Craniofacial morphology in a patient with Simpson-Golabi-Behmel syndrome.
We present the case of a 6-year-old boy with a coarse face, cleft palate, and malocclusion with anterior open bite who had been diagnosed with Simpson-Golabi-Behmel syndrome. Morphology of the craniofacial structures was examined on the basis of conventional radiographs, three-dimensional (3D) computed tomography (CT) and magnetic resonance (MR) scanning. This patient had 13 ribs on the right side, slight scoliosis, supernumerary nipples, a coarse face, hypertelorism, a short broad upturned nose, a wide mouth, a straight facial profile with incompetence of the lips, midline groove of tongue, and cleft palate. The patient also had severe anterior open bite, a distal step-type molar relationship, five congenitally missing teeth, and a supernumerary tooth. Lateral cephalometric analysis revealed a large anterior cranial base, a large maxilla and mandible, a large inferior face height, and skeletal Class I jaw relationship with a high mandibular plane angle and large gonial angle. The 3D CT image showed a large cranium, a long face height, and prominent skull sutures. The MR image showed a large tongue, midline groove of the tongue, and a small space between tongue and palate.


Neurohormonal host defense in endotoxin shock.
Lipopolysaccharide (LPS) of gram-negative bacteria is capable of activating the immune system of higher animals, which may lead to cytokine-induced lethal shock and death. LPS has little toxicity for the frog and fish, but it kills the horseshoe crab instantly by causing intravascular blood coagulation. The response to LPS evolved from simple reactions in lower animals into an intense reaction in mammals that involves a massive immune activation leading to a profound neuroendocrine and metabolic response. This is now known as the acute-phase response (APR). During APR, LPS-binding proteins (LBP) are produced by the liver in rapidly increasing quantities under the influence of interleukin-6, glucocorticoids, and catecholamines. After combination with LPS, LPB is capable of activating monocyte-macrophages and granulocytes via the CD14 surface receptor. Other receptors (CD18, 80-kDa receptor) allow for direct action by LPS of phagocytes, B and T lymphocytes, and other cells. Numerous other acute-phase proteins are produced in the liver, including C-reactive protein, complement components, fibrinogen, enzyme inhibitors, and anti-inflammatory proteins. Similar responses may be stimulated by subtoxic doses of LPS or by detoxified LPS, which manifest in endotoxin tolerance. Tolerant animals and man show increased resistance to LPS, to infections, and to various noxious insults. Infection and various forms of tissue injury are also capable of causing APR. There is much evidence to indicate that APR, which manifests in febrile illness, is an efficient host defense reaction. It is an emergency response in cases where specific immunity fails to protect the host. Therefore, the neuroimmunoregulatory network converts the immune system to a less specific, but rapid and more efficient response, APR. The hypothesis is presented that intestinal LPS serves to amplify the APR in response to various insults, which contribute to host defense, regeneration, and healing.


Zinc transport in rabbit tissues. Some hormonal aspects of the turnover of zinc in female reproductive organs, liver and body fluids.
1. To investigate the influence of hormonal conditions upon the kinetics of zinc transport, specific radioactivity of (65)Zn was determined in certain tissues and fluids from unmated or pregnant rabbits during the first half of gestation. 2. Compartmental analysis was used to find the simplest mathematical model that simulated satisfactorily tracer behaviour. Models were fitted to experimental results by a numerical procedure using a computer. 3. The kinetics of zinc exchange in most tissues investigated could adequately be described by a three-compartment model, in which total tissue zinc content was divided into a rapidly exchanging pool, with a turnover time of about 1h, and a slowly exchanging pool, the turnover time of which was in liver 15h, in peak-stage corpus luteum 8h, and in the other tissues 30-70h. 4. In rabbit endometrium zinc transport varied with hormonal conditions, the turnover rate being higher in non-pregnant than pregnant endometrium. 5. Uptake of (65)Zn by uterine fluid was slow, and in the free-lying embryos (blastocysts) slower still, in keeping with uterine fluid acting as carrier of zinc into the unimplanted embryos. 6. In placental tissue zinc transport varied with gestational stage. Foetal placenta exchanged zinc with blood plasma four times faster than maternal placenta. In foetuses zinc turnover time and flux equalled that of the slow zinc compartment in foetal placenta. 7. Corpus luteum on days 5-6 of gestation showed peak specific radioactivity and zinc flux values, which exceeded those of all other tissues. 8. In liver the slow zinc compartment had a higher rate of turnover than corresponding compartments in tissues other than peak-stage corpus luteum, but no hormone-dependent changes were observed. 9. Zinc uptake by erythrocytes was the slowest of all examined.


Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts.
Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing and microarray data displayed substantially higher resolution and dynamic range than gene expression-based inferences, and they also showed strong CNA conservation from PTs through late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-late trios confirmed high-resolution CNA retention. We observed no significant enrichment of cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between patient and PDX tumors were comparable to variations in multiregion samples within patients. Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse host.


Influence of pacing manipulation on performance of juniors in simulated 400-m swim competition.
To date, there has been limited research examining the influence of pacing pattern (PP) on middle-distance swimming performance. As such, the purpose of the current study was to examine the influence of PP manipulation on 400-m freestyle swimming performance. 15 front-crawl swimmers (5 female, 10 male; age 18 ± 2 y) performed 3 simulated 400-m swimming events. The initial trial was self-selected pacing (PPSS). The following 2 trials were performed in a counterbalanced order and required participants to complete the first 100 m more slowly (PPSLOW: 4.5% ± 2.2%) or quickly (PPFAST: 2.4% ± 1.6%) than the PPSS trial. 50-m split times were recorded during each trial. Overall performance time was faster in PPSS (275.0 ± 15.9 s) than in PPFAST (278.5 ± 16.4 s, P = .05) but not significantly different from PPSLOW (277.5 ± 16.2 s, P = .22). However, analysis for practical relevance revealed that pacing manipulation resulted in a "likely" (>88.2%) decrease in performance compared with PPSS. Moderate manipulation of the starting speed during simulated 400-m freestyle races seems to affect overall performance. The observed results indicate that PPSS is optimal in most individuals, yet it seems to fail in some swimmers. Future research should focus on the identification of athletes possibly profiting from manipulations.


Verbal autopsy to assess causes of mortality among the economically productive age group in the tribal region of Melghat, central India.
Verbal autopsy (VA) is the systematic and retrospective inquiry (from relatives) about the symptoms of an illness prior to death. In tribal India, 67-75 per cent of deaths occur at home with an unknown cause of death (CoD). Hence, the aim of this study was to determine the CoD in the 16-60 yr age group utilizing VA. A prospective, community based longitudinal study was conducted in 32 tribal villages in the Melghat region of Maharashtra, between 2004 and 2020. Number of deaths and VAs in 16-60 yr age group were collected by village health workers (VHWs) and supervisors, verified by five different persons (internal-external) and cross-checked by three VA interpretation trained physicians. A modified version of WHO VA was used. Cause-specific mortality fractions were calculated. Of the 1011 deaths recorded, mortality in males was significantly higher than females (P<0.001). A total of 763 VAs were conducted which revealed that tuberculosis was the leading CoD, followed by jaundice, heart diseases, diarrhoea, central nervous system infections and suicide. Suicides were significantly more common among males than in females (P=0.046). Significantly, more deaths occurred during the monsoon (P=0.002), especially diarrhoeal deaths (P=0.024). The findings of this study suggest that, in Indian tribal areas, infectious diseases are the leading causes of morbidity and one of the major causes of deaths in economically productive age group. Intensified VHW-mediated interventions are required to reduce the premature deaths.


A physical interaction between viral replicase and capsid protein is required for genome-packaging specificity in an RNA virus.
Genome packaging is functionally coupled to replication in RNA viruses pathogenic to humans (Poliovirus), insects (Flock house virus [FHV]), and plants (Brome mosaic virus [BMV]). However, the underlying mechanism is not fully understood. We have observed previously that in FHV and BMV, unlike ectopically expressed capsid protein (CP), packaging specificity results from RNA encapsidation by CP that has been translated from mRNA produced from replicating genomic RNA. Consequently, we hypothesize that a physical interaction with replicase increases the CP specificity for packaging viral RNAs. We tested this hypothesis by evaluating the molecular interaction between replicase protein and CP using a FHV-Nicotiana benthamiana system. Bimolecular fluorescence complementation in conjunction with fluorescent cellular protein markers and coimmunoprecipitation assays demonstrated that FHV replicase (protein A) and CP physically interact at the mitochondrial site of replication and that this interaction requires the N-proximal region from either amino acids 1 to 31 or amino acids 32 to 50 of the CP. In contrast to the mitochondrial localization of CP derived from FHV replication, ectopic expression displayed a characteristic punctate pattern on the endoplasmic reticulum (ER). This pattern was altered to relocalize the CP throughout the cytoplasm when the C-proximal hydrophobic domain was deleted. Analysis of the packaging phenotypes of the CP mutants defective either in protein A-CP interactions or ER localization suggested that synchronization between protein A-CP interaction and its subcellular localization is imperative to confer packaging specificity.


[What have we learned about inhibitors of the renin-angiotensin system?].
With orally active angiotensin converting inhibitors it is now possible to block the renin-angiotensin system chronically. These agents given alone normalize blood pressure of many hypertensive patients. In the remaining, an additional salt subtraction, induced for example by diuretics, is necessary to further reduce blood pressure. In patients with congestive heart failure, angiotensin converting enzyme inhibitors increase cardiac output and exercise capacity, both acutely and chronically. Adverse reactions resulting from blockade of the renin-angiotensin system can be predicted to a large extent and therefore are most often easily avoided. Angiotensin converting enzyme inhibitors like captopril and enalapril, because of their efficacy and good acceptability are likely to become important drugs for the treatment of hypertension and congestive heart failure.


Coexistence of two asexual strains on a single resource.
A stable equilibrium was obtained for two F(-) strains of Escherichia coli in a glucose minimal medium. This equilibrium cannot readily be explained by traditional models of population genetics and apparently violates some forms of the ecological principle of competition exclusion. A mechanism involving an inverse relationship between the growth rates of these strains at the exponential and "stationary" phases is suggested as a possible explanation for the observed stable equilibrium.


