps based on the finding are included for practitioners and researchers who work in the area of adolescent sexual and reproductive health.


Seeing the big picture: Broadening attention relieves sadness and depressed mood.
We examined whether the broadened attentional scope would affect people's sad or depressed mood with two experiments, enlightened by the meaning of "seeing the big picture" and the broaden-and-build model. Experiment 1 (n = 164) is a laboratory-based experiment, in which we manipulated the attentional scope by showing participants zoomed-out or zoomed-in scenes. In Experiment 2 (n = 44), we studied how depressed mood and positive and negative emotions were affected when participants watched distant versus proximal scenes for eight weeks in real life. Healthy participants in Experiment 1, who were induced to feel sad, could return to the baseline mood after having the broadened attention task but not after having the narrowed attention task, which indicated that immediate attention broadening manipulation could function as antidotes for the lingering effects of induced negative emotions. Participants with depressed mood in Experiment 2 showed reduced depressed mood, increased positive affect, and decreased negative affect after receiving attention broadening training compared to those receiving attention narrowing training. Our findings suggest a robust role of broadened attentional scope in relieving negative emotions and even mildly depressed mood in the long run.


Signature of snaking states in the conductance of core-shell nanowires.
We model a core-shell nanowire (CSN) by a cylindrical surface of finite length. A uniform magnetic field perpendicular to the axis of the cylinder forms electron states along the lines of zero radial field projection, which can classically be described as snaking states. In a strong field, these states converge pairwise to quasidegenerate levels, which are situated at the bottom of the energy spectrum. We calculate the conductance of the CSN by coupling it to leads and predict that the snaking states govern transport at low chemical potential, forming isolated peaks, each of which may be split in two by applying a transverse electric field. If the contacts with the leads do not completely surround the CSN, as is usually the case in experiments, the amplitude of the snaking peaks changes when the magnetic field is rotated, determined by the overlap of the contacts with the snaking states.


Identification of epidermal growth factor as a component of the rat urinary bladder tumor-enhancing urinary fractions.
Using the heterotopically transplanted rat urinary bladder, we have shown that normal rat urine has a potent tumor-enhancing effect on bladder carcinogenesis. In an attempt to isolate tumor-enhancing factor(s), urine was fractionated by Bio-Gel P-100 column chromatography and each eluate fraction was examined for inducibility of ornithine decarboxylase (ODC) in a target rat bladder carcinoma cell line, 804G. We have identified two ODC-inducible peaks, one located in a high molecular weight region designated as Fraction I (Fr. I) and the second in a low molecular weight region designated as Fraction II (Fr. II). Fr. I consisted of two principal elements, transferrin and a component which induced ODC. The present investigation was conducted to characterize the ODC-inducible activity in Fr. I and II. Chromatographic analysis of Fr. I by Sephacryl S-200 and Fr. II by Bio-Gel P-10 chromatography separated several ODC-inducible peaks. However, the major ODC inducibility was due to a high concentration (460 ng/mg Fr. I residue, approximate Mr 54,000, and 580 ng/mg Fr. II residue, approximate Mr 6,100) of epidermal growth factor (EGF) as determined by radioimmunoassay. Aliquots obtained from these peaks competed with mouse EGF for EGF receptors in A431 cells. Preincubation of Fr. I and II with rabbit anti-rat EGF IgG significantly reduced ODC inducibility. Transforming growth factor alpha activity as determined by radioimmunoassay was also demonstrated in both Fr. I (34 ng/mg) and Fr. II (9 ng/mg). The results of the present study together with our previous data indicate that the majority of the ODC-inducing activity in the tumor-enhancing urinary components Fr. I and Fr. II is due to EGF itself and EGF-related growth factors of high molecular weight and that Fr. I also contains transferrin.


Comparative Evaluation of Different Doses of Intravenous Dexmedetomidine on Hemodynamic Response during Laryngoscopy and Endotracheal Intubation in Geriatric Patients Undergoing Spine Surgeries: A Prospective, Double-Blind Study.
Dexmedetomidine, a selective alpha 2 (α2)-adrenergic receptor agonist, has been used to blunt the hemodynamic response associated with laryngoscopy and tracheal intubation, which is a common concern for the anesthesiologist, especially in high-risk patients and geriatric age group. The current study is to evaluate and compare the effects of different doses of dexmedetomidine in controlling hemodynamic response during tracheal intubation in geriatric patients. After getting approval from the Ethical Committee, 90 patients of the American Society of Anesthesiologist Physical Status Classes I and II, aged ≥60 years, were randomly assigned into three groups: Group I (normal saline, n = 30), Group II - dexmedetomidine (0.50 μg/kg, n = 30), and Group III - dexmedetomidine (1.00 μg/kg, n = 30). Dexmedetomidine was infused for 10 min before induction. Data were recorded as before infusion (T0), at the end of infusion (T1), before tracheal intubation (T2), at the moment of tracheal intubation (T3) 5 min after tracheal intubation (T4), and 10 min after tracheal intubation (T5). Modified observer's assessment of alertness/sedation scale score was observed at the time of T0 and T1. All statistical analyses were done using SPSS version 22. Mean systolic blood pressure was statistically significantly (P < 0.05) more among Group I compared to Group II and III at T2, T3, and T4. Mean heart rate (HR) value was significantly (P < 0.05) more among Group I compared to Group III from T1 to T5, whereas there was no significant change in HR between Group I and Group II and at T4 and T5 h was comparable in Group II and Group III. This study concluded that more acceptable hemodynamic changes were seen with 0.50 μg/kg dexmedetomidine when compared with 1.0 μg/kg dexmedetomidine during intubation. A lower dose besides being cost-effective is also free of side effects associated with the higher dose of 1 μg/kg dexmedetomidine.


Effect of a liquid diet on the protein composition of rat parotid saliva.
The object of the present study was to determine of the secretory proteins of rats parotid saliva were altered following parotid gland atrophy induced by feeding rats a liquid stock diet which eliminated mastication. Compared to rats fed the pelleted stock diet, the parotid glands of rats fed liquid stock diet showed 40% to 55% reductions in gland weight and content of RNA, amylase, and protein. Gland DNA content was reduced by 26%. The concentration of protein and the activities of three secretory enzymes in parotid saliva were reduced by 40% to 70%. The secretory enzymes were affected in a nonparallel manner so that per milligram of secretory protein DNase was increased, while RNase and amylase were reduced. Examination of the protein composition by acrylamide gel electrophoresis showed that several secretory proteins were no longer present. This study showed that feeding rats a standard stock diet, but in liquid form to eliminate mastication, results in a reduction in the protein concentration of parotid saliva, a loss of several secretory proteins and nonparallel changes in some of the proteins which remain.


[Management of heart failure in the elderly patient].
The prevalence of heart failure increases exponentially in the elderly population, particularly in western countries. Heart failure is associated with multiple and lengthy hospital stays and carries a high mortality rate. The authors analyzed management modalities of 2780 octogenarians enrolled in the 11 000-patient cohort of the Euro Heart Failure Survey I study. The patients were admitted for suspected or confirmed heart failure to 115 hospitals in 24 countries belonging to the European Society of Cardiology. The results show that diagnostic investigations and treatment modalities do not comply with international guidelines. The in-hospital and 12-week mortality rates were high.


[Candida humicola infection of the central nervous system in an HIV-infected patient: a case report].
HIV infection and parenteral drug abuse are at increased risk of developing Candida infection. Central nervous system (CNS) infection is an exceptional finding. We present fatal CNS infection by Candida humicola in drug abuser at late stage of HIV disease. In MEDLINE we have found only 3 reports about pathogenicity Candida humicola in humans (ophthalmopathy, conjunctivitis, melanonychia). Our case report suggests, that spectrum of pathogens dangerous to persons with AIDS increases.


A case of abdominal tuberculosis lymphadenitis extending into the gallbladder and duodenum in a human T-cell lymphotropic virus type 1 carrier.
A 69-year-old man with a history of pulmonary tuberculosis presented with fever. He tested positive for the QuantiFERON TB-2G and human T-cell lymphotropic virus type 1 antibodies. Imaging revealed a mass in the neck of the gallbladder, with periportal lymph node enlargement and penetration into the duodenum. A definite diagnosis could not be made, even with a subsequent detailed examination. Finally, cholecystectomy and a lymph node biopsy were performed. Histopathology revealed a caseating granuloma in the lymph nodes and in the serosa of the gallbladder, and polymerase chain reaction was positive for tuberculosis. Therefore, the patient was diagnosed with abdominal tuberculosis lymphadenitis extending into the gallbladder and duodenum.


MANAGING TEMPOROMANDIBULAR JOINT DISLOCATION IN IBADAN: A REVIEW OF 11 CASES.
The study presents a case series which evaluates the presentation, management and outcome of TMJ dislocation in a tertiary health centre in Nigeria. Case review of 11 patients with TMJ dislocation seen in the University College Hospital (UCH) Ibadan over a period of 10 years. The criteria for the diagnosis of TMJ dislocation were based on history, clinical examination and radiologic findings. Mean age of patients was 44.4 years (SD +/-15.9years); age range was 25-65 years with 4 males and 7 females. Aetiology was trauma in 4 cases, wide mouth opening in 6 cases and unknown in a patient. There were 7 acute presentations, 2 recurrences and 2 chronic presentations; bilateral anterior presentation in 10 cases, unilateral (right) anterior presentation in 1 case. 4 of the acute cases were successfully managed using the Hippocrates manoeuvre, 1 had the manoeuvre under GA, and 2 had spontaneous reduction. All recurrent cases were successfully managed with the Hippocrates manoeuvre and IMF. Fifty percent of the chronic cases were successfully managed with the Hippocrates manoeuvre. Follow up was ≤ 2 weeks in 7 of the cases. The pattern of presentation of TMJ dislocation in the above named hospital was anterior dislocation, the female gender predominance, aetiology of wide mouth opening, as well as early presentation. A conservative method of management - the Hippocrates manoeuvre - was effective in most cases irrespective of duration of dislocation. Most patients had a poor attitude to follow up.


A boy with severe manifestations of type A1 brachydactyly.
We describe a male with type A1 brachydactyly, a descendant of Drinkwaters second family. In addition to absence of the middle phalanges of his hands and feet he has generalised skeletal abnormalities, nystagmus and a squint. We suggest that his clinical findings represent the more severe manifestations of this autosomal dominant gene.


