Tumor-suppressive microRNA-1291 directly regulates glucose transporter 1 in renal cell carcinoma.
Our recent studies of microRNA (miRNA) expression signatures demonstrated that microRNA-1291 (miR-1291) was significantly downregulated in renal cell carcinoma (RCC) clinical specimens and was a putative tumor-suppressive miRNA in RCC. The aim of the present study was to investigate the functional significance of miR-1291 in cancer cells and to identify novel miR-1291-mediated cancer pathways and target genes in RCC. Expression of miR-1291 was significantly downregulated in RCC tissues compared with adjacent non-cancerous tissues. Restoration of mature miR-1291 in RCC cell lines (A498 and 786-O) revealed significant inhibition of cell proliferation, migration and invasion, suggesting that miR-1291 functioned as a tumor suppressor. To identify miR-1291-mediated molecular pathways and targets, we used gene expression analysis (expression of RCC clinical specimens and miR-1291-transfected A498 cells) and in silico database analysis. Our data demonstrated that 79 signaling pathways were significantly regulated by tumor-suppressive miR-1291 in RCC cells. Moreover, solute career family 2 member 1 (SLC2A1) was a candidate target of miR-1291 regulation. The SLC2A1 gene provides instructions for producing glucose transporter protein type 1 (GLUT1). Luciferase reporter assays showed that miR-1291 directly regulated SLC2A1/GLUT1. In RCC clinical specimens, the expression of SLC2A1/GLUT1 mRNA was significantly higher in cancer tissues than in non-cancerous tissues. A significant inverse correlation was recognized between SLC2A1/GLUT1 and miR-1291 expression (r = -0.55, P < 0.0001). Loss of tumor-suppressive miR-1291 enhanced RCC cell proliferation, migration and invasion through targeting SLC2A1/GLUT1. The identification of novel tumor-suppressive miR-1291-mediated molecular pathways and targets has provided new insights into RCC oncogenesis and metastasis.


Word and text processing in developmental prosopagnosia.
The "many-to-many" hypothesis proposes that visual object processing is supported by distributed circuits that overlap for different object categories. For faces and words the hypothesis posits that both posterior fusiform regions contribute to both face and visual word perception and predicts that unilateral lesions impairing one will affect the other. However, studies testing this hypothesis have produced mixed results. We evaluated visual word processing in subjects with developmental prosopagnosia, a condition linked to right posterior fusiform abnormalities. Ten developmental prosopagnosic subjects performed a word-length effect task and a task evaluating the recognition of word content across variations in text style, and the recognition of style across variations in word content. All subjects had normal word-length effects. One had prolonged sorting time for word recognition in handwritten stimuli. These results suggest that the deficit in developmental prosopagnosia is unlikely to affect visual word processing, contrary to predictions of the many-to-many hypothesis.


Cardiotoxicity screening of illicit drugs and new psychoactive substances (NPS) in human iPSC-derived cardiomyocytes using microelectrode array (MEA) recordings.
The use of recreational drugs, including new psychoactive substances (NPS), is paralleled by emergency department visits of drug users with severe cardiotoxicity. Drug-induced cardiotoxicity can be the (secondary) result of increased norepinephrine blood concentrations, but data on potential drug-induced direct effects on cardiomyocyte function are scarce. The presence of hundreds of NPS therefore calls for efficient screening models to assess direct cardiotoxicity. We investigated effects of four reference compounds (3-30 nM dofetilide, nifedipine and isoproterenol, and 1-10 μM mexiletine) and six recreational drugs (0.01-100 μM cocaine, 0.01-1000 μM amphetamine, MDMA, 4-fluoroamphetamine, α-PVP and MDPV) on cardiomyocyte function (beat rate, spike amplitude and field potential duration (FPD ≈ QT interval in ECGs)), using Pluricyte® human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes cultured on ready-to-use CardioPlate™ multi-well microelectrode arrays (mwMEAs). Moreover, the effects of exposure to recreational drugs on cell viability were assessed. Effects of reference compounds were in accordance with the literature, indicating the presence of hERG potassium (dofetilide), sodium (mexiletine) and calcium (nifedipine) channels and α-adrenergic receptors (isoproterenol). All recreational drugs decreased the spike amplitude at 10-100 μM. All amphetamine-type stimulants and α-PVP decreased the beat rate at 300 μM, while cocaine and MDPV did so at 10 μM and 30 μM, respectively. All drugs increased the FPD, however at varying concentrations. MDMA, MDPV and amphetamine affected cardiomyocyte function at concentrations relevant for human exposure, while other drugs affected cardiomyocyte function only at higher concentrations (≥ 10 μM). Cell viability was only mildly affected at concentrations well above the lowest concentrations affecting cardiomyocyte function. We demonstrate that MEA recordings of hiPSC-derived cardiomyocytes enable screening for acute, direct effects on cardiomyocyte function. Our data further indicate that tachycardia in patients exposed to recreational drugs is likely due to indirect drug effects, while prolonged repolarization periods (prolonged QTc interval) could (partly) result from direct drug effects on cardiomyocyte function.


Beyond the Role of ExtenderIndependent and Interdependent Contributions of Nursing to Geriatric Rehabilitation.
Too often, the role of nursing in geriatric neurorehabilitation is defined in terms of extending the care of other disciplines and assuring continuity of selected aspects of care over 24 hours. This article argues that nursing has made significant clinical and scientific progress in contributing, independently and interdependently, to quality rehabilitation care for older adults; and that the role of nursing clearly exceeds the realm of mere extension and continuity of care. Reviewed are nursing's innovations in the areas of promoting comprehensive assessment; fostering functional independence, self-care, and self-care agency; enhancing communication; encouraging family involvement; improving cognitive status; and assuring quality physical care. We conclude with a discussion of the relationship of nursing to other disciplines, and how nursing's contributions can be optimized within the broader context of multidisciplinary geriatric rehabilitation.


Phylogeny of the bee genus Halictus (Hymenoptera: halictidae) based on parsimony and likelihood analyses of nuclear EF-1alpha sequence data.
We investigated higher-level phylogenetic relationships within the genus Halictus based on parsimony and maximum likelihood (ML) analysis of elongation factor-1alpha DNA sequence data. Our data set includes 41 OTUs representing 35 species of halictine bees from a diverse sample of outgroup genera and from the three widely recognized subgenera of Halictus (Halictus s.s., Seladonia, and Vestitohalictus). We analyzed 1513 total aligned nucleotide sites spanning three exons and two introns. Equal-weights parsimony analysis of the overall data set yielded 144 equally parsimonious trees. Major conclusions supported in this analysis (and in all subsequent analyses) included the following: (1) Thrincohalictus is the sister group to Halictus s.l., (2) Halictus s.l. is monophyletic, (3) Vestitohalictus renders Seladonia paraphyletic but together Seladonia + Vestitohalictus is monophyletic, (4) Michener's Groups 1 and 3 are monophyletic, and (5) Michener's Group 1 renders Group 2 paraphyletic. In order to resolve basal relationships within Halictus we applied various weighting schemes under parsimony (successive approximations character weighting and implied weights) and employed ML under 17 models of sequence evolution. Weighted parsimony yielded conflicting results but, in general, supported the hypothesis that Seladonia + Vestitohalictus is sister to Michener's Group 3 and renders Halictus s.s. paraphyletic. ML analyses using the GTR model with site-specific rates supported an alternative hypothesis: Seladonia + Vestitohalictus is sister to Halictus s.s. We mapped social behavior onto trees obtained under ML and parsimony in order to reconstruct the likely historical pattern of social evolution. Our results are unambiguous: the ancestral state for the genus Halictus is eusociality. Reversal to solitary behavior has occurred at least four times among the species included in our analysis.


Ten years' experience with four cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, procarbazine (BEACOPP)-escalated followed by four cycles of baseline-dose BEACOPP in patients with advanced stage Hodgkin lymphoma: a single-center, retrospective study.
The HD-9 trial showed that eight cycles of BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, procarbazine)-escalated led to significant improvements in response rate, progression-free survival and overall survival over COPP/ABVD (cyclophosphamide, vincristine, prednisone, procarbazine/doxorubicin, bleomycin, vinblastine, dacarbazine) therapy. This monocentric retrospective study was performed to evaluate 10 years of experience with four cycles of BEACOPP-escalated and four cycles of BEACOPP-baseline outside of clinical trials. The outcomes were assessed in 78 patients with newly diagnosed advanced stage Hodgkin lymphoma. A complete response after chemotherapy ± radiotherapy was achieved in 75 patients (96%). At the median follow-up of 74 months, the actuarial 5- and 10-year freedom from treatment failure (FFTF) rates were 91% and 89%, and actuarial 5- and 10-year overall survival rates for the entire group were 93% and 90%, respectively. These results suggest that the combination of escalated and baseline BEACOPP chemotherapy is feasible in routine practice with good efficacy and acceptable toxicity.


Barriers to adherence to antiretroviral treatment: the perspectives of patient advocates.
Patient advocates were asked for their perspectives on the structural barriers to adherence to antiretroviral treatment among patients living with HIV. Poverty-related barriers were transport difficulties, food insecurity and patients' receipt of a disability grant. Institutional barriers were long waiting times at clinics, negative experiences with clinic staff, low levels of health literacy and poor access to substance abuse treatment. Social and cultural barriers were the role of traditional healing practices, the influence of charismatic churches and perceived stigmatization. We offer a perspective on assisting patients living with HIV in addressing these key structural barriers to adherence.


Increased expression of EMMPRIN in the tissue around loosened hip prostheses.
Matrix metalloproteinases (MMPs) have been shown to play a role in aseptic loosening of total hip replacement (THR). Extracellular matrix metalloproteinase inducer (EMMPRIN) can upregulate expression of several MMPs but has little effect on their tissue inhibitor (TIMP). Using the avidin-biotin-peroxidase complex immunostaining method, we detected strong immunoreactivity of EMMPRIN in the lining-like layers, sublining area and vascular endothelium of synovial membrane-like interface tissue around loosened prostheses. In contrast, EMMPRIN staining was very weak in the synovial samples from patients with hip arthrosis. Double immunofluorescence labeling revealed EMMPRIN/MMP-1 double-positive cells in lining-like layers and the sublining area of interface tissue. Our findings indicate that EMMPRIN expression is upregulated in interface tissue, and that locally accumulated EMMPRIN may modulate MMP-1 expression. An imbalance in the activity of MMPs and TIMP may lead to tissue destruction and periprosthetic osteolysis. These biological responses, combined with mechanical stress caused by micromotion and oscillating fluid pressure, may eventually cause aseptic loosening of THR.


