Preserved acoustic hearing in cochlear implantation improves speech perception.
With improved surgical techniques and electrode design, an increasing number of cochlear implant (CI) recipients have preserved acoustic hearing in the implanted ear, thereby resulting in bilateral acoustic hearing. There are currently no guidelines, however, for clinicians with respect to audiometric criteria and the recommendation of amplification in the implanted ear. The acoustic bandwidth necessary to obtain speech perception benefit from acoustic hearing in the implanted ear is unknown. Additionally, it is important to determine if, and in which listening environments, acoustic hearing in both ears provides more benefit than hearing in just one ear, even with limited residual hearing. The purposes of this study were to (1) determine whether acoustic hearing in an ear with a CI provides as much speech perception benefit as an equivalent bandwidth of acoustic hearing in the nonimplanted ear, and (2) determine whether acoustic hearing in both ears provides more benefit than hearing in just one ear. A repeated-measures, within-participant design was used to compare performance across listening conditions. Seven adults with CIs and bilateral residual acoustic hearing (hearing preservation) were recruited for the study. Consonant-nucleus-consonant word recognition was tested in four conditions: CI alone, CI + acoustic hearing in the nonimplanted ear, CI + acoustic hearing in the implanted ear, and CI + bilateral acoustic hearing. A series of low-pass filters were used to examine the effects of acoustic bandwidth through an insert earphone with amplification. Benefit was defined as the difference among conditions. The benefit of bilateral acoustic hearing was tested in both diffuse and single-source background noise. RESULTS were analyzed using repeated-measures analysis of variance. Similar benefit was obtained for equivalent acoustic frequency bandwidth in either ear. Acoustic hearing in the nonimplanted ear provided more benefit than the implanted ear only in the wideband condition, most likely because of better audiometric thresholds (>500 Hz) in the nonimplanted ear. Bilateral acoustic hearing provided more benefit than unilateral hearing in either ear alone, but only in diffuse background noise. RESULTS support use of amplification in the implanted ear if residual hearing is present. The benefit of bilateral acoustic hearing (hearing preservation) should not be tested in quiet or with spatially coincident speech and noise, but rather in spatially separated speech and noise (e.g., diffuse background noise).


Exploring the Versatility of the Amidation of Aryl Acid Fluorides using the Germylamines R3 GeNMe2.
The formation of amide bonds is an important process since this linkage is an essential component in proteins, pharmaceuticals, and other medicinally and biologically significant molecules. Recently, it was demonstrated that germylamines R3 GeNR'2 were useful reagents for the conversion of acid fluorides to amides. This transformation occurs readily at room temperature and has a low activation energy. In the present study, the versatility of this amidation reaction with aryl acid fluorides is investigated. A series of thirteen acid fluorides with various substituents on the aromatic ring were reacted with the germylamine Ph3 GeNMe2 and twelve of these were converted to the corresponding amides in high yields, the exception being 1,4-benzenedicarbonyl difluoride. The germylamines Bun 3 GeNMe2 and Pri 3 GeNMe2 also could be used for this interconversion, and both of these species successfully converted 1,4-benzenedicarbonyl difluoride to the corresponding amide. In addition, the crystal structure of Ph3 GeNMe2 is reported. This represents one of only three crystallographically characterized germylamines. The synthesis and 19 F NMR characterization of three fluorogermanes R3 GeF (R=Bun , Pri , and Mes) are also reported herein.


Induction of prodigiosin biosynthesis after shift-down in temperature of nonproliferating cells of Serratia marcescens.
Nonpigmented bacteria obtained by growth of Serratia marcescens at 38 C synthesized prodigiosin at 25 C if certain individual amino acids were added to cultures of nonproliferating cells. In order of effectiveness, the amino acids were: DL-histidine, L-proline, L-hydroxyproline, DL-alanine, L-alanine, DL-aspartic acid, D-alanine, DL-proline, L-serine, L-ornithine, L-glutamic acid, and D-proline. DL-Histidine at its optimal concentration (20 mg/ml) induced formation of prodigiosin (198 mug of prodigiosin per mg of bacterial protein) after incubation of cultures for 54 hr. Lower concentrations (10 mg/ml) of the other amino acids usually were optimum but less prodigiosin was synthesized, and the maximal amount of pigment occurred between 36 and 48 hr. DL-Methionine was not effective alone but at a low concentration (40 mug/ml) enhanced and accelerated biosynthesis of prodigiosin in the presence of other suitable amino acids. Addition of 2 mg of L-proline per ml at 0 hr induced formation of only 30 mug of prodigiosin after incubation for 42 hr, but addition at 36 hr of 5 mg more of L-proline per ml increased synthesis to 120 mug at 42 hr. Again, DL-methionine markedly augmented prodigiosin biosynthesis in these cultures. Synthesis of prodigiosin ceased if cultures were shifted from 25 to 38 C. Prodigiosin biosynthesis by the nonproliferating cells was maximum when cultures were aerated, the amount of bacterial protein was about 2.0 mg/ml, and amino acids were added at 0 hr. Bacteria synthesized prodigiosin most efficiently when they were harvested from aerated cultures grown at 38 C for 24 hr in a complete medium in a fermentor.


Effect of echinacoside on kidney fibrosis by inhibition of TGF-β1/Smads signaling pathway in the db/db mice model of diabetic nephropathy.
Kidney fibrosis and renal tubular epithelial-to-mesenchymal transition (EMT) are the main pathological changes of diabetic nephropathy (DN), which eventually leads to end-stage renal disease. Previous studies have suggested that echinacoside (ECH) is antifibrotic in the liver. However, the effect of ECH on kidney fibrosis in DN and its mechanisms are unknown. This study was performed to explore the effect of ECH on kidney fibrosis and also the molecular mechanisms of ECH in a db/db mice model of DN. Our results showed that, relative to db/db mice, the mice in the ECH group had an improved general state and reduced blood glucose and 24-hour urinary protein levels. The deterioration of renal function was delayed due to treatment with ECH. We also observed that ECH can improve histopathological findings in the kidneys of db/db mice, including collagen deposition, mesangial cell and mesangial matrix hyperplasia, basement membrane thickening, and podocyte reduction. Moreover, ECH inhibited the TGF-β1/Smads signaling pathway, downregulated fibronectin (FN), collagen IV, and alpha-smooth muscle actin (α-SMA) levels, and upregulated E-cadherin level in the db/db mice model of DN. Our findings indicate that ECH has a therapeutic effect on DN, including the inhibition of renal tubular EMT and kidney fibrosis. Furthermore, ECH inhibits kidney fibrosis through regulation of the TGF-β1/Smads signaling pathway.


A supramolecular hydrogel prepared from a thymine-containing artificial nucleolipid: study of assembly and lyotropic mesophases.
An artificial nucleolipid containing thymine, a triazole-ring, and phosphatidylcholine (TTPC) moieties was prepared by copper catalyzed azide alkyne cycloaddition (CuAAC) under aqueous conditions. The resulting TTPC molecules assembled in situ into a fibrous aggregation. The study of the TTPC fiber assembly using XRD and NMR spectroscopy revealed that the formation of fibers was driven by the unique combination of the lipid and nucleobase moieties in the structure of TTPC. At a critical TTPC concentration, entanglement of the fibers resulted in the formation of a supramolecular hydrogel. Investigation of the lyotropic mesophases in the TTPC supramolecular hydrogel showed the presence of multiple phases including two liquid crystal phases (i.e., nematic and lamellar), which have a certain degree of structural order and are promising templates for constructing functional biomaterials.


Advanced Methods for Dose and Regimen Finding During Drug Development: Summary of the EMA/EFPIA Workshop on Dose Finding (London 4-5 December 2014).
Inadequate dose selection for confirmatory trials is currently still one of the most challenging issues in drug development, as illustrated by high rates of late-stage attritions in clinical development and postmarketing commitments required by regulatory institutions. In an effort to shift the current paradigm in dose and regimen selection and highlight the availability and usefulness of well-established and regulatory-acceptable methods, the European Medicines Agency (EMA) in collaboration with the European Federation of Pharmaceutical Industries Association (EFPIA) hosted a multistakeholder workshop on dose finding (London 4-5 December 2014). Some methodologies that could constitute a toolkit for drug developers and regulators were presented. These methods are described in the present report: they include five advanced methods for data analysis (empirical regression models, pharmacometrics models, quantitative systems pharmacology models, MCP-Mod, and model averaging) and three methods for study design optimization (Fisher information matrix (FIM)-based methods, clinical trial simulations, and adaptive studies). Pairwise comparisons were also discussed during the workshop; however, mostly for historical reasons. This paper discusses the added value and limitations of these methods as well as challenges for their implementation. Some applications in different therapeutic areas are also summarized, in line with the discussions at the workshop. There was agreement at the workshop on the fact that selection of dose for phase III is an estimation problem and should not be addressed via hypothesis testing. Dose selection for phase III trials should be informed by well-designed dose-finding studies; however, the specific choice of method(s) will depend on several aspects and it is not possible to recommend a generalized decision tree. There are many valuable methods available, the methods are not mutually exclusive, and they should be used in conjunction to ensure a scientifically rigorous understanding of the dosing rationale.