Circadian clock in photoperiodic time measurement: a test of the Bünning hypothesis.
A technique has been developed for effectively separating the direct inductive effect of a light signal from its effect on the phase of the rhythm of sensitivity to photoperiodic induction. With this technique it has been shown that a 75-minute pulse of light per day, when appropriately positioned with respect to the circadian activity cycle of the sparrow Passer domesticus, is sufficient to produce a response normally produced only by long days. The results cannot be interpreted in terms of a requirement of an absolute amount of either darkness or light and offer strong confirmation of Bünning's hypothesis concerning the mechanism of photoperiodic time measurement.


Downregulation of caveolin-1 in a murine model of acute allergic airway disease.
Airway remodeling refers to the structural changes in the airways of asthma. Caveolin-1 reduces cell growth and negatively regulates smooth muscle cell proliferation. The aim was to investigate lung caveolin-1 status in a murine model of acute allergic airway disease. Six- to eight-week-old female BALB/c mice were sensitized by intraperitoneal injections of phosphate-buffered saline or ovalbumin (OVA) and aluminium hydroxide on Days 0 and 14, challenged with aerosolized saline or OVA (1%) on Days 21-25, 28-32, and 35. The mice were killed 1 day after the last OVA/saline challenge. Serum OVA-specific immunoglobulin E (IgE) was measured by enzyme-linked immunosorbent assay. Peribronchial inflammation was quantified by morphometric analysis. Lung caveolin-1 and Type I collagen mRNA expression was determined by real-time reverse-transcription polymerase chain reaction. Total lung collagen was measured using Sircol Assay Kit. Serum OVA-specific IgE levels were significantly elevated in OVA-challenged mice when compared with saline-challenged mice. Percentage of inflammatory cells in the bronchoalveolar lavage was significantly higher in the OVA-challenged animals. The animals' lungs that were sensitized and challenged with OVA contained large numbers of inflammatory cells concentrated near the airways and in the perivascular areas. The thickness of the bronchial epithelial layer and smooth muscle layer and the numbers of total inflammatory cells and eosinophils significantly increased in OVA-challenged mice. Caveolin-1 mRNA expression significantly decreased and Type I collagen mRNA expression significantly increased in the lung tissue of OVA-challenged mice. These results suggest that caveolin-1 seems to be involved in the pathogenesis of airway remodeling of acute allergic airway disease.


Paracardial lipodystrophy versus pericardial effusion in HIV positive patients.
To present an epicardial manifestation of the lipodystrophy syndrome, a side effect of antiretroviral treatment in HIV positive patients, which illustrates the important danger of false diagnosis. A 52 year old man with HIV (stage C3), diagnosed 10 years previously, was being treated with a combination of nelfinavir, nevirapine, and stavudine. Echocardiographic examination showed a low echogenic pericardial space that had increased from 4 mm to 18 mm over a 10 month period. The diagnosis of paracardial adipose tissue was verified by magnetic resonance tomography. Doppler echocardiographic parameters were not significantly altered (ratio of early to late ventricular filling 0.88 v 0.73, Tei index 0.30 v 0.36). Even a pericardial manifestation of lipodystrophy causes negligible functional impairment, misinterpretation of the lipodystrophy as a pericardial effusion and a subsequent puncture can have serious complications. Hence, it is strongly suggested that further differential diagnosis be used for HIV positive patients with an echocardiographic suspicion of pericardial effusion. Differential diagnosis by magnetic resonance tomography is possible.


Glucocorticoid-lens protein adducts in experimentally induced steroid cataracts.
The injection of glucocorticoids into the vitreous chamber of the rabbit eye results in the development of posterior subcapsular opacities. These lesions appear to be similar in morphology to human steroid-induced cataracts. Electron microscopic analysis revealed fiber cell separation, vacuolization, and changes within the matrix of the crystallins. Opacification could only be produced by glucocorticoids possessing a reactive C-20,21 hydroxylcarbonyl function, supporting the hypothesis that glucocorticoid addition products are involved in the induction of these lesions. The occurrence of glucocorticoid-lens proteins adducts was confirmed by tritium incorporation and by radioimmunoassay of protein hydrolysates obtained from these lenses.


Ward-based clinical teaching in gynaecology: principles and practice.
Clinical teaching on the wards remains a prime method of educational instruction. Despite changes in modern educational climate and patient expectations, its value is still irrefutable. There is evidence to suggest that such teaching is beneficial to students and patients alike. This paper describes the planning and delivery steps of a ward-based teaching session with 'pregnancy of unknown location' as an example. The organisation, following-up and feedback after the session are also mentioned. We have discussed the models applicable to clinical teaching and explored ways how the 'microskill' technique could be potentially used in such a situation. The paper also focuses on the use of clinical reasoning processes. Finally, the six domains of knowledge necessary to become a good preceptor have been applied to the session. A good teaching exercise is moored to sound pedagogical principles. Its success relies on mutual trust and understanding between the teacher and the taught.


A primary care "friendly" cognitive behavioral insomnia therapy.
This study was conducted to test the effectiveness of an abbreviated cognitive-behavioral insomnia therapy (ACBT) with primary A single-blind, randomized group design was used in which study patients were randomized to either a brief, 2-session ACBT or a similarly brief intervention (SHC) that included only generic sleep hygiene recommendations. A university-affiliated Department of Veterans Affairs medical center. Twenty (2 women) veteran patients (M(age) = 51.0 yrs., SD = 13.7 years) who met criteria for chronic primary insomnia. Participants completed sleep logs for 2 weeks and questionnaires to measures insomnia symptoms, sleep-related self-efficacy, and dysfunctional beliefs about sleep before treatment, during a 2-week posttreatment assessment, and again at a 3-month posttreatment follow-up. Statistical analyses showed that ACBT produced significantly larger improvements across a majority of outcome measures than did SHC. Case-by-case analyses showed that only the ACBT produced consistent positive effects across study patients, and a sizeable proportion of these patients receiving this treatment achieved clinically significant improvements by their study endpoints. Approximately 52% of those receiving the ACBT reported at least a 50% reduction in their wake time after sleep onset, and 55.6% of ACBT-treated patients who entered the study with pathologic scores on an Insomnia Symptom Questionnaire (ISQ), achieved normal ISQ scores by their final outcome assessment. ACBT is effective for reducing subjective sleep disturbance and insomnia symptoms in primary care patients.


Participation and health-related quality of life in adults with spastic bilateral cerebral palsy and the role of self-efficacy.
To assess participation and health-related quality of life in adults with bilateral spastic cerebral palsy, and explore associations with self-efficacy. Cross-sectional study. A sample of 56 adults with bilateral spastic cerebral palsy (mean age 36.4 (standard deviation 5.8) years; 62% male). Daily activities and social participation (Life Habits 3.0), health-related quality of life (SF-36 Health Survey), demographic and clinical characteristics, and self-efficacy (General Self-Efficacy Scale (GSES-12)) were assessed. Associations were studied using multivariate logistic regression analyses. At least 60% of the sample had difficulties with mobility, recreation and housing, and 44% had difficulty with personal care and employment. They perceived low health-related quality of life for physical functions, but not for mental functions. Corrected for demographic and clinical characteristics, general self-efficacy explained 49% of the variance in outcome on social participation, and the subscale Effort (GSES-12) 32% of the variance for the physical health-related quality of life and 16% of the mental health-related quality of life. A significant number of adults with bilateral spastic cerebral palsy encountered difficulties in social participation and had a low perceived health-related quality of life for physical functions. Higher general self-efficacy or a greater willingness to expend effort in achieving behaviour was related to better participation and a higher physical and mental health-related quality of life.


[New concepts in ultrasound education in gastroenterology by simulator training].
Ultrasound is one of the most important imaging methods in medicine. However, ultrasound education is complicated by varying quantities and qualities of specific pathologies resulting from distinct patient collectives. Furthermore, under current clinical conditions ultrasound educators as well as trainees frequently lack the time necessary for a sufficient ultrasound education. Finally, current ultrasound education materials including "gold standard" images are not ideally suited for teaching scanning three-dimensional pathologies. In a direct cross over study we recently proved, that the ultrasound simulator we developed simulated the real patient examination reliably and reproducibly. By using this simulator as well in the classical beginner and advanced level courses as in focused courses of abdominal emergencies for instance, ultrasound trainees are able to practice scanning of well defined pathologies under realistic conditions, which has not been possible before. Furthermore, the ultrasound simulator is well suited for a structured ultrasound training in single hospitals as well as in continuous medical education. Finally, objective, standardized ultrasound quality control has become possible with the simulator.


Dynamic upper limb proprioception in multidirectional shoulder instability.
The ability of subjects with multidirectional shoulder instability to use proprioception to complete a series of upper limb repositioning tasks was investigated. Twelve subjects with multidirectional instability and 12 control subjects were blindfolded and instructed to use proprioception to reproduce a self-selected target position as accurately as possible. Subjects completed 10 repetitions for each limb using three distinct upper limb movements: overhead reaching, scapular plane pointing, and humeral external rotation with abduction. A three-dimensional video motion analysis system tracked limb position and determined spatial hand position error. Subjects with multidirectional shoulder instability showed significantly greater hand position error than control subjects. No hand position error differences were found between the symptomatic and the asymptomatic limbs of subjects in the instability group. Inter-repetition error for subjects in both groups improved significantly during the first three movement cycles. These results suggest that after movement initiation, dynamic proprioception was a factor in improving hand position accuracy in both groups, but to a lesser degree in subjects with multidirectional instability. Consequently, subjects with multidirectional instability may have a reduced capacity to use proprioception to refine and control the motor output of the upper limb.