A way to screen for suffering in palliative care.
We report a new tool for screening the suffering of terminally ill patients in a palliative care service. We systematically asked 371 terminal oncological and AIDS patients on 665 different occasions, "How long did yesterday seem to you?"; we then asked them to assess their current condition. The simple answer about subjective length of time correlated well with subjective suffering in approximately half the patients. Thus it may be a good starting point for future assessment and more extensive explorations.


Literature review: Afghanistan women's health crisis, health service delivery, and ethical issues for international aid.
The literature indicates that the health of women in Afghanistan is poor. In 1997 maternal mortality in Afghanistan was one of the worst in the world. Difficulties in establishing health services revolve around fundamentalist Islamic ideas and ongoing violence within Afghanistan. The literature holds advice on key behaviours for health professionals who may chose to work in Afghanistan. The literature also identifies the local level action that is occurring as the issue of women's health is recognised. Humanitarian assistance has been provided, with international aid agencies having to weigh the ethical responsibilities they hold and one agency tragically facing the violent loss of its own staff. Easy answers are not in the literature, merely an opportunity to understand, consider, and take action about what is facing women in Afghanistan and those who try to help.


Bone mineral density in immigrants from southern China to Denmark. A cross-sectional study.
Immigration from Japan to USA has been shown to increase bone mineral density (BMD) and body fat in women. The effects of immigration between other geographical areas on bone mass and body composition are largely unknown, especially in men. In the present study, we measured bone mass and body composition by dual energy X-ray absorptiometry (Hologic QDR-2000) in 73 healthy premenopausal women (age 35 +/- 8 years) and 69 men (age 40 +/- 12 years) who had immigrated from southern China to Denmark 2 months to 36 years ago. The BMD measurements (Total BMD, trunk BMD and leg BMD) were related positively to years since immigration (YSI) (R2 = 0.10-0.16, p < 0.05) in premenopausal women, but not in men. Fat distribution was related mainly to age in both premenopausal women and men (R2 = 0.16-0.26, p < 0.05). For comparison, we included 51 white, Danish premenopausal women (age 36 +/- 6 years). Chinese premenopausal women with a YSI below or equal to 12 years (N = 38) had significantly lower total and regional BMD (trunk, legs, arms) (p < 0.05), while women with a YSI above 12 years (N = 35) had significantly lower BMD in the legs only (p < 0.05) when compared to the Danish premenopausal women. After correction for age weight and height, Chinese premenopausal women with a YSI below or equal to 12 years still had significantly lower BMD in all regions (4-7%, p < 0.05), whereas no differences in BMD were found between Chinese premenopausal women with a YSI above 12 years compared with Danish premenopausal women. In conclusion, Chinese premenopausal women who immigrated to Denmark more than 12 years ago have a similar BMD to that of Danish premenopausal women. In the group who immigrated less than 12 years ago, a significantly lower BMD was found.


Rostral mandibulectomy for the management of trismus in a cat.
A 5-year-old domestic shorthair cat was evaluated for weight loss and poor coat condition due to an inability to open its mouth (trismus) following head trauma 2 months previously. Contrast CT, electromyography and temporal muscle biopsy identified findings consistent with muscle atrophy, denervation and degeneration. Conservative treatment failed to improve the trismus so a rostral mandibulectomy was performed. Following surgery, the patient resumed normal grooming behaviour and was able to eat soft food unaided. The cat re-presented 5 months postoperatively at which time its body condition had improved; however, episodes of sneezing had been noted. An oronasal fistula was diagnosed and treated successfully with a silicon nasal septum button. Follow-up at 30 months reported an excellent outcome. Management of trismus with rostral mandibulectomy may be associated with a good return to function, including prehension and ingestion of food, and restoration of normal grooming activity. Rostral mandibulectomy could be considered for animals with trismus for other aetiologies such as masticatory myositis where other management options are not available.


Expanding the genetic architecture and phenotypic spectrum in the skeletal ciliopathies.
Defects in the biosynthesis and/or function of primary cilia cause a spectrum of disorders collectively referred to as ciliopathies. A subset of these disorders is distinguished by profound abnormalities of the skeleton that include a long narrow chest with markedly short ribs, extremely short limbs, and polydactyly. These include the perinatal lethal short-rib polydactyly syndromes (SRPS) and the less severe asphyxiating thoracic dystrophy (ATD), Ellis-van Creveld (EVC) syndrome, and cranioectodermal dysplasia (CED) phenotypes. To identify new genes and define the spectrum of mutations in the skeletal ciliopathies, we analyzed 152 unrelated families with SRPS, ATD, and EVC. Causal variants were discovered in 14 genes in 120 families, including one newly associated gene and two genes previously associated with other ciliopathies. These three genes encode components of three different ciliary complexes; FUZ, which encodes a planar cell polarity complex molecule; TRAF3IP1, which encodes an anterograde ciliary transport protein; and LBR, which encodes a nuclear membrane protein with sterol reductase activity. The results established the molecular basis of SRPS type IV, in which mutations were identified in four different ciliary genes. The data provide systematic insight regarding the genotypes associated with a large cohort of these genetically heterogeneous phenotypes and identified new ciliary components required for normal skeletal development.


An ergonomics program designed to reduce the incidence of upper extremity work related musculoskeletal disorders.
In 1992, the Johns Hopkins Hospital and University initiated a program aimed at the early diagnosis and treatment of potential upper extremity work related musculoskeletal disorders (UEWMSDs), ergonomic assessment and abatement of work areas where individuals with UEWMSDs are employed, as well as the identification and correction of areas throughout the hospital and university where UEWMSDs could possibly occur. The program resulted in an initial increase in the number and cost for the treatment of UEWMSDs. Subsequently, there was a significant decrease in the number of UEWMSDs reported and virtual elimination of the need to use surgical procedures to correct these conditions. This article suggests that a coordinated program of medical care, ergonomic assessment, and intervention can be efficacious in the primary, secondary, and tertiary prevention of UEWMSD.


Thyroid hormone control of thermogenesis and energy balance.
The mechanisms whereby thyroid hormone increases heat production have been analyzed with emphasis in more recent developments. Thyroid hormone increases obligatory thermogenesis as a result of the stimulation of numerous metabolic pathways involved in development, remodeling, and delivery of energy to the tissues. In addition, thyroid hormone may specifically stimulate some thermogenic mechanisms selected during evolution of homeotherms (e.g., Na/K-ATPase, Ca2+ cycling in muscle). Thyroid hormone also plays an essential role in facultative thermogenesis interacting with the sympathetic nervous system (SNS) at various levels. Peripherally, thyroid hormone potentiates the effects of the SNS at the level of the adrenergic receptor and adenylyl cyclase complex as well as distal from this point. Synergistic interactions between T3 and cAMP on the regulation of gene expression have been described. Brown adipose tissue (BAT) T4-5'-deiodinase plays a central role in controlling heat production. When this enzyme is stimulated by norepinephrine in the euthyroid and hypothyroid condition, it provides high concentrations of T3 to BAT; inhibition by T4 in hyperthyroidism may limit brown fat thermogenic responses. Also, thyrotoxicosis uniquely reduces the expression of beta 3-adrenergic receptors in brown adipose tissue, and the increased obligatory thermogenesis of this condition, via afferent neural pathways, may reduce the hypothalamic stimulation of brown fat, providing additional mechanisms to limit brown adipose tissue thermogenesis in hyperthyroidism.


Prevention and mental illness: a new era for a healthier tomorrow.
The Department of Mental Health and Substance Abuse Services strives to provide the best possible care for Oklahoma communities through preventative programs and approaches such as QPR, Mental Health First Aid and mental health screenings. All of these techniques have been proven in providing adequate knowledge of risk factors in Oklahoma communities for mental health disorders and help to prevent those predisposed to mental illness from experiencing an onset of the disorder.


Gonadal responses of the male tau mutant Syrian hamster to short-day-like programmed infusions of melatonin.
Changes in the duration of the nocturnal peak of the circadian rhythm of melatonin secretion by the pineal gland mediate pohotoperiodic control of reproductive cycles in mammals. The present study examined whether the tau mutation of the circadian clock of the Syrian hamster altered the ability of the animals to exhibit photoperiodic, gonadal responses to timed infusions of exogenous melatonin. Pinealectomized tau mutant and wild-type hamsters received s.c. infusions of vehicle or melatonin solution (50 ng/h) for either 8 h or 6.67 h (i.e., 83% of 8 h, a reduction by the same proportion as circadian period is shortened by the mutation, 20 h vs. 24 h) once every 20 h for 6 wk. Testicular weight and serum levels of LH and prolactin were measured to assess the effects of the infusions on the reproductive axis. Both genotypes exhibited significant gonadal regression to the 8 h and 6.67 h melatonin signals, versus saline controls, although in taus the magnitude of the response to 6.67 h melatonin was significantly greater and more consistent than in wild-types. Compared to saline-infused hamsters, animals that received infusions of melatonin of either duration showed significantly reduced serum levels of LH and prolactin. There was no significant difference between the two genotypes in the observed endocrine responses to melatonin infusions. These preliminary data demonstrate that tau mutant hamsters can respond to programmed systemic infusions of melatonin in a manner comparable to that observed in wild-type hamsters, and therefore, that the tau mutation of the circadian clock has not impaired the ability of the hamster to measure photoperiodic time, as represented by melatonin.


An unusual case of massive subcutaneous chest wall haemorrhage with enoxaparin.
Enoxaparin is used in the treatment of acute coronary syndromes and offers improved outcome in the composite endpoint of death, myocardial infarction and major bleeding when compared with unfractionated heparin (UFH). Our report describes a rare case of massive life-threatening subcutaneous chest wall haemorrhage, distant to the injection site. Clinicians should be aware of atypical presentations of haemorrhage when using combination antiplatelet and antithrombotic therapy.


Measurement of distortion product phase in the ear canal of the cat.
Amplitudes of odd order distortion products (DPs) that are detected in animal ear canals have been used to probe cochlear health, to search for cochlear amplification, and to measure aspects of cochlear mechanical frequency response. Like the DP amplitude, DP phase is also an important measure of the cochlear mechanical response. Reported here are measurements of DP phase in the ear canal of the cat. The phase data show frequency-dependent time delays. One of these delays is a function of f2, the frequency of the higher-frequency primary. Hence the DP phase phi d is of the form phi d = phi 0 + omega d tau, where omega d is the DP angular frequency and tau is a fixed time delay. Our results show that phi d is independent of input level a2 as long as the ratio a2/a1 < or = 2, where a2 and a1 are the amplitudes of the input tones. As a2/a1 becomes greater than two, the fixed time delays increase for DPs whose frequencies are less than the frequencies of the input tones. When both levels are varied together the delay increases as the levels decrease. There can be phase changes as large as pi associated with deep nulls in the DP magnitude for the two lower-frequency DPs. Features of the nulls may be modeled assuming that there is partial reflection of the DP wave from the DP place. The assumption of energy remitted from the DP place also explains amplitude-ratio-dependent time delays and 2 pi level-dependent bifurcations in phase. The DP phase shows different dependencies for f2 < 1 kHz compared to f2 > 2 kHz.