Effect of acute modafinil ingestion on cognitive and physical performance following mental exertion.
Modafinil is a psychostimulant that has been shown to enhance cognitive and physical performance. Given its long half-life, it may provide operational advantages if it can improve tolerance to the deleterious effects of prolonged mental exertion. Physically active males (n = 13, 23 ± 4 years, peak oxygen consumption 45.3 ± 3.2 ml kg-1 min-1 ) took part in a placebo controlled, double-blind randomised crossover study to investigate if modafinil could improve cognitive and physical performance following a prolonged period of mental exertion. Overall modafinil improved performance on a task of executive function over time (p = .023; η2 = 0.376) but did not improve subsequent physical endurance performance (mean difference 2.3 ± 11.5%, p = .50), despite improvement in 10 out of the 13 participants. Task demand was reported as lower with modafinil, although perceptual measures of fatigue and motivation did not consistently improve. Heart rate during submaximal exercise was higher (134 ± 11 vs. 119 ± 14 bpm, p < .001), and sleep was reduced (5.5 ± 1.4 vs. 7.5 ± 1.4 hr, p < .001) and less efficient (64 ± 13 vs. 83 ± 9%, p < .001) compared with placebo. Operationally, modafinil may offer advantages given the established longer half-life than other psychostimulants, despite the variable response. The impact of higher heart rates and disrupted sleep on performance must also be considered.


Giant magnetoresistance sensors. 1. Internally calibrated readout of scanned magnetic arrays.
This paper describes efforts aimed at setting the stage for the application of giant magnetoresistance sensor (GMRs) networks as readers for quantification of biolytes selectively captured and then labeled with superparamagnetic particles on a scanned chip-scale array. The novelty and long-range goal of this research draws from the potential development of a card-swipe instrument through which an array of micrometer-sized, magnetically tagged addresses (i.e., a sample stick) can be interrogated in a manner analogous to a credit card reader. This work describes the construction and testing of a first-generation instrument that uses a GMR sensor network to read the response of a "simulated" sample stick. The glass sample stick is composed of 20-nm-thick films of permalloy that have square or rectangular lateral footprints of up to a few hundred micrometers. Experiments were carried out to gain a fundamental understanding of the dependence of the GMR response on the separation between, and planarity of, the scanned sample stick and sensor. Results showed that the complex interplay between these experimentally controllable variables strongly affect the shape and magnitude of the observed signal and, ultimately, the limit of detection. This study also assessed the merits of using on-sample standards as internal references as a facile means to account for small variations in the gap between the sample stick and sensor. These findings were then analyzed to determine various analytical figures of merit (e.g., limit of detection in terms of the amount of magnetizable material on each address) for this readout strategy. An in-depth description of the first-generation test equipment is presented, along with a brief discussion of the potential widespread applicability of the concept.


Differential cellular localization of DNA gyrase and topoisomerase IB in response to DNA damage in Deinococcus radiodurans.
Topoisomerases are crucial enzymes in genome maintenance that modulate the topological changes during DNA metabolism. Deinococcus radiodurans, a Gram-positive bacterium is characterized by its resistance to many abiotic stresses including gamma radiation. Its multipartite genome encodes both type I and type II topoisomerases. Time-lapse studies using fluorescently tagged topoisomerase IB (drTopoIB-RFP) and DNA gyrase (GyrA-RFP) were performed to check the dynamics and localization with respect to DNA repair and cell division under normal and post-irradiation growth conditions. Results suggested that TopoIB and DNA gyrase are mostly found on nucleoid, highly dynamic, and show growth phase-dependent subcellular localization. The drTopoIB-RFP was also present at peripheral and septum regions but does not co-localize with the cell division protein, drFtsZ. On the other hand, DNA gyrase co-localizes with PprA a pleiotropic protein involved in radioresistance, on the nucleoid during the post-irradiation recovery (PIR). The topoIB mutant was found to be sensitive to hydroxyurea treatment, and showed more accumulation of single-stranded DNA during the PIR, compared to the wild type suggesting its role in DNA replication stress. Together, these results suggest differential localization of drTopoIB-RFP and GyrA-RFP in D. radiodurans and their interaction with PprA protein, emphasizing the functional significance and role in radioresistance.


Absorbed dose rate conversion coefficients for reference terrestrial biota for external photon and internal exposures.
The paper describes dosimetric models that allow the estimation of average radiation exposures to terrestrial biota due to environmental sources in the soil as well as internal uniform distributions of radionuclides. Simple three-dimensional phantoms for 13 faunal reference organisms are specified. The calculation of absorbed dose per unit source strength for these targets is based on photon and electron transport simulations using the Monte Carlo method. The presented absorbed dose rate conversion coefficients are derived for terrestrial reference species. This allows the assessment of internal exposure as well as external photon exposure depending on the nuclide, habitat, target size and environmental contamination. To enable the application of specific radiation weighting factors for alpha-, low energy beta- (E0 < 10 keV), beta- and gamma-radiations, their partial contributions to the total absorbed dose are provided separately. The coefficients for external exposure are listed for organisms living above the ground for an infinite plane source 3 mm deep in soil, as well as for a horizontally infinite volume source uniformly distributed to a depth of 10 cm. Furthermore, the coefficients are also presented for organisms living in a contaminated 50 cm thick soil layer. A multi-layer canopy model for plants is also described. The conversion coefficients are given for 3H, 14C, 40K, 36Cl, 59,63Ni, 89,90Sr, 94Nb, 99Tc, 106Ru, 129,131I, 134,135,137Cs, 210Po, 210Pb, 226Ra, 227,228,230,231,232,234Th, 234,235,238U, 238,239,240,241Pu, 241Am, 237Np and 242,243,244Cm, together with their


A Case of Superficial Papular Neuroma: A Rare Neural Neoplasm.
A case of 67-year-old male patient with superficial papular neuroma (SPN) on the occiput is reported. This is the second report of SPN and the first with clinical images. Histologically, in the superficial dermis and periadnexa, the specimen exhibits a nodule of bland spindle cells with an S-shaped and spindle nucleus, surrounded by eosinophilic collagen fibers and scattered mast cells, which forms focally peripheral nerve-like structures. Lichen simplex chronicus-like changes are observed. Immunostaining result revealed that the tumor cells are positive for S-100, neurofilament, collagen IV, and CD34 but negative for Melan A, epithelial membrane antigen, and glial fibrillary acidic protein. Histological differential diagnosis includes prurigo nodularis, neurotized nevus, benign peripheral nerve sheath tumor, such as neurofibroma or schwannoma, a type of neuroma, such as traumatic neuroma, mucosal neuroma, and palisaded encapsulated neuroma, or a type of neural hamartoma. A careful histological investigation will enable dermatopathologists to make a diagnosis of SPN.


2-D companding for noise reduction in strain imaging.
Companding is a signal preprocessing technique for improving the precision of correlation-based time delay measurements. In strain imaging, companding is applied to warp 2-D or 3-D ultrasonic echo fields to improve coherence between data acquired before and after compression. It minimizes decorrelation errors, which are the dominant source of strain image noise. The word refers to a spatially variable signal scaling that compresses and expands waveforms acquired in an ultrasonic scan plane or volume. Temporal stretching by the applied strain is a single-scale (global), 1-D companding process that has been used successfully to reduce strain noise. This paper describes a two-scale (global and local), 2-D companding technique that is based on a sum-absolute-difference (SAD) algorithm for blood velocity estimation. Several experiments are presented that demonstrate improvements in target visibility for strain imaging. The results show that, if tissue motion can be confined to the scan plane of a linear array transducer, displacement variance can be reduced two orders of magnitude using 2-D local companding relative to temporal stretching.


O'nyong-nyong fever in south-central Uganda, 1996-1997: description of the epidemic and results of a household-based seroprevalence survey.
O'nyong-nyong (ONN) fever, an acute, nonfatal illness characterized by polyarthralgia, is caused by infection with a mosquito-borne central African alphavirus. During 1996-1997, south-central Uganda experienced the second ONN fever epidemic ever recognized. During January and early February 1997, active case-finding and a household cluster serosurvey were conducted in two affected and two comparison areas. A confirmed case was defined as an acute febrile illness with polyarthralgia occurring within the previous 9 months plus serologic confirmation or isolation of ONN virus from blood. In affected (n=129) and comparison (n=115) areas, the estimated infection rates were 45% and 3%, respectively, and the estimated attack rates were 29% and 0%, respectively, for an apparent:inapparent infection ratio of nearly 2 in affected areas. In villages sampled near Lake Kijanebalola, Rakai District, the estimated infection and attack rates were 68% and 41%, respectively, and 55% of sampled households had >/=1 case of ONN fever. In conclusion, this epidemic was focused near lakes and swamps, where it was associated with high infection and attack rates.


Drosophila EHBP1 regulates Scabrous secretion during Notch-mediated lateral inhibition.
Notch signaling is an evolutionarily conserved pathway that plays a central role in numerous developmental and disease processes. The versatility of the Notch pathway relies on the activity of context-dependent regulators. These include rab11, sec15, arp3 and Drosophila EHBP1 (dEHBP1), which control Notch signaling and cell fate acquisition in asymmetrically dividing mechanosensory lineages by regulating the trafficking of the ligand Delta. Here, we show that dEHBP1 also controls the specification of R8 photoreceptors, as its loss results in the emergence of supernumerary R8 photoreceptors. Given the requirements for Notch signaling during lateral inhibition, we propose that dEHBP1 regulates distinct aspects of Notch signaling in different developmental contexts. We show that dEHBP1 regulates the exocytosis of Scabrous, a positive regulator of Notch signaling. In conclusion, dEHBP1 provides developmental versatility of intercellular signaling by regulating the trafficking of distinct Notch signaling components.