Automated extraction of genomic DNA from medically important yeast species and filamentous fungi by using the MagNA Pure LC system.
A fully automated assay was established for the extraction of DNA from clinically important fungi by using the MagNA Pure LC instrument. The test was evaluated by DNA isolation from 23 species of yeast and filamentous fungi and by extractions (n = 28) of serially diluted Aspergillus fumigatus conidia (10(5) to 0 CFU/ml). Additionally, DNA from 67 clinical specimens was extracted and compared to the manual protocol. The detection limit of the MagNA Pure LC assay of 10 CFU corresponded to the sensitivity when DNA was extracted manually; in 9 of 28 runs, we could achieve a higher sensitivity of 1 CFU/ml blood, which was found to be significant (p <or= 0.004). DNA from all fungal species analyzed could be extracted and amplified by real-time PCR. Negative controls from all MagNA Pure isolations remained negative. Sixty-three clinical samples showed identical results by both methods, whereas in 4 of 67 samples, discordant results were obtained. Thus, the MagNA Pure LC technique offers a fast protocol for automated DNA isolation from numerous fungi, revealing high sensitivity and purity.


How Important is Position in Adaptive Treadmill Control?
To more closely mimic overground walking, researchers are developing adaptive treadmills (ATMs) that update belt speed in real-time based on user gait mechanics. Many existing ATM control schemes are solely based on position on the belt and do not respond to changes in gait mechanics, like propulsive forces, that result in increased overground walking speed. To target natural causal mechanisms to alter speed, we developed an ATM controller that adjusts speed via changes in position, step length, and propulsion. Gains on each input dictate the impact of the corresponding parameter on belt speed. The study objective was to determine the effect of modifying the position gain on self-selected walking speed, measures of propulsion, and step length. Twenty-two participants walked at their self-selected speed with four ATM controllers, each with a unique position gain. Walking speed, anterior and posterior ground reaction force peaks and impulses, net impulse, and step length were compared between conditions. Smaller position gains promoted more equivalent anterior and posterior impulses, resulting in a net impulse closer to zero (p = 0.0043), a characteristic of healthy gait. Walking speed, anterior and posterior ground reaction force peaks and impulses, and step length did not change between conditions (all p > 0.05). These results suggest that reducing the importance of position in the ATM controller may promote more balanced anterior and posterior impulses, possibly improving the efficacy of the ATM for gait rehabilitation by emphasizing changes in gait mechanics instead of position to naturally adjust speed.


From Wurtzite Nanoplatelets to Zinc Blende Nanorods: Simultaneous Control of Shape and Phase in Ultrathin ZnS Nanocrystals.
Ultrathin semiconductor nanocrystals (NCs) with at least one dimension below their exciton Bohr radius receive a rapidly increasing attention due to their unique physicochemical properties. These superior properties highly depend on the shape and crystal phase of semiconductor NCs. Here, we demonstrate not only the synthesis of well-defined ultrathin ZnS nanoplatelets (NPLs) with excitonic absorption and emission, but also the shape/phase transformation between wurtzite (WZ) NPLs and zinc blende (ZB) nanorods (NRs). UV-vis absorption spectra of WZ-ZnS NPLs clearly exhibit a sharp excitonic peak that is not observed in ZB-ZnS NRs. Besides, the photoluminescence characterization shows that WZ-ZnS NPLs have a narrow excitonic emission peak, while ZB-ZnS NRs exhibit a broad collective emission band consisting of four emission peaks. The appearance of excitonic features in the absorption spectra of ZnS NPLs is explained by interband electronic transitions, which is simulated in the framework of atomic effective pseudopotentials (AEP).


First record of Mantibaria Kirby, 1900 (Hymenoptera, Scelionidae, Scelioninae) in the New World: a probable case of accidental introduction.
Mantibaria Kirby, 1900 has four valid species: M. seefelderiana (De Stefani), M. mantis (Dodd), M. solygiea Risbec and M. kerouaci Veenakumari & Rajmohana. It is found in the Palaearctic, Afro-tropical, Oriental and Australian regions, and now is known from the New World. There are some taxonomic barriers that hinder the understanding and the boundaries between the four species, some of which were discussed by Masner (1976), Mineo (1980) and Galloway & Austin (1984). These authors argued that there are no reliable differences to separate M. solygiea (Europe), M. seefelderiana (= M. anomala, Africa) and M. mantis (Australia), hypothesizing that these three species actually comprise only one species that is widely distributed in the Old World.


Forensic odontology: a global activity.
Forensic odontology is an important and expanding field of dentistry. The application of these forensic techniques in identification, criminal justice and dental liability are being practiced worldwide. In some mass disaster events, notably large commercial aircraft crashes, the traumatic forces are such that fragmentation and conflagration result in only the most durable of human tissues-dentition survive and become a potential source of identification.


Extreme multiplicity in cylindrical Rayleigh-Bénard convection. II. Bifurcation diagram and symmetry classification.
A large number of flows with distinctive patterns have been observed in experiments and simulations of Rayleigh-Bénard convection in a water-filled cylinder whose radius is twice the height. We have adapted a time-dependent pseudospectral code, first, to carry out Newton's method and branch continuation and, second, to carry out the exponential power method and Arnoldi iteration to calculate leading eigenpairs and determine the stability of the steady states. The resulting bifurcation diagram represents a compromise between the tendency in the bulk toward parallel rolls and the requirement imposed by the boundary conditions that primary bifurcations be toward states whose azimuthal dependence is trigonometric. The diagram contains 17 branches of stable and unstable steady states. These can be classified geometrically as roll states containing two, three, and four rolls; axisymmetric patterns with one or two tori; threefold-symmetric patterns called Mercedes, Mitsubishi, marigold, and cloverleaf; trigonometric patterns called dipole and pizza; and less symmetric patterns called CO and asymmetric three rolls. The convective branches are connected to the conductive state and to each other by 16 primary and secondary pitchfork bifurcations and turning points. In order to better understand this complicated bifurcation diagram, we have partitioned it according to azimuthal symmetry. We have been able to determine the bifurcation-theoretic origin from the conductive state of all the branches observed at high Rayleigh number.


Imaging findings in spinal sarcoidosis: a report of 18 cases and review of the current literature.
Spinal sarcoidosis, referring to involvement of the spine in sarcoidosis, is relatively rare and may mimic other neurological disease affecting the spine. The authors present a clinic radiological review of 18 spinal sarcoidosis patients who presented to a tertiary hospital, with emphasis on initial imaging and radiological response to treatment. We retrospectively reviewed our departmental imaging archives over a 15-year period and found 49 cases of neurosarcoidosis out of which 18 patients had spinal magnetic resonance imaging. Approximately 72% (13/18) of the neurosarcoidosis patients showed some form of spinal involvement. The clinical, epidemiological and imaging data were reviewed for these 13 patients at presentation and follow-up. The findings on magnetic resonance imaging included leptomeningeal enhancement (61%), pachymeningeal (23%), intramedullary enhancing lesions (38%) and bony involvement (15%). The cervical segment was most frequently involved followed by the thoracic segment. Involvement was often long segment (4.2 spinal segments) with proclivity for the dorsal cord. Mean follow-up was 23.2 months. A complete or near-complete radiological response occurred in 66% while partial response was seen in 25% patients. Four patients had isolated central nervous system involvement including one with isolated spinal cord involvement. On diffusion-weighted imaging, the apparent diffusion coefficient of intramedullary lesions was increased compared to normal-appearing cord on baseline and subsequent follow-up scans. Spinal sarcoidosis was previously considered uncommon but is being increasingly recognized with widespread use of magnetic resonance imaging. Proclivity for dorsal surface involvement is characteristic, although not necessarily pathognomonic. Also, quantitative diffusion studies may serve as a biomarker for the disease activity and parenchymal injury.


Miliary tuberculosis following transrectal ultrasonography (TRUS)-guided prostate biopsy.
Miliary tuberculosis (TB) after transrectal ultrasonography (TRUS)-guided prostate biopsy is an extremely rare complication. A 75-year-old patient who presented with high fever and cough following TRUS-guided prostate biopsy for his high serum prostate-specific antigen (PSA) level (13.104 ng/ml) was diagnosed with miliary TB after clinical, laboratory, and radiological assessments. Histopathological examination of the prostate revealed TB with acid-fast bacilli. He was treated with chemotherapy for 9 months. The patient is now symptom-free, and his post-treatment PSA level was 5.023 ng/ml. This case is reported to acknowledge the possibility that miliary TB can occur as a complication of prostate biopsy if the patient suffers from prostate TB.


Probing the Small-x Gluon Tomography in Correlated Hard Diffractive Dijet Production in Deep Inelastic Scattering.
We investigate the close connection between the quantum phase space Wigner distribution of small-x gluons and the color dipole scattering amplitude, and we propose studying it experimentally in the hard diffractive dijet production at the planned electron-ion collider. The angular correlation between the nucleon recoiled momentum and the dijet transverse momentum probes the nontrivial correlation in the phase space Wigner distribution. This experimental study not only provides us with three-dimensional tomographic pictures of gluons inside high energy protons-it gives a unique and interesting signal for the small-x dynamics with QCD evolution effects.


Genetic comparison of water molds from embryos of amphibians Rana cascadae, Bufo boreas and Pseudacris regilla.
Water molds that cause the disease saprolegniasis have been implicated in widespread mortality of amphibian embryos. However, because of the limitations of traditional identification methods, water mold species involved in die-offs or utilized in ecological studies often remain unidentified or identified only as Saprolegnia ferax. Furthermore, water mold taxonomy requires revision, so very distinct organisms may all be called S. ferax. Recent DNA-based studies indicate that the diversity of water molds infecting amphibian embryos is significantly higher than what was previously known, but these studies rely on culture methods, which may be biased towards taxa that grow best under laboratory conditions. In this study, total embryo-associated DNA was extracted from 3 amphibian species in a pond in central Washington, USA. The internal transcribed spacer (ITS) region of DNA was amplified with primers capable of amplifying a broad array of eukaryotic microorgansisms, and was used to construct clone libraries. Individual clones were sequenced and relationships among newly recovered sequences and previously studied taxa were analyzed using phylogenetics. These methods recovered several new taxa in association with amphibian embryos. Samples grouped into 11 distinct phylotypes with ITS sequence differences ranging from 4 to 28%. The water mold communities recovered differed among Rana cascadae, Bufo boreas, and Pseudacris regilla egg masses. Furthermore, the diversity of water molds increased as egg masses aged, and members comprising this diversity changed over time.