Cerebrospinal fluid and serum neopterin levels in patients with Lyme neuroborreliosis.
Elevated (greater than 3.0 nmol/l) cerebrospinal fluid neopterin concentrations were observed in 20 of 21 patients with Lyme neuroborreliosis compared with three of 11 control patients with headache, back pain or psychoneurotic disorders. Neopterin concentrations were correlated to mononuclear cell counts and protein concentrations in the cerebrospinal fluid (CSF). Following antibiotic treatment, CSF neopterin levels decreased. Serum neopterin levels were not significantly raised in patients with neuroborreliosis when compared to control subjects. Neopterin levels as well as cell count and protein concentration in the CSF are valuable inflammation markers of disease activity in Lyme neuroborreliosis.


Electrical anharmonicity and vibronic couplings contributions to optical nonlinearity of N-benzyl-2-methyl-4-nitroaniline crystal studied by FT-IR, polarized FT-NIR, resonance Raman and UV-vis spectroscopy.
FT-IR and Raman spectra of the orthorhombic and monoclinic N-benzyl-2-methyl-4-nitroaniline (BNA) single crystals, powders, and BNA solutions were measured in the 15-4000 cm(-1) range, and complete assignments of bands to normal vibrations are proposed. The assignments have been reinforced by density functional theory (DFT) calculations. Polarized FT-NIR spectra of the orthorhombic (010) BNA plate were measured for the overtones and combinations analysis and for the mechanical and electrical anharmonicity estimation. Resonance Raman spectra of the orthorhombic BNA polymorph together with the resonance excitation profiles of fundamental and lattice vibrations, compared with the band maxima in the measured UV-vis-NIR spectra of BNA, have revealed vibronic couplings with intramolecular and intermolecular charge transfers. The role of anharmonicity, vibronic couplings and intermolecular hydrogen bonds as well as of the N-benzyl substituent are discussed and the origin of second harmonic generation in the orthorhombic BNA crystal is proposed.


Biliary and colonic cutaneous fistula successfully treated by endoscopic insertion of biliary stents.
We report a case in which a large, postoperative cutaneous biliary and a colonic fistula were successfully treated by means of endoscopic insertion of two endoprostheses into the common bile duct. Twenty-four hours after the procedure, bile flow through the leak ceased completely while the colonic fistula closed in 6 days. Six months after the treatment, when a new endoscopic cholangiography showed no evidence of leak or stricture, the stents were removed. For the treatment of postoperative biliary leaks, insertion of endoprostheses is a good and safe alternative to surgery.


Evaluation of the relationship between plaque formation leading to symptomatic carotid artery stenosis and cytomegalovirus by investigating the virus DNA.
The most common etiologic factor of coronary artery disease (CAD), carotid artery disease, and peripheral artery disease is atherosclerosis. In our study, we aimed to show the effect of cytomegalovirus (CMV), which can occur almost everywhere in the human body, on triggering the chronic inflammatory process in the pathophysiology of atherosclerosis, and its presence and impact in the plaques leading to carotid artery stenosis. Thirty-six patients, who underwent carotid endarterectomy at the Department of Cardiovascular Surgery, Istanbul University Istanbul Medical Faculty between April 2017 and April 2018, were included in this study upon their consent. Patients with additional immunosuppressive conditions were not included in the study. Unilateral atheromatous plaque was preferred for patients undergoing bilateral carotid endarterectomy and all risk factors (DM, HT, hyperlipidemia, etc.) were evaluated together for all patients. When the relationship between CMV (DNA) presence in samples taken from patients' plaques and sex, age and comorbidities was examined, CMV (DNA) positivity (45.8%) was significantly higher in DM patients than non-DM patients (8.3%) (p = 0.024). Likewise, CMV(DNA) positivity (40%) was significantly higher in HT patients than in non-HT patients (25%) (p = 0.008). CMV(DNA) positivity (63%) was significantly higher in patients with bilateral carotid artery stenosis than patients without bilateral carotid artery stenosis (0%) (p < 0.001). It has not yet been clarified whether CMV is a primary trigger for atherosclerosis on the vascular wall, or whether it presents incidentally due to its affinity. When CMV (DNA) positivity was examined according to the presence of bilateral carotid artery stenosis in our study, CMV (DNA) positivity was found to be significantly higher in patients with bilateral carotid artery stenosis (63.16%).


[Catamenial pneumothorax with diaphragmatic and visceral plural endometriosis].
A 47-year-old woman was admitted to our hospital because of two episodes of right pneumothorax. After continuous suction through a thoracic drain, a computerized tomographic scan showed that air was still trapped between lung lobes. Video-assisted thoracic surgery revealed a bulla on the visceral pleural of the upper lobe (S2) and several dark-red spots and white-coated lesions surrounding a defect of the diaphragm. The involved portions of the diaphragm and of the lung were excised. Microscopic examination of the excised specimens showed endometriosis. Catamenial pneumothorax may be caused by intrathoracic endometriosis, but very few cases in which pulmonary or visceral pleural endometriosis was demonstrated histologically have been reported.


Rice Blast Lesions: an Unexplored Phyllosphere Microhabitat for Novel Antagonistic Bacterial Species Against Magnaporthe oryzae.
Dark brown necrotic lesions caused by Magnaporthe oryzae on rice foliage is a contrasting microhabitat for leaf-colonizing microbiome as compared with the surrounding healthy chlorophyll-rich tissues. We explored culturable bacterial communities of blast lesions by adopting microbiological tools for isolating effective biocontrol bacterial strains against M. oryzae. 16S rRNA gene sequencing-based molecular identification revealed a total of 17 bacterial species belonging to Achromobacter (2), Comamonas (1), Curtobacterium (1), Enterobacter (1), Leclercia (2), Microbacterium (1), Pantoea (3), Sphingobacterium (1), and Stenotrophomonas (5) found colonizing the lesion. Over 50% of the bacterial isolates were able to suppress the mycelial growth of M. oryzae either by secretory or volatile metabolites. Volatiles released by Achromobacter sp., Curtobacterium luteum, Microbacterium oleivorans, Pantoea ananatis, Stenotrophomonas maltophilia, and Stenotrophomonas sp., and were found to be fungicidal while others showed fungistatic action. In planta pathogen challenged evaluation trial revealed the biocontrol potential of Stenotrophomonas sp. and Microbacterium oleivorans that showed over 60% blast severity suppression on the rice leaf. The lesion-associated bacterial isolates were found to trigger expression of defense genes such as OsCEBiP, OsCERK1, OsEDS1, and OsPAD4 indicating their capability to elicit innate defense in rice against blast disease. The investigation culminated in the identification of potential biocontrol agents for the management of rice blast disease.


[The in vivo pediculicidal efficac of Prioderm Cream Shampoo formulation].
Head louse infestations are prevalent worldwide. Over the past 20-25 years, 15-20% of all children in Israel between 4 and 13 years of age have been infested with head lice. This is mainly due to the existence of ineffective pediculicides on the market. To examine the pediculicidal efficacy and safety of Prioderm Cream Shampoo in an open clinical study. The active ingredient of Prioderm Cream Shampoo is malathion (1%) and it was applied to the hair of infested children three times for 10 minutes at 5-day intervals. Of 419 children examined, aged 6-14 years, from four schools in Jerusalem, 109 (26.0%) were infested with lice and eggs, while 110 (26.3%) were infested only with nits. All 109 louse-infested children were included in the study while 86 (78.8%) complied with the instructions for use. Treatment was successful in 79 children (91.8%), while failure was observed in 3 children after the first treatment and in 4 children after the third treatment. Although 21.5% of the children disliked the odor of the product, there were no significant side effects related to this formulation. The product was very effective in controlling louse infestations under clinical conditions and caused no serious side effects.


Pharmacists' familiarity, utilization, and beliefs about Health Information Exchange: a survey of pharmacists in an Indiana pharmacy organization.
To gauge pharmacists' familiarity, utilization, and beliefs about Health Information Exchange (HIE). A survey questionnaire was developed by the authors in Qualtrics (Provo, UT) and administered to 358 Indiana Pharmacists Alliance (IPA) members via e-mail listserv in May and August 2013. The questionnaire consisted of 18 questions on familiarity, utilization, and beliefs about HIE. The response rate was 19% (67/358). Pharmacy practice experience of respondents ranged from 0 to 5 years (18%, n = 12) to more than 20 years (61%, n = 41). More than one-half (70%) of respondents practiced in hospital settings. Many respondents (75%) were familiar with the concept of HIE; 54% currently use some type of HIE technology. Nearly all respondents felt that data in electronic health records (EHRs) should be shared between pharmacists and other health care providers. Respondents identified improved coordination of care as the greatest potential benefit, and difficulty implementing and maintaining technology as the greatest barrier of HIE. Many respondents were familiar with HIE and in favor of sharing patient records between providers. Respondents agreed that HIE has the potential to improve coordination of care but were concerned about implementing and maintaining technology. Larger pharmacy samples should be studied to determine how the results of this study compare to pharmacy populations at state and national levels.


A new double-labeling method demonstrates transmitter-specific projections.
We report a method which combines retrograde transport of the fluorescent dye, diamidino yellow dihydrochloride (DY), with peroxidase immunocytochemical staining for glutamic acid decarboxylase (GAD), an enzyme essential for the synthesis of gamma-aminobutyric acid (GABA). Cells exhibiting both retrograde fluorescent label and GAD-positive immunoreactivity were observed in the cerebellar cortex, the striatum and the ventrobasal complex following injections of DY into the superior vestibular nucleus, substantia nigra and dorsal thalamus. The method, which can in principle be applied to any antigen, takes advantage of the differential nuclear/cytoplasmic distribution of the two stains. By using appropriate filter combinations and balanced epi- and transillumination, double-labeled cells are readily identifiable.