Quality of death in patients in advanced chronic liver disease and cancer patients managed by gastroenterologists in Portugal: are we doing it right?
The incidence of chronic progressive diseases is rising and investment on quality of death and dying is of utmost importance to minimize physical and emotional suffering. There is still a gap in palliative care (PC) between patients with cancer and those with advanced chronic liver disease (ACLD). Our objectives were to characterize clinical attitudes and therapeutic interventions and to evaluate the differences in end-of-life care between inpatients with cancer and ACLD under gastroenterology care. Retrospective cohort study, including patients with cancer or ACLD who died in a Gastroenterology department between 2012 and 2021. Demographic characteristics, clinical and endoscopic procedures and symptom control were compared between the groups. From 150 patients, 118 (78.7%) died with cancer and 32 (21.3%) died from ACLD without concomitant hepatocellular carcinoma. ACLD patients were more frequently male (P = 0.001) and younger (P = 0.001) than patients with cancer. Median time of hospitalization in the last month of life was 16 days for both groups. Discussion of prognosis with the patient was more frequent for cancer patients (35.6% versus 3.2%, P < 0.001). Referral to PC occurred in 18.8% and 61% of the patients with ACLD and cancer respectively (P < 0.001). Endoscopic procedures were performed in half of the patients and were more likely to be unsuccessful in those with cancer. Clinical decisions were different between groups in terms of PC access and discussion of prognostic with the patient. It is urgent to define and implement metrics of quality of death and dying to prevent potentially inappropriate treatment.


[Clinical efficacy of antihypertensive therapy of pregnant women with arterial hypertension with long acting nifedipine and bisoprolol].
Study aim was assessment of clinical efficacy of mono therapy with nifedipine SR/GITS and combination of nifedipine SR/GITS and bisoprolol as well as investigation of functional state of sympathoadrenal system (SAS) in pregnant women with arterial hypertension. Examination and treatment with nifedipine SR/GITS 30 mg/day and bisoprolol 2,5 - 5 mg/day was carried out in 21 patients with stage II hypertensive disease (HD) during trimester II of pregnancy. Initially all women including 20 practically healthy pregnant women (control group) had elevation of functional activity of SAS what was determined by high values of b-adrenoception of membranes of erythrocytes. In patients with stage II HD this parameter significantly exceeded that of control group. Administration of antihypertensive drugs for 3 weeks promoted significant lowering of all parameters of 24 hour blood pressure monitoring down to optimal level, lessening of pathological types of 24 hour blood pressure profile and lowering of functional activity of SAS.


Mitochondria Participate in Chemoresistance to Cisplatin in Human Ovarian Cancer Cells.
Ovarian cancer is an aggressive disease that affects about 300,000 patients worldwide, with a yearly death count of about 185,000. Following surgery, treatment involves adjuvant or neoadjuvant administration of taxane with platinum compounds cisplatin or carboplatin, which alkylate DNA through the same chemical intermediates. However, although platinum-based therapy can cure patients in a number of cases, a majority of them discontinues treatment owing to side effects and to the emergence of resistance. In this study, we focused on resistance to cisplatin and investigated whether metabolic changes could be involved. As models, we used matched pairs of cisplatin-sensitive (SKOV-3 and COV-362) and cisplatin-resistant (SKOV-3-R and COV-362-R) human ovarian carcinoma cells that were selected in vitro following exposure to increasing doses of the chemotherapy. Metabolic comparison revealed that resistant cells undergo a shift toward a more oxidative metabolism. The shift goes along with a reorganization of the mitochondrial network, with a generally increased mitochondrial compartment. More functional mitochondria in cisplatin-resistant compared with cisplatin-sensitive cells were associated to enzymatic changes affecting either the electron transport chain (SKOV-3/SKOV-3-R model) or mitochondrial coupling (COV-362/COV-362-R model). Our findings further indicate that the preservation of functional mitochondria in these cells could be due to an increased mitochondrial turnover rate, suggesting mitophagy inhibition as a potential strategy to tackle cisplatin-resistant human ovarian cancer progression. IMPLICATIONS: Besides classical mechanisms related to drug efflux and target modification, we report that preserving functional mitochondria is a strategy used by human ovarian cancer cells to resist to cisplatin chemotherapy.


Hypotensive response to captopril: a potential pitfall of scintigraphic assessment for renal artery stenosis.
A characteristic pattern seen on captopril renography is described that is due to systemic hypotensive response. Most patients with these findings on captopril renography do not receive renal artery angiograms in our clinic because it is usually recognized. However, this pattern has received little attention in the medical literature and may be misinterpreted as being due to physiologically significant renal artery hypertension. Over the last 3 y, renal artery angiograms were performed on three patients with systemic hypotensive response pattern on captopril renography. This allowed a unique opportunity to correlate the results of the captopril renogram with the renal artery angiograms in this patient population. Captopril renography was performed with a glomerular filtration agent, diethylenetriamine pentaacetic acid (DTPA), and a tubular agent, o-iodohipurate (OIH). Renal artery angiograms showed no evidence of renal artery stenosis in three patients with systemic hypotensive response pattern on captopril renography. Systemic hypotension on captopril renograms results in preserved uptake of both DTPA and OIH and hyperconcentration in the cortex and collecting system. The systemic hypotensive response pattern seen on captopril renography is a distinctive pattern that does not represent physiologically significant renal artery stenosis.


Factors influencing fungal and aflatoxin levels in Turkish hazelnuts (Corylus avellana L.) during growth, harvest, drying and storage: a 3-year study.
The levels aflatoxins in Turkish hazelnuts have been monitored over a 3-years period (2002-2004). Periodical sampling was made in 72 different orchards at different locations representative of the hazelnut-growing areas and post-harvest applications. Various parameters (aflatoxins, water activity, moulds) were analysed and environmental conditions (temperature and relative humidity) recorded during growing and at different stages of harvest and post-harvest processing, involving three different harvesting methods (collection in nets, from the ground, etc.) and four drying techniques (traditional sun-drying, mechanical drying, etc.). Fungal and aflatoxin analyses (HPLC) showed no significant difference except between samples which had been in contact with the ground and those which had not (at 95% confidence level). Aflatoxins levels from the orchard recorded a maximum of 0.77+/-0.08 ng g(-1) from a total of 1624 samples. Regarding harvesting and post-harvest processes, the only application where aflatoxins were detected was in samples which had been in direct contact with the ground (max. 3.18+/-0.03 ng g(-1)). Aflatoxin formation was low during storage (max. 0.34+/-0.003 ng g(-1)). As a result of mycological studies, a total of 5546 Aspergillus flavus (89%) and A. parasiticus (11%) species were isolated and identified from samples. The results indicated that harvesting hazelnuts into a canvas by shaking the trees, manual harvesting of mature hazelnuts where possible, use of jute instead of nylon sacks and mechanical drying technique would minimize aflatoxin levels in hazelnuts. These recommendations have been implemented and about 4000 people in the hazelnut industry have been trained in these practices.


Neonatal asphyxia induces the nitration of cardiac myosin light chain 2 that is associated with cardiac systolic dysfunction.
Hypoxia followed by reoxygenation (H-R) observed during perinatal asphyxia is a serious complication with high mortality and morbidity rates that may cause adverse cardiovascular effects in neonates. Our aim was to determine if oxidative stress related to H-R induces peroxynitrite-dependent modifications of the cardiac contractile protein, myosin regulatory light chain 2 (MLC2), and whether this is associated with development of cardiac systolic dysfunction. Twelve newborn piglets were acutely instrumented for hemodynamic monitoring and randomized to a control group ventilated with only atmospheric air or to the H-R study group exposed to alveolar normocapnic hypoxia followed by reoxygenation. Afterward, animals were euthanized, and the hearts were harvested for biochemical analyses. Systolic function as well as cardiac MLC2 levels decreased in H-R animals, whereas nitrates and nitrotyrosine levels increased. Negative correlations between nitrates, nitrotyrosine, and MLC2 levels were observed. Moreover, H-R induced nitration of two tyrosine residues within the MLC2 protein. Similarly, in vitro exposure of MLC2 to peroxynitrite resulted in the nitration of tyrosine, which increased the susceptibility of MLC2 to subsequent degradation by matrix metalloproteinase 2. Substitution of this tyrosine with phenylalanine prevented the matrix metalloproteinase 2-dependent degradation of MLC2. In addition, a large decrease in MLC2 phosphorylation caused by H-R was observed. Oxidative stress related to asphyxia induces nitration of cardiac MLC2 protein and thus increases its degradation. This and a large decrease in MLC2 phosphorylation contribute to the development of systolic dysfunction. Inhibition of MLC2 nitration and/or direct inhibition of its degradation by MMP-2 could be potential therapeutic targets aiming at reduction of myocardial damage during resuscitation of asphyxiated newborns.