Three- and four-dimensional arterial and venous perforasomes of the internal mammary artery perforator flap.
The internal mammary artery perforator flap has been used in head and neck reconstruction. Although anatomical and perfusion studies with ink have been performed previously, the authors now use three- and four-dimensional computed tomographic angiography to precisely visualize vascular anatomy of individual perforators (perforasomes) and the axiality of perfusion. Eleven hemichest adipocutaneous flaps were dissected from cadavers. Measurements were recorded, such as the distance of each internal mammary artery perforator from the sternal edge, diameter of vessels, and number and location of internal mammary artery perforators per hemichest. Single internal mammary artery perforator injections with Isovue contrast were carried out, and the flaps were subjected to dynamic computed tomographic scanning. Static computed tomographic scanning was also undertaken using a barium-gelatin mixture. Images were viewed using both General Electric and TeraRecon systems, allowing the appreciation of vascular territory (three-dimensional), and analysis of perfusion flow (four-dimensional). Each hemichest flap had one to three internal mammary artery perforators, most commonly in intercostal spaces 1, 2, and 3. Twenty-six internal mammary artery perforators were dissected, and 19 perforator arteries and six perforator veins were injected with contrast. The internal mammary artery perforator in the second intercostal space had the largest mean diameter and a large vascular territory. Linking vessels, both direct and indirect, communicate between perforators and can enlarge perforasomes. Linking vessels were also found between internal mammary artery perforators and the lateral thoracic artery. Three- and four-dimensional computed tomographic angiography allows detailed analysis of vascular anatomy. Important information such as internal mammary artery perforator flap dimensions, linking vessels, and axiality of perfusion is elucidated, thus contributing to a better understanding of perforator flaps.


Encystation and Stress Responses under the Control of Ubiquitin-like Proteins in Pathogenic Amoebae.
Amoebae found in aquatic and terrestrial environments encompass various pathogenic species, including the parasite Entamoeba histolytica and the free-living Acanthamoeba castellanii. Both microorganisms pose significant threats to public health, capable of inducing life-threatening effects on humans. These amoebae exist in two cellular forms: trophozoites and cysts. The trophozoite stage is the form used for growth and reproduction while the cyst stage is the resistant and disseminating form. Cysts occur after cellular metabolism slowdown due to nutritional deprivation or the appearance of environmental conditions unfavourable to the amoebae's growth and division. The initiation of encystation is accompanied by the activation of stress responses, and scarce data indicate that encystation shares factors and mechanisms identified in stress responses occurring in trophozoites exposed to toxic compounds derived from human immune defence. Although some "omics" analyses have explored how amoebae respond to diverse stresses, these studies remain limited and rarely report post-translational modifications that would provide knowledge on the molecular mechanisms underlying amoebae-specific stress responses. In this review, we discuss ubiquitin-like proteins associated with encystation and cell survival during oxidative damage. We aim to shed light on the signalling pathways involved in amoebic defence mechanisms, with a focus on their potential clinical implications against pathogenic amoebae, addressing the pressing need for effective therapies.


Identification of human cytochromes P-450 analogous to forms induced by phenobarbital and 3-methylcholanthrene in the rat.
Antibodies to four rat liver forms of cytochrome P-450, two phenobarbital-inducible (PB1 and PB2) and two 3-methylcholanthrene-inducible (MC1 and MC2) proteins, have been used to make a structural and functional comparison of rat and human cytochromes P-450. Proteins from both species were identified on Western blots by their reaction with these antibodies. In the human liver preparations, structurally related proteins to PB1 and to PB2 were identified in all the samples tested with apparent Mr values of 51 800 and 54 800 for PB1 and 53 600 and 57 200 for PB2. Considerable variation in the content of the lower-Mr proteins was measured between samples and, as with the rat enzymes, samples which reacted well with anti-PB1 also reacted with anti-PB2, indicating that these proteins are regulated at least to some degree, co-ordinately. The apparent Mr values of the major human proteins identified with anti-MC1 and anti-MC2 were 54 400 and 57 000 respectively. Only six (of 31) human samples contained significant amounts of these proteins. The same six samples which reacted with anti-MC1 also reacted with anti-MC2, again indicating co-ordinate regulation of these two proteins. Antibody inhibition of microsomal 7-ethoxycoumarin and 7-ethoxyresorufin metabolism demonstrated a degree of conservation of substrate specificity related to specific P-450 isoenzymes between the species. However, the contributions of the different P-450 isoenzymes to the human microsomal activity were not always related to the rat enzyme with the highest activity towards these substrates.


Contact-type line image sensor using Pb(2)CrO(5) thin film.
A contact-type line image sensor using a semiinsulating Pb(2)CrO(5) thin film deposited on a glass substrate by an electron beam evaporation deposition technique is described. The sensor has a simple structure and a high scanning rate of 1 ms/line. An individual sensor element responds to light modulated at 100-kHz frequency, so a higher scanning rate is expected. A matrix driving method using a simple reading circuit is used to operate a sensor composed of 32 elements at a rate of 8 elements/mm. Some practical results on image reading are demonstrated.


Psychiatric disorders and large interdialytic weight gain in patients on chronic haemodialysis.
Psychiatric disorders have been considered in terms of non-compliant behaviour and low life quality in haemodialysis patients. The aim of this study is to investigate the potential association of psychiatric disorders with compliance of fluid restriction and nutritional status and to measure the effects of psychiatric disorders on the life quality in chronic renal failure patients on haemodialysis. The study was conducted between April 2002 and December 2002 at a University hospital haemodialysis unit. The study population included 40 chronic renal failure patients (15 females/25 males). The Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS) and Primary Care Evaluation of Mental Disorders (PRIME-MD), The Mini Mental State Examination (MMSE) and Short Form Health Survey 36 (SF-36) were used for patient assessment by a trained psychiatrist. The subjects' medical charts were reviewed by a physician who was unaware of the the results of the psychiatric assesments. Interdialytic weight gain (IDWG %) and nutritional status were used as an index of diet compliance. Nutrition was assessed by using subjective global assessment (SGA), serum albumin, predialysis phosphorus and potassium levels. All patients' MMSE were normal. A diagnosis of a depressive or anxiety or somatoform disorder by the PRIME MD was made in 65% of the patients. Fourteen (35%) of the patients had a depressive disorder, 13 (32.5%) of the patients had a somatoform disorder, and 12 (30%) had an anxiety disorder. We found no relationship between any psychiatric disorder and age, sex, duration of dialysis therapy, education, marital status, employment, socioeconomic status, serum albumin, phosphorus, potassium or SGA (P > 0.05). In patients with depression or a somatoform disorder, the interdialytic weight (%) was significantly higher than those of the patients without these disorders (P < 0.05). All indices of quality of life decreased in patients diagnosed with a psychiatric disorder. Depressive symptoms are important determinants of patients' large interdialytic weight gain and psychiatric disorders that effect a patients' overall quality of life. Evaluation of psychiatric status should be part of the care provided to haemodialysis patients.


Thymidylate synthase expression and prognosis of patients with gastrointestinal cancers receiving adjuvant chemotherapy: a review.
Many studies have been published that report an association between thymidylate synthase (TS) and response to fluoropyrimidine-based chemotherapy and the overall outcome of patients with gastrointestinal cancer. The results have given rise to the possibility that, by determination of TS levels, the physician may decide if the patient has a potential benefit from fluoropyrimidine-based treatment, similar to measurements of oestrogen receptors in breast cancer. The purpose of this review is to summarize critically the reports on TS measurement in gastrointestinal cancer, focusing on the adjuvant fluoropyrimidine treatment situation. We reviewed more than 20 studies that reported the association of TS with the clinical outcome in patients with gastrointestinal cancer who had undergone complete resection of the primary tumour only or were receiving additional adjuvant chemotherapy. Patients with metastasized disease who expressed high TS levels display a low probability of responding to fluoropyrimidine-based treatment and have a poorer survival rate. Patients with high TS levels who undergo complete surgical resection of the primary tumour also have a poorer prognosis than those with tumours with low TS expression. In contrast to advanced disease and to surgery alone, patients with high TS levels appear to benefit, especially, from adjuvant fluoropyrimidine-based chemotherapy after complete primary tumour resection, while patients with low TS levels do not. Patients with gastrointestinal cancers that express high TS levels have a poor prognosis with regard to fluoropyrimidine-based palliative chemotherapy or complete primary tumour resection. In contrast, patients with high TS levels might benefit from adjuvant fluoropyrimidine-based treatment after primary tumour resection. However, additional prospective studies are mandatory to define the precise role of TS in adjuvant therapy.


Liver parenchyma access and lesion marker via the endovascular route.
Neoadjuvant chemotherapeutic regimens for metastatic colorectal cancer are now so effective that they can cause "vanishing" lesions. With new advances such as local ablation, intra-arterial treatments in bolus with pumps or with beads, and isolation of hepatic perfusion, the need for a working channel to the liver may be warranted, ideally reducing the risk of spreading neoplastic cells. The endovascular trans-vessel wall Extroducer device makes it possible to gain direct access to the liver parenchyma. The distal tip is then detached, to act as both a marker and a securing plug in the vessel defect. We used ex vivo and in vivo tests to evaluate the device as a working channel for local administration of substances to the parenchyma and as a marker for detection with both transabdominal and intraoperative ultrasonography. We could deploy the Extroducer device without any hemorrhagic or thromboembolic complications in vivo, and we were able to detect all markers ex vivo and in vivo using both transabdominal and intraoperative ultrasonography. Furthermore, we found that it is possible to administer substances to the liver parenchyma using the catheter. The trans-vessel wall technique can be used to establish a working channel to the liver parenchyma for administration of any substance, such as chemotherapeutic agents or cells. The detached device can also be used as a marker for ultrasound-guided partial liver resection in "vanishing lesions." The technique should have a low risk of seeding of neoplastic cells. This study in large animals forms a strong basis for translation to clinical studies.


Obstructive sleep apnea syndrome: evaluation of subcritical continuous positive airway pressure.
Twenty eight of 48 patients diagnosed of obstructive sleep apnea syndrome over a six month duration opted for CPAP therapy. Half of them were given critical CPAP (Group A) and other half were prescribed subcritical level of CPAP (Group B). Re-evaluation after 3 months revealed that side effects like headache and feeling of inconvenience were more in Group A, though beneficial effects were same in both groups. It is concluded that subcritical level of CPAP should be adopted to treat patients of obstructive sleep apnea syndrome.