Kernel optimization in discriminant analysis.
Kernel mapping is one of the most used approaches to intrinsically derive nonlinear classifiers. The idea is to use a kernel function which maps the original nonlinearly separable problem to a space of intrinsically larger dimensionality where the classes are linearly separable. A major problem in the design of kernel methods is to find the kernel parameters that make the problem linear in the mapped representation. This paper derives the first criterion that specifically aims to find a kernel representation where the Bayes classifier becomes linear. We illustrate how this result can be successfully applied in several kernel discriminant analysis algorithms. Experimental results, using a large number of databases and classifiers, demonstrate the utility of the proposed approach. The paper also shows (theoretically and experimentally) that a kernel version of Subclass Discriminant Analysis yields the highest recognition rates.


Matched-filter detection of mode-locked laser signals.
The passive Fabry-Perot cavity is shown to be a good practical approach to the match-filter optimization for the sensitive detection of mode-locked laser signals. Doppler measurements of relative motion over a wide range of velocities are possible simply by measuring the cavity length for a peak output.


High prevalence of human papillomavirus (HPV) in oral mucosal lesions of patients at the Ambulatory of Oral Diagnosis of the Federal University of Sergipe, Northeastern Brazil.
The aim of this study was to evaluate the frequency of HPV infection and its genotypes in patients with oral lesions at the Ambulatory of Oral Diagnosis of the Federal University of Sergipe, Brazil. We conducted a molecular study with 21 patients (15 females) aged from two to 83 years with clinically detectable oral lesions. Samples were collected through exfoliation of lesions and HPV-DNA was identified using MY09/11 and GP5+/6+ primers. Genotyping was performed by multiplex PCR. Benign, premalignant and malignant lesions were diagnosed by histopathology. HPV was detected in 17 samples. Of these, HPV-6 was detected in 10 samples, HPV-18 in four and HPV-16 in one sample. When samples were categorized by lesion types, HPV was detected in two papilloma cases (2/3), five carcinomas (5/6), one hyperplasia (1/1) and nine dysplasia cases (9/11). Unlike other studies in the literature, we reported high occurrence of HPV in oral lesions. Further studies are required to enhance the comprehension of natural history of oral lesions.


Effectiveness of a partnership-based self-management programme for patients with mild and moderate chronic obstructive pulmonary disease: a pragmatic randomized controlled trial.
To evaluate the effectiveness of a 6-month, partnership-based self-management programme for patients with mild and moderate chronic obstructive pulmonary disease. Self-management is a widely valued concept used to address contemporary issues of chronic health problems. Findings of self-management programmes for people with chronic obstructive pulmonary disease are inconclusive. Pragmatic randomized control trial. Patients, 45-65 years old, with mild and moderate chronic obstructive pulmonary disease were invited with a family member. Experimental group (n = 48) participated in a 6-month, partnership-based self-management programme consisting of: (a) three to four conversations between nurse and patient-family member; (b) 6 months of smoking cessation; and (c) interdisciplinary team-patient-family member group meeting. Control group (n = 52) received usual care. Data were collected at months zero, six and 12. The trial lasted from June 2009-March 2013. Patients with mild and moderate chronic obstructive pulmonary disease who participated in the partnership-based self-management programme perceived less intrusiveness of the disease and its treatment than patients in the control group. Patients in the experimental group did not have better health-related quality of life, less anxiety or depression, increased physical activity, fewer exacerbations or better smoking status than patients in the control group. Patients in both groups found participation in the research useful and important. The partnership-based self-management programme had benefits concerning perception of the intrusiveness of chronic obstructive pulmonary disease and its treatment on lifestyles, activities and interests for young patients with the disease in its early stages. High satisfaction in control group, low family attendance and the relatively short treatment period may explain the less than expected benefits of the programme.


Sjogren's syndrome complicated with IgA nephropathy and leukocytoclastic vasculitis.
We report a case of primary Sjogren's syndrome (SS) with cutaneous leukocytoclastic vasculitis and IgA nephropathy. The accurate diagnosis of SS was established based on objective signs and symptoms of ocular and oral dryness, a characteristic appearance of a biopsy sample from a minor salivary gland, and the presence of anti-SS-A autoantibody. A second autoimmune disorder was not present, so the diagnosis of primary SS was established. A histologic finding of skin biopsy of purpuric lesion was typical for leukocytoclastic vasculitis. Renal biopsy was performed for nephrotic range proteinuria. The pathologic finding of renal biopsy was IgA glomerulonephritis with crescent formation. The patient was treated with small doses of glucocorticoids and maintenance hemodialysis. Leukocytoclastic vasculitis is one of the most characteristic extraglandular manifestations of SS. However, IgA nephropathy associated with SS and leukocytoclastic vasculitis is a rare finding. SS patients with glomerulonephritis present a more diverse outcome, even requiring hemodialysis. Therefore, renal biopsy is warranted in SS with glomerulonephritis and systemic vasculitis.


Nanohertz frequency determination for the gravity probe B high frequency superconducting quantum interference device signal.
In this paper, we present a method to measure the frequency and the frequency change rate of a digital signal. This method consists of three consecutive algorithms: frequency interpolation, phase differencing, and a third algorithm specifically designed and tested by the authors. The succession of these three algorithms allowed a 5 parts in 10(10) resolution in frequency determination. The algorithm developed by the authors can be applied to a sampled scalar signal such that a model linking the harmonics of its main frequency to the underlying physical phenomenon is available. This method was developed in the framework of the gravity probe B (GP-B) mission. It was applied to the high frequency (HF) component of GP-B's superconducting quantum interference device signal, whose main frequency f(z) is close to the spin frequency of the gyroscopes used in the experiment. A 30 nHz resolution in signal frequency and a 0.1 pHz/s resolution in its decay rate were achieved out of a succession of 1.86 s-long stretches of signal sampled at 2200 Hz. This paper describes the underlying theory of the frequency measurement method as well as its application to GP-B's HF science signal.


Sporadic Parkinson's Disease Potential Risk Loci Identified in Han Ancestry of Chinese Mainland.
Recent investigations demonstrated that genetic factors might play an important role in sporadic Parkinson's disease (sPD). To clarify the specific loci susceptibility to sPD, we analyze the relationship between 30 candidate single nucleotide polymorphisms (SNPs) and sPD in the population of Han ancestry from Chinese mainland (HACM) by using genome-wide association study, sequenom massARRAY, DNA sequence, and biological information analysis. Results showed that the subjects carrying the T allele of rs863108 and rs28499371 exhibited a decreased risk for sPD. The subjects carrying the T allele of rs80315856 exhibited an increased risk for sPD. The A/T genotype of rs863108 and the C/T genotype of rs28499371 were a potential increased risk for sPD, and the G/T genotype of rs80315856 and T/T genotype of rs2270568 were a potential decreased risk for sPD. The minor allele frequency (MAF) of rs80315856 and rs2270568 was higher in sPD. The T allele of rs80315856 and rs2270568 might be a risk locus for sPD. Our data suggested that the alteration of these SNPs might play some roles through changing/affecting LINC01524/LOC105372666, DMRT2/SMARCA2, PLEKHN1, and FLJ23172/FNDC3B genes in the pathogenesis of sPD.


Impact of nitric oxide on renal hemodynamics and glomerular function: modulation by atherogenic lipoproteins?
During the last decade, our understanding of the role of nitric oxide for central renal functions has greatly been enhanced. We know now that nitric oxide is produced in renal arteries, macula densa, glomeruli, and tubules by different NO-synthases. Nitric oxide contributes to physiological regulation of renal blood flow, renal autoregulation, tubuloglomerular feedback, renin release, pressure natriuresis, and tubular function. The physiological role of nitric oxide can be modulated by a variety of pathophysiological influences, such as dyslipidemia, diabetes mellitus, hypertension, specific drugs, or radiocontrast agents. In this article, the possible interactions between nitric oxide and atherogenic lipoproteins with regard to important renal functions and development of glomerulosclerosis have been stressed. Atherogenic lipoproteins impair endothelium-dependent, nitric oxide-mediated dilations of renal arteries. The underlying mechanism involves formation of reactive oxygen species which inactivate nitric oxide. Lipoproteins induce formation of oxygen radicals not only in arteries, but also in glomeruli and juxtaglomerular cells, causing, e.g., stimulation of renin release. Although interactions between lipoprotein and nitric oxide take place at different levels, they finally may contribute to renovascular hypertension. Future studies will have to prove that treating hyperlipidemia has a positive influence on nitric oxide-mediated renal functions.


[Aspiration bronchopneumonia as a complication of acute poisoning with psychotropic drugs].
In the five year period, retrospectively and prospectively, the frequency, clinical, radiographic and bacteriological characteristics of the aspiration bronchopneumonia (ABPN) were followed in the acute poisoning by psychotropic drugs (PD). In 1769 patients with acute poisoning by PD, ABPN was determined in 44 (2.49%) patients, and most frequently in groups with polymedicamentous (5.99%) and neuroleptic (5.17%) poisoning, and rarely in the group poisoned by anxiolytics (0.77%). Severest poisonings by PD were complicated by ABPN in 16.84% of cases. High conformity of clinical and radiographic finding of bronchopneumonia was achieved. The diagnosis of bronchopneumonia was established on the day of admission at the Clinic in 81.9% of cases on the other day in 13.6% and on the third day in 4.5% of patients. Bacteriological examination of sputum revealed the pathogens in 63.6% of patients, but in no patients the anaerobic bacteria were isolated. The treatment was very complex, and beside the detoxification measures, it was necessary to remove the aspirated contents from the respiratory tract (usually during endotracheal intubation or therapeutic bronchoscopy) and immediately apply antibiotics. The examinees were hospitalized twice longer than the patients whose course of poisoning by PD was not complicated by ABPN. The poisoning ended lethally in two (4.5%) patients. In no cases the ABPN was the immediate cause of death, but it significantly contributed to the lethal outcome.


Does neck stage predict local control after irradiation for head and neck cancer?
The impact of neck stage (N stage) on local control after treatment for head and neck cancer is controversial. This article reviews the pertinent literature. Based on this review, the authors conclude that although N stage may be inversely related to local control, the relationship is relatively weak. Hence, current data are insufficient to justify altering treatment of the primary lesion based solely on N stage.