[Course of mother-child relations in cases of maternal HIV infection].
32 children born from HIV infected mothers (8 HIV infected and 24 seroreverted uninfected) were followed up from 1990 to 1995 at the Neurological Institute "C. Mondino" in Pavia to study the mother and baby relationship. At the end of the follow-up period, from the birth to the end of the second year of age, all children had psychosomatic disorders (repeated rejections, anorexia, sleep disturbances characterised by difficulty in falling asleep and frequent wake-ups, gaseous colics many times during the day). The psychosomatic disorders are considered as the result of an early distortion of the mother and baby relationship. Thus children born from HIV positive mothers are exposed to the possibility of developing psychological problems related to a distorted relationship with their mother.


Executive functions in patients with familial versus sporadic schizophrenia and their parents.
The aim of this study was to investigate the executive functions in patients with sporadic schizophrenia (SS) and familial schizophrenia (FS), and the executive functions in their parents. The study included 30 patients with FS and their 37 parents with a positive family history of schizophrenia; 30 patients with SS and their 44 parents; 30 controls matched with the patients for gender, age and education, and 40 controls matched with the parents for gender, age and education (211 subjects in total). All the subjects were interviewed with the Structured Clinical Interview for DSM-IV-Axis I (SCID-I). The executive functions were assessed using the Verbal Fluency Test (VFT), the Trail Making Test (TMT), the Wisconsin Card Sorting Test (WCST) and the Stroop Test. Patients with FS and their parents, and patients with SS performed significantly worse than their controls on the VFT, TMT, WCST and the Stroop test. There were no statistically significant differences between parents of patients with SS and their controls on any of the tests except for the Stroop color score. FS parents performed significantly worse than SS parents on all tests. FS patients performed significantly worse than SS patients on the VFT, TMT, Stroop test. Previous studies that investigated the cognitive functions of relatives of patients with schizophrenia brought out inconsistent results. The present study investigated relatives with and without a family history of schizophrenia separately and found that executive functions were impaired only in parents with a positive family history of schizophrenia. These findings suggest that impairment in executive functions may represent a genetic endophenotype for schizophrenia.


Venezuelan haemorrhagic fever.
An outbreak of severe haemorrhagic illness began in the municipality of Guanarito, Portuguesa State, Venezuela, in September, 1989. Subsequent detailed study of 15 cases confirmed the presence of a new viral disease, designated Venezuelan haemorrhagic fever. Characteristic features are fever, toxicity, headache, arthralgia, diarrhoea, conjunctivitis, pharyngitis, leucopenia, thrombocytopenia, and haemorrhagic manifestations. Other features include facial oedema, cervical lymphadenopathy, nausea/vomiting, cough, chest or abdominal pain, and convulsions. The patients ranged in age from 6 to 54 years; all were residents of rural areas in central Venezuela, and 9 died. Infection with Guanarito virus, a newly recognised arenavirus, was shown by direct culture or by serological confirmation in all cases. Epidemiological studies suggest that the disease is endemic in some rural areas of central Venezuela and that it is rodent-borne. Venezuelan haemorrhagic fever has many similarities to Lassa fever and to the arenavirus haemorrhagic fevers that occur in Argentina and Bolivia.


A B-cell actomyosin arc network couples integrin co-stimulation to mechanical force-dependent immune synapse formation.
B-cell activation and immune synapse (IS) formation with membrane-bound antigens are actin-dependent processes that scale positively with the strength of antigen-induced signals. Importantly, ligating the B-cell integrin, LFA-1, with ICAM-1 promotes IS formation when antigen is limiting. Whether the actin cytoskeleton plays a specific role in integrin-dependent IS formation is unknown. Here, we show using super-resolution imaging of mouse primary B cells that LFA-1:ICAM-1 interactions promote the formation of an actomyosin network that dominates the B-cell IS. This network is created by the formin mDia1, organized into concentric, contractile arcs by myosin 2A, and flows inward at the same rate as B-cell receptor (BCR):antigen clusters. Consistently, individual BCR microclusters are swept inward by individual actomyosin arcs. Under conditions where integrin is required for synapse formation, inhibiting myosin impairs synapse formation, as evidenced by reduced antigen centralization, diminished BCR signaling, and defective signaling protein distribution at the synapse. Together, these results argue that a contractile actomyosin arc network plays a key role in the mechanism by which LFA-1 co-stimulation promotes B-cell activation and IS formation.


Lobar pulmonary hemorrhage. An unusual complication of Swan-Ganz catheterization.
Massive lobar pulmonary hemorrhage related to Swan-Ganz catheterization represents a catastrophic complication that, to our knowledge, has received little attention in the literature. Our experience with two recent cases emphasizes the life-threatening nature of such bleeding as well as the potential for patient salvage after urgent resectional therapy. A spectrum of pulmonary vascular injuries is incurred after the insertion of a balloon-tipped catheter, and there are therapeutic approaches for each. The anticoagulation associated with cardiac surgical procedures prompts us to suggest that the technique of insertion and the use of the Swan-Ganz catheter in these patients be modified to avoid this complication.


Expression of drug resistance proteins in breast cancer, in relation to chemotherapy.
Drug resistance plays an important role in chemotherapy failure in breast cancer. We studied the expression of MDR1, MRP, LRP, DNA topoisomerases, p53 and Ki-67 in different groups of breast cancer patients in relation to chemotherapy. Tissues from 6 normal breasts and 20 primary operable, 40 locally advanced and 10 anthracycline-resistant metastatic breast cancers were assessed. Sequential samples of the same patient were available from 17 patients with locally advanced breast cancer undergoing neo-adjuvant chemotherapy and in 7 metastatic patients undergoing paclitaxel treatment. Protein expression was investigated by immunohistochemistry. Significantly higher protein expression was observed for Pgp, Ki-67 and p53 in the locally advanced breast cancers than in primary operable breast cancers. No other significant differences in protein expression were found among the 3 breast cancer groups. Expression of none of the markers that could be assessed (Pgp, MRP, LRP, p53 and Ki-67) in locally advanced breast cancer had predictive value for pathological response. Interestingly, after chemotherapy a significant decrease in percentage of Ki-67 positive tumor cells was observed, whereas the other markers did not vary substantially. Furthermore, considering all breast cancer samples, a cumulative dose of doxorubicin >400 mg/m2 inversely correlated with Ki-67 positivity. However, 2 patients with a pathological complete remission had only 5-10% Ki67-positive tumor cells before chemotherapy, indicating that Ki67 negativity itself is not responsible for chemoresistance. In conclusion, none of the known proteins related to multidrug resistance predicted response to chemotherapy in breast cancer, and resistant clones left behind generally had a low proliferation rate.


Physiological predictors of survival in patients with sarcoidosis-associated pulmonary hypertension: results from an international registry.
Sarcoidosis-associated pulmonary hypertension (SAPH) is associated with reduced survival in single-centre studies. The international Registry for SAPH (ReSAPH) with long-term follow-up was established to enrich our knowledge of this complication of sarcoidosis. This analysis aims to elucidate factors associated with reduced transplant-free survival in SAPH patients. ReSAPH contains prospectively collected outcomes of SAPH patients since the time of registry enrolment. Information analysed includes right heart catheterisation data, pulmonary function testing, chest radiography, Scadding stage and 6-min walk distance (6MWD), among others. Cox regression models were used to identify independent predictors of transplant-free survival. Data from 215 patients followed for a mean±sd 2.5±1.9 years were available for analysis. In the 159 precapillary patients, the Kaplan-Meier-adjusted 1-, 3- and 5-year transplant-free survival was 89.2%, 71.7% and 62.0%, respectively. Kaplan-Meier-adjusted 1-, 3- and 5-year transplant-free survival in the incident group was 83.5%, 70.3% and 58.3%, respectively, and in the prevalent group was 94.7%, 72.2% and 66.3%, respectively. Patients with reduced diffusing capacity of the lung for carbon monoxide (D LCO) (<35% predicted) and 6MWD <300 m in the precapillary cohort had significantly worse transplant-free survival. Reduced 6MWD and preserved forced expiratory volume (FEV1)/forced vital capacity (FVC) ratio were identified as independent risk factors for reduced transplant-free survival in the precapillary cohort. Reduced D LCO (<35% pred) and 6MWD (<300 m) at the time of registry enrolment were associated with reduced transplant-free survival in the overall precapillary cohort. Preserved FEV1/FVC ratio was identified as an independent risk factor for worsened outcomes.


Coordinating role of His216 in MgATP binding and cleavage in pyruvate carboxylase.
His216 is a well-conserved residue in pyruvate carboxylases and, on the basis of structures of the enzyme, appears to have a role in the binding of MgATP, forming an interaction with the 3'-hydroxyl group of the ribose ring. Mutation of this residue to asparagine results in a 9-fold increase in the Km for MgATP in its steady-state cleavage in the absence of pyruvate and a 3-fold increase in the Km for MgADP in its steady-state phosphorylation by carbamoyl phosphate. However, from single-turnover experiments of MgATP cleavage, the Kd of the enzyme·MgATP complex is essentially the same in the wild-type enzyme and H216N. Direct stopped-flow measurements of nucleotide binding and release using the fluorescent analogue FTP support these observations. However, the first-order rate constant for MgATP cleavage in the single-turnover experiments in H216N is only 0.75% of that for the wild-type enzyme, and thus, the MgATP cleavage step is rate-limiting in the steady state for H216N but not for the wild-type enzyme. Close examination of the structure of the enzyme suggested that His216 may also interact with Glu218, which in turn interacts with Glu305 to form a proton relay system involved in the deprotonation of bicarbonate. Single-turnover MgATP cleavage experiments with mutations of these two residues resulted in kinetic parameters similar to those observed in H216N. We suggest that the primary role of His216 is to coordinate the binding of MgATP and the deprotonation of bicarbonate in the reaction to form the putative carboxyphosphate intermediate by participation in a proton relay system involving Glu218 and Glu305.