GFR-estimating models in kidney transplant recipients on a steroid-free regimen.
How to best estimate glomerular filtration rate (GFR) in kidney transplant recipients on steroid-free immunosuppression has not been established. Within 3 months of transplantation, iothalamate GFR (iGFR) was measured in 107 recipients on steroid-free and 27 on steroid-maintenance immunosuppression. A year later, a second GFR was performed. Serum creatinine was calibrated against a reference laboratory, and GFR was estimated (eGFR) using the re-expressed Cockcroft-Gault equation, eGFRCG; the Mayo Clinic equation, eGFRMC; the Modification of Diet in Renal Disease (MDRD) study equation, eGFRMDRD; and the newly introduced Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. All models overestimated GFR regardless of steroid use or timing of GFR. In those not receiving steroids, eGFRCG was least biased: 1.85 +/- 15.2 ml/min at the first GFR and 0.23 +/- 15.2 ml/min at the second. eGFRMC and eGFRCKD-EPI were most biased and were within 30% of iGFR less than 60% of the time in contrast to eGFRCG which was within 30% of iGFR 80.2% of the time. eGFRMDRD was intermediate in its performance at the first GFR but was comparable to eGFRCG at the second measurement. Importantly, the four models had comparable but poor precision. Exposure to steroids for a whole year did not appreciably alter the models' bias or relative accuracy but resulted in a dramatic fall in their precision, R2 = 0.05-0.12. GFR prediction equations overestimate measured GFR in recipients on and off steroid regimens. Long-term exposure to steroids results in a marked reduction in the precision of all models. In all, eGFRCG and eGFRMDRD are the two best available models.


Higher levels of albuminuria within the normal range predict incident hypertension.
Higher levels of albumin excretion within the normal range are associated with cardiovascular disease in high-risk individuals. Whether incremental increases in urinary albumin excretion, even within the normal range, are associated with the development of hypertension in low-risk individuals is unknown. This study included 1065 postmenopausal women from the first Nurses' Health Study and 1114 premenopausal women from the second Nurses' Health Study who had an albumin/creatinine ratio <25 mg/g and who did not have diabetes or hypertension. Among the older women, 271 incident cases of hypertension occurred during 4 yr of follow-up, and among the younger women, 296 incident cases of hypertension occurred during 8 yr of follow-up. Cox proportional hazards regression was used to examine prospectively the association between the albumin/creatinine ratio and incident hypertension after adjustment for age, body mass index, estimated GFR, baseline BP, physical activity, smoking, and family history of hypertension. Participants who had an albumin/creatinine ratio in the highest quartile (4.34 to 24.17 mg/g for older women and 3.68 to 23.84 mg/g for younger women) were more likely to develop hypertension than those who had an albumin/creatinine ratio in the lowest quartile (hazard ratio 1.76 [95% confidence interval 1.21 to 2.56] and hazard ratio 1.35 [95% confidence interval 0.97 to 1.91] for older and younger women, respectively). Higher albumin/creatinine ratios, even within the normal range, are independently associated with increased risk for development of hypertension among women without diabetes. The definition of normal albumin excretion should be reevaluated.


Prior bariatric surgery lowers complication rates following spine surgery in obese patients.
Bariatric surgery (BS) is an increasingly common treatment for morbid obesity that has the potential to effect bone and mineral metabolism. The effect of prior BS on spine surgery outcomes has not been well established. The aim of this study was to assess differences in complication rates following spinal surgery for patients with and without a history of BS. Retrospective analysis of the prospectively collected New York State Inpatient Database (NYSID) years 2004-2013. BS patients and morbidly obese patients (non-BS) were divided into cervical and thoracolumbar surgical groups and propensity score matched for age, gender, and invasiveness and complications compared. One thousand nine hundred thirty-nine spine surgery patients with a history of BS were compared to 1625 non-BS spine surgery patients. The average time from bariatric surgery to spine surgery is 2.95 years. After propensity score matching, 740 BS patients were compared to 740 non-BS patients undergoing thoracolumbar surgery, with similar comorbidity rates. The overall complication rate for BS thoracolumbar patients was lower than non-BS (45.8% vs 58.1%, P < 0.001), with lower rates of device-related (6.1% vs 23.2%, P < 0.001), DVT (1.2% vs 2.7%, P = 0.039), and hematomas (1.5% vs 4.5%, P < 0.001). Neurologic complications were similar between BS patients and non-BS patients (2.3% vs 2.7%, P = 0.62). For patients undergoing cervical spine surgery, BS patients experienced lower rates of bowel issues, device-related, and overall complication than non-BS patients (P < 0.05). Bariatric surgery patients undergoing spine surgery experience lower overall complication rates than morbidly obese patients. This study warrants further investigation into these populations to mitigate risks associated with spine surgery for bariatric patients.


Morphology of the Female and Male Reproductive Tracts and More Data on the Spermatostyle in the Brazilian Gyretes sp. (Coleoptera, Adephaga, Gyrinidae).
We investigated the male and female reproductive tracts of Gyretes sp. with light and transmission electron microscopies. The male has a pair of testes with a single coiled follicle, followed by short efferent ducts, which have a similar shape and diameter to the testes. Long ducts (epididymides) with differential epithelium open in a pair of long vasa deferentia that lead to the accessory glands. Glycoprotein secretions from the vas deferens epithelium constitute the spermatostyle for spermatozoa aggregation. The female has numerous ovarioles per ovary, a coiled fertilization duct, an accessory gland, and an elongated vagina. Spermatozoa are stored as unaggregated cells in the fertilization duct. In Gyrinidae, the testes and accessory glands show diverse shapes, and the female sperm storage organs vary in shape, size, and type and may play a role in the interaction with sperm aggregates. Testes with a single follicle and vasa deferentia opening in the accessory glands of Gyretes sp. are features shared with other Gyrinidae and other Adephaga. We proposed adding this latter trait to characterize this suborder of beetles. The morphology of the reproductive organs in both sexes contributes to comparative analyses and knowledge of the reproductive biology of Gyretes and may provide additional features for systematics.


Measurement of Inflammatory Bowel Disease Symptoms: Reliability of an Abbreviated Approach to Data Collection.
The Crohn's Disease Activity Index (CDAI) and Mayo score for ulcerative colitis (UC) require symptom recall and/or use of a symptom diary. We examined patients' abilities to recall their symptoms and the day-to-day variability of symptoms. Patients with UC or CD completed a questionnaire including items from the short CDAI (sCDAI) and the 6-point Mayo score. Patients were randomized to receive a follow-up questionnaire testing recall of the bowel symptom items between 1 and 7 days later. In a second study, patients completed a 7-day electronic diary recording their symptoms. sCDAI and 6-point Mayo scores were computed. Analyses estimated daily variability in the indices and misclassification rates when using fewer than 7 days of data. 100%, 82%, and 90% of CD participants recalled the same disease activity status (i.e., active versus remission) as reported on the initial survey when the follow-up questionnaire was administered 1 to 2, 3 to 5, and 6 to 8 days later, respectively. Compared with using 7 days of data, when using only day 7 data, 3.7% of patients with CD were misclassified as active or inactive. Disease activity was misclassified in 2.8%, 4.9%, and 3.3% of patients by using the last 2, 3, or 4 days, respectively. Results were similar for patients with UC. Patients with CD and UC demonstrated good recall of bowel symptoms for up to 8 days. Additionally, bowel symptoms have relatively little variability within a 7-day period allowing for accurate computation of the sCDAI and 6-point Mayo score using 1 to 3 days of data.


Sorting of newly synthesized galactosphingolipids to the two surface domains of epithelial cells.
The high concentration of glycosphingolipids on the apical surface of epithelial cells may be generated by selective transport from their site of synthesis to the cell surface. Previously, we showed that canine kidney MDCK and human intestinal Caco-2 cells converted a ceramide carrying the short fluorescent fatty acid C6-NBD to glucosylceramide (GlcCer) and sphingomyelin (SM), and that GlcCer was preferentially transported to the apical surface as compared to SM. Here, we address the point that not all glycosphingolipid classes are apically enriched in epithelia. We show that a ceramide containing the 2-hydroxy fatty acid C6OH was preferentially converted by MDCK and Caco-2 cells to galactosylceramide (GalCer) and its derivatives galabiosylceramide (Ga2Cer) and sulfatide (SGalCer) as compared to SM and GlcCer--all endogenous lipid classes of these cells. Transport to the apical and basolateral cell surface was monitored by a BSA-depletion assay. In MDCK cells, GalCer reached the cell surface with two- to sixfold lower apical/basolateral polarity than GlcCer. Remarkably, in Caco-2 cells GalCer and GlcCer displayed the same apical/basolateral polarity, but it was sixfold lower for lipids with a C6OH chain than for C6-NBD lipids. Therefore, the sorting of a sphingolipid appears to depend on lipid structure and cell type. We propose that the different ratios of gluco- and galactosphingolipid synthesis in the various epithelial tissues govern lipid sorting in the membrane of the trans Golgi network by dictating the composition of the domains from where vesicles bud to the apical and basolateral cell surface.


Concerns of parents and teachers of children with autism in elementary school.
Many consensus guidelines encourage parents and teachers to openly communicate about their concerns regarding their children. These guidelines attest to the importance of achieving consensus about what issues are most critical and how to address them. The purpose of this study was to examine whether parents and teachers (1) agree about their concerns for their children with autism and (2) when given the opportunity, whether they discussed these concerns. Participants were 39 parent-teacher dyads of children with autism in kindergarten-through-fifth grade autism support classrooms. Each parent and teacher was interviewed separately about their concerns and then observed together in a discussion about the child. Parents and teachers generally agreed about their primary and secondary concerns. When given an opportunity to communicate their concerns, 49% of the parent-teacher dyads discussed problems that neither reported as their primary concern, and 31% discussed problems that neither reported as their primary or secondary concern. These findings suggest that interventions should target parent-teacher communication, rather than agreement, to facilitate home-school collaboration.