Retrotransposon Domestication and Control in Dictyostelium discoideum.
Transposable elements, identified in all eukaryotes, are mobile genetic units that can change their genomic position. Transposons usually employ an excision and reintegration mechanism, by which they change position, but not copy number. In contrast, retrotransposons amplify via RNA intermediates, increasing their genomic copy number. Hence, they represent a particular threat to the structural and informational integrity of the invaded genome. The social amoeba Dictyostelium discoideum, model organism of the evolutionary Amoebozoa supergroup, features a haploid, gene-dense genome that offers limited space for damage-free transposition. Several of its contemporary retrotransposons display intrinsic integration preferences, for example by inserting next to transfer RNA genes or other retroelements. Likely, any retrotransposons that invaded the genome of the amoeba in a non-directed manner were lost during evolution, as this would result in decreased fitness of the organism. Thus, the positional preference of the Dictyostelium retroelements might represent a domestication of the selfish elements. Likewise, the reduced danger of such domesticated transposable elements led to their accumulation, and they represent about 10% of the current genome of D. discoideum. To prevent the uncontrolled spreading of retrotransposons, the amoeba employs control mechanisms including RNA interference and heterochromatization. Here, we review TRE5-A, DIRS-1 and Skipper-1, as representatives of the three retrotransposon classes in D. discoideum, which make up 5.7% of the Dictyostelium genome. We compile open questions with respect to their mobility and cellular regulation, and suggest strategies, how these questions might be addressed experimentally.


Ultra-wide operation band of the high-frequency underwater acoustic transducer realized by two-layer 1-3 piezoelectric composite.
In this paper, the two-layer 1-3 composite transducer using an unconventional part-excitation method is presented to achieve the ultra-wide operation band for the high-frequency underwater devices, in which the part-excitation refers to the method that only the lower-layer is excited, while the upper-layer in contact with the propagation medium is not excited. This method is first proposed by analyzing the longitudinal vibration modes of one piezoelectric rod in the 1-3 composite and finally, we conclude that if the excited lower-layer can be controlled to have thickness given by 3l/2n, where l is the whole thickness of the two-layer rod and n (n > 1) denotes the number of the coupled modes, then first n order modes can be activated simultaneously to form an ultra-wide operation band containing n response peaks. Finite element method (FEM) is employed to investigate the two-layer 1-3 composite with a thickness of 10 mm. The results show that when the thickness of the excited lower-layer is 3 mm (n = 5), the transducer attains the ultra-wideband by coupling five resonances, nearly covering the frequency range from 100 kHz to 1 MHz. According to the difference of response level, the whole band can be divided into multiple local wide bands. A prototype transducer is fabricated based on the FEM results, and the measured results show that the whole band contains three wide bands, covering the frequency ranges 125-295 kHz, 300-480 kHz, and 500-915 kHz, respectively.


Catheter dysfunction and thrombosis of double-lumen hemodialysis catheters placed in the femoral vein.
Intraluminal thrombosis of the catheter was thought to be a major cause of catheter dysfunction. We evaluated if thrombi appear in the luminal side or outside of the catheters placed in the femoral vein in 21 hemodialysis patients. 23 double-lumen catheter (25 cm long and 4 mm diameter polyurethane) strippings were consecutively performed. Mean catheter dwell time was 17.9 +/- 11.2 days (2-45 days). The femoral vein was observed with ultrasound echography, and thrombo-venous ratio (thrombus diameter/vein diameter) was calculated. X-rays were also taken to clearly visualize the thrombi followed by contrast medium injection through the catheter. Tube-shaped thrombi were echographically detected in 22 of 23 catheters (95.7%) when the catheter was stripped. Ten catheters (43.5%) were stripped due to the reduced blood flow, and tube-shaped thrombi were observed in the femoral vein, whereas no thrombus was found in the intraluminal side of the catheter. In 7 of 23 patients (30.4%) with leg edema on the same side of the catheter, the thrombovenous ratio was 78.9 +/- 7.4%, which was higher than that in the patients without leg edema (52.1 +/- 11.1%). The tube-shaped thrombi, formed around the double-lumen catheter, may cause catheter dysfunction and reduced venous return of the lower legs. The catheter should be removed as soon as thrombosis is diagnosed, especially when accompanied by leg edema.


COPD in individuals with the PiMZ alpha-1 antitrypsin genotype.
Since the discovery of severe alpha-1 antitrypsin deficiency as a genetic risk factor for emphysema, there has been ongoing debate over whether individuals with intermediate deficiency with one protease inhibitor Z allele (PiMZ, or MZ) are at some risk for emphysema. This is important, because MZ individuals comprise 2-5% of the general population. In this review we summarise the evidence about the risks of the MZ population to develop emphysema or asthma. We discuss the different study designs that have tried to answer this question. The risk of emphysema is more pronounced in case-control than in population-based studies, perhaps due to inadequate power. Carefully designed family studies show an increased risk of emphysema in MZ smokers. This is supported by the rapid decline in lung function of MZ individuals when compared to the general population after massive environmental exposures. The risk of asthma in MZ subjects is less studied, and more literature is needed before firm conclusions can be made. Augmentation therapy in MZ individuals is not supported by any objective studies. MZ smokers are at increased risk for emphysema that is more pronounced when other environmental challenges are present.


[Quality of life survey on patients with peripheral facial paralysis by using Chinese version of the FaCE scale].
To explore the health related quality of life (QOL) status of patients with peripheral facial paralysis. By introducing, translating and adjusting of the FaCE (Facial Clinimetric Evaluation) scale, a Chinese version came into being. The scale was further strictly tested in eighty-one patients with peripheral facial paralysis and thirty healthy volunteers. The feasibility, reliability, validity and responsibility of Chinese version of FaCE scale all passed the test. The split-half reliability, Cronbach's alpha and intraclass correlation coefficient were 0.79, 0.88 and 0.87, respectively. The criteria validity calculated between FaCE and SF-36 was 0.41 (P < 0.05). Factor analysis of the construct validity showed that the 15 items were classified into six domains, which were in accordance with the original version. Every domain was sensitive and effective to discriminate between patient population and healthy population (P < 0.05). Chinese version of FaCE scale showed significant correlation with HBGS and SBGS scores (r = -0.40 and 0.42, P < 0.05). Chinese version of the FaCE scale can effectively assess QOL status of patients with facial paralysis in China.


Serum GGT and serum ferritin as early markers for metabolic syndrome.
In India, the prevalence of lifestyle diseases like diabetes, hypertension, and metabolic syndrome (MetS) is showing an upward trend. Gamma glutamate transferase (GGT) and ferritin increase oxidant stress in the body through their role in glutathione homeostasis and iron metabolism, respectively. The increase in oxidant stress increases the inflammatory load, a risk factor for metabolic syndrome. These parameters are cheap, patient-friendly, and available in routine diagnostic labs compatible for follow-up, relieving the already overburdened healthcare system. In a case-control study, samples of 77 cases of metabolic syndrome and 77 age and sex-matched controls were analyzed for serum GGT (by modified IFCC) and serum ferritin (by CLIA). Statistical analysis was done by SPSS 20.0 version. The mean ± SD for ferritin and GGT were 101.58 ± 84.20 ng/dL and 36.67 ± 26.40 IU/L, respectively in cases, whereas in control group these values were 38.38 ± 29.26 ng/dL and 16.5 3 ± 6.79 IU/L (P < 0.001). Positive and significant correlation was seen between GGT with TG (r-value- 0.376/P-value-0.001) and GGT with waist circumference (r-value- 0.298/P-value- 0.022). A positive and significant correlation was seen between GGT and ferritin in cases with an r-value of 0.307 (P-value - 0.01). The increased values of GGT and ferritin in cases suggest an inflammatory load. The positive and significant correlation between GGT and triglyceride indicates its role in increasing oxidants' stress leading to inflammation and the development of MetS. The association of ferritin with MetS though insignificant may be considered as a biomarker.


Differential diagnosis of solitary pulmonary nodules with dual-source spiral computed tomography.
The aim of the present study was to analyze the value of applying dual-source 64-layer spiral computed tomography (CT) in the differential diagnosis of solitary pulmonary nodules (SPNs). Mediastinal windows from 45 cases were selected to study SPNs (maximum diameter, ≤3 cm), and the pathological nature of lesions was determined by clinical and pathological diagnosis. Conventional 64-layer spiral CT scanning, local enhancement and 3D recombination technologies were used to determine the occurrence rate, lesion diameter, degree of enhancement, lobular sign, spicule sign, pleural indentation sign, vessel convergence sign and bronchus sign. The final diagnoses indicated 34 cases of malignant SPNs (75.6%) and 11 benign cases (24.4%). When the nodule diameter in the malignant group was compared with that of the benign group, the difference was not statistically significant (P>0.05). Nodules in the malignant group showed inhomogeneous enhancement while nodules in the benign group showed homogeneous enhancement. The enhanced CT values in the malignant group were higher than those in the benign group, and the difference was statistically significant (P<0.05). The proportion of nodules with lobular sign in the malignant group was significantly higher than that in the benign group (P<0.05). The proportion of nodules with calcification, vessel convergence sign and bronchus sign in the malignant group were significantly higher than those in the benign group, and the differences were statistically significant (P<0.05). A comparison of vacuole sign, pleural indentation sign, spiculate protuberance and fat occurrence between the two groups yielded no statistically significant differences (P>0.05). The sensitivity of CT enhancement was 85.6%, specificity was 79.6%, positive predicated value was 92.3%, and the negative predicted value was 85.2%. In conclusion, SPNs diagnosed by CT enhancement manifested with enhancement degree, lobular sign, calcification, vessel convergence sign and bronchus sign with high diagnostic accuracy.


Case report: postoperative false aneurysm of the thoracic aorta demonstrated by helical scanning.
The article describes a case of postoperative false aneurysm of the thoracic aorta that was superbly demonstrated by helical computed tomography. This technique provides a simple method for obtaining rapid diagnostic studies in patients with this and similar conditions.