Allostatic load model associated with indoor environmental quality and sick building syndrome among office workers.
This study investigates whether indoor environmental quality (IEQ) influences allostatic load (AL) and whether AL can be a predictor for sick building syndrome (SBS). We also assessed and compared the associations between AL and SBS versus 8-hydroxydeoxyguanosine (8-OHdG) and SBS. A total of 115 office workers from 21 offices completed self-reported SBS questionnaires, and provided 11 biomarkers for their AL. Multiple linear regressions and logistic regression analysis were applied to examine the correlations between IEQ and AL or 8-OHdG and between AL or 8-OHdG and SBS, respectively. Our data revealed that the neuroendocrine system was correlated with CO2, the difference between indoor and outdoor CO2 levels (dCO2), and the indoor-outdoor ratio of CO2 (CO2 I/O). Metabolic system effects were associated with illumination. The relationships between illumination, CO2, dCO2, CO2 I/O and 8-OHdG were consistent with those and AL in specific systems. Furthermore, we found that risks for SBS syndromes were related with neuroendocrine and metabolic system of the AL. 8-OHdG was associated with eye dryness or irritation, eye tiredness and vomiting. We conclude that IEQ significantly influences AL and that AL can be a predictor for reporting SBS with information on system-specific effects.


Chi-square analysis of the reduction of ATP levels in L-02 hepatocytes by hexavalent chromium.
This study explored the reduction of adenosine triphosphate (ATP) levels in L-02 hepatocytes by hexavalent chromium (Cr(VI)) using chi-square analysis. Cells were treated with 2, 4, 8, 16, or 32 μM Cr(VI) for 12, 24, or 36 h. Methyl thiazolyl tetrazolium (MTT) experiments and measurements of intracellular ATP levels were performed by spectrophotometry or bioluminescence assays following Cr(VI) treatment. The chi-square test was used to determine the difference between cell survival rate and ATP levels. For the chi-square analysis, the results of the MTT or ATP experiments were transformed into a relative ratio with respect to the control (%). The relative ATP levels increased at 12 h, decreased at 24 h, and increased slightly again at 36 h following 4, 8, 16, 32 μM Cr(VI) treatment, corresponding to a "V-shaped" curve. Furthermore, the results of the chi-square analysis demonstrated a significant difference of the ATP level in the 32-μM Cr(VI) group (P < 0.05). The results suggest that the chi-square test can be applied to analyze the interference effects of Cr(VI) on ATP levels in L-02 hepatocytes. The decreased ATP levels at 24 h indicated disruption of mitochondrial energy metabolism and the slight increase of ATP levels at 36 h indicated partial recovery of mitochondrial function or activated glycolysis in L-02 hepatocytes.


Calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1C) is induced in human arterial smooth muscle cells of the synthetic, proliferative phenotype.
The diversity among cyclic nucleotide phosphodiesterases provides multiple mechanisms for regulation of cAMP and cGMP in the cardiovascular system. Here we report that a calmodulin-stimulated phosphodiesterase (PDE1C) is highly expressed in proliferating human arterial smooth muscle cells (SMCs) in primary culture, but not in the quiescent SMCs of intact human aorta. High levels of PDE1C were found in primary cultures of SMCs derived from explants of human newborn and adult aortas, and in SMCs cultured from severe atherosclerotic lesions. PDE1C was the major cAMP hydrolytic activity in these SMCs. PDE expression patterns in primary SMC cultures from monkey and rat aortas were different from those from human cells. In monkey, high expression of PDE1B was found, whereas PDE1C was not detected. In rat SMCs, PDE1A was the only detectable calmodulin-stimulated PDE. These findings suggest that many of the commonly used animal species may not provide good models for studying the roles of PDEs in proliferation of human SMCs. More importantly, the observation that PDE1C is induced only in proliferating SMCs suggests that it may be both an indicator of proliferation and a possible target for treatment of atherosclerosis or restenosis after angioplasty, conditions in which proliferation of arterial SMCs is negatively modulated by cyclic nucleotides.


A most painful knee does not induce interlimb differences in knee and hip moments during gait in patients with knee osteoarthritis.
Patients with knee osteoarthritis can adapt their gait to unload the most painful knee joint in order to try to reduce pain and improve physical function. However, these gait adaptations can cause higher loads on the contralateral joints. The aim of the study was to investigate the interlimb differences in knee and hip frontal plane moments during gait in patients with knee osteoarthritis and in healthy controls. Forty patients with knee osteoarthritis and 19 healthy matched controls were measured during comfortable treadmill walking. Frontal plane joint moments were obtained of both hip and knee joints. Differences in interlimb moments within each group were assessed using statistical parametric mapping and discrete gait parameters. No interlimb differences were observed in patients with knee osteoarthritis and control subjects at group level. Furthermore, the patients presented similar interlimb variability as the controls. In a small subgroup (n = 12) of patients, the moments in the most painful knee were lower than in the contralateral knee, while the other patients (n = 28) showed higher moments in the most painful knee compared to the contralateral knee. However, no interlimb differences in the hip moments were observed within the subgroups. Patients with knee osteoarthritis do not have interlimb differences in knee and hip joint moments. Patients and healthy subjects demonstrate a similar interlimb variability in the moments of the lower extremities. In this context, differences in knee pain in patients with knee osteoarthritis did not induce any interlimb differences in the frontal plane knee and hip moments.


[Ipsilateral gustatory disturbance by thalamic hemorrhage].
Animal studies have recently demonstrated that the gustatory pathway ascends in the brainstem ipsilaterally without crossing, and terminates in the ipsilateral lower caudal limit of the thalamus, i.e., the nucleus ventralis posteromedialis parvocellularis (VPMpc). However, little is yet known about the corresponding anatomical arrangement in man. Some clinical reports on cases of ipsilateral gustatory disturbance caused by tegmental pontine hemorrhage have suggested that the human gustatory pathway may also ascend ipsilaterally in the brainstem. Our case is a 35-year-old man, who was admitted to the hospital because of double vision. Computed tomography revealed a small high density area in the right paramedian tegmentum of the upper midbrain. On the 7th hospital day, the patient suddenly complained of dysesthesia on the right side of the oral cavity. Neurological examination demonstrated remarkable total hypogeusia on the right side of the tongue. MR imaging revealed upward extension of the hematoma toward the lower caudal portion of right thalamus. This is first report to demonstrate unilateral gustatory disturbance due to lesion in the ipsilateral thalamus. It is also worth of note that unilateral gustatory disturbance caused by thalamic lesion can be accompanied by sensory impairment in the ipsilateral oral cavity.


Body composition at menarche: The Frisch-Revelle hypothesis revisited.
Figures for height and weight and derived values for total body water and fat were assembled for groups of girls with a variety of disorders to examine their conformity to the hypothesis of Frisch and Revelle that menarche occurs at a "critical" weight associated with a decline in metabolic rate and achievement of a characteristic body composition. The groups examined included girls with unusually tall stature, central idiopathic precocity, precocity associated with hypothyroidism, girls with hypothyroidism but lacking signs of sexual maturation, one group with gonadal dysgenesis, and another of girls with obesity. Girls with tall stature significantly exceeded the "critical" weight of 47.8 kg before achieving menarche but had onset of menses in accordance with the body composition hypothesis. The body composition of girls with idiopathic sex precocity was altered toward that at menarche of normals although the patients were much smaller and younger. The same trend was exaggerated in girls in whom precocity was associated with hypothyroidism; equally hypothyroid girls showing no signs of adolescent development had body compositions similar to those of age-matched controls. Girls with gonadal dysgenesis showed an alteration in body composition paralleling that of normals between the ages when the latter begin the pubertal growth spurt and achieve menarche. Girls under 8 years of age with simple obesity had an even greater percentage of body fat than normal menarchal girls but showed no signs of puberty. It is concluded that menarche is not necessarily triggered by achievement of a critical body weight or lowering of metabolism. Neither are the rising levels of estrogen in adolescence solely responsible for the characteristic increase in body fat. Only the data on girls with obesity failed to accord with the generalization that, when the ovaries are competent, menarche is highly correlated with achievement of a characteristic body composition. The observations, particularly in gonadal dysgenesis, suggest the pituitary gonadotropins may play a role in determining body composition in menarche.


[Retroperitoneal fibrosis caused by extensive perirenal hematoma].
We report a case of direct renal trauma with formation of subcapsular hematoma in an anticoagulated patient. After an initial conservative approach, patient condition spontaneously evolved to subcapsular rupture resulting in perirenal spread of the hematoma enveloping the ureter up to the sacral level thus causing severe hydronephrosis. Surgical exploration permitted ureterolysis and postoperative radiologic work up revealed patency. We briefly discuss the current controversy relative to the different therapeutic approaches.