Weathered MC252 crude oil-induced anemia and abnormal erythroid morphology in double-crested cormorants (Phalacrocorax auritus) with light microscopic and ultrastructural description of Heinz bodies.
Injury assessment of birds following the Deepwater Horizon (DWH) oil spill in 2010 was part of the Natural Resource Damage Assessment. One reported effect was hemolytic anemia with the presence of Heinz bodies (HB) in birds, however, the role of route and magnitude of exposure to oil is unknown. The purpose of the present study was to determine if double-crested cormorants (Phalacocorax auritis; DCCO) exposed orally and dermally to artificially weathered crude oil would develop hemolytic anemia including HB and reticulocytosis. In the oral experiment, sub-adult, mixed-sex DCCOs were fed control (n = 8) or oil-injected fish with a daily target dose of 5 (n = 9) or 10 (n = 9) ml oil/kg for 21 days. Then, subadult control (n = 12) and treated (n = 13) cormorant groups of similar sex-ratio were dermally treated with approximately 13ml of water or weathered MC252 crude oil, respectively, every 3 days for 6 dosages approximating 20% surface coverage. Collected whole blood samples were analyzed by light (new methylene blue) and transmission electron microscopy. Both oral and dermal treatment with weathered DWH MC252 crude oil induced regenerative, but inadequately compensated, anemia due to hemolysis and hematochezia as indicated by decreased packed cell volume, relative increase in reticulocytes with lack of difference in corrected reticulocyte count, and morphologic evidence of oxidant damage at the ultrastructural level. Hemoglobin precipitation, HB formation, degenerate organelles, and systemic oxidant damage were documented. Heinz bodies were typically <2µm in length and smaller than in mammals. These oblong cytoplasmic inclusions were difficult to see upon routine blood smear evaluation and lacked the classic button appearance found in mammalian red blood cells. They could be found as light, homogeneous blue inclusions upon new methylene blue staining. Ultrastructurally, HB appeared as homogeneous, electron-dense structures within the cytosol and lacked membranous structure. Oxidant damage in avian red blood cells results in degenerate organelles and precipitated hemoglobin or HB with different morphology than that found in mammalian red blood cells. Ultrastructural evaluation is needed to definitively identify HB and damaged organelles to confirm oxidant damage. The best field technique based on the data in this study is assessment of PCV with storage of blood in glutaraldehyde for possible TEM analysis.


Genetic Variants Affecting Skeletal Morphology in Domestic Dogs.
Purebred dog breeds provide a powerful resource for the discovery of genetic variants affecting skeletal morphology. Domesticated and subsequently purebred dogs have undergone strong artificial selection for a broad range of skeletal variation, which include both the size and shapes of their bones. While the phenotypic variation between breeds is high, within-breed morphological variation is typically low. Approaches for defining genetic variants associated with canine morphology include quantitative within-breed analyses, as well as across-breed analyses, using breed standards as proxies for individual measurements. The ability to identify variants across the genomes of individual dogs can now be paired with precise measures of morphological variation to define the genetic interactions and the phenotypic effect of variants on skeletal morphology.


A comparison of chronic pain patients and controls on traumatic events in childhood.
The purpose was to examine the incidence of traumatic events in childhood, such as sexual and physical abuse, in a chronic pain group and a control group of hospital employees without chronic pain. Ninety two patients with chronic pain, age range 20-62, were consecutively recruited from the outpatient clinics of a rehabilitation hospital and a general hospital. Ninety eight hospital employees, age range 20-62, were consecutively recruited from the employee health office of a rehabilitation hospital. All participants responded to nine questions related to sexual, physical and verbal abuse in childhood and completed the Childhood Traumatic Events Scale. A logistic regression with age, gender, sexual, physical, and verbal abuse, death of a family member, childhood illness, major upheaval before age 17, as independent variables were used to predict membership in the pain group contrasted with the control group. Child abuse was reported in the childhood history by 54.4% of the chronic pain group, compared with 21.4% of the control group. A logistic regression showed that after adjusting for gender and age, sexual and verbal abuse were statistically significant predictors of being a member of the pain group. Odds ratios were sexual abuse: 2.67, p < 0.05, CI 1.00-7.14. Verbal abuse: 4.39, p < 0.001, CI 1.93-9.97. A logistic regression was modelled to predict child abuse when gender was taken into account. The results of the logistic regression showed that pain was a significant predictor for sexual abuse after adjusting for gender and age: odds ratio 4.37, p < 0.001, CI 1.80-10.60. Gender was not a statistically significant predictor for sexual abuse, after adjusting for pain and age: odds ratio 2.92, p < 0.072, CI 0.91-9.42. A history of physical, sexual and verbal abuse is more likely to occur in a chronic pain group than in a control group of hospital employees. Although child abuse is reported to be as high as 25% in the general American population, the statistics for chronic pain patients are twice as high as in the general population. The mechanisms for abuse include age, gender, and early family environment.


Antigenic differences between infective and noninfective strains of Rhizobium trifolii.
Immunodiffusion and immunoelectrophoresis techniques have revealed the presence of soluble antigens in sonicated preparations of four infective strains of Rhizobium trifolii which were absent in similar preparations of related noninfective mutants derived from the infective strains. The soluble antigens unique to the infective strains were cross-reactive with one another.


Adipose tissue supports normalization of macrophage and liver lipid handling in obesity reversal.
Adipose tissue inflammation and dysfunction are considered central in the pathogenesis of obesity-related dysmetabolism, but their role in the rapid metabolic recovery upon obesity reversal is less well defined. We hypothesized that changes in adipose tissue endocrine and paracrine mechanisms may support the rapid improvement of obesity-induced impairment in cellular lipid handling. C57Bl-6J mice were fed ad libitum either normal chow (NC) or high-fat diet (HFF) for 10 weeks. A dietary obesity reversal group was fed HFF for 8 weeks and then switched to NC for 2 weeks (HFF→NC). Whole-body glucose homeostasis rapidly nearly normalized in the HFF→NC mice (fasting glucose and insulin fully normalized, glucose and insulin tolerance tests reversed 82% to the NC group levels). During 2 weeks of the dietary reversal, the liver was significantly cleared from ectopic fat, and functionally, glucose production from pyruvate, alanine or fructose was normalized. In contrast, adipose tissue inflammation (macrophage infiltration and polarization) largely remained as in HFF, though obesity-induced adipose tissue macrophage lipid accumulation decreased by ~50%, and adipose tissue MAP kinase hyperactivation was reversed. Ex vivo, mild changes in adipose tissue adipocytokine secretion profile were noted. These corresponded to partial or full reversal of the excess cellular lipid droplet accumulation induced by HFF adipose tissue conditioned media in hepatoma or macrophage cells, respectively. We propose that early after initiating reversal of nutritional obesity, rapid metabolic normalization largely precedes resolution of adipose tissue inflammation. Nevertheless, we demonstrate a hitherto unrecognized contribution of adipose tissue to the rapid improvement in lipid handling by the liver and by macrophages.


[Acarbose (glucobai) effects on lipid metabolism in patients with non-insulin dependent diabetes mellitus].
To investigate the effect of acarbose, intestinal alpha-glucosidase inhibitor, on lipid metabolism in patients with non-insulin-dependent diabetes mellitus (NIDDM). Glucobai was given for 6 months in a dose 300 mg/day to 63 NIDDM patients aged 40-69 years. The examination covered indices of glycemia, glycosylated hemoglobin, pancreatic insulin secretion, total cholesterol (TC), triglycerides (TG), HDLP and LDLP cholesterol, atherogenic index. Glucobai has improved glycemic profile, reduced insulinemia and body mass index, TC, TG, atherogenic index. Blood levels of HDLP cholesterol elevated by 62%. Long-term intake of acarbose improves carbohydrate metabolism and produces a hypolipidemic effect.


Organization of F-actin by Fesselin (avian smooth muscle synaptopodin 2).
Fesselin or avian synaptopodin 2 is a member of the synaptopodin family of actin binding proteins. Fesselin promotes G-actin polymerization and the formation of large actin complexes that can be collected by low-speed centrifugation. Because of the potential role of fesselin in some cancers and its effects on actin, we further investigated the effect of fesselin on actin. Fesselin initiated actin polymerization under a variety of conditions, including the virtual absence of salt. Actin filaments formed at low salt concentrations in the presence of fesselin were similar to filaments polymerized in the presence of 100 mM KCl. In both cases, the filaments were long and straight with a common orientation. Highly ordered actin bundles formed with increasing times of incubation. Blockers of actin growth at the barbed end (cytochalasin D and CapZ) did not prevent fesselin from polymerizing actin. Low concentrations of fesselin increased the critical concentration of actin. Both observations are consistent with preferential growth at the pointed end of actin filaments. These results indicate a role of fesselin in organizing cellular actin. These and other results indicate that fesselin is part of a cellular actin organizing center.


Carbapenemase-producing Enterobacteriaceae, U.S. rivers.
Our study was initiated by previous isolation of 30 imipenem-resistant, gram-negative rods from 7 of 16 U.S. rivers sampled from 1999 to 2001. Imipenem hydrolysis was detected in 22 of those isolates identified as Enterobacter asburiae. Random amplified polymorphism DNA analysis showed that these E. asburiae isolates were genetically indistinguishable. An identical clavulanic acid-inhibited beta-lactamase IMI-2 was identified from each isolate that shared 99% and 97% amino acid identity with the chromosome-encoded beta-lactamases IMI-1 and NmcA, respectively, from E. cloacae clinical isolates. The blaIMI-2 gene was located on a self-transferable 66-kb plasmid. Sequence analysis of a cloned 5.5-kb DNA fragment obtained from 1 of the imipenem-resistant E. asburiae isolates identified an upstream LysR-type regulator gene that explained inducibility of IMI-2 expression. beta-Lactamase IMI-2 is the first inducible and plasmid-encoded carbapenemase. Identification of clonally related E. asburiae isolates from distant rivers indicates an environmental and enterobacterial reservoir for carbapenemase genes.


Laminin in testicular germ cell tumours. An immunohistochemical study.
Thirty-five testicular germ cell tumours comprising 16 yolk sac tumours, 15 embryonal carcinomas and 13 seminomas were examined for the presence and distribution of laminin using an indirect immunoperoxidase technique. In addition, nine normal yolk sacs and 23 carcinomas of the lung were studied. All the yolk sac tumours were positively stained for laminin. Both extra- and intracellular staining were found. Hyaline, eosinophilic material present within the tumours was positively stained, although with varying intensity. In 12 out of 15 embryonal carcinomas, laminin was found as a membrane staining but cytoplasmic staining also occurred. In 10 out of 13 classical seminomas, a membrane staining of many tumour cells was found, while cytoplasmic staining occurred in only a few seminomas. In all but one of the yolk sacs, laminin was present in the membrane beneath both the mesoblastic outer cell layer and the visceral endoderm. Intracellular staining was seen in some of the cells in both cell layers. In nine out of 23 carcinomas of the lung, laminin occurred extra- as well as intracellularly. Thus, this study showed that in normal yolk sacs the presence of laminin was not found to be particularly associated with any of the cell layers. Likewise, demonstration of laminin within yolk sac tumours did not define different patterns or subtypes of the yolk sac tumour. In addition, demonstration of laminin was not found to be useful in differentiating either between yolk sac tumours and embryonal carcinomas or between seminomas and non-seminomatous germ cell tumours. The findings add, however, interesting knowledge to histogenesis and embryogenesis.