Zinc concentration in tissues and performance of weanling pigs fed pharmacological levels of zinc from ZnO, Zn-methionine, Zn-lysine, or ZnSO4.
Four trials were conducted to examine concentration of zinc in tissues and performance of pigs fed high levels of Zn from ZnO, Zn-methionine, Zn-lysine, or ZnSO4. In Trials 1 (n = 80, 28 d of age, 7.5 kg BW), 2 (n = 80, 26 d of age, 7.1 kg BW), and 3 (n = 70, 23 d of age, 5.3 kg BW), pigs were assigned either to a control diet containing 105 mg/kg of Zn and 15 mg/kg of Cu or to supplemental dietary treatments of 3,000, 2,000, or 1,000 mg of Zn/kg of diet. In all three trials, dietary sources were ZnO, Zn-methionine, Zn-lysine, or ZnSO4. The trials lasted 2 wk. In Trial 1, performance of pigs generally was not improved by feeding 3,000 mg of Zn/kg from any of the Zn sources. Serum, liver, and rib Zn concentrations (P < .01) and liver Zn concentrations (P < .05) were greater for pigs fed the high Zn diets. In Trial 2, feeding high Zn did not affect overall performance. Pigs fed the high Zn diets had greater (P < .01) serum, liver, kidney, and rib Zn concentrations. In Trial 3, there were no differences (P > .10) in ADG or ADFI, but serum and liver Zn concentrations were greater (P < .01 and .05, respectively) for pigs fed high Zn diets. Within Zn sources, serum and liver concentrations of Zn were greater (P < .05) for pigs fed ZnSO4 rather than ZnO in Trials 1 and 2. In Trial 4 (n = 72, 7.1 kg), 25-d-old pigs fed diets containing 3,000 mg/kg of Zn from feed-grade ZnSO4, reagent-grade ZnSO4, or feed-grade ZnO in a 4-wk growth trial had similar ADG and ADFI, but the gain:feed ratio was lower (P < .05) for pigs fed the reagent-grade ZnSO4. Serum, liver, and kidney Zn concentrations were lower (P < .05) for pigs fed the ZnO diet after wk 2 than for pigs fed the ZnSO4 diets, but no differences (P > .10) were observed at the end of wk 4. In summary, performance was not enhanced by feeding pharmacological levels of zinc after weaning, although serum and tissue Zn concentrations were increased. When compared with the bioavailability of Zn in ZnSO4, the bioavailability of Zn was lowest for ZnO and intermediate for Zn-lysine and Zn-methionine.


Sexuality of Moroccan Survivors of Cervical Cancer: A Prospective Data
Introduction: This is a prospective study aiming to describe how cervical cancer and its treatment can affect the sexuality of a specific population of Moroccan women survivors of this disease. Materiels and Methods: It is a comparison of clinical features and Female Sexual Function Index (FSFI) of 3 balanced groups of women, made up of 100 survivors of cervical cancer, 100 survivors of non-gynecological cancer and a group of 100 healthy women. Results: 97% of the patients stopped their full sexual activity at the time of treatment; the time interval between treatment and regular sexual activity was 8 months for the cervical cancer group, and 5.8 months for non-gynecologic cancer (P =0.001). Vaginal length assessed by pelvic examination during follow up visits was estimated at about 6.2 cm, 9.2 cm and 9.5 cm respectively for the cervical cancer group, non-gynecologic cancer group and the control group (p=0.04). On the basis of the FSFI questionnaire, the analysis of the 6 main sexuality parameter scores did attest worse results for the variables related to sexual function for cervical cancer group, but not in a statistically significant way. Conclusion: In order to preserve an optimal quality of life after cervical cancer, the sexual dimension is a crucial parameter to take into consideration throughout treatment phases, especially radiation (by encouraging sexual intercourses, and using vaginal dilators during the treatment). Moroccan survivors of this disease must be treated according to a multidisciplinary approach, that includs the psychological component.


Gene cloning, expression and serological evaluation of the 12-kDa antigen-B subunit from Echinococcus granulosus.
A 12-kDa subunit of antigen B from Echinococcus granulosus has recently been cloned, expressed and used in diagnostic ELISA to test human sera for evidence of cystic echinococcosis. The performance of the ELISA based on the recombinant antigen (rAgB) was compared with that of similar assays based on native antigen B (nAgB) or hydatid-cyst fluid. For the preparation of the rAgB, total RNA was extracted from Ec. granulosus protoscoleces so that antigen-B complementary DNA could be synthesised, amplified by PCR, and then cloned into the pQE30 expression vector. The recombinant plasmid was transformed in Escherichia coli and induced using isopropyl-beta-D-thiogalactopyrano-side. Bacterial samples were collected, lysed and then analysed by SDS-PAGE and western blotting. The recombinant protein was purified by affinity chromatography. Although the performance of the ELISA based on cyst fluid appeared identical to that of the assay based on the recombinant antigen (with a sensitivity, specificity, positive predictive value and negative predictive value of 96.0%, 97.0%, 97.2% and 95.5%, respectively), the corresponding results for the ELISA based on nAgB (98.6%, 100%, 100% and 98.5%) were slightly better. Despite this difference (which was not statistically significant), the comparative ease with which large quantities of the recombinant antigen could be produced make the antigen a potentially useful tool in the diagnosis of cystic echinococcosis.


[Esophageal cancer metastatic to the kidney: report of a case].
On December 12, 1988, 51-years-old man was admitted to our clinic with asymptomatic gross hematuria. He had been undergone total esophagectomy for esophageal cancer in the surgery service of our hospital on June 22, 1987, and histopathological diagnosis was squamous cell carcinoma, Stage III, a2, n(-), m0, pl0, ly(+), V(+). X-ray CT revealed a irregular, obscure bordered tumor image in the left kidney and angiography showed a hypovascular tumor. On December 20, nephrectomy was performed. Histologically, it proved to be squamous cell carcinoma metastasized from esophageal cancer. The present case is the 11th of those cases which have been clinically diagnosed as renal metastasis of esophageal cancer in Japan. An extremely small number of clinically reported cases compared with autopsy cases are thought to be ascribable to scarce detectability while living of such metastasis, but not to its rare occurrence. The coming diagnostic improvement may well make such case more and more increasing.


Synergistic role of E1A-binding proteins and tissue-specific transcription factors in differentiation.
In this review, the complex relationship between tissue-specific transcription factors and genes regulating cell cycle is taken into account. Both E1-A binding proteins belonging to the family of the retinoblastoma gene product and the CBP/p300 coactivator of transcription interact physically and functionally with tissue-specific transcription factor. The relationship between these two classes of molecules regulates cell fate in differentiating cells, deciding whether cells continue to replicate, undergo apoptosis or terminally differentiate. We provide here an update on the recent advances in this field and some models of interaction between E1A binding protein and tissue-specific transcription factors.


Osteochondroma of the atlas: a case report.
An extremely rare case of osteochondroma arising from the right lateral mass of an atlas was successfully treated by a complete removal through an oblique high cervical incision coupled with a transection of the underlying sternocleidomastoid muscle and careful freeing and retraction of the adjacent vital neurovascular structures.


Increased retinoic acid metabolism following 3,3',4,4',5,5'-hexabromobiphenyl injection.
Young male Wistar rats received single i.p. injections of 3,3',4,4',5,5'-hexabromobiphenyl. In rats dosed with 40 mg/kg, food consumption and growth as well as liver retinol and retinyl palmitate concentrations decreased, while serum retinol and liver weight increased within 28 days following the injection. In rats receiving a 20-mg/kg dose, food consumption, growth, liver weight, and serum retinol were not affect, although liver retinol and retinyl palmitate concentrations declined to 23 and 21% of their respective control values. Vitamin A metabolism was studied in liver microsomes prepared from rats sacrificed 7 days after the 20-mg/kg injection. The rate of retinoic acid hydroxylation via the cytochrome P-450 system to 4-hydroxyretinoic acid plus the subsequent oxidation to 4-ketoretinoic acid was significantly elevated. Retinoic acid conjugation by UDP-glucuronyl transferase was also significantly increased. These changes corresponded with increased activities of cytochrome P-450-dependent aryl hydrocarbon hydroxylase and UDP-glucuronyltransferase conjugation of p-nitrophenol. These results provide a direct link between enzyme induction due to xenobiotics and specific steps in the vitamin A metabolic pathway.


The role of radiotherapy in the local management of dermatofibrosarcoma protuberans. Soft Tissue Tumours Working Group.
Dermatofibrosarcoma protuberans (DFSP), a fibrohistiocytic tumour of intermediate malignancy, has a strong tendency to recur locally. Wide local excision is the recommended treatment modality. A retrospective analysis was performed on 38 consecutive DFSP patients presenting to The Netherlands Cancer Institute, to define the role of radiotherapy. Of the 21 patients treated surgically (all with negative resection margins) seven recurred, a local control probability of 67%. Combined modality treatment was given to 17 patients. Prior to radiotherapy, these patients experienced 33 occurrences of DFSP, but after irradiation only three recurrences were seen, a local control probability of 82%. These results are in keeping with the recent literature where increasing value is being given to both adjuvant and curative radiotherapy in the local management of DFSP. We recommend radiotherapy in DFSP patients where repeated surgery may cause mutilation or functional impairment.


Outcomes in rheumatoid arthritis patients treated with abatacept: a UK multi-centre observational study.
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that causes chronic synovitis, resulting in progressive joint destruction and functional disability and affects approximately 400,000 people in the UK. This real-world study aimed to describe the characteristics, treatment patterns and clinical outcomes of patients who received abatacept in UK clinical practice. This was a multi-centre, retrospective, observational study of patients with RA treated with abatacept at four UK centres between 01 January 2013 and 31 December 2017. Data were collected from medical records of each patient from the index date (date of first bDMARD initiation) until the most recent visit, death or end of study (31 December 2017). In total, 213 patients were included in the study. Patients received up to eight lines of therapy (LOTs). Treatment with abatacept, or any other bDMARD, was associated with reductions in DAS28-ESR and DAS28-CRP scores at 6 and 12 months. The distribution of EULAR responses (good/moderate/no response) tended to be more favourable for patients when receiving abatacept than when receiving other bDMARDs (22.8%/41.3%/35.9% versus 16.6%/41.4%/42.1% at 6 months, and 27.9%/36.1%/36.1% versus 21.2%/34.5%/44.2% at 12 months). Patients receiving abatacept at LOT1 (n = 68) spent significantly longer on treatment compared with patients receiving other bDMARDs (53.4 vs. 17.4 months; p< 0.01); a similar trend was observed for LOT2. Among patients who discontinued after 6 months, a greater proportion experienced infection requiring antibiotics when receiving other bDMARDs compared to those receiving abatacept. RA patients who received bDMARDs, including abatacept, experienced reduced disease activity. When receiving abatacept as first or second line of therapy, patients persisted with treatment significantly longer than those receiving other bDMARDs.


A strategy for extending the applicability of a validated plasma calibration curve to quantitative measurements in multiple tissue homogenate samples: a case study from a rat tissue distribution study of JI-101, a triple kinase inhibitor.
A general practice in bioanalysis is that, whatever the biological matrix the analyte is being quantified in, the validation is performed in the same matrix as per regulatory guidelines. In this paper, we are presenting the applicability of a validated LC-MS/MS method in rat plasma for JI-101, to estimate the concentrations of JI-101 in various tissues that were harvested in a rat tissue distribution study. A simple protein precipitation technique was used to extract JI-101 and internal standard from the tissue homogenates. The recovery of JI-101 in all the matrices was found to be >70%. Chromatographic separation was achieved using a binary gradient using mobile phase A (acetonitrile) and B (0.2% formic acid in water) at a flow rate of 0.30 mL/min on a Prodigy ODS column with a total run time of 4.0 min. The MS/MS ion transitions monitored were 466.1 → 265 for JI-101 and 180.1 → 110.1 for internal standard. The linearity range was 5.02-4017 ng/mL. The JI-101 levels were quantifiable in the various tissue samples harvested in this study. Therefore, the use of a previously validated JI-101 assay in plasma circumvented the tedious process of method development/validation in various tissue matrices.