Stabilization of femtosecond optical parametric oscillators for infrared frequency comb generation.
A synchronously pumped optical parametric oscillator (SP-OPO) is one of the most common techniques to generate femtosecond frequency combs in the mid-infrared region. Stable long-term operation of an SP-OPO requires active locking of the OPO resonator round-trip time to the pump pulse interval. A simple modulation-free locking method based on stabilization of narrow-band frequency-doubled power of the SP-OPO output comb is demonstrated in this Letter. The method relies on the strong dependency of frequency-doubled power on spectral shape of the comb, leading to better stability of the comb envelope spectrum than the commonly used dither-and-lock method.


Development and validation of the canine visual function instrument.
In this study, we created the Canine Visual Function Instrument (CVFI) and tested its validity and reliability for assessing the quality of vision of dogs. We used Cronbach's alpha to test the strength of the consistency of the questions in the instrument and factor analysis to assess whether the questions achieved unidimensionality in the measurement of dogs' vision quality. Our analysis shows that the CVFI is a valid and reliable tool to seek self-reported observations about dogs' vision quality from owners. Our results also show that the vision quality scale has high empirical validity and therefore can be used to determine whether a dog has normal vision or moderate or serious visual impairments. The CVFI might have important practical applications in the field of veterinary ophthalmology in two important ways. First, it can be used to determine whether the treatment of dogs with visual impairment improves vision quality. Second, it can be used as a warning system to alert owners about their dogs' quality of vision.


Comparison of laser in situ ketatomileusis and photorefractive keratectomy for myopia using a mixed-effects model.
To compare the results of laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) for myopia using a mixed-effects model. This comparative retrospective study was conducted in 1,127 eyes of 579 patients after LASIK and 270 eyes of 144 patients after PRK who had two or more postoperative follow-ups after 3 months. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest refractive spherical equivalent (MRSE), percentage of eyes within ± 0.5 diopters (D) and ± 1.0 D of targeted refraction, and central corneal thickness were compared between PRK and LASIK groups using a mixed-effects model. Compared with the LASIK group, UCVA in the PRK group was significantly worse in the initial year but was significantly better after 4 years. The average BSCVA was not significantly different between the LASIK and PRK groups after 4 years. The average gain of BSCVA in the PRK group was significantly larger than that of the LASIK group after 2 years. MRSE in the LASIK and PRK groups showed a gradual myopic shift until 6 years after surgery. After 6 years, MRSE in the PRK group remained stable whereas MRSE in the LASIK group continued a myopic shift. The percentages of eyes within ± 0.5 D or ± 1.0 D in the LASIK group were significantly higher than those in the PRK group at 3 months but were significantly lower than those in the PRK group at 10 years. PRK for myopia shows better efficacy than LASIK for myopia after 4 years.


Risk of impaired cognition after prenatal exposure to psychotropic drugs.
Prenatal exposure to psychotropic drugs may affect the trajectories of brain development. In a register study, we investigated whether such exposure is associated with long-term impaired cognitive abilities. Individuals born in Denmark in 1995-2008 were included. As proxies for cognitive impairment, requiring special needs education, attending special needs school, diagnoses of neurological/mental disorder, missed final examinations, and low school grade average were used. We accounted for maternal confounders. We identified 868 159 individuals of whom 13 983 (1.6%) were prenatally exposed. The adjusted odds ratio (OR) was 0.97[0.92-1.02] for requiring special needs education, 1.28[1.14-1.43] for attending special needs school, 1.32[1.20-1.46] for a neurological/mental disorder diagnosis, 1.37[1.22-1.54] for missing the final examinations, and 1.13[0.82-1.55] for obtaining a low school grade average. Exposure to psycholeptics (primarily antipsychotics and sedatives) was correlated with significantly increased risk for four outcomes. The highest was the risk of missing the primary school examinations (OR: 1.51[1.29-1.76]). The overall highest risk concerned the presence of a neurological/mental disorder after prenatal exposure to psychoanaleptics (primarily antidepressants) (OR: 1.86[1.24-2.78). Prenatal exposure to psychotropic drugs affects proxy outcomes of cognitive disabilities at school age. Exposure to psycholeptics carries the largest risk. The role of psychoanaleptics is currently unclear.


Hospital-sponsored primary care: II. Impact on patient access.
This article, the second of two, considers the impact of a nationwide demonstration of 53 community hospital sponsored group practices (CHPs). Surveys of a sample of the communities in which the CHPs were introduced suggest that about half of the communities were socioeconomically and, to some extent, medically disadvantaged. The CHPs tended to attract people who had previously not had a regular source of care or who used hospital outpatient departments or emergency rooms, as well as patients of established primary care physicians. Access to care and satisfaction appeared to be as good or better for CHP patients compared to regular patients of physicians in the target areas. The programs did not increase the use of inpatient services, emergency rooms, or hospital outpatient departments. The findings suggest that at present community hospital sponsored group practices would not have a profound effect on access to care if adopted nationally, but that targeted implementation by hospitals in lower income and minority communities can improve patient opportunities for appropriate primary care services.


Exploring the potential of expatriate social networks to reduce HIV and STI transmission: a protocol for a qualitative study.
HIV diagnoses acquired among Australian men working or travelling overseas including Southeast Asia are increasing. This change within transmission dynamics means traditional approaches to prevention need to be considered in new contexts. The significance and role of social networks in mediating sexual risk behaviours may be influential. Greater understanding of expatriate and traveller behaviour is required to understand how local relationships are formed, how individuals enter and are socialised into networks, and how these networks may affect sexual intentions and behaviours. This paper describes the development of a qualitative protocol to investigate how social networks of Australian expatriates and long-term travellers might support interventions to reduce transmission of HIV and sexually transmitted infections. To explore the interactions of male expatriates and long-term travellers within and between their environments, symbolic interactionism will be the theoretical framework used. Grounded theory methods provide the ability to explain social processes through the development of explanatory theory. The primary data source will be interviews conducted in several rounds in both Australia and Southeast Asia. Purposive and theoretical sampling will be used to access participants whose data can provide depth and individual meaning. The role of expatriate and long-term traveller networks and their potential to impact health are uncertain. This study seeks to gain a deeper understanding of the Australian expatriate culture, behavioural contexts and experiences within social networks in Southeast Asia. This research will provide tangible recommendations for policy and practice as the findings will be disseminated to health professionals and other stakeholders, academics and the community via local research and evaluation networks, conference presentations and online forums. The Curtin University Human Research Ethics Committee has granted approval for this research.


Concise Synthesis of Phospholene and Its P-Stereogenic Derivatives.
A simple method to build phospholene derivatives has been achieved in a one-pot reaction with readily available o-alkynylaryl bromides and alkylphosphine oxides. This method is also applicable to synthesize P-stereogenic phospholenes, and the resulting chiral phosphine was utilized as a ligand for coordination chemistry.


The 2014 crude 4-methylcyclohexanemethanol chemical release and birth outcomes in West Virginia.
Approximately 10,000 gallons of crude 4-methylcyclohexanemethanol and propylene glycol phenyl ether were accidentally released into the Elk River upstream from a water treatment facility in West Virginia. The objective of this study was to use logistic and Poisson regression analyses to determine the effect potential exposures had on adverse birth outcomes (birth weight, small for gestational age, and abnormal Apgar score). We adjusted for confounding factors and assessed prevalence of adverse birth outcomes by residential location and timing of the pregnancy. There were no statistically significant interactions between residential location and timing of the pregnancy (range of p values: .157-.806). Changes in the prevalence of birth outcomes were consistent before and after the spill regardless of residential location. There was no evidence of an association between adverse birth outcomes and potential exposure to the released chemicals.


Similarities in the harmonic structure of EEG activity provoked by intermittent photic stimulation in epileptic and healthy subjects.
The goal of the present study was to analyze the power spectra for two groups of subjects: epileptic patients and healthy subjects in order to investigate the harmonic structure of resonance provoked by Intermittent Photic Stimulation (IPS) in the range between 6 Hz and 33 Hz in 3 Hz steps. Electroencephalogram data were recorded from 11 female subjects at the age between 15 and 25. The harmonic structure of frequencies observed in the power spectra of EEG in the epileptic patients and healthy subjects is similar. A possible explanation to those results is the fact, that epilepsy is a functional disorder, which under specific clinical conditions can be provoked by IPS. If there is no epileptic reaction to the IPS, the brain of an epileptic subject behaves like in a healthy one.


PHOSPHOLIPID-SUGAR COMPLEXES IN RELATION TO CELL MEMBRANE MONOSACCHARIDE TRANSPORT.
Phospholipids extracted from "ghosts" of human erythrocytes or from other sources carry substantial quantities of glucose or other monosaccharides from the dry state into highly nonpolar solvents. Various characteristics of this weak association phenomenon show suggestive parallels with known properties of the mediated sugar-transfer system in the membrane of the intact red cell.


Treatment options and outcomes of hospitalised tuberculosis patients: a nationwide study.
Although standardised multidrug treatments exist, mortality among hospitalised tuberculosis (TB) patients is high. To characterise TB patients requiring acute hospital care and identify factors associated with in-hospital mortality. Using a Japanese national database of acute-care hospitals, we identified patients with sputum smear-positive pulmonary TB who were discharged (both deceased and alive) between July 2010 and March 2013. Demographic characteristics, comorbidity, procedures and treatments were examined. We performed a multivariable logistic regression analysis to identify risk factors for in-hospital mortality. Of 877 treated patients (566 males, mean age 74.5 years) identified, 152 (17.3%) died. A standard four-drug regimen of isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and pyrazinamide was given to 279 (31.8%) patients, and INH, RMP and EMB to 335 (38.2%) patients. Multivariable analysis showed that the three-drug regimen was significantly associated with higher rates of in-hospital mortality (OR 1.87, 95%CI 1.07-3.27, P = 0.028). Other factors associated with in-hospital death were age, male sex, smoking habit, emergency admission, dementia and severe respiratory condition. The risk factors for in-hospital death identified include the use of the three-drug regimen. Treatment choice could influence the outcome of hospitalised TB patients.