Effects of S-nitrosation on oxygen binding by normal and sickle cell hemoglobin.
S-Nitrosated hemoglobin (SNO-Hb) is of interest because of the allosteric control of NO delivery from SNO-Hb made possible by the conformational differences between the R- and T-states of Hb. To better understand SNO-Hb, the oxygen binding properties of S-nitrosated forms of normal and sickle cell Hb were investigated. Spectral assays and electrospray ionization mass spectrometry were used to quantify the degree of S-nitrosation. Hb A(0) and unpolymerized Hb S exhibit similar shifts toward their R-state conformations in response to S-nitrosation, with increased oxygen affinity and decreased cooperativity. Responses to 2, 3-diphosphoglycerate were unaltered, indicating regional changes in the deoxy structure of SNO-Hb that accommodate NO adduction. A cycle of deoxygenation/reoxygenation does not cause loss of NO or appreciable heme oxidation. There is, however, appreciable loss of NO and heme oxidation when oxygen-binding experiments are carried out in the presence of glutathione. These results indicate that the in vivo stability of SNO-Hb and its associated vasoactivity depend on the abundance of thiols and other factors that influence transnitrosation reactions. The increased oxygen affinity and R-state character that result from S-nitrosation of Hb S would be expected to decrease its polymerization and thereby lessen the associated symptoms of sickle cell disease.


Non-factor replacement therapy for haemophilia: a current update.
One of the most challenging issues facing us in the treatment of haemophilia is the development of alloantibodies against infused factor VIII (FVIII) or factor IX (FIX). Inhibitors render factor replacement therapy ineffective, exposing patients to an unacceptably high risk of morbidity and mortality. Besides the well-known bypassing agents (i.e. activated prothrombin complex concentrate and recombinant activated factor VII) used to treat or prevent bleeding in haemophilia patients with inhibitors, there is growing interest in a new class of therapeutic agents which act by enhancing coagulation (i.e. emicizumab) or inhibiting anticoagulant pathways (i.e. fitusiran and concizumab). This review will focus on these innovative therapies, providing an update on their current stage of clinical development.


Cobalt(ii) cation binding by proteins.
Herein, a set of non-homologous proteins (238) that could bind the cobalt(ii) cations was selected from all the available Protein Data Bank structures with Co2+ cations. The secondary structure motifs around the amino acid residues that most frequently bind the Co2+ cations (His, Asp, and Glu) as well as the amino acid contents of the inner and outer spheres of complexes were studied. The residues forming coordination bonds to Co2+ (from the inner spheres of the complexes) are overrepresented in the regions of random coil between two β strands, between a β strand and α helix, and in all types of β strands, except that situated between an α helix and β strand. The residues situated at a distance of less than 5 Å from the Co2+ cations, but unable to form coordination bond to them (from the outer spheres of the complexes), are overrepresented in the regions of coil between the β strand and α helix and between two β strands. The data obtained for the Co2+ binding sites was compared with the data obtained for the Mg2+ and Mn2+ binding sites. Although the preferable motifs of the secondary structure for Co2+ binding (beta strand-loop-beta strand and beta strand-loop-alpha helix) are the same as those for Mg2+ and Mn2+, there are some differences in the amino acid contents of the inner and outer spheres of these complexes. The Co2+ cations are preferably coordinated by a combination of His and Glu residues, whereas the Mn2+ and Mg2+ cations prefer a combination of His and Asp and just Asp residues, respectively. As a result, two computer algorithms were developed that could evaluate the possibility of Mg2+ and Mn2+ replacement by the Co2+ cations (chemres.bsmu.by). These algorithms should help to investigate the pathogenesis of cobalt intoxication occurring in patients with cobalt-containing artificial joints.


[Congenital encephalomyelopathy as a possible slow infection in humans].
A slow influenzal congenital infection of man (in a child aged 2.5 years) is described for the first time. The infection manifests itself by encephalomyelopathy (retarded psychomotor development, sluggish spinal pareses of the limbs) and resembles Werdnig-Hoffmann amyotrophy. Besides, one can ses neuroendocrine disorders (hypophyseal nanism, hypogonadism ) and the signs of immunodeficiency. The long-term persistence of influenza A virus, its defective form was detected in the blood and CSF by means of molecular hybridization. In addition, the summarized data on the clinical studies of congenital influenzal injuries to the CNS in children, carried out by the author are provided. The theoretical evidence for the work was experimental slow influenzal infection in mice obtained for the first time at the N.F.Gamaleia Institute of Epidemiology and Microbiology (Moscow).


Application of collagen hydrogel/sponge scaffold facilitates periodontal wound healing in class II furcation defects in beagle dogs.
A three-dimensional scaffold may play an important role in periodontal tissue engineering. We prepared bio-safe collagen hydrogel, which exhibits properties similar to those of native extracellular matrix. The aim of this study was to examine the effect of implantation of collagen hydrogel/sponge scaffold on periodontal wound healing in class II furcation defects in dogs. The collagen hydrogel/sponge scaffold was prepared by injecting collagen hydrogel, cross-linked to the ascorbate-copper ion system, into a collagen sponge. Class II furcation defects (of 5 mm depth and 3 mm width) were surgically created in beagle dogs. The exposed root surface was planed and demineralized with EDTA. In the experimental group, the defect was filled with collagen hydrogel/sponge scaffold. In the control group, no implantation was performed. Histometric parameters were evaluated 2 and 4 wk after surgery. At 2 wk, the collagen hydrogel/sponge scaffold displayed high biocompatibility and biodegradability with numerous cells infiltrating the scaffold. In the experimental group, reconstruction of alveolar bone and cementum was frequently observed 4 wk after surgery. Periodontal ligament tissue was also re-established between alveolar bone and cementum. Volumes of new bone, new cementum and new periodontal ligament were significantly greater in the experimental group than in the control group. In addition, epithelial down-growth was suppressed by application of collagen hydrogel. The collagen hydrogel/sponge scaffold possessed high tissue compatibility and degradability. Implantation of the scaffold facilitated periodontal wound healing in class II furcation defects in beagle dogs.


[Effect of chemical sympathectomy on the function of the pulmonary surfactant system in white rats].
Rats received guanethidine (50 mg/kg) daily during the period from 2 weeks to 3 months to exclude selectively sympathetic irritation in order to study its influence on the phospholipid status of the lung surfactant component. An increase in total phospholipids of lung extracts as well as that of separate fractions of phospholipids especially of phosphatidylcholine was revealed along with a direct interrelationship between the alveoli area and the phosphatidylcholine rate. The alterations in surfactant phospholipids are regarded as a compensatory reaction maintaining alveolar stabilization in the case of sympathectomy.


Chirality-Dependent and Intrinsic Auxeticity for Single-Walled Carbon Nanotubes.
Single-walled carbon nanotubes (SWCNTs) have superior mechanical properties which originate from a strong C-C covalent bond and unique nanostructure. Chirality, one of the helical structural parameters of SWCNTs, leads to differences in mechanical performance. In this work, molecular dynamics (MD) simulation was performed to analyze engineering Poisson's ratio (EPR) and incremental Poisson's ratio (IPR) of SWCNTs with different chiral angles, respectively, under tensile and compressive load, as well as the chiral effect on rigidity. We reported the minimum EPR for (4, 1) SWCNT and obtained the distribution and trend of EPR which is dependent on chiral index m. In addition, a new observation showed two exactly opposite trends of EPR existing not only in tension and compression but also in the longitudinal and radial directions. Furthermore, we found that the critical strain, over which SWCNT would be auxetic, ranged from 6% to 18% and was also chirality-dependent. Three representative SWCNTs with chiral angle of 0° (zigzag), 10.89° (chiral), and 30° (armchair) were selected for the mechanism study of auxeticity. Finally, a method of the contribution to radial strain for two main deformation modes proposed in this paper could well explain the negative IPR phenomenon.


The control of growth.
The growth of a cell or tissue involves complex interactions between genes, metabolism, nutrition and hormones. Until recently, separate lines of investigation have concentrated in isolated sections of each of the many independent levels of growth control; the interactions within and between the diverse pathways that affect growth and size at the cellular, tissue and organismal level were little understood. However, new insights into the control of growth are now emerging in the context of signalling, ageing, evolution, cancer and nutrition. In particular, it is becoming clear that the insulin signaling network is a key player that integrates not only metabolism and the response to nutrition, but also the regulation of cell death, ageing and longevity, as well as the regulation of growth and body size.


Lipoid pneumonia in infants and children in South India.
Oil-aspiration pneumonia is a common cause of mortality and morbidity in infants and young children in South India. The high incidence of this condition results from the local custom of giving oil baths to infants and of cleansing the mouth, throat, and nose with oil. The clinical findings in 12 cases, 10 of them in babies aged under 8 months, are described. The signs range from an acute segmental collapse of the lung, clearing in a few days, to a chronic picture mimicking pulmonary tuberculosis or mucoviscoidosis. Mothers in South India should be advised to abandon the practice of cleansing their baby's mouth and nose with oil.


Chimeric RNAs as potential biomarkers for tumor diagnosis.
Cancers claim millions of lives each year. Early detection that can enable a higher chance of cure is of paramount importance to cancer patients. However, diagnostic tools for many forms of tumors have been lacking. Over the last few years, studies of chimeric RNAs as biomarkers have emerged. Numerous reports using bioinformatics and screening methodologies have described more than 30,000 expressed sequence tags (EST) or cDNA sequences as putative chimeric RNAs. While cancer cells have been well known to contain fusion genes derived from chromosomal translocations, rearrangements or deletions, recent studies suggest that trans-splicing in cells may be another source of chimeric RNA production. Unlike cis-splicing, trans-splicing takes place between two pre-mRNA molecules, which are in most cases derived from two different genes, generating a chimeric non-co-linear RNA. It is possible that trans-splicing occurs in normal cells at high frequencies but the resulting chimeric RNAs exist only at low levels. However the levels of certain RNA chimeras may be elevated in cancers, leading to the formation of fusion genes. In light of the fact that chimeric RNAs have been shown to be overrepresented in various tumors, studies of the mechanisms that produce chimeric RNAs and identification of signature RNA chimeras as biomarkers present an opportunity for the development of diagnoses for early tumor detection.