Relationship between motivation instability and type of motivation level in University learning based on self-determination theory: A cross-lagged panel model.
In this study, we used a longitudinal survey of two time-points to investigate the relationship between motivation instability and type of motivation level toward university learning using a cross-lagged panel model. We measured four types of motivation level based on self-determination theory. A total of 127 Japanese students from two universities participated in two longitudinal surveys; their data were used in the analysis. We investigated the relationship between motivation instability and motivation level by employing the cross-lagged panel model, and found that intrinsic regulation at Time 1 was positively related to the instability of motivation at Time 2, while identified regulation at Time 1 was negatively related to instability of motivation at Time 2. These results indicate that two processes may exist: one where instability of motivation increases depending on the level of motivation, and one where it decreases. Moreover, instability of motivation at Time 1 was positively related to the identified regulation and introjected regulation at Time 2, although the values of the path coefficients were very small. Finally, instability of motivation at Time 1 was positively related to the instability of motivation at Time 2. Based on the results of this study, we discuss the relationship between motivation level and instability in university learning.


Synthesis of Sorption Materials from Low Grade Titanium Raw Materials.
In this paper, a universal technology is proposed for processing low-titanium mineral raw material-apatite-nepheline ore waste, including its treatment with sulfuric or hydrochloric acid in a two-stage mode with a sequential increase in the concentration. This technique allowed us to remove nepheline and apatite in the first stage and achieve a titanium mineral content of TiO2 of more than 30%; in the second stage, we were able to convert the titanium into its precursors-titanyl sulfate monohydrate TiOSO4·H2O and a hybrid rutile-silica composition. The key stage in the sorbent synthesis is the reaction of the precursor with a phosphoric acid solution. The preferred sequence of operations begins with the mechanical activation of the precursor, causing morphological changes in it, and subsequent treatment with phosphoric acid at different concentrations under atmospheric conditions and in an autoclave, accompanied by phase transformations. Conditions for the chemical reactions which regulated the composition and structure of the final product and, accordingly, its sorption activity were found. With the help of XFA, the phase compositions of the sorbents were identified, including the individual crystalline phase α-TiP obtained from TS or the crystalline phase αTi(HPO4)2∙H2O, which is in an amorphous silica matrix obtained from a rutile-silica composition.


Effects of Curcumin Supplementation on Clinical Features and Inflammation, in Migraine Patients: A Double-Blind Controlled, Placebo Randomized Clinical Trial.
Migraine is a prevalent health condition associated with significant pain and disability. Neurogenic inflammation has a key role in migraine pathophysiology. Curcumin is a well-known herb compound with anti-inflammatory function. This study was aimed to evaluate the effects of curcumin supplementation on clinical features, as well as on serum levels of calcitonine gene-related peptide (CGRP) and interleukin-6 (IL-6). This randomized double-blind placebo-controlled clinical trial was carried out on 44 women with migraine, receiving either 500 mg curcumin twice a day or placebo supplements for 8 weeks. Serum CGRP and IL-6 concentration, and clinical symptoms including headache severity, duration and frequency were measured at the baseline and end of study. After 8-week intervention, compared with placebo, curcumin supplementation led to significand reduction in CGRP (P < 0.001), IL-6 (P = 0.041), severity (P = 0.001), and duration of headache (P = 0.007). Headache frequency showed marginal improvement in curcumin group, compared to controls (P = 0.052). Within-analysis indicated significant decrease in CGRP and severity (P < 0.001), frequency (P = 0.014) and duration (P = 0.003) and no significant decrease in IL-6 (P = 0.454), compared to baseline in curcumin group. There were no significant changes in body mass index (BMI), weight, percent body fat (PBF), and percent body muscle (PBM) between the two groups. Curcumin supplementation improved the pro-inflammatory markers and clinical features of migraine headaches and that could be contributed to could be to its anti-inflammatory properties.


Vaccine adverse events: separating myth from reality.
Vaccines have turned many childhood diseases into distant memories in industrialized countries. However, questions have been raised about the safety of some vaccines because of rare but serious adverse effects that have been attributed to them. Pain, swelling, and redness at the injection site are common local reactions to vaccines. Fever and irritability may occur after some immunizations. Currently, no substantial evidence links measles-mumps-rubella vaccine to autism, or hepatitis B vaccine to multiple sclerosis. Thimerosal is being eliminated from routine childhood vaccines because of concerns that multiple immunizations with vaccines containing this preservative could exceed recommended mercury exposures. Family physicians should be knowledgeable about vaccines so that they can inform their patients of the benefits of immunization and any proven risks. If immunization rates fall, the incidence of vaccine-preventable illnesses may rise.


Land use as an effective factor on the occurrence of chromosomal diseases in Brazil.
The occurrence of chromosomal diseases is a worldwide health problem. The use of agrochemicals, urbanization processes, and solar radiation can be predictive factors of the elevated risk of congenital malformations. In this sense, predicting the geographical potential of the distribution of chromosomal diseases has high relevance for public health. This study aimed to describe chromosomal prevalence in Brazil regions, from 2005 to 2015, to model a potential distribution of chromosomal disease occurrence probability associated with land use. We used chromosomal prevalence to model a potential distribution of chromosomal diseases using machine learning algorithms. As the predictors of the models, we used the variables global forest canopy height, distance from the built-up area, and solar radiation. We characterized the predictive areas as potential occurrence of chromosomal diseases by land use and occupation. Georeferenced data of 43,672 karyotypes detected 7,237 cases of chromosomal diseases and used 5,362 to build the models. The models generated were accurate (TSS>0.5). The areas with greater occurrence of chromosomal diseases present a significant association with pasture areas, crops and agroforestry systems, and urbanized areas. This research is the first Brazilian study with this approach that seems promising in predicting the potential distribution of chromosomal diseases. Therefore, it can be an excellent management tool in public health.


In vivo metabolite detection and identification in drug discovery via LC-MS/MS with data-dependent scanning and postacquisition data mining.
An important aspect in drug discovery is the early structural identification of the metabolites of potential new drugs. This gives information on the metabolically labile points in the molecules under investigation, suggesting structural modifications to improve their metabolic stability, and allowing an early safety assessment via the identification of metabolic activation products. From an analytical point of view, metabolite identification still remains a challenging task, especially for in vivo samples, in which they occur at trace levels together with high amounts of endogenous compounds. Here we describe a method, based on LC-ion trap tandem MS, for the rapid in vivo metabolite identification. It is based on the automatic, data-dependent acquisition of multiple product ion MS/MS scans, followed by a postacquisition search, within the entire MS/MS data set obtained, for specific neutral losses or marker ions in the tandem mass spectra of parent molecule and putative metabolites. One advantage of the method is speed, since it requires minimum sample preparation and all the necessary data can be obtained in one chromatographic run. In addition, it is highly sensitive and selective, allowing detection of trace metabolites even in the presence of a complex matrix. As an example of application, we present the studies of the in vivo metabolism of the compound MEN 15916 (1). The method allowed identification of monohydroxy ([M + H](+) = m/z 655), dihydroxy ([M + H](+) = m/z 671), and trihydroxy ([M + H](+) = m/z 687) metabolites, as well as some unexpected biotransformation products such as a carboxylic acid ([M + H](+) = m/z 669), a N-dealkylated metabolite ([M + H](+) = m/z 541), and its hydroxy-analog ([M + H](+) = m/z 557).


Siphonobacter aquaeclarae gen. nov., sp. nov., a novel member of the family 'Flexibacteraceae', phylum Bacteroidetes.
A Gram-negative bacterium, designated P2(T), was isolated from the biofilm developed on the inner surface of an ultrapure cooling water system in a Hungarian power plant and was characterized by a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain P2(T) was affiliated with the family 'Flexibacteraceae' in the phylum Bacteroidetes. Its closest relative was Flectobacillus lacus CL-GP79(T) (88.7 % 16S rRNA gene sequence similarity) followed by Arcicella rosea TW5(T) (86.5 %), Arcicella aquatica NO-502(T) (86.4 %), Flectobacillus roseus GFA-11(T) (86.3 %) and Flectobacillus major DSM 103(T) (85.4 %). Cells of strain P2(T) were facultatively anaerobic, non-motile rods. The major fatty acids were C(16 : 1)ω5c (42.5 %), iso-C(15 : 0) 2-OH (17.2 %), iso-C(17 : 0) 3-OH (16.1 %) and iso-C(15 : 0) (8.5 %). The major menaquinone was MK-7 and the predominant polar lipid was phosphatidylethanolamine. The DNA G+C content was 54.5 mol%. Thus, the phenotypic and genotypic analyses clearly showed that strain P2(T) is considerably different from members of other genera in the family 'Flexibacteraceae'. Based on these results, it is concluded that strain P2(T) represents a novel species in a new genus, for which the name Siphonobacter aquaeclarae gen. nov., sp. nov. is proposed, with type strain P2(T) (=DSM 21668(T) =NCAIM B 02328(T)).


Triterpenoids from Psidium guajava leaves.
Three pentacyclic triterpenoids including one new guajavanoic acid (2) and two known obtusinin (1) and goreishic acid I (3) have been isolated from the leaves of Psidium guajava. The new constituent 2 has been characterized as 2alpha-hydroxy-3beta-p-E-coumaroyloxyurs-12, 18-dien-28-oic acid through 1H-NMR and 13C-NMR (broad band and DEPT). This is the first report of isolation of compound 1 and 3 from the genus Psidium.