Evaluation of operative imaging techniques in surgical education.
Certain open surgical procedures are difficult to observe, and poor visualization of the surgical field results in a compromised teaching environment for residents and medical students. In an attempt to improve the visualization of the open surgical field, we performed an open surgical procedure while viewing it via a laparoscope mounted to the side of the operating room table with an alpha port. These images were then compared in a blinded fashion with images from a boom-mounted camera positioned above the surgical field and a head-mounted camera positioned on the operating surgeon. Participants viewed all 3 images from a remote location in a blinded, random fashion. All participants then completed a Likert questionnaire evaluating each image. Fourteen participants were in the study. The alpha port/laparoscope image was superior to the head-cam image in all 8 categories. The alpha port/laparoscope image was superior to the sky-cam image in 4 of 8 categories. All 14 participants felt the alpha port/laparoscope image would benefit surgical education Use of a laparoscope mounted via an alpha port to an operating room table provides superior images during open surgery. This provides a unique and affordable way to teach residents and medical students operative procedures that are otherwise difficult to view.


Developmental changes in the perception of pitch contour: distinguishing up from down.
Musically untrained participants in five age groups (5-, 6-, 8-, and 11-year-olds, and adults) heard sequences of three 1 s piano tones in which the first and third tones were identical (A5, or 880 Hz) but the middle tone was displaced upward or downward in pitch. Their task was to identify whether the middle tone was higher or lower than the other two tones. In experiment 1, 5-year-olds successfully identified upward and downward shifts of 4, 2, 1, 0.5, and 0.3 semitones. In experiment 2, older children (6-, 8-, and 11-year-olds) and adults successfully identified the same shifts as well as a smaller shift (0.1 semitone). For all age groups, performance accuracy decreased as the size of the shift decreased. Performance improved from 5 to 8 years of age, reaching adult levels at 8 years.


Critical involvement of the hinge region of the follicle-stimulating hormone receptor in the activation of the receptor.
The follicle-stimulating hormone receptor (FSHR) is a G-protein-coupled receptor with a large hormone-specific extracellular domain (amino acids (aa) 1-366) and a characteristic seven-transmembrane domain (TMD; aa 367-695). The extracellular domain is composed of leucine-rich repeats (LRRs; aa 18-259) connected to TMD by a hinge region (HinR; aa 260-366), whose role in the hormone action is not clearly understood. We generated a novel polyclonal HinR antibody that specifically stimulates cAMP production by HEK 293 cells expressing FSHR in a hormone-independent manner. The monovalent antibody retained the stimulatory potential. The segment of aa 296-331 in HinR was identified as the binding site for the stimulatory antibody. Deletions of this entire segment or any 10 amino acids within this segment from FSHR led to complete loss of antibody response and, surprisingly, response to the hormone as well despite all mutants exhibiting cell surface receptor density and affinity comparable with the wild type receptor. Interestingly, these mutants exhibited higher basal cAMP production. The mutant lacking LRRs with the intact HinR (Delta18-259) showed suppressed basal activity, which increased significantly with deletions extending to aa 331. These data suggest that the segment 296-331 acts as a tethered inverse agonist of the TMD and plays a very critical role in the hormonal activation of FSHR. The mutants lacking LRRs failed to bind FSH, whereas deletions in HinR had no effect on hormone binding, indicating that the LRRs constitute the primary high affinity binding site, whereas HinR may not play a significant role in FSH binding.


A tool for multi-scale modelling of the renal nephron.
We present the development of a tool, which provides users with the ability to visualize and interact with a comprehensive description of a multi-scale model of the renal nephron. A one-dimensional anatomical model of the nephron has been created and is used for visualization and modelling of tubule transport in various nephron anatomical segments. Mathematical models of nephron segments are embedded in the one-dimensional model. At the cellular level, these segment models use models encoded in CellML to describe cellular and subcellular transport kinetics. A web-based presentation environment has been developed that allows the user to visualize and navigate through the multi-scale nephron model, including simulation results, at the different spatial scales encompassed by the model description. The Zinc extension to Firefox is used to provide an interactive three-dimensional view of the tubule model and the native Firefox rendering of scalable vector graphics is used to present schematic diagrams for cellular and subcellular scale models. The model viewer is embedded in a web page that dynamically presents content based on user input. For example, when viewing the whole nephron model, the user might be presented with information on the various embedded segment models as they select them in the three-dimensional model view. Alternatively, the user chooses to focus the model viewer on a cellular model located in a particular nephron segment in order to view the various membrane transport proteins. Selecting a specific protein may then present the user with a description of the mathematical model governing the behaviour of that protein-including the mathematical model itself and various simulation experiments used to validate the model against the literature.


Effects of low concentrations of di-(2-ethylhexyl) and mono-(2-ethylhexyl) phthalate on steroidogenesis pathways and apoptosis in the murine leydig tumor cell line MLTC-1.
The aim of this study was to evaluate the effects of low concentrations of DEHP and MEHP on steroidogenesis in a murine Leydig tumor cell line (MLTC-1) in vitro. The result of flow cytometry analysis revealed that the proportion of apoptotic cells was significantly increased after the exposure to DEHP. All three genes (P450scc, P450c17, and 3βHSD) under study showed an increased expression following exposure to DEHP or MEHP, although some insignificant inhibitory effects appeared in the 10 μmol/L treatment group as compared with the controls. It was also found that compared with the controls. It was also found that DEHP or MEHP stimulated INSL3 mRNA and protein especially in the 0.001 μmol/L treatment group. Testosterone secretions were stimulated after the exposure to DEHP or MEHP. Alternations of steroidogenic enzymes and INSL3 in MLTC-1 cells might be involved in the biphasic effects of DEHP/MEHP on androgen production.


Clinical Characteristics and Visual Outcomes in Patients with Intralenticular Foreign Bodies with Self-Sealing Corneal Penetrating Wounds.
Siderosis bulbi may occur as a result of retained intralenticular foreign bodies (ILFBs) that were missed during examination in patients with self-sealing wounds and without a significant decrease in visual acuity. This study aimed to explore the clinical characteristics and visual outcomes of ILFBs with self-sealing corneal penetrating wounds. Fifteen eyes of 15 patients with ILFBs and self-sealing corneal penetrating wounds, seen between October 2014 and September 2019, were retrospectively analyzed. Data regarding the patient demographics, clinical features, surgical procedure, and initial and final best-corrected visual acuity (BCVA) were analyzed. All patients were male with a mean age of 41 years. The foreign bodies passed through the cornea, sometimes through the iris, through the anterior capsule, and finally localized in the lens. All ILFBs were pointed and metallic objects and were successfully removed with phacoemulsification and posterior chamber intraocular lens (IOL) implantation. Anterior capsule violation was found in three eyes, but no posterior capsule rupture was found. The IOL was placed in a capsule bag in all the cases. The BCVA ranged from 20/200 to 20/25 preoperatively and improved to between 20/32 and 20/20 at the last follow-up visit. The IOLs were well-centered. Apart from posterior capsule opacity in four eyes, no other postoperative complications were found. In patients with a pointed metallic ILFB and self-sealing corneal penetrating wounds (with or without cataracts), early diagnosis and removal of the metallic ILFB combined with lens removal and IOL implantation may avoid late complications and achieve good visual outcomes.


SH2 binding site comparison: a new application of the SURFCOMP method.
To avoid side effects, it is often desirable to increase the specificity of a drug candidate when targeting one member of a family of related proteins, whereby one exploits small differences between the structures of the binding sites. Identification of such differences can be carried out by analyzing the distributions of physicochemical properties mapped onto molecular surfaces. Here we demonstrate that SURFCOMP, our local surface similarity detection method, is able to detect differences between the binding sites of two closely related proteins. We analyzed the SH2 domains of Sap and Eat-2, two highly similar signal transduction molecules involved in inflammatory processes and found differences between their binding sites that can possibly lead to a better understanding of the different specificities of the two proteins.


Distinguishing of 2-MAPB and 6-MAPB: Solution of the problem.
Differentiation of new psychoactive substance (NPS), 6-(2-methylaminopropyl)benzofuran (6-MAPB), and its positional isomer, 2-(2-methylaminopropyl)benzofuran (2-MAPB), by means of gas chromatography/mass spectrometry (GC/MS) with quadrupole detection is ambiguous. Reliable distinguishing of the two isomers could be achieved by MS/MS spectra recorded after collision-induced dissociation (CID) of precursor ions. Both electron ionization (EI) and electrospray ionization (ESI) methods could be used for these purposes.


[16S rDNA-RFLP analysis of structure and diversity of an aerobic microbial community degrading hexachlorobenzene].
Hexachlorobenzene is a chlorinated aromatic hydrocarbon that was widely used as a seed dressing for prevention of fungal growth on crops, and is also a component of fireworks, ammunition, and synthetic rubbers. Because of the bioaccumulation and persistence of hexachlorobenzene as well as its potential toxicity, hexachlorobenzene must be removed from environment. The potential for aerobic dechlorination of hexachlorobenzene by a hexachlorobenzene-adapted mixed culture was investigated. An aerobic microbial community which was able to grow at the presence of hexachlorobenzene was enriched from sediment from contaminated site after incubating about 2 months. During the growth of the mixed microorganisms on hexachlorobenzene, the accumulating consumption of oxygen, the microbial population curve and the release of Cl- were investigated. The data suggest the rapid degradation of hexachlorobenzene to support microbial growth and the aerobic decholrination of hexachlorobenzene was observed. The result showed that the mixed microorganisms were able to utilize hexachlorobenzene as sole carbon and energy source. It was shown that up to 55% of HCB could be degraded during 18 days incubation at 30 degrees C in mineral salts medium (pH 7.0) with 4.5mg/L HCB. The calculated rate of hexachlorobenzene biodegradation was 137.5 microg/ (L x d). The 16S rDNA genes were amplified from community DNA by using primers specific to bacteria and were subsequently cloned. The cloned 16S rDNA fragments were reamplified, and restriction analysis was performed following separate digestion with enzymes Hae III and Rsa I. Application of restriction fragment length polymorphism screening approach revealed 9 clusters, and 3 major clusters were sequenced. Nearly complete 16S rDNA sequence analysis show that the microbial community was dominated by Alcaligenes and Azospirillum groups. This is the first report describing aerobic dechlorination of hexachlorobenzene via dehalorespiration by a microbial community which was enriched from contaminated site. The microbial community can be used to degrade highly recalcitrant chlorinated pollutants.