Conformational Behavior, Topographical Features, and Antioxidant Activity of Partly De-Esterified Arabinoxylans.
This study aimed to investigate the effect of arabinoxylans (AX) partial de-esterification with feruloyl esterase on the polysaccharide conformational behavior, topographical features, and antioxidant activity. After enzyme treatment, the ferulic acid (FA) content in AX was reduced from 7.30 to 5.48 µg FA/mg polysaccharide, and the molecule registered a small reduction in radius of gyration (RG), hydrodynamic radius (Rh), characteristic ratio (C∞), and persistence length (q). A slight decrease in α and a small increase in K constants in the Mark-Houwink-Sakurada equation for partially de-esterified AX (FAX) suggested a reduction in molecule structural rigidity and a more expanded coil conformation, respectively, in relation to AX. Fourier transform infrared spectroscopy spectra of AX and FAX presented a pattern characteristic for this polysaccharide. Atomic force microscopy topographic analysis of FAX showed a more regular surface without larger hollows in relation to AX. The antioxidant activity of FAX, compared to AX, was reduced by 30 and 41% using both 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS+) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) methods, respectively. These results suggest that feruloyl esterase treatment of AX could offer a strategy to tailor AX chains conformation, morphological features, and antioxidant activity, impacting the development of advanced biomaterials for biomedical and pharmaceutical applications.


PBRM1 Regulates the Expression of Genes Involved in Metabolism and Cell Adhesion in Renal Clear Cell Carcinoma.
Polybromo-1 (PBRM1) is a component of the PBAF (Polybromo-associated-BRG1- or BRM-associated factors) chromatin remodeling complex and is the second most frequently mutated gene in clear-cell renal cell Carcinoma (ccRCC). Mutation of PBRM1 is believed to be an early event in carcinogenesis, however its function as a tumor suppressor is not understood. In this study, we have employed Next Generation Sequencing to profile the differentially expressed genes upon PBRM1 re-expression in a cellular model of ccRCC. PBRM1 re-expression led to upregulation of genes involved in cellular adhesion, carbohydrate metabolism, apoptotic process and response to hypoxia, and a downregulation of genes involved in different stages of cell division. The decrease in cellular proliferation upon PBRM1 re-expression was confirmed, validating the functional role of PBRM1 as a tumor suppressor in a cell-based model. In addition, we identified a role for PBRM1 in regulating metabolic pathways known to be important for driving ccRCC, including the regulation of hypoxia response genes, PI3K signaling, glucose uptake, and cholesterol homeostasis. Of particular novelty is the identification of cell adhesion as a major downstream process uniquely regulated by PBRM1 expression. Cytoskeletal reorganization was induced upon PBRM1 reexpression as evidenced from the increase in the number of cells displaying cortical actin, a hallmark of epithelial cells. Genes involved in cell adhesion featured prominently in our transcriptional dataset and overlapped with genes uniquely regulated by PBRM1 in clinical specimens of ccRCC. Genes involved in cell adhesion serve as tumor suppressor and maybe involved in inhibiting cell migration. Here we report for the first time genes linked to cell adhesion serve as downstream targets of PBRM1, and hope to lay the foundation of future studies focusing on the role of chromatin remodelers in bringing about these alterations during malignancies.


Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial.
Cilengitide is a selective αvβ3 and αvβ5 integrin inhibitor. Data from phase 2 trials suggest that it has antitumour activity as a single agent in recurrent glioblastoma and in combination with standard temozolomide chemoradiotherapy in newly diagnosed glioblastoma (particularly in tumours with methylated MGMT promoter). We aimed to assess cilengitide combined with temozolomide chemoradiotherapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter. In this multicentre, open-label, phase 3 study, we investigated the efficacy of cilengitide in patients from 146 study sites in 25 countries. Eligible patients (newly diagnosed, histologically proven supratentorial glioblastoma, methylated MGMT promoter, and age ≥18 years) were stratified for prognostic Radiation Therapy Oncology Group recursive partitioning analysis class and geographic region and centrally randomised in a 1:1 ratio with interactive voice response system to receive temozolomide chemoradiotherapy with cilengitide 2000 mg intravenously twice weekly (cilengitide group) or temozolomide chemoradiotherapy alone (control group). Patients and investigators were unmasked to treatment allocation. Maintenance temozolomide was given for up to six cycles, and cilengitide was given for up to 18 months or until disease progression or unacceptable toxic effects. The primary endpoint was overall survival. We analysed survival outcomes by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00689221. Overall, 3471 patients were screened. Of these patients, 3060 had tumour MGMT status tested; 926 patients had a methylated MGMT promoter, and 545 were randomly assigned to the cilengitide (n=272) or control groups (n=273) between Oct 31, 2008, and May 12, 2011. Median overall survival was 26·3 months (95% CI 23·8-28·8) in the cilengitide group and 26·3 months (23·9-34·7) in the control group (hazard ratio 1·02, 95% CI 0·81-1·29, p=0·86). None of the predefined clinical subgroups showed a benefit from cilengitide. We noted no overall additional toxic effects with cilengitide treatment. The most commonly reported adverse events of grade 3 or worse in the safety population were lymphopenia (31 [12%] in the cilengitide group vs 26 [10%] in the control group), thrombocytopenia (28 [11%] vs 46 [18%]), neutropenia (19 [7%] vs 24 [9%]), leucopenia (18 [7%] vs 20 [8%]), and convulsion (14 [5%] vs 15 [6%]). The addition of cilengitide to temozolomide chemoradiotherapy did not improve outcomes; cilengitide will not be further developed as an anticancer drug. Nevertheless, integrins remain a potential treatment target for glioblastoma. Merck KGaA, Darmstadt, Germany.


High-level expression of modified gene encoding human adiponectin in transgenic rice.
Adiponectin is a polypeptide specifically secreted from human adipocytes, and its deficiency is closely linked to increased obesity and type II diabetes. There is an urgent demand for large-scale production of human adiponectin for pharmaceutical applications. Here, we report that we have successfully obtained a high-level of expression of modified genes encoding human adiponectin in transgenic rice. The 735 bp cDNA of the native human sequence was adopted to rice codon usage, fused to the translation initiation sequence in the N terminus and to the KDEL signal sequence in the C terminus. An amplification promoting sequence acting as an enhancer of transcription was also introduced to enhance gene expression. The presence of the transgene and mRNA transcripts was confirmed by PCR, Southern blot and RT-PCR. Western blot analysis revealed that a protein of approximately 30 kDa was produced in rice leaves. ELISA analysis was used to determine the amount of recombinant adiponectin in transformants with the modified gene in up to 0.32% of total soluble leaf protein. Our results establish the feasibility of high-level expression of recombinant human adiponectin in transgenic rice.


A possible correlation between the type of bcr-abl hybrid messenger RNA and platelet count in Philadelphia-positive chronic myelogenous leukemia.
The Philadelphia (Ph1) chromosome, in which the hybrid bcr-abl gene is formed, is thought to be the initial event in chronic myelogenous leukemia (CML). The position of the breakpoint within the breakpoint cluster region (bcr) on Ph1 chromosome and the splicing pattern determine the species of the fused bcr-abl messenger RNA (mRNA). We tried to detect the two types of fused mRNAs in 57 chronic-phase cases of Ph1-positive CML using the polymerase chain reaction procedure (RT-PCR). The bcr exon 2/abl exon 2 fused mRNA (b2-a2) was detected in 17 patients, the bcr exon 3/abl exon 2 fused mRNA (b3-a2) was detected in 34 patients, and both types of mRNA were detected in six patients. The platelet counts of patients who expressed b3-a2 mRNA or both types were significantly higher than those of patients who expressed only b2-a2 (841.5 v 373.5 x 10(9)/L; P less than .015), although there was no significant difference in the white blood cell counts or hemoglobin. This finding suggests a possibility that the type of bcr-abl mRNA may affect the thrombopoietic activity in CML.


The v-src oncogene may not be responsible for the increased radioresistance of hematopoietic progenitor cells expressing v-src.
Infection of the IL-3-dependent, myeloid progenitor cell line 32D cl 3 with murine retroviruses that contain either the wild-type or a temperature-sensitive mutant v-src can render these cells growth-factor independent. These cells also became resistant to gamma irradiation administered at the low-dose rate of 0.05 Gy/min, which is used clinically. The v-src-dependent nature of resistance to gamma irradiation was examined by studying four clones of 32D cl 3 cells that had been infected with a retrovirus carrying the tsLA31A mutant of v-src. The tyrosine-specific kinase activity of this mutant is dramatically reduced at the nonpermissive temperature of 39 degrees C. Cells transformed by v-src and grown at either 34 or 39 degrees C, in the presence or absence of IL-3, demonstrated a significantly higher D0 compared to parental cells examined under identical conditions. In addition, expression of v-src abrogated the synergistic killing effect of heat and gamma irradiation. The D0 of parental 32D cl 3 cells kept at 39 degrees C after gamma irradiation was reduced significantly compared to the D0 of these cells kept at 34 degrees C. This contrasts with data from 32D cl 3 cells infected with either the wild-type v-src or the temperature-sensitive mutant, neither exhibited a synergistic effect in the D0 at either 34 or 39 degrees C. Therefore, while continuous expression of a v-src gene product is required for maintenance of the growth-factor-independent state, v-src does not appear to be responsible for the increased gamma-radiation resistance of these cells at low dose rate.