Neonatal neurological assessment of offspring in maternal phenylketonuria.
This study assesses the impact of prenatal and postnatal factors in maternal phenylketonuria (PKU). The Dubowitz Neurological Assessment of the Preterm and Full-term Newborn Infant was administered within the first 8 days of life to 56 offspring of women with PKU and 45 controls. Follow-up testing of the maternal PKU offspring at age 1 year consisted of the Bayley Scales of Infant Development and the Receptive-Expressive Emergent Language Scale (REEL). In addition, the Home Observation for Measurement of the Environment (HOME Scale) was given. Birth weight was lower (z = 2.0, p = 0.045), birth length was lower (z = 2.1, p = 0.03) and birth head circumference was smaller (z = 3.5, p = 0.0005) in the maternal PKU offspring than in the control infants. Examiners rated 29% of the maternal PKU offspring and 9% of the control infants abnormal (Fisher's exact test, p = 0.01). At 1 year of age, 19% of the maternal PKU offspring attained a Bayley Developmental Quotient (DQ) and a score on the Bayley Motor Scale below 85; 19% had receptive language delay; and 26% had expressive language delay. The gestational age at which the mother attained metabolic control was an important factor associated with birth measurements, the Dubowitz Rating and subsequent developmental scores. The Dubowitz Neurological Assessment score did not predict developmental outcome (chi-square = 1.3, p = 0.53), while the HOME score correlated with the DQ (r = 0.36, p = 0.02). In logistic regression analyses, the home environment was a greater determinant of risk for a low DQ than whether or not the mother attained metabolic control prior to pregnancy (OR = 0.85, p = 0.02). These results suggest that treatment strategies addressing both prenatal and postnatal factors will most effectively reduce risks in maternal PKU.


[Personal and collective mechanisms for protecting and enhancing the quality of life during childhood and adolescence].
Based on recent literature, this paper presents individual and collective strategies for protecting and promoting the quality of life during childhood and adolescence. Addressing the core principles of an all-round protection policy aligned with the Universal Declaration of Human Rights and the Children's and Adolescents' Statute, it also encompasses practical aspects of professional approaches to children and adolescents in terms of ethics and confidentiality. Additionally, it discusses the determining factors that shape the development of individual and collective resilience, on scientific and theoretical bases, in addition to risk factors, health protection and the cognitive and psychosocial development of this segment of the population.The roles played by adults are stressed as protection factors in the macro and micro environments, especially the roles assigned to family members and other adults in the social surroundings such as healthcare practitioners those engaged with education, social welfare and mental health. The important role played by Social Networks is stressed, as a key strategy for implementing inter-disciplinary and trans-sector practices designed to enhance well-being and quality of life throughout the entire community.


Treatment of localized vitiligo by autologous minigrafting.
Autologous minigrafting has been reported as an effective method for repigmenting diverse types of stable leukoderma. A group of 22 patients with localized vitiligo, 17 segmental and five focal, who are under treatment with this method, are described. Thirteen patients attained a 90% to 100% repigmentation, two others achieved a partial improvement, and five patients had a positive test area indicating the possibility of repigmentation by means of this procedure. Only two patients had a negative test with minigrafts and, consequently, they were left untreated. Autologous minigrafting is suggested as an alternative for treating localized vitiligo, particularly when other medical therapeutic attempts have failed in repigmenting this often refractory condition.


Axl molecular targeting counteracts aggressiveness but not platinum-resistance of ovarian carcinoma cells.
Ovarian carcinoma, the most common gynaecological cancer, is characterized by high lethality mainly due to late diagnosis and treatment failure. The efficacy of platinum drug-based therapy in the disease is limited by the occurrence of drug resistance, a phenomenon often associated with increased metastatic potential. Because the Tyr-kinase receptor Axl can be deregulated in ovarian carcinoma and plays a pro-metastatic/anti-apoptotic role, the aim of this study was to examine if Axl inhibition modulates drug resistance and aggressive features of ovarian carcinoma cells, using various pairs of cisplatin-sensitive and -resistant cell lines. We found that mRNA and protein levels of Axl were increased in the platinum-resistant IGROV-1/Pt1 and IGROV-1/OHP cell lines compared to the parental IGROV-1 cells. IGROV-1/Pt1 cells displayed increased migratory and invasive capabilities. When Axl was silenced, these cells exhibited reduced growth and invasive/migratory capabilities compared to control siRNA-transfected cells, associated with decreased p38 and STAT3 phosphorylation. In keeping with this evidence, pharmacological inhibition of p38 and STAT3 decreased IGROV-1/Pt1 invasive capability. Molecular inhibition of Axl did not sensitize IGROV-1/Pt1 cells to cisplatin, but enhanced ErbB3 activation in IGROV-1/Pt1 cells and suppressed the clonogenic capability of various ovarian carcinoma cell lines. The combination of cisplatin and AZD8931, a small molecule which inhibits ErbB3, produced a synergistic effect in IGROV-1/Pt1 cells. Thus, Axl targeting per se reduces invasive capability of drug-resistant cells, but sensitization to cisplatin requires the concomitant inhibition of additional survival pathways.


Illness duration and total brain gray matter in bipolar disorder: evidence for neurodegeneration?
Previous studies have suggested that bipolar disorder (BD) is associated with alterations in neuronal plasticity, but the effects of the progression of illness on brain anatomy have been poorly investigated. We studied the correlation between length of illness, age, age at onset, and the number of previous episodes and total brain, total gray, and total white matter volumes in BD, unipolar (UP) and healthy control (HC) subjects. Thirty-six BD, 31 UP and 55 HCs underwent a 1.5 T brain magnetic resonance imaging scan, and gray and white matter volumes were manually traced blinded to the subjects' diagnosis. Partial correlation analysis showed that length of illness was inversely correlated with total gray matter volume after adjusting for total intracranial volume in BD (r(p)= -0.51; p=0.003) but not in UP subjects (r(p)= -0.23; p=0.21). Age at illness onset and the number of previous episodes were not significantly correlated with gray matter volumes in BD or UP subjects. No significant correlation with total white matter volume was observed. These results suggest that the progression of illness may be associated with abnormal cellular plasticity. Prospective longitudinal studies are necessary to elucidate the long-term effects of illness progression on brain structure in major mood disorders.


Exome sequencing in suspected monogenic dyslipidemias.
Exome sequencing is a promising tool for gene mapping in Mendelian disorders. We used this technique in an attempt to identify novel genes underlying monogenic dyslipidemias. We performed exome sequencing on 213 selected family members from 41 kindreds with suspected Mendelian inheritance of extreme levels of low-density lipoprotein cholesterol (after candidate gene sequencing excluded known genetic causes for high low-density lipoprotein cholesterol families) or high-density lipoprotein cholesterol. We used standard analytic approaches to identify candidate variants and also assigned a polygenic score to each individual to account for their burden of common genetic variants known to influence lipid levels. In 9 families, we identified likely pathogenic variants in known lipid genes (ABCA1, APOB, APOE, LDLR, LIPA, and PCSK9); however, we were unable to identify obvious genetic etiologies in the remaining 32 families, despite follow-up analyses. We identified 3 factors that limited novel gene discovery: (1) imperfect sequencing coverage across the exome hid potentially causal variants; (2) large numbers of shared rare alleles within families obfuscated causal variant identification; and (3) individuals from 15% of families carried a significant burden of common lipid-related alleles, suggesting complex inheritance can masquerade as monogenic disease. We identified the genetic basis of disease in 9 of 41 families; however, none of these represented novel gene discoveries. Our results highlight the promise and limitations of exome sequencing as a discovery technique in suspected monogenic dyslipidemias. Considering the confounders identified may inform the design of future exome sequencing studies.


BACE1 activity in cerebrospinal fluid and its relation to markers of AD pathology.
Several studies have shown that reduced amyloid-beta 1-42 (Abeta(42)) and increased tau levels in cerebrospinal fluid (CSF) reflect increased Alzheimer's disease (AD) pathology in the brain. beta-site APP cleaving enzyme (BACE1) is thought to be the major beta-secretase involved in Abeta production in the brain, and therefore we investigated the relation between BACE1 activity and CSF markers Abeta(40), Abeta(42), total tau (t-tau), and tau phosphorylated at threonine 181 (p-tau) in CSF of control (n=12), mild cognitive impairment (n=18), and AD (n=17) subjects. Patients were classified according to their Abeta(42), t-tau, and p-tau CSF biomarker levels, with either an AD-like biomarker profile (two or three biomarkers abnormal: Abeta(42) < 495 pg/ml in combination with t-tau > 356 pg/ml, and/or p-tau > 54 pg/ml) or a normal biomarker profile (<or= one biomarker abnormal). This resulted in 19 subjects with an AD-like biomarker profile (66 +/- 6 years, 53% female, and Mini-Mental Status Examination (MMSE) score: 23 +/- 5) and 28 subjects with a normal biomarker profile (62 +/- 11 years, 43% female, and MMSE score: 27 +/- 4). Subjects with an AD-like biomarker profile had higher CSF BACE1 activity levels, compared to patients with a normal biomarker profile (20 pg/ml and 16 pg/ml respectively; p=0.01), when controlled for age and gender. In the whole sample, BACE1 activity correlated with CSF levels of Abeta(40), t-tau, and p-tau (r=0.38, r=0.63, and r=0.65; all p< 0.05), but not with Abeta(42). These data suggest that increased BACE1 activity in CSF relates to AD pathology in the brain.