Anti-glucose-6-phosphate isomerase, anti-cyclic citrullinated peptide antibodies and HLA-DRB1 genotypes in Japanese patients with early rheumatoid arthritis.
Our goal was to evaluate the associations of antibodies (Abs) to glucose-6-phosphate isomerase (GPI) with Abs to cyclic citrullinated peptide (CCP) and HLA-DRB1 genotypes in Japanese patients with early rheumatoid arthritis (RA). One hundred and eight patients with early RA (85 female, 23 male) who visited our clinic within 1 year of symptom onset were examined for anti-GPI and anti-CCP Ab levels, and HLA-DRB1 genotype. Anti-GPI and anti-CCP Ab levels, and HLA-DRB1 genotypes were also determined in 63 controls and 265 healthy controls, respectively. Of the 108 patients with early RA and the 63 controls, 20 (18.5%) and 3 (4.8%) were anti-GPI Ab-positive, respectively. Of the 20 patients with anti-GPI Abs, 17 (85%) were positive for anti-CCP Abs. HLA-DRB1*0405 and shared epitope (SE) carrier frequencies were significantly increased not only in anti-GPI Ab-positive patients (p=0.00057, odds ratio [OR] 4.6, 95% CI 1.8-11.8; p=0.0011, OR 5.0, 95% CI 1.7-14.0), but also in anti-GPI Ab-negative patients (p=0.0017, OR 2.2, 95% CI 1.3-3.7; p=0.00011, OR 2.6, 95% CI 1.6-4.3), when compared with controls. In addition, the carrier frequency of HLA-DRB1*1201 was significantly increased in anti-GPI Ab-positive patients compared with controls (p=0.0056, OR 4.3, 95% CI 1.4-13.2). The majority of anti-GPI Ab-positive RA patients constitute a subset of HLA-DRB1* SE-associated, anti-CCP Ab-positive RA patients.


The Impact of the Secondary Binding Pocket on the Pharmacology of Class A GPCRs.
G-protein coupled receptors (GPCRs) are considered important therapeutic targets due to their pathophysiological significance and pharmacological relevance. Class A receptors represent the largest group of GPCRs that gives the highest number of validated drug targets. Endogenous ligands bind to the orthosteric binding pocket (OBP) embedded in the intrahelical space of the receptor. During the last 10 years, however, it has been turned out that in many receptors there is secondary binding pocket (SBP) located in the extracellular vestibule that is much less conserved. In some cases, it serves as a stable allosteric site harbouring allosteric ligands that modulate the pharmacology of orthosteric binders. In other cases it is used by bitopic compounds occupying both the OBP and SBP. In these terms, SBP binding moieties might influence the pharmacology of the bitopic ligands. Together with others, our research group showed that SBP binders contribute significantly to the affinity, selectivity, functional activity, functional selectivity and binding kinetics of bitopic ligands. Based on these observations we developed a structure-based protocol for designing bitopic compounds with desired pharmacological profile.


2-(aminoacylamino)benzophenones: farnesyltransferase inhibition and antimalarial activity.
The use of amino acids as acyl substitutents at the 2-amino group of our benzophenone core structure yielded compounds with mainly good to moderate farnesyltransferase inhibitory and moderate antimalarial activity. However, these farnesyltransferase inhibitors display some degree of selectivity towards malarial parasites since there was no cytotoxic activity observed at 70-80 microM.


[The advantages for Snail expression to promote cell migration and induce actin reorganization and to protect against the serum-deprivation-triggered apoptosis of bone marrow stem cells].
The Snail transcription factor has been described as a strong repressor of E-cadherin and its stable expression induces epithelial-mesenchymal transitions responsible for the acquisition of motile and invasive properties during tumor progression. A fascinating analogy that has been raised is the seemingly similar and shared characteristics of stem cells and tumorigenic cells, which prompted us to investigate whether the mechanisms of the acquisition of invasiveness during tumor progression are also involved in bone marrow stem cells (MSCs). In this study, we examined whether Snail gene expression acts in the mobility, cytoskeleton and anti-apoptosis of MSCs. Cell Transmigration Assay and Western Blotting were performed to evaluate the cell migratory capability and the related Signaling pathways in MSCs transfected with the Snail expression vector of pCAGGSneo-SnailHA (MSCs-Sna), compared with MSCs(MSCs-neo) transducted with the control vector(pCAGGSneo). Actin cytoskeleton by Immunofluorescence and Sub-G1 detection by a FACScan flow cytometer were performed to analyze the cytoskeleton and antiapoptotic capability of MSCs-Sna. Compared with MSCs-neo, MSCs-Sna show significantly more migration in the transwell migration system (P < 0.05). And suppression of PI-3K activation by the specific PI-3K inhibitor, Wortmannin, brought on a reduction in Snail-mediated MSCs migration. In addition, we provide evidences that high expression of Snail inhibited the serum-deprivation triggered apoptosis and cytoskeleton changement of MSCs. These data suggest the possibility of facilitating MSCs migration to injured tissue and subsequent survival and maintenance in the local microenvironment after their transplantation, by investigating and increasing the advantage factors such as Snail high expression in MSCs.


Rapid screening of colonies from Listeria selective agar.
A rapid method ('Liststrip', Lab M) of screening aesculin-positive colonies from Oxford selective agar was evaluated. This method relies on the ability of all Listeria spp. to hydrolyse aesculin and to have a rapid phosphatase but neither a pyroglutamic acid beta-naphthylamide amidase nor produce indole. Of 198 Listeria spp., all gave identical results (as above) in 10 min (except four isolates of L. murrayi), whereas of 112 aesculin-positive colonies from Oxford agar that were not Listeria only one gave a similar result. The method was compared with Gram stain and oxidase as a screening procedure. This strip test method is simple enough to be used by relatively unskilled staff and provides a rapid and reliable method to screen colonies from Oxford selective agar.


Myelination Is Associated with Processing Speed in Early Childhood: Preliminary Insights.
Processing speed is an important contributor to working memory performance and fluid intelligence in young children. Myelinated white matter plays a central role in brain messaging, and likely mediates processing speed, but little is known about the relationship between myelination and processing speed in young children. In the present study, processing speed was measured through inspection times, and myelin volume fraction (VFM) was quantified using a multicomponent magnetic resonance imaging (MRI) approach in 2- to 5-years of age. Both inspection times and VFM were found to increase with age. Greater VFM in the right and left occipital lobes, the body of the corpus callosum, and the right cerebellum was significantly associated with shorter inspection times, after controlling for age. A hierarchical regression showed that VFM in the left occipital lobe predicted inspection times over and beyond the effects of age and the VFM in the other brain regions. These findings are consistent with the hypothesis that myelin supports processing speed in early childhood.


Operational Load Monitoring of a Composite Panel Using Artificial Neural Networks.
Operational Load Monitoring consists of the real-time reading and recording of the number and level of strains and stresses during load cycles withstood by a structure in its normal operating environment, in order to make more reliable predictions about its remaining lifetime in service. This is particularly important in aeronautical and aerospace industries, where it is very relevant to extend the components useful life without compromising flight safety. Sensors, like strain gauges, should be mounted on points of the structure where highest strains or stresses are expected. However, if the structure in its normal operating environment is subjected to variable exciting forces acting in different points over time, the number of places where data will have be acquired largely increases. The main idea presented in this paper is that instead of mounting a high number of sensors, an artificial neural network can be trained on the base of finite element simulations in order to estimate the state of the structure in its most stressed points based on data acquired just by a few sensors. The model should also be validated using experimental data to confirm proper predictions of the artificial neural network. An example with an omega-stiffened composite structural panel (a typical part used in aerospace applications) is provided. Artificial neural network was trained using a high-accuracy finite element model of the structure to process data from six strain gauges and return information about the state of the panel during different load cases. The trained neural network was tested in an experimental stand and the measurements confirmed the usefulness of presented approach.


The interweaving roles of mineral and microbiome in shaping the antibacterial activity of archaeological medicinal clays.
Medicinal Earths (MEs), natural aluminosilicate-based substances (largely kaolinite and montmorillonite), have been part of the European pharmacopoeia for well over two millennia; they were used generically as antidotes to 'poison'. To test the antibacterial activity of three Lemnian and three Silesian Earths, medicinal earths in the collection of the Pharmacy Museum of the University of Basel, dating to 16th-18th century and following the methodology outlined in the graphical abstract. To compare them with natural clays of the same composition (reference clays) and synthetic clays (natural clays spiked with elements such as B, Al, Ti and Fe); to assess the parameters which drive antibacterial activity, when present, in each group of samples. a total of 31 samples are investigated chemically (ICP-MS), mineralogically (both bulk (XRD) and at the nano-sized level (TEM-EDAX)); their organic load (bacterial and fungal) is DNA-sequenced; their bioactivity (MIC60) is tested against Gram-positive, S. aureus and Gram-negative, P. aeruginosa. Reference smectites and kaolinites show no antibacterial activity against the above pathogens. However, the same clays when spiked with B or Al (but not with Ti or Fe) do show antibacterial activity. Of the six MEs, only two are antibacterial against both pathogens. Following DNA sequencing of the bioactive MEs, we show the presence within of a fungal component, Talaromyces sp, a fungus of the family of Trichocomaceae (order Eurotiales), historically associated with Penicillium. Talaromyces is a known producer of the exometabolite bioxanthracene B, and in an earlier publication we have already identified a closely related member of the bioxanthracene group, in association with one of the LE samples examined here. By linking fungus to its exometabolite we suggest that this fungal load may be the key parameter driving antibacterial activity of the MEs. Antibacterial activity in kaolinite and smectite clays can arise either from spiking natural clays with elements like B and Al, or from an organic (fungal) load found only within some archaeological earths. It cannot be assumed, a priori, that this organic load was acquired randomly and as a result of long-term storage in museum collections. This is because, at least in the case of medicinal Lemnian Earth, there is historical evidence to suggest that the addition of a fungal component may have been deliberate.