High-fructose, medium chain trans fat diet induces liver fibrosis and elevates plasma coenzyme Q9 in a novel murine model of obesity and nonalcoholic steatohepatitis.
Diets high in saturated fat and fructose have been implicated in the development of obesity and nonalcoholic steatohepatitis (NASH) in humans. We hypothesized that mice exposed to a similar diet would develop NASH with fibrosis associated with increased hepatic oxidative stress that would be further reflected by increased plasma levels of the respiratory chain component, oxidized coenzyme Q9 ((ox)CoQ9). Adult male C57Bl/6 mice were randomly assigned to chow, high-fat (HF), or high-fat high-carbohydrate (HFHC) diets for 16 weeks. The chow and HF mice had free access to pure water, whereas the HFHC group received water with 55% fructose and 45% sucrose (wt/vol). The HFHC and HF groups had increased body weight, body fat mass, fasting glucose, and were insulin-resistant compared with chow mice. HF and HFHC consumed similar calories. Hepatic triglyceride content, plasma alanine aminotransferase, and liver weight were significantly increased in HF and HFHC mice compared with chow mice. Plasma cholesterol (P < 0.001), histological hepatic fibrosis, liver hydroxyproline content (P = 0.006), collagen 1 messenger RNA (P = 0.003), CD11b-F4/80+Gr1+ monocytes (P < 0.0001), transforming growth factor beta1 mRNA (P = 0.04), and alpha-smooth muscle actin messenger RNA (P = 0.001) levels were significantly increased in HFHC mice. Hepatic oxidative stress, as indicated by liver superoxide expression (P = 0.002), 4-hydroxynonenal, and plasma (ox)CoQ9 (P < 0.001) levels, was highest in HFHC mice. These findings demonstrate that nongenetically modified mice maintained on an HFHC diet in addition to developing obesity have increased hepatic ROS and a NASH-like phenotype with significant fibrosis. Plasma (ox)CoQ9 correlated with fibrosis progression. The mechanism of fibrosis may involve fructose inducing increased ROS associated with CD11b+F4/80+Gr1+ hepatic macrophage aggregation, resulting in transforming growth factor beta1-signaled collagen deposition and histologically visible hepatic fibrosis.


Transition and self-healing process between chaotic and self-organized patterns observed during femtosecond laser writing.
We report evidence of intermittent behavior between chaotic and self-organized patterns while writing lines with a femtosecond lasers on the surface of a fused silica substrate. The patterns are accompanied by resolidified sub-microspheres and non-aligned grating lamellae. We observe that such dynamic behavior exhibits a striking similarity with the fluctuating content of a queuing system which alternate between random busy and idle periods.


Machine learning models for predicting depression in Korean young employees.
The incidence of depression among employees has gradually risen. Previous studies have focused on predicting the risk of depression, but most studies were conducted using basic statistical methods. This study used machine learning algorithms to build models that detect and identify the important factors associated with depression in the workplace. A total of 503 employees completed an online survey that included questionnaires on general characteristics, physical health, job-related factors, psychosocial protective, and risk factors in the workplace. The dataset contained 27 predictor variables and one dependent variable which referred to the status of employees (normal or at the risk of depression). The prediction accuracy of three machine learning models using sparse logistic regression, support vector machine, and random forest was compared with the accuracy, precision, sensitivity, specificity, and AUC. Additionally, the important factors identified via sparse logistic regression and random forest. All machine learning models demonstrated similar results, with the lowest accuracy obtained from sparse logistic regression and support vector machine (86.8%) and the highest accuracy from random forest (88.7%). The important factors identified in this study were gender, physical health, job, psychosocial protective factors, and psychosocial risk and protective factors in the workplace. The results of this study indicated the potential of machine learning models to accurately predict the risk of depression among employees. The identified factors that influence the risk of depression can contribute to the development of intelligent mental healthcare systems that can detect early signs of depressive symptoms in the workplace.


The effect of sodium thiosulfate administration on nephrocalcinosis in a rat model.
Sodium thiosulfate (STS) is a U.S. Food and Drug Administration (FDA)-approved chelating agent that is used for the treatment of cyanide poisoning and prophylaxis against cisplatin nephropathy. Recently, STS has also been used in the treatment of calciphylaxis, which is a disease characterized by calcification in the soft tissues with vascular calcification and thrombosis causing nonhealing ulcers. We proposed a rat model to evaluate whether STS has any possible beneficial effect on calcium nephrolithiasis or nephrocalcinosis. Twenty-one male Sprague-Dawley rats were used in the study. All animals received standard rat chow throughout the experiment. The animals were started on special drinking water containing 0.4% ethylene glycol plus 1.0% ammonium chloride for 7 days to induce crystalluria and nephrocalcinosis. The animals were then randomized to two groups. Group 1 served as a control and received daily intraperitoneal injections of normal saline. Group 2 received daily intraperitoneal injections of STS solution. Special drinking water containing 0.8% ethylene glycol was continued during the treatment period. Group 2 gained significantly less weight than group 1 (18.0% v 8.5%, p < 0.05). The amount of crystalluria in group 2 was much less than that in group 1, but did not reach statistical significance (0.7 v 4.2, p = 0.09). Degree of calcification noted in the kidneys was not statistically different between the two groups. The current study did not reveal any significant benefit of STS administration on calcium stone disease. However, many more studies are necessary before the possibility of a beneficial effect is completely disproved.


Impact of an Offline Pain Management Protocol on Prehospital Provider Self-Efficacy: A Randomized Trial.
Pain in children is inadequately treated in the prehospital setting despite the reported recognition by prehospital providers (PHPs) of pain treatment as an important part of patient care. The impact of pediatric pain management protocol (PPP) implementation on PHP self-efficacy (SE), a measure congruent with performance, is unknown. The aim of this study was to evaluate the impact of PPP implementation and pain management education on PHP SE. This was a prospective study evaluating the change in PHP SE after a PPP was implemented. Prehospital providers were randomized to 3 groups: protocol introduction alone, protocol introduction with education, and protocol introduction with education and a 3-month interim review. Prehospital provider SE was assessed for pain management given 3 age-based scenarios. Self-efficacy was measured with a tool that uses a ranked ordinal scale ranging from "certain I cannot do it" (0) to "completely certain I can do it" (100) for 10 pain management actions: pain assessment (3), medication administration (4), dosing (1), and reassessment (2). An averaged composite score (0-100) was calculated for each of the 3 age groups (adult, child, toddler). Paired-sample t tests compared post-PPP and 13-month scores to pre-PPP scores. Of 264 PHPs who completed initial surveys, 142 PHPs completed 13-month surveys. Ninety-three (65%) received education with protocol review, and 49 (35%) had protocol review only. Self-efficacy scores increased over the study period, most notably for pain assessment. This increase persisted at 13 months for child (6.6 [95% confidence interval {CI}, 1.4-11.8]) and toddler pain assessment (22.3 [95% CI, 16.4-28.3]). Composite SE scores increased immediately for all age groups (adult, 3.1 [95% CI, 1.3-4.9]; child, 6.1 [95% CI, 3.8-8.5]; toddler, 12.0 [95% CI, 9.5-14.5]) and persisted at 13 months for the toddler group alone (7.0 [95% CI, 4.3-9.7]). There was no difference between groups who received protocol review alone compared with those with education or education plus a 3-month interim review. After a pain management protocol was introduced, SE scores among PHPs increased immediately and remained elevated for some individual actions involved in pain management, most notably pain assessment. Prehospital provider pain assessment SE scores declined 13 months after protocol introduction for adults, but remained elevated compared with baseline for the pediatric age groups.


Progress of clinical oncology guidelines development using the Practice Guidelines Development Cycle: the role of practitioner feedback.
To present an update on the development of oncology practice guidelines (PGs) using the Practice Guidelines Development Cycle (Cycle), and to present the results of surveys of oncologists on the first 10 guidelines from the Cancer Care Ontario Practice Guidelines Initiative. Practitioners' opinions about guidelines in development were sought using a mail survey method with systematic follow-up. Practitioners were identified by cancer center representatives. Survey packages included evidence-based recommendations (EBRs) and a one-page, nine-item feedback questionnaire. Data were collected between February 1995 and February 1996. Nine hundred fourteen surveys that pertained to 10 guidelines were mailed to 423 practitioners in Ontario. Practitioners included 112 medical oncologists/hematologists, 34 radiation oncologists, 195 surgeons, and 82 practitioners from other medical specialities. One hundred practitioners were located in cancer centers and 323 had community-based practices. The overall response rate by practitioner was 72% and by survey questionnaire, 70%. For the five questionnaire items that assessed guideline quality, approval ratings ranged from 86% to 92%. For the 10 recommendations, 77% ( 63% to 82%) of respondents agreed that the EBR could be approved as a PG. Response and approval rates were consistent across medical specialities and locations of practice. The process of obtaining practitioner feedback in the development of PGs is both feasible and useful. The high response rates to the survey indicate that it is possible to obtain broad participation in evidence-based guidelines development throughout Ontario. The changes made to the EBRs in response to feedback suggest that practitioners' opinions can be valuable in shaping evidence-based guidelines.


The Shape of Parotid DVH Predicts the Entity of Gland Deformation During IMRT for Head and Neck Cancers.
The Jacobian of the deformation field of the registration between images taken during Radiotherapy is a measure of compression/expansion of the voxels within an organ. The Jacobian mean value was applied to investigate possible correlations between parotid deformation and anatomical, clinical and dosimetric parameters. Data of 84 patients were analyzed. Parotid deformation was evaluated through Jacobian maps of images taken at the start and at the end of the treatment. Several clinical, geometrical and dosimetric factors were considered. Correlation between Jacobian mean value and these parameters was assessed through Spearman's test. Univariate and multivariate logistic analyses were performed by considering as the end point the first quartile value of the Jacobian mean value. Parotid dose volume histograms were stratified according to gland deformation, assessing the most predictive dose-volume combination. At multivariate analysis, age (p = 0.02), overlap between tumor volume and parotid gland (p = 0.0006) and the parotid volume receiving more than 10 Gy (p = 0.02) were found as the best independent predictors, by considering Jacobian mean value <first quartile as the end point. By comparing the average dose volume histogram of parotids with Jacobian mean value <first quartile and >fist quartile, the parotid volume receiving more than 10 Gy and 40 Gy were found as the most predictive dosimetric parameters. Parotid glands were divided in three different sub-groups (bad-, medium- and good dose volume histogram). The risk to have Jacobian means value lower than first quartile was 39.6% versus 19.6% versus 11.3% in these three groups. By including in the multivariate analysis this "dose volume grouping" parameter, age and bad dose volume histogram were found as the most predictive parameters for large shrinkage. The pattern of parotid deformation may be well predicted by some pre-treatment variables; a bad dose volume histogram seems the most important predictor.