[Cardiac natriuretic peptides and hypertension: experimental study].
The peculiarities of cardiac natriuretic peptide secretion have been investigated during ontogenesis using the hypertonic disease model in ISIAH rat line (with inherited stress induced arterial hypertension). The qualitative and quantitative ultrastructural investigations of right atrium myocardium revealed that the cardiac hormonal synthetic and secretory activities in ISIAH rats are higher as compared with normotensive even-aged rats from control group. Secretory hyperactivity of atrial myocytes in ISIAH rats during early ontogeny precedes the manifestations of hereditary hypertension. Natriuretic peptides present the hypotensive circuit of hemodynamic regulation during the whole ontogeny and the complementary chain in hypertension development.


A Rare Collision Tumour of Uterus- Squamous Cell Carcinoma and Endometrial Stromal Sarcoma.
Collision tumours are defined by co-existence of two tumours in the same or adjacent organs which are topographically and histologically distinct with minimal or no histological admixture. Collision tumours have been described in many organs notably thyroid, brain, adrenal gland, stomach and rarely uterus. Most of the collision tumours reported in uterus have two components; an adenocarcinoma and a sarcoma. We report a case of a 60-year-old lady who presented with complaints of post-menopausal bleeding. A cervical biopsy was performed which showed a non-keratinizing squamous cell carcinoma of cervix. Intra-operatively the uterus was bulky with a 6 cm x 5 cm polypoidal mass in the endometrial canal along with a 2 cm friable cervical growth. The fleshy uterine cavity mass was a spindle cell tumour with moderate pleomorphism and frequent mitosis. It was immunopositive for CD10 and negative for smooth muscle actin and cytokeratin 5/6. The other growth showed non-keratinizing squamous cell carcinoma which was positive for cytokeratin 5/6. Based on the distinct topographical location and limited areas of tumour admixture of the two tumours, a diagnosis of collision tumour of uterus comprising of endometrial stromal sarcoma (high grade) uterus and squamous cell carcinoma cervix was made.


Fine needle aspiration of the thyroid: correlation with final histopathology in a surgical series of 797 patients.
Fine needle aspiration (FNA) is accepted as the diagnostic procedure of choice in the management of patients with thyroid nodules. Follicular/Hürthle cell neoplasms have traditionally been grouped under the category of indeterminate FNA results. This study examined the experience with FNA in a large cohort of patients undergoing thyroidectomy before adoption of the Bethesda system for reporting thyroid cytopathology (BSTC) at a single academic medical center. A retrospective review of prospectively collected data of 797 consecutive patients with dominant nodules >1 cm who underwent FNA and thyroidectomy from 2003 to 2009 was performed. Patients were categorized into groups based on FNA results: malignant, benign, indeterminate, and nondiagnostic. The indeterminate group had FNA results that included follicular neoplasm, Hürthle cell neoplasm, and suspicion of papillary thyroid cancer. FNA results were compared with final histopathology after thyroidectomy. FNA results included 147 (18%) positive for malignancy, 255 (32%) benign, 358 (45%) indeterminate, and 37 (5%) nondiagnostic. The overall malignancy rate on final histopathology was 369 of 797 (46%). Overall, there was a false positive rate of 2% and false negative rate of 8.6%. Among the 358 indeterminate FNA results, carcinoma was found in 81 (36%) of 223 follicular neoplasms, 18 (36%) of 50 Hürthle cell neoplasms, and 78 (92%) of 85 that were suspicious for papillary thyroid cancer. When FNA was nondiagnostic, cancer was present in 9 of 37 (24%). Among 39 patients with benign FNA who had cancer on final histopathology, 22 of 255 (8.6%) had cancer in the index thyroid nodule, and 81% of cancers were >1 cm. Patients with FNA and dominant nodules >1 cm, who underwent thyroidectomy, had an overall rate of thyroid malignancy of 46%. There was a cancer prevalence of 8.6% in patients with benign FNA results referred for surgical resection. Despite not yet implementing the BSTC at this medical center, the majority of thyroidectomies were adequately performed for indeterminate FNAs with underlying malignancy.


Molecular analysis of tra-2, a sex determining gene in C.elegans.
We have cloned the Caenorhabditis elegans sex determining gene, tra-2, by transposon tagging. The tra-2 region is delineated by mapping Southern blot differences associated with 11 tra-2 mutations, mutant rescue, and analysis of tra-2 RNAs. The tra-2 gene encodes three transcripts. One transcript, a 1.8 kb RNA, is not detected in animals lacking a germ line, and therefore may be germline specific. Comparison of the two sexes shows that adult hermaphrodites have approximately 15-fold more tra-2 RNA than adult males. In addition, adult hermaphrodites contain 5 kb and 1.8 kb tra-2 RNAs whereas adult males possess 5 kb and 1.9 kb RNAs. A 1.9 kb tra-2 RNA is also found during hermaphrodite larval development, prior to sexual differentiation of the XX germ line. Surprisingly, analysis of tra-2 expression in selected sex determination mutants reveals that the sex specificity of tra-2 RNAs is not dictated by the pathway of sex determination that has been established by genetic experiments. This result can be interpreted in two ways. Either the sex specificity of the tra-2 RNAs is irrelevant to regulation of the sexual phenotype, which seems unlikely, or there is additional complexity within the hierarchy of sex determining genes, such as feedback regulation, which ensures that the tra-2 product corresponds to phenotypic sex.


Germ granule-mediated RNA regulation in male germ cells.
Germ cells have exceptionally diverse transcriptomes. Furthermore, the progress of spermatogenesis is accompanied by dramatic changes in gene expression patterns, the most drastic of them being near-to-complete transcriptional silencing during the final steps of differentiation. Therefore, accurate RNA regulatory mechanisms are critical for normal spermatogenesis. Cytoplasmic germ cell-specific ribonucleoprotein (RNP) granules, known as germ granules, participate in posttranscriptional regulation in developing male germ cells. Particularly, germ granules provide platforms for the PIWI-interacting RNA (piRNA) pathway and appear to be involved both in piRNA biogenesis and piRNA-targeted RNA degradation. Recently, other RNA regulatory mechanisms, such as the nonsense-mediated mRNA decay pathway have also been associated to germ granules providing new exciting insights into the function of germ granules. In this review article, we will summarize our current knowledge on the role of germ granules in the control of mammalian male germ cell's transcriptome and in the maintenance of fertility.


The BiSciCol Triplifier: bringing biodiversity data to the Semantic Web.
Recent years have brought great progress in efforts to digitize the world's biodiversity data, but integrating data from many different providers, and across research domains, remains challenging. Semantic Web technologies have been widely recognized by biodiversity scientists for their potential to help solve this problem, yet these technologies have so far seen little use for biodiversity data. Such slow uptake has been due, in part, to the relative complexity of Semantic Web technologies along with a lack of domain-specific software tools to help non-experts publish their data to the Semantic Web. The BiSciCol Triplifier is new software that greatly simplifies the process of converting biodiversity data in standard, tabular formats, such as Darwin Core-Archives, into Semantic Web-ready Resource Description Framework (RDF) representations. The Triplifier uses a vocabulary based on the popular Darwin Core standard, includes both Web-based and command-line interfaces, and is fully open-source software. Unlike most other RDF conversion tools, the Triplifier does not require detailed familiarity with core Semantic Web technologies, and it is tailored to a widely popular biodiversity data format and vocabulary standard. As a result, the Triplifier can often fully automate the conversion of biodiversity data to RDF, thereby making the Semantic Web much more accessible to biodiversity scientists who might otherwise have relatively little knowledge of Semantic Web technologies. Easy availability of biodiversity data as RDF will allow researchers to combine data from disparate sources and analyze them with powerful linked data querying tools. However, before software like the Triplifier, and Semantic Web technologies in general, can reach their full potential for biodiversity science, the biodiversity informatics community must address several critical challenges, such as the widespread failure to use robust, globally unique identifiers for biodiversity data.


Pleural disease and acquired immune deficiency syndrome.
Patients with acquired immune deficiency syndrome (AIDS) do not frequently have pleural complications. However, pneumothorax is a troublesome complication of patients with AIDS. At some medical centres, more than 50% of patients with spontaneous pneumothorax have AIDS. Most patients with spontaneous pneumothorax and AIDS have Pneumocystis carinii infection and necrotic subpleural blebs. The pneumothoraces in these patients usually cannot be managed with tube thoracostomy alone. Patients who do not respond to tube thoracostomy are best managed with a Heimlich valve or with thoracostomy with stapling of blebs and pleural abrasion. Approximately 2% of human immunodeficiency virus (HIV)-positive individuals will have a pleural effusion. Parapneumonic effusions or empyema, tuberculosis and Kaposi's sarcoma are the three leading causes. P. carinii infection is frequently responsible for pulmonary infections, but is only occasionally responsible for a pleural effusion. Pleural effusions may also develop from non-Hodgkin's lymphoma (NHL). There is one relatively rare NHL that is associated with the Kaposi's sarcoma associated virus that produces a lymphoma confined to the body cavity.