Frontotemporal lobar degeneration: epidemiology, pathophysiology, diagnosis and management.
Frontotemporal lobar degeneration (FTLD) is a clinically and pathologically heterogeneous syndrome, characterized by progressive decline in behaviour or language associated with degeneration of the frontal and anterior temporal lobes. While the seminal cases were described at the turn of the 20th century, FTLD has only recently been appreciated as a leading cause of dementia, particularly in patients presenting before the age of 65 years. Three distinct clinical variants of FTLD have been described: (i) behavioural-variant frontotemporal dementia, characterized by changes in behaviour and personality in association with frontal-predominant cortical degeneration; (ii) semantic dementia, a syndrome of progressive loss of knowledge about words and objects associated with anterior temporal neuronal loss; and (iii) progressive nonfluent aphasia, characterized by effortful language output, loss of grammar and motor speech deficits in the setting of left perisylvian cortical atrophy. The majority of pathologies associated with FTLD clinical syndromes include either tau-positive (FTLD-TAU) or TAR DNA-binding protein 43 (TDP-43)-positive (FTLD-TDP) inclusion bodies. FTLD overlaps clinically and pathologically with the atypical parkinsonian disorders corticobasal degeneration and progressive supranuclear palsy, and with amyotrophic lateral sclerosis. The majority of familial FTLD cases are caused by mutations in the genes encoding microtubule-associated protein tau (leading to FTLD-TAU) or progranulin (leading to FTLD-TDP). The clinical and pathological heterogeneity of FTLD poses a significant diagnostic challenge, and in vivo prediction of underlying histopathology can be significantly improved by supplementing the clinical evaluation with genetic tests and emerging biological markers. Current pharmacotherapy for FTLD focuses on manipulating serotonergic or dopaminergic neurotransmitter systems to ameliorate behavioural or motor symptoms. However, recent advances in FTLD genetics and molecular pathology make the prospect of biologically driven, disease-specific therapies for FTLD seem closer than ever.


Spontaneous Splenic Rupture Unveiled: A Non-traumatic Case Associated With Infective Endocarditis.
Spontaneous splenic rupture (SSR) is a rare and potentially life-threatening condition often associated with trauma. However, SSR can occur without evident trauma, presenting unique diagnostic challenges. We present a case report of a 32-year-old postpartum female who experienced sudden-onset abdominal pain and was diagnosed with SSR. Despite the absence of trauma, she exhibited hypovolemic shock, requiring rapid intervention. Diagnostic imaging, including CT scans, revealed a substantial splenic laceration, which led to an emergent splenectomy. The patient's postoperative course was complicated by infective endocarditis (IE) with aortic involvement, elucidated as the underlying cause of SSR. The patient underwent aortic valve replacement, received antibiotic therapy, and achieved a successful recovery. This case underscores the importance of early recognition, timely intervention, and collaboration among diverse medical specialties in managing SSR cases. Furthermore, it highlights the potential link between SSR and IE, emphasizing the meaning of considering infectious etiologies even in non-traumatic scenarios. Early identification of the underlying cause is crucial for effective management and positive patient outcomes in cases of SSR.


[Effect of novocaine incorporation into the structure of a water-soluble polymer on its pharmacological activity].
The topically anesthesizing action and acute toxicity of two polymetric derivatives of novocaine-celnovocaine and polynovocaine No 5 (PN-5) were studied. The polymeric derivatives differ in the orientation of the novocaine molecule with respect to the macro-molecule of the water-soluble polymer-the modified cellulose. In celnovocaine novocaine joins the macromolecule through the intermediary of diethylamino-ethanol nitrogen and in PN-5-through the intermediary of paraaminobenzoic acid nitrogen. The ratio of the polymer-carrier (mol. weight 20 000-26 000) to novocaine is 1:1. The chemical bonding between novacaine and modified cellulose potentiates ad prolongs the infiltrative and terminal anesthesia, without changing (PN-5) or lowering (celnovocaine) the toxicity. The extent to which the action and duration of the effect, as well as changes in the toxicity depend upon the orientation of the novocaine molecule relative to the water-soluble polymer molecule.


ABO-Incompatible Liver Transplantation: State of Art and Future Perspectives.
ABO-incompatible (ABO-I) liver transplantation (LT) has been limited due to the increased rate of complications, including severe cellular and antibody-mediated rejection, hepatic necrosis, hepatic artery thrombosis, and biliary complications. However, several strategies for reducing preformed anti-donor ABO antibodies and B cell desensitization have improved the outcomes of ABO-I LT. As a result, ABO-I LT has become a routine procedure and is a feasible option in countries with a scarce deceased-organ donation or in cases without an available compatible organ donor. In this review, we describe past and present desensitizing protocols as well as emergent therapies for depleting B cell and anti-ABO antibodies with the objective of identifying approaches that could lead to new, refined strategies for maximizing the results of ABO-I LT.


Emerging role of extracellular vesicles in multiple sclerosis: From cellular surrogates to pathogenic mediators and beyond.
Multiple Sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system (CNS) driven by a complex interplay of genetic and environmental factors. While the therapeutic arsenal has expanded significantly for management of relapsing forms of MS, treatment of individuals with progressive MS is suboptimal. This treatment inequality is in part due to an incomplete understanding of pathomechanisms at different stages of the disease-underscoring the critical need for new biomarkers. Extracellular vesicles (EVs) and their bioactive cargo have emerged as endogenous nanoparticles with great theranostic potential-as diagnostic and prognostic biomarkers and ultimately as therapeutic candidates for precision nanotherapeutics. The goals of this review are to: 1) summarize the current data investigating the role of EVs and their bioactive cargo in MS pathogenesis, 2) provide a high level overview of advances and challenges in EV isolation and characterization for translational studies, and 3) conclude with future perspectives on this evolving field.


Focal adhesion kinase: a potential target in cancer therapy.
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays an important role in signal transduction pathways that are initiated at sites of integrin-mediated cell adhesions and by growth factor receptors. FAK is a key regulator of survival, proliferation, migration and invasion: processes that are all involved in the development and progression of cancer. FAK is also linked to oncogenes at both a biochemical and functional level. Moreover, overexpression and/or increased activity of FAK is common in a wide variety of human cancers, implicating a role for FAK in carcinogenesis. Given the important role of FAK in a large number of processes involved in tumorigenesis, metastasis and survival signalling FAK should be regarded as a potential target in the development of anti-cancer drugs. Therefore, selective inhibitors of FAK need to be developed. Combination of these selective FAK inhibitors with cytotoxic agents could be a very promising anti-cancer therapy.


Routine transfusion of platelet concentrates effectively reduces reoperation rate for bleeding and pericardial effusion after elective operations for ascending aortic aneurysm.
Patients with ascending aortic aneurysm undergoing complex surgical procedures are at increased risk of early postoperative excessive blood loss. The aim of this study was to analyze safety and efficacy of routine transfusions of platelet (PLT) concentrates in reduction of hemorrhagic postoperative complications. The study involved 396 consecutive patients (289 males and 107 females) with the mean age of 55.9 ± 13.6 years who underwent elective operations for aortic aneurysms. They were divided retrospectively into two groups, without (group A; n = 123) or with the routine use of PLTs (group B; n = 273). PLTs were transfused intraoperatively just after completion of cardiopulmonary bypass. Twelve patients in group A (9.8%) and 10 (3.7%) in group B required re-thoracotomy due to hemorrhage (p = 0.027). Routine transfusions of PLT concentrates reduced postoperative incidence of excessive pericardial effusion from 24.1% in group A to 2.1% in group B (p = 0.002). In a consequence, significantly less units (p < 0.0001) of red blood concentrates and fresh frozen plasma were transfused in group B than in group A. The rates of other adverse events in the early postoperative period did not differ between groups. Patients with pericardial effusion required 6.3 ± 2.7 additional days of hospitalization due to surgical re-intervention. Neither blood transfusion-related infections nor adverse reactions were noted. In conclusion, routine intraoperative transfusions of PLT concentrates in patients with ascending aortic aneurysms significantly reduced a need for re-intervention due to both early bleeding and late cardiac tamponade.


Protracted diarrhea of unknown etiology in Israeli soldiers.
Twenty-five Israeli soldiers, seen over a period of five years, suffered from diarrhea lasting from one month to three years. This was accompanied by weight loss and, in some cases, by evidence of malabsorption and/or mild abnormalities in small bowel and rectal biopsies. The etiology of the diarrhea is unknown, since a routine search for parasites or pathogenic bacteria was unrewarding. An infectious etiology is, however, most likely.


Hand contamination before and after different hand hygiene techniques: a randomized clinical trial.
The efficacy of alcohol-based handrubs (ABH) for hand hygiene (HH) compared with handwashing (HW) remains to be established in the clinical setting. Factors associated with severe hand contamination before HH techniques were medical ward, physician and not wearing gloves. Forty-three healthcare workers [HCW, 26 nurses (N), nine nurse assistants (NA) and eight physicians (P)] each performed six HH techniques in random order, immediately after a patient care activity: HW with non-antiseptic soap for 10 (US10) and 30 (US30) s; HW with antiseptic (polyvidone iodine- or chlorhexidine-based) soap for 10 (AS10), 30 (AS30) or 60 (AS60) s; and ABH (Sterillium, Bode Chemie, Germany). The fingertips of the dominant hand were pressed on to agar for culture before and after each HH technique. Five hundred and sixteen specimens were obtained. Log(10)-transformed bacterial count reductions after HH were 0.74, 0.51, 1.13, 1.14, 1.21 and 1.40 for US10, US30, AS10, AS30, AS60 and ABH, respectively; both AS and ABH were significantly better than US. Qualitative assessment showed that 11 of the 256 pre-HH specimens (4.3%) had pathogenic bacteria, and that two of these 11 remained positive after HH (US in both instances).


Crystal structure of wild-type penicillin-binding protein 5 from Escherichia coli: implications for deacylation of the acyl-enzyme complex.
Penicillin-binding protein 5 (PBP 5) of Escherichia coli functions as a d-alanine carboxypeptidase (CPase), cleaving d-alanine from the C terminus of cell wall peptides. Like all PBPs, PBP 5 forms a covalent acyl-enzyme complex with beta-lactam antibiotics; however, PBP 5 is distinguished by its high rate of deacylation of the acylenzyme complex (t(1/2) approximately 10 min). A Gly105 --> Asp mutation in PBP 5 markedly impairs deacylation with only minor effects on acylation, and abolishes CPase activity. We have determined the three-dimensional structure of a soluble form of wild-type PBP 5 at 1.85-A resolution and have also refined the structure of the G105D mutant form of PBP 5 to 1.9-A resolution. Comparison of the two structures reveals that the major effect of the mutation is to disorder a loop comprising residues 74-90 that sits atop the SXN motif of the active site. Deletion of the 74-90 loop in wild-type PBP 5 markedly diminished the deacylation rate of penicillin G with a minimal impact on acylation, and abolished CPase activity. These effects were very similar to those observed in the G105D mutant, reinforcing the idea that this mutation causes disordering of the 74-90 loop. Mutation of two consecutive serines within this loop, which hydrogen bond to Ser110 and Asn112 in the SXN motif, had marked effects on CPase activity, but not beta-lactam antibiotic binding or hydrolysis. These data suggest a direct role for the SXN motif in deacylation of the acyl-enzyme complex and imply that the functioning of this motif is modulated by the 74-90 loop.