[Specific antiepileptic therapy in childhood].
This paper deals with basic rational antiepileptic therapeutic procedures in children with special consideration of numerous specificities which occur in childhood: difficulties in establishing correct syndrome diagnosis, predominantly after the first or first few seizures which makes it difficult to decide about appropriate syndrome-specific therapy in regard to efficacy, mechanism of action and range of antiepileptic action; difficulties in assessment of subjective factors (their adverse effects and recognition of seizures with subjective symptoms), children's vulnerability in regard to drug toxicity; age-specific pharmacokinetics of these drugs. The number of available antiepileptics today is great due to new drugs, but carbamazepine (CBZ) and valproate (VAL) are still basic antiepileptics, although carbamazepine's action is reduced to partial epilepsies. The paper describes range of action of available antiepileptics in regard to classification of epileptic seizures and most frequent epileptic syndromes. Adverse effects of antiepileptic agents depend on the age, so examples of age-dependent adverse effects are given considering conventional and new antiepileptics. It is well known that optimal control of seizures depends not only on correct choice of drug, but also on appropriate dosage; it is necessary to be informed about age-dependent characteristics of clinical pharmacokinetics: resorption, metabolism, elimination and half-life of antiepileptics. Although 70-80% of children may be well treated with monotherapy, 15% of children require combination of 2 or more drugs causing drug interactions in resorption, distribution, metabolism and elimination. Examples of antiepileptic interactions as well as interactions of other drugs and antiepileptics are given. The paper also deals with special importance of the psychosocial aspects of epilepsy. These children are often unaccepted by others, mostly because others are afraid of their disease, which contributes to poor quality of life of these children. Development of intellectual, emotional functions, physical development and socialization, apart from affecting the choice of drug, make epilepsy treatment in children more complex, with special emphasis on mental-hygienic aspects of complete management of children. Only a complex approach to child suffering from epilepsy may provide optimal development, quality of life improvement and complete social integration. Rational therapy of epilepsy in children requires good knowledge not only of age-specific syndromes, clinical pharmacology of anticonvulsants, their efficacy and range of action, but also specificity of their metabolism in children, profile of adverse effects as well as facing numerous nonmedical problems.


Population pharmacokinetics of intravenous amoxicillin in very low birth weight infants.
The population pharmacokinetics of amoxicillin were determined in 40 very premature infants (< or = 32 week gestational age, < 1500 g birth weight) who were receiving intravenous amoxicillin (50 mg/ kg, every 12 h) during the first days after birth. Serum amoxicillin concentrations were measured by HPLC. Clearance (CL) and volume of distribution (Vd) were modeled alone and under the influence of demographic and clinical covariates with a 1-compartment model with first-order elimination. The final population models with influential covariates were: CL(L/h) = 0.0000610 x body weight (g) and CL (L/h) = 0.0000805 x body weight (g), for infants also receiving gentamicin and not receiving gentamicin, respectively; Vd(L) = 0.678. The interpatient standard deviation (SD) for CL was 0.0351 L/h, and for Vd was 0.365 L. The intrapatient variability (SD) among observed and model-predicted serum concentrations was 13.7 mg/L. Evaluation of the predictive performance of this model in another group of infants (n = 16) indicated statistically insignificant bias (p > 0.05) of 3 mg/L among pairs of observed and Bayesian-predicted amoxicillin concentrations. The average population CL was smaller, but the average Vd and terminal half-life (t1/2) were larger than previously reported for healthy adults.


Phospholipase C beta 4 in the medial septum controls cholinergic theta oscillations and anxiety behaviors.
Anxiety is among the most prevalent and costly diseases of the CNS, but its underlying mechanisms are not fully understood. Although attenuated theta rhythms have been observed in human subjects with increased anxiety, no study has been done on the possible physiological link between these two manifestations. We found that the mutant mouse for phospholipase C beta 4 (PLC-beta 4(-/-)) showed attenuated theta rhythm and increased anxiety, presenting the first animal model for the human condition. PLC-beta 4 is abundantly expressed in the medial septum, a region implicated in anxiety behavior. RNA interference-mediated PLC-beta 4 knockdown in the medial septum produced a phenotype similar to that of PLC-beta 4(-/-) mice. Furthermore, increasing cholinergic signaling by administering an acetylcholinesterase inhibitor cured the anomalies in both cholinergic theta rhythm and anxiety behavior observed in PLC-beta 4(-/-) mice. These findings suggest that (1) PLC-beta 4 in the medial septum is involved in controlling cholinergic theta oscillation and (2) cholinergic theta rhythm plays a critical role in suppressing anxiety. We propose that defining the cholinergic theta rhythm profile may provide guidance in subtyping anxiety disorders in humans for more effective diagnosis and treatments.


THE EFFECT OF ENTERAL LACTOFERRIN SUPPLEMENTATION IN PREVENTION OF MORBIDITY ASSOCIATED WITH IMMATURE DIGESTIVE TRACT IN PREMATURE INFANTS: PROSPECTIVE COHORT STUDY.
Premature infants are at high risk for diseases associated with impaired adaptation of the immature digestive tract, such as necrotizing enterocolitis (NEC) or late-onset sepsis (LOS), as well as severe neonatal morbidities associated with these diseases. This study was aimed to evaluate the effectiveness of prophylactic enteral use of bovine lactoferrin for the prevention of severe neonatal diseases in premature infants. The prospective cohort study included 117 premature infants with gestational age (GA) of ≤32 weeks, a birth weight of ≤1,500 g, and an age of ≤72 hours. 27 infants who were receiving enteral feeds were randomized to receive lactoferrin at a dose of 100 mg/day until postmenstrual age (PMA) of 36 weeks or discharge (at least 4 weeks). 90 infants formed the control group and received standard treatment. The primary outcome was the incidence of LOS, the secondary outcomes were the incidence of necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), severe brain damage, bronchopulmonary dysplasia (BPD), overall mortality, as well as the age of achieving full enteral feeds, duration of antibacterial therapy, length of stay in NICU and the total length of hospital stay. Enteral lactoferrin supplementation did not reduce the incidence of LOS (29.6% in the lactoferrin group against 22.7% in the control group; p=0.85), NEC (5.6% vs. 1.8%, respectively; p=0.11) and overall mortality (18.5% vs. 9.1%, respectively; p=0.06), as well as the incidence of severe intraventricular hemorrhages (18.5% vs. 9.8%, respectively; p=0.17), PVL (11.1% vs. 2.2%, respectively; p=0.17) and BPD (14.8% vs. 25.6%, respectively; p = 0.25). Infants receiving lactoferrin were achieving full enteral feeds significantly faster compared to the control group (14 (10-17) days vs. 19 (13-32) days, respectively; p=0.007). The total length of hospital stay of infants with GA ≤28 weeks in the lactoferrin group was significantly shorter compared to the control group (74 (68-89) vs. 98 (83-109) days, respectively; p=0.048). Enteral lactoferrin supplementation at a dose of 100 mg/day does not affect the main morbidity and mortality of prematurely born infants with GA ≤ 32 weeks but may facilitate significantly faster achievement of the full enteral feeds and the reduction of the length of hospital stay in the tiniest infants.


Synchronicity and the meaning-making psyche.
This paper contrasts Jung's account of synchronicity as evidence of an objective principle of meaning in Nature with a view that emphasizes human meaning-making. All synchronicities generate indicative signs but only where this becomes a 'living symbol' of a transcendent intentionality at work in a living universe does synchronicity generate the kind of symbolic meaning that led Jung to posit the existence of a Universal Mind. This is regarded as a form of personal, experiential knowledge belonging to the 'imaginal world of meaning' characteristic of the 'primordial mind', as opposed to the 'rational world of knowledge' in which Jung attempted to present his experiences as if they were empirically and publicly verifiable. Whereas rational knowledge depends on a form of meaning in which causal chains and logical links are paramount, imaginal meaning is generated by forms of congruent correspondence-a feature that synchronicity shares with metaphor and symbol-and the creation of narratives by means of retroactive organization of its constituent elements.


Using social marketing to manage population health performance.
Population health can be affected by implementing pay-for-performance measures with key players. From a social marketing perspective, people (both consumers and managers) have choices and will do what they perceive enhances their own self-interest. The bottom-up focus of social marketing begins with an understanding of the people whose behaviors are targeted. Desired behavior results when people perceive that they will get more value than the cost of behaving and when the resulting offer is perceived to be better than what is obtainable through alternative choices. Incentives should be offered to consumers; managers should receive motivation for their own behavior and understand how to motivate relevant consumers. Pay can be monetary or nonmonetary, tangible or intangible. Everyone is paid for performance. Some are paid well enough to behave as desired; others are offered a poor rate of pay and choose not to behave.


A Disposable Microfluidic Device with a Screen Printed Electrode for Mimicking Phase II Metabolism.
Human metabolism is investigated using several in vitro methods. However, the current methodologies are often expensive, tedious and complicated. Over the last decade, the combination of electrochemistry (EC) with mass spectrometry (MS) has a simpler and a cheaper alternative to mimic the human metabolism. This paper describes the development of a disposable microfluidic device with a screen-printed electrode (SPE) for monitoring phase II GSH reactions. The proposed chip has the potential to be used as a primary screening tool, thus complementing the current in vitro methods.


Perspectives on the Mental Health Act 2014 (Vic).
This article will consider the potential impact of Victoria's new Mental Health Act 2014 (Vic) from the perspectives of consumers, careers and members of the treating team. This article will examine how some of the more drastic legal reforms will impact clinical processes, procedures and decision making. The new Act takes significant steps towards empowering consumers. However, its practical application will take some time to appraise. Only time will reveal how the Mental Health Tribunal handles its newfound powers, whether consumers will benefit from a more collaborative approach to clinical decision making and ultimately whether the Act will empower consumers.


Delayed osseous metastasis from low-grade endometrial stromal sarcoma: Uncommon occurrence deserving recognition.
Despite excellent prognosis, low-grade endometrial stromal sarcoma (ESS) is notorious for late recurrence even in stage I disease. Bone metastases are distinctly rare and only six cases have so far been reported. Two patients presented with back pain due to spinal metastatic low-grade ESS after 15 and 9 years free of disease after resection of the stage 1 primary uterine tumor. Plain radiograph showed an ivory first lumbar vertebra in the first patient and an osteolytic lesion involving the second thoracic vertebra in the second. In both cases, magnetic resonance imaging showed vertebral tumor with intra-spinal extension and spinal cord compression; biopsy confirmed the diagnosis of metastatic low-grade ESS. The first patient received palliative radiotherapy and chemotherapy while the second underwent surgical decompression followed by adjuvant radiotherapy and chemotherapy. The neurologic symptoms in both patients returned 12 months afterwards and progressed relentlessly despite adjuvant chemotherapy and radiotherapy. The first patient developed multiple bone and lung metastasis, culminating in death 44 months after recurrence. While surviving at 24 months from recurrent disease, the second became paraplegic with double incontinence and was wheelchair bound. Delayed osseous metastatic low-grade ESS, although uncommon, deserves recognition given the predilection for spine as the site of involvement. In such a location, where complete surgical removal is notoriously difficult, if not impossible, the prognosis of spinal metastatic low-grade ESS appears grave with considerable morbidity and mortality.