Echocardiography-guided endomyocardial biopsy. A 5-year experience.
The number of cardiac transplant procedures performed each year continues to increase and may exceed 1,600 procedures in 1987. In these patients, the diagnosis of rejection is obtained from serial endomyocardial biopsy. The absence of clinical symptoms associated with allograft rejection with cyclosporine therapy has necessitated a predetermined routine biopsy frequency that averages 10-15 biopsies per patient in the first posttransplant year. Traditionally, fluoroscopy has been used to guide the biopsy, but this technique has a number of negative features, including cumulative radiation exposure in the physician and the patient, limited portability, and the limited area of access (intraventricular septum) for biopsy. In contrast, echocardiography provides greater portability and flexibility for location of procedure performance, eliminates radiation exposure, provides important information about cardiac function, and safely allows biopsy of any area of the right ventricle, including the free wall and apex. We performed over 4,700 individual biopsies for evaluation of rejection in 58 patients who underwent orthotopic cardiac transplantation. Fluoroscopy was not required for any of the echocardiography-guided biopsies, and only two complications occurred in 4,700 biopsies. We propose, therefore, that echocardiography is a useful alternative or adjunct to fluoroscopy for guiding endocardial biopsy and is a technique that can be learned easily by anyone now performing biopsies.


Spectrotypic analysis of humoral response in human hydatidosis.
The spectrotypic patterns of anti-Echinococcus granulosus and anti-F(ab')2 antibodies were analysed in 13 patients with different forms of hydatidosis by means of isoelectric focusing (IEF). Specific anti-echinococcus antibodies and specific echinococcus antigens were obtained by crossed affinity chromatography between patient serum and cyst fluid, as previously described (D'Amelio et al., 1985). A wide spectrotype in the pattern of anti-Echinococcus antibodies was observed, with strong homologies among the different sera mainly at acid and neutral pH. One serum displayed faint, nearly inapparent bands. Conversely, the pattern of anti-F(ab')2 antibodies in the six patients in whom they were positive was limited but heterogeneous, ranging from monoclonal through oligoclonal to polyclonal. A predominant clone was identified in the patient with a polyclonal pattern. A correlation between qualitative IEF spectrotypic patterns and the quantitative results of immunoenzymatic assays was observed for both types of antibodies.


Purging human ovarian cortex of contaminating leukaemic cells by targeting the mitotic catastrophe signalling pathway.
Is it possible to eliminate metastasised chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) cells from ovarian cortex fragments by inhibition of Aurora B/C kinases (AURKB/C) without compromising ovarian tissue or follicles? Human ovarian cortex tissue with experimentally induced tumour foci of CML, AML and primary cells of AML patients were exposed to a 24h treatment with 1 μM GSK1070916, an AURKB/C inhibitor, to eliminate malignant cells by invoking mitotic catastrophe. After treatment, the inhibitor was removed, followed by an additional culture period of 6 days to allow any remaining tumour cells to form new foci. Ovarian tissue integrity after treatment was analysed by four different assays. Appropriate controls were included in all experiments. Foci of metastasised CML and AML cells in ovarian cortex tissue were severely affected by a 24h ex vivo treatment with an AURKB/C inhibitor, leading to the formation of multi-nuclear syncytia and large-scale apoptosis. Ovarian tissue morphology and viability was not compromised by the treatment, as no significant difference was observed regarding the percentage of morphologically normal follicles, follicular viability, glucose uptake or in vitro growth of small follicles between ovarian cortex treated with 1 μM GSK1070916 and the control. Purging of CML/AML metastases in ovarian cortex is possible by targeting the Mitotic Catastrophe Signalling Pathway using GSK1070916 without affecting the ovarian tissue. This provides a therapeutic strategy to prevent reintroduction of leukaemia and enhances safety of autotransplantation in leukaemia patients currently considered at high risk for ovarian involvement.


Effect of three-body interactions on the phase behavior of charge-stabilized colloidal suspensions.
We study numerically the effect of attractive triplet interactions on the phase behavior of suspensions of highly charged colloidal particles at low salinity. In our computer simulations, we employ the pair and triplet potentials that were obtained from a numerical Poisson-Boltzmann study [Phys. Rev. E 66, 011402 (2002)]]. On the basis of free energy calculations, we determine the phase diagram of an aqueous suspension of identical spheres of diameter sigma=32 nm and charge Z=80 as a function of colloid concentration and salinity, both for the purely pairwise additive system and for the system with pair and triplet interactions. The main effect of including the triplet interactions is a destabilization of the body-centered-cubic (bcc) crystal phase in favor of the face-centered-cubic (fcc) crystal phase. As a consequence the phase diagram features the coexistence of a rather dilute fluid with an almost-close-packed fcc phase at low salinity and bcc-fcc coexistence with a big density jump at intermediate salinity. The triplet attractions do not affect the phase behavior at sufficiently high salinity; under these conditions the system is well described by the pairwise potential.


Salient features of mesenchymal stem cells-implications for Ewing sarcoma modeling.
Despite a heightened appreciation of the many defining molecular aberrations in Ewing sarcoma, the cooperative genetic environment and permissive cell of origin essential for EWS/ETS-mediated oncogenesis remain elusive. Consequently, inducible animal and in vitro models of Ewing sarcoma from a native cellular context are unable to fully recapitulate malignant transformation. Despite these shortcomings, human, and murine mesenchymal stem cells (MSCs) are the closest working in vitro systems available. MSCs are tolerant of ectopic EWS/FLI expression, which is accompanied by a molecular signature most similar to Ewing sarcoma. Whether MSCs are the elusive cell of origin or simply a tolerant platform of the EWS/FLI transcriptome, these cells have become an excellent molecular tool to investigate and manipulate oncogenesis in Ewing sarcoma. Our understanding of the biological complexity and heterogeneity of human MSCs (hMSCs) has increased substantially over time and as such, appreciation and utilization of these salient complexities may greatly enhance the efficient use of these cells as surrogate models for Ewing sarcoma tumorigenesis.


Antagonists of calmodulin delay injury development in the severely ischemic perfused working rat heart.
The effects of calmodulin antagonists trifluoperazine (TFP) and calmidazolium (CMZ) and of ethmozine (a phenothiazine without anticalmodulin activity) on the postischemic recovery in the perfused working rat hearts were studied. In the hearts subjected to 25 min zero-flow ischemia coronary flow, cardiac output, MVO2 and external work recovered to about 50% of the preischemic values during 40 min of reperfusion. TFP (5 x 10(-7) M and 10(-6) M) or CMZ (10(-7) M) improved the functional recovery to 75-94% whereas 5 x 10(-7) M ethmozine was not effective. In all experimental groups a prolongation of the ischemic period caused a progressive deterioration of the functional recovery while the total postischemic LDH release showed an initial gradual rise followed by a later decay. TFP and CMZ prolonged the time-to-half decay of the hemodynamic functions (tHF50) by 4-7 min and the time-to-peak of total LDH release (tLDHmax) by 5-10 min. In the hearts subjected to 0.2 ml/min low-flow ischemia tHF50 and tLDHmax were increased to 40 min, CMZ prolonged these times by further 5-10 min. Thus, TFP and CMZ delayed the development of the myocardial ischemic injury. Although other interpretations are possible, our data are consistent with the hypothesis that calmodulin-sensitive process is involved in the ischemic damage of the myocardium.


Direct measurement of pressure-independent aqueous humour flow using iPerfusion.
Reduction of intraocular pressure is the sole therapeutic target for glaucoma. Intraocular pressure is determined by the dynamics of aqueous humour secretion and outflow, which comprise several pressure-dependent and pressure-independent mechanisms. Accurately quantifying the components of aqueous humour dynamics is essential in understanding the pathology of glaucoma and the development of new treatments. To better characterise aqueous humour dynamics, we propose a method to directly measure pressure-independent aqueous humour flow. Using the iPerfusion system, we directly measure the flow into the eye when the pressure drop across the pressure-dependent pathways is eliminated. Using this approach we address i) the magnitude of pressure-independent flow in ex vivo eyes, ii) whether we can accurately measure an artificially imposed pressure-independent flow, and iii) whether the presence of a pressure-independent flow affects our ability to measure outflow facility. These studies are conducted in mice, which are a common animal model for aqueous humour dynamics. In eyes perfused with a single cannula, the average pressure-independent flow was 1 [-3, 5] nl/min (mean [95% confidence interval]) (N = 6). Paired ex vivo eyes were then cannulated with two needles, connecting the eye to both iPerfusion and a syringe pump, which was used to impose a known pressure-independent flow of 120 nl/min into the experimental eye only. The measured pressure-independent flow was then 121 [117, 125] nl/min (N = 7), indicating that the method could measure pressure-independent flow with high accuracy. Finally, we showed that the artificially imposed pressure-independent flow did not affect our ability to measure facility, provided that the pressure-dependence of facility and the true pressure-independent flow were accounted for. The present study provides a robust method for measurement of pressure-independent flow, and demonstrates the importance of accurately quantifying this parameter when investigating pressure-dependent flow or outflow facility.


Clinical outcomes after treatment of quadriceps tendon ruptures show equal results independent of suture anchor or transosseus repair technique used - A pilot study.
Biomechanical studies have shown the use of suture anchors (SA) to be superior to the traditional transosseous sutures (TS) in the repair of quadriceps tendon rupture (QTR). This study aimed to analyze and compare the functional outcomes of patients treated for quadriceps tendon ruptures using suture anchors or transosseous sutures. Patients having undergone suture anchor repair or transosseous suture repair for quadriceps tendon rupture between 2010 and 2015 at one of the two participating hospitals were included. Patients from site A underwent TS repair (TS group) while patients from site B underwent SA repair (SA group). Exclusion criteria included previous or concomitant injuries of the involved knee, penetrating injuries and pre-existing neurological conditions. Clinical outcome was assessed by subjective scores (Lysholm and Tegner Scores, International Knee Documentation Committee (IKDC) Score, Visual Analog Scale (VAS) for pain), quadriceps isokinetic strength testing, Insall-Salvati Index (ISI), and physical examination. Non-parametrical statistical analysis was conducted using the Mann-Whitney U test. Twenty-seven patients were included in the study of which 17 patients (63%) were available for follow-up (SA group: 9, TS group: 8). All patients were male with a mean age of 62.7 (SD: 8.8) and 57.9 (SD: 12.7) years for the SA group and TS group, respectively. The groups did not differ in terms of demographic characteristics. No clinically significant differences were identified between the two groups. There were no re-ruptures in either group. Treatment of quadriceps tendon rupture using suture anchors provides a clinically valid alternative treatment to the gold-standard transosseous suture repair.


Quinoline-based antifungals.
Although the assortment of antifungal drugs is broad, the most commonly used agents have major drawbacks. Toxicity, serious side effects or the emergence of drug resistance are amongst them. New drugs and drug candidates under clinical trials do not guarantee better pharmacological parameters. These new medicines may appear effective; however; they may cause serious side effects. This current review is focused on the recent findings in the design of quinoline based antifungal agents. This field seems to be especially interesting as 8-hydroxyquinoline and its metal complexes have been well known as antifungals for years. Structural similarities between quinoline based antifungals and allylamines or homoallylamines, e.g. terbinafine is another interesting fact. Quinoline can be identified in a number of synthetic and natural antifungals, which indicates nature's preference for this fragment and identifying it as one of the so-called privileged structures. We have discussed new trends in the design of quinolines with antifungal properties, their possible targets and the structure activity relationships within the antifungal series developed.


Resting energy expenditure during mechanical ventilation and its relationship with the type of lesion.
Resting energy expenditure (REE) of critically ill patients is usually calculated according to basal energy expenditure obtained from Harris-Benedict equations traditionally corrected by different stress factors, resulting in a variable accuracy for the individual patient. The objective of this study was to investigate whether or not the type of lesion affects the metabolism level of critically ill patients treated with mechanical ventilation. We performed a retrospective study measuring the REE of critically ill patients with 3 different types of lesions (trauma, medical, surgical) who were treated with mechanical ventilation and sedation. Each lesion group of patients was matched with another group, differing in the type of lesion, according to gender, age, and weight. Eighty-seven from a database of 175 critically ill patients undergoing indirect calorimetry were necessary for matching. Twenty matched pairs of patients for each of the following different type of lesion were obtained: medical vs surgical, medical vs trauma, and surgical vs trauma. The mean REE difference was 52 kcal/d (95% confidence interval [CI] of -136 -241 kcal/d) for the medical vs surgical group, 5 kcal/d (95% CI -236 -247 kcal/d) for the medical vs trauma group and 43 kcal/d (95% CI of -132-219 kcal/d) for the surgical vs trauma group. No statistically significant differences between groups were found in the measured REE. We did not find statistically significant differences in the measured REE of patients with and without infection. Critically ill patients with different types of lesion treated with mechanical ventilation have similar measured REE.


Corporal punishment.
Pediatricians differ on the optimal ways to discipline children. The major controversy surrounds the use of corporal punishment. In an effort to resolve this controversy, the American Academy of Pediatrics (AAP) cosponsored a conference entitled "The Short and Long-Term Consequences of Corporal Punishment" in February 1996. This article reviews scientific literature on corporal punishment and summarizes the proceedings from the conference. The authors conclude that, although the research data are inadequate to resolve the controversy, there are areas of consensus. Practitioners should assess the spanking practices of the parent they see and counsel parents to avoid those that are, by AAP consensus, dangerous, ineffective, or abusive.


Primary nephrectomy and intraoperative tumor spill: report from the Children's Oncology Group (COG) renal tumors committee.
Initial Children's Oncology Group (COG) management for Wilms' tumor (WT) consists of primary nephroureterectomy with lymph node sampling. While this provides accurate staging to define further treatment, it may result in intraoperative spill (IOS), which is associated with higher recurrence rates and therefore requires more intensive therapy. The purpose of this study is to determine current rates and identify factors which may predispose a patient to IOS. The study population was drawn from the AREN03B2 renal tumor banking and classification study of the Children's Oncology Group. All children with a first time occurrence of a renal mass were eligible for the study. At the time of enrollment and prior to risk stratification, the institution is required to submit operative notes, pathology specimens, a chest computed tomography scan (CT), and a contrast-enhanced CT or magnetic resonance imaging (MRI) of the abdomen and pelvis for central imaging review. These data are then used to determine an initial risk classification and therapeutic protocol eligibility. Patients who had a unilateral nephroureterectomy for favorable histology WT underwent further review to assure data accuracy and to clarify details regarding the spill. Analyses were performed using chi square and logistic regression. Odd ratios (OR) are shown with 95% confidence intervals. There were 1,131 primary nephrectomies for unilateral WT with an IOS rate of 9.7% with an additional 1.8% having possible tumor spill during renal vein or IVC tumor thrombectomy. IOS correlated with diameter (>12 cm, p<0.0001) and laterality (right, p=0.0414). Simple logistic regression indicated that IOS increased 2.7% [p=0.0240, OR 1.027 (1.004, 1.052)] with each 1 cm increase in diameter (3 - 21 cm) and 4.7% [p=0.0147 OR 1.047 (1.009, 1.086)] with each 100 g increase in weight (80 - 1800 g). Multiple logistic regression indicated that laterality [right p=0.048, OR 1.46 (1.004, 2.110)] and weight (p=0.03, OR 1.039 (1.003, 1.075) were predictive of IOS when diameter was included as a continuous variable. Diameter as a binary variable was highly prognostic of IOS (p=0.0002), while laterality and weight were not significant. Intraoperative tumor spill occurs in about one out of every ten cases of primary nephroureterectomies for WT. Right-sided and larger tumors are at higher risk of IOS.


[Expression of proto-oncogene Wip1 in breast cancer and its clinical significance].
To investigate the expression of proto-oncogene Wip1 in breast cancer tissue and its clinical significance. Through the uses of semi-RT-PCR, immunohistochemical technique and Western blot, the specimens from 70 patients of breast cancer and 20 normal controls were detected for Wip1 mRNA and protein expression. At the same time, the authors analyzed the relations between the expression of Wip1 in human breast cancer and different clinical pathologic parameters. RT-PCR: The values of gene expression of Wip1 mRNA in breast cancer tissue, pericancerous tissue and normal breast tissue were 0.715 +/- 0.087, 0.175 +/- 0.021 and 0.154 +/- 0.022 respectively. Thus the value of gene expression in breast cancer tissue was significantly higher than that in pericancerous tissue or normal breast tissue (P < 0.01). Immunohistochemistry: The high expression rates of Wip1 protein in breast cancer tissue, pericancerous tissue and normal breast tissue were 62.9% (44/70), 2.9% (2/70) and 0 (0/20) respectively and there was a significant difference among these three different tissues (P < 0.01). Western blot: The relative contents of Wip1 protein in breast cancer tissue, pericancerous tissue and normal breast tissue were 0.688 +/- 0.151, 0.251 +/- 0.043 and 0.234 +/- 0.044 respectively. The relative content of Wip1 protein in breast cancer tissue was significantly higher than that in pericancerous tissue or normal breast tissue (P < 0.01). The high expression of Wip1 protein was negatively correlated with the expression of p53, but it had nothing to do with tumor size, age, tumor staging, axillary lymph node metastasis and expressions of ER and PR. The high expression of Wip1 mRNA and its protein in breast cancer tissue may promote the growth of breast cancer. Wip1 may become a new target for therapy of breast cancer.


Tetracycline labeling of bone in vivo.
We have analyzed various aspects of tetracycline labeling technique for the measurement of bone apposition rate in vivo. Our efforts were restricted to those aspects that are frequently questioned when data obtained using this technique are interpreted as representing the rate of bone apposition. Rat bone was labeled in vivo by sequential injections of oxytetracycline at a dose range of 3 to 24 mg/kg body weight and at intervals ranging from 24 to 72 h. The bone apposition rate was calculated by measuring the distance from the first dose of label to the subsequent ones. As these distances are by far too small to be determined accurately by any available micrometer eyepiece, we have used a scanning microscope photometer which allows measurements on slow-forming sites that otherwise would have been considered nongrowing sites. Using these techniques, we have demonstrated that oxytetracycline has no effect on the bone apposition rate when used in the concentrations indicated. In addition, we found that at labeling intervals of 96 h or more, periods of osteoblastic inactivity are likely to be included in measurements at individual sites. The instantaneous apposition rate is thus underestimated at these long time intervals.


Regulation of lac operon expression in mixed sugar chemostat cultures.
Expression of the lactose (lac) operon in the Escherichia coli chromosome has been studied in mixed-sugar chemostat cultures under steady-state and transient conditions. A unified model has been formulated which involves regulation of active inducer (lactose) transport, promoter-operator regulated expression of the lac operon, glucose-mediated inducer exclusion, and catabolite repression. The model of the lac operon control system focuses on the molecular interactions among the regulatory species and the genetic control elements for the initiation of transcription. The role of catabolite modulator factor (CMF) in the regulation of transcription is described. The modeling of glucose-mediated regulation of intracellular cyclic adenosine monophosphate (cAMP) and inducer exclusion is based on the recently elucidated mechanisms of the involvement of the PTS (phosphoen-olpyruvate dependent sugar transport system) enzymes, in the presence of glucose, in regulation of adenylate cyclase and non-PTS sugar transport proteins (i.e. per-meases). The adequacy of the unified model was verified with experimental data.


Hysteresis and the role of nucleation and growth in the hydrogenation of Mg nanolayers.
We investigated the hydrogenation of 3 and 10 nm Mg layers sandwiched between Ti using an optical transmission technique (hydrogenography). We observe in situ the two dimensional nucleation and growth of single hydride domains of up to several millimeters in diameter. The low density of nuclei points to preferential nucleation at heterogeneous sites. From an analysis of the growth kinetics we deduce an extremely large edge boundary energy, which we relate to the plastic deformations inherent to the 30% volume expansion of the MgH(2). We find that the nucleation and growth process affects the hysteresis between absorption and desorption. Especially, the absorption branch can be lowered when nucleation barriers are removed. Our results show that when discussing the effect of nano-structuring on hydrogenation it may be quite complex to distinguish the thermodynamic and kinetic effects involved.