Chemical and enzymatic fractionation of cell walls from Fucales: insights into the structure of the extracellular matrix of brown algae.
Brown algae are photosynthetic multicellular marine organisms evolutionarily distant from land plants, with a distinctive cell wall. They feature carbohydrates shared with plants (cellulose), animals (fucose-containing sulfated polysaccharides, FCSPs) or bacteria (alginates). How these components are organized into a three-dimensional extracellular matrix (ECM) still remains unclear. Recent molecular analysis of the corresponding biosynthetic routes points toward a complex evolutionary history that shaped the ECM structure in brown algae. Exhaustive sequential extractions and composition analyses of cell wall material from various brown algae of the order Fucales were performed. Dedicated enzymatic degradations were used to release and identify cell wall partners. This approach was complemented by systematic chromatographic analysis to study polymer interlinks further. An additional structural assessment of the sulfated fucan extracted from Himanthalia elongata was made. The data indicate that FCSPs are tightly associated with proteins and cellulose within the walls. Alginates are associated with most phenolic compounds. The sulfated fucans from H. elongata were shown to have a regular α-(1→3) backbone structure, while an alternating α-(1→3), (1→4) structure has been described in some brown algae from the order Fucales. The data provide a global snapshot of the cell wall architecture in brown algae, and contribute to the understanding of the structure-function relationships of the main cell wall components. Enzymatic cross-linking of alginates by phenols may regulate the strengthening of the wall, and sulfated polysaccharides may play a key role in the adaptation to osmotic stress. The emergence and evolution of ECM components is further discussed in relation to the evolution of multicellularity in brown algae.


Coercion in substance use disorders: clinical course of compulsory admissions in a Swiss psychiatric hospital.
According to the Swiss legal system, involuntary admission is one of the farthest-reaching incursions into personal autonomy. The effect of compulsory admission in treatment of substance use disorders (SUDs) on variables such as length of stay or leaving treatment before recommended discharge remains elusive. In order to elucidate these effects, we retrospectively analysed the clinical course of treatment of 608 patients who were admitted between November 2016 and October 2017 to the Department of Addictive Disorders of the canton of Aargau. Involuntarily admitted patients showed lower health and social functioning, as measured by the Health of the Nation Outcome Scales (HoNOS), compared with those with voluntary status. In involuntary admissions for SUD treatment, length of stay was significantly shorter and the proportion of patients who left treatment against recommendation was twice as high as in voluntarily admitted patients. Furthermore, if treatment was initiated on a compulsory basis, a subsequent switch to voluntary treatment status appeared to be very uncommon. We conclude that, at least in involuntary admission according to the Swiss legal system, these admissions do not lead to sustained inpatient treatment.


Should Surgical Treatment Be Provided to Patients with Colorectal Cancer Who Are Aged 90 Years or Older?
The number of patients aged ≥ 90 years is increasing worldwide; however, the treatment guidelines for colorectal cancer in elderly patients remain unclear. This study aimed to investigate the clinical outcomes of patients with primary colorectal cancer aged ≥ 90 years. We retrospectively reviewed the medical records of 100 patients (aged ≥ 90 years) with primary colorectal adenocarcinoma. Their demographic and clinical characteristics and surgical outcomes were assessed. The patients who underwent tumor resections (n = 71) showed longer overall and cancer-specific survival than those who underwent non-operative treatments (n = 29) (median overall survival time: 23.92 months vs. 2.99 months, P < 0.0001). Age, body mass index, performance status, advanced cancer stage (stages 3 and 4), and treatment strategy were identified as risk factors, prognostic factors, and predictors of overall survival. No significant differences in the postoperative morbidity rate, in-hospital mortality rate, and survival time were found between the elective laparoscopic (n = 27) and elective open (n = 37) surgery subgroups. However, the in-hospital mortality rate was 6.25% (4/64) in the patients who underwent elective open surgeries and 42.9% (3/7) in those who underwent emergent open surgeries (p = 0.0179). In clinical practice, surgical treatment should not be denied to patients with primary colorectal cancer aged ≥ 90 years. However, the high complication and mortality rates for emergency surgeries act as a deterrent. Further studies to eliminate the bias between operative and non-operative groups may be needed to validate our results.


Risk avoidance of screw-induced suprascapular nerve injury in arthroscopic Latarjet procedure and reliable anatomical landmark analysis of Latarjet surgery.
Shoulder dislocation represents a prevalent category within joint dislocation, accounting for about 40% of all joint dislocations, and anterior dislocation stands out as the prevailing type. It has been reported that in 1.6% of patients, the Latarjet procedure performed under arthroscopy involves transferring the coracoid process to the anterior-inferior aspect of the glenoid and fixing it with two bicortical screws. The tip of the screws may impinge the suprascapular nerve located behind the scapula, resulting in shoulder pain and weakness. This study was performed to analyze the risk of suprascapular nerve (SSN) injury caused by bicortical screws during arthroscopic Latarjet surgery and to identify reliable anatomical landmarks for Latarjet surgery. Dissection was conducted on 23 fresh adult intact shoulder joint specimens, and the experimental protocol complied with the hospital's ethical requirements for research. Using the glenoid clock face as a reference, the distances between the suprascapular nerve and the anterior edge of the glenoid were measured at the 12:00, 11:00, 10:00, and 9:00 positions, as well as at the level of the suprascapular notch and the level of the spinoglenoid notch. The distances between the suprascapular nerve and the narrowest point of the glenoid rim and the clock scale were recorded. The scapula was divided into three zones, and the number of nerve branches in each zone was recorded. The collected data were subjected to statistical analysis. The suprascapular nerve trunk and branches were marked using radiopaque lines, and measurements were taken at three positions in computed tomography horizontal scans: the suprascapular foramen, the spinoglenoid notch, and the point of entry of the outermost nerve branch into the muscle. The suprascapular nerve originates from the brachial plexus, passes downward and backward through the suprascapular foramen, closely adheres to the bone surface, and runs outward and downward deep to the supraspinatus muscle. The distances between the suprascapular nerve and the glenoid rim at the 12:00, 11:00, 10:00, and 9:00 positions were 335.18±2.31 mm, 28.23±3.47 mm, 22.32±2.78 mm, and 22.12±2.07 mm, respectively. There was a mean of 1.12 nerve branches in zone 1, 2.86 in zone 2, and 3.64 in zone 3. In the neutral position of the shoulder joint, the horizontal distance between point A and the axillary nerve was 27.37 (19.80, 34.55) mm, and the vertical distance was 16.67 (12.85, 20.35) mm. The use of bicortical screws, especially upper screws, for Latarjet fixation at the level of the spinoglenoid notch, is associated with the risk of suprascapular nerve injury. The narrowest distance between the glenoid rim and the suprascapular nerve was found between 9:00 and 9:30 at the glenoid clock surface. Therefore, caution should be exercised when performing any procedure related to this area. Overall, the Latarjet procedure is a reliable and effective surgical technique, providing benefits such as favorable positioning of the coracoid graft and low bone absorption rate, while also avoiding the potential for suprascapular nerve injury.


Effect of treatment on systolic time intervals in systemic arterial hypertension.
Twenty six hypertensive patients and 25 control subjects were studied and their systolic time intervals (STI) were measured. It was found that an alteration in STI, signifying left ventricular dysfunction sets in most of the hypertensives earlier than any evidence of left ventricular hypertrophy (LVH) by clinical, radiological or electrocardiographic criteria. The parameters affected are the PEP interval which shows prolongation and PEP/LVET ratio which is increased. After treatment the left ventricular performance was found to improve in those who did not reveal evidence of LVH. Thus STI may be a sensitive indicator of early left ventricular dysfunction in hypertensives and a useful guide to assess improvement after treatment at a stage when other non-invasive methods are not so useful.


The effects of transient attention on spatial resolution and the size of the attentional cue.
It has been shown that transient attention enhances spatial resolution, but is the effect of transient attention on spatial resolution modulated by the size of the attentional cue? Would a gradual increase in the size of the cue lead to a gradual decrement in spatial resolution? To test these hypotheses, we used a texture segmentation task in which performance depends on spatial resolution, and systematically manipulated the size of the attentional cue: A bar of different lengths (Experiment 1) or a frame of different sizes (Experiments 2-3) indicated the target region in a texture segmentation display. Observers indicated whether a target patch region (oriented line elements in a background of an orthogonal orientation), appearing at a range of eccentricities, was present in the first or the second interval. We replicated the attentional enhancement of spatial resolution found with small cues; attention improved performance at peripheral locations but impaired performance at central locations. However, there was no evidence of gradual resolution decrement with large cues. Transient attention enhanced spatial resolution at the attended location when it was attracted to that location by a small cue but did not affect resolution when it was attracted by a large cue. These results indicate that transient attention cannot adapt its operation on spatial resolution on the basis of the size of the attentional cue.


A new formalism for the quantification of tissue perfusion by the destruction-replenishment method in contrast ultrasound imaging.
A new formalism is presented for the destruction-replenishment perfusion quantification approach at low mechanical index. On the basis of physical considerations, best-fit methods should be applied using perfusion functions with S-shape characteristics. These functions are first described for the case of a geometry with a single flow velocity, then extended to the case of vascular beds with blood vessels having multiple flow velocity values and directions. The principles guiding the analysis are, on one hand, a linearization of video echo signals to overcome the log-compression of the imaging instrument, and, on the other hand, the spatial distribution of the transmit-receive ultrasound beam in the elevation direction. An in vitro model also is described; it was used to confirm experimentally the validity of the approach using a commercial contrast agent. The approach was implemented in the form of a computer program, taking as input a sequence of contrast-specific images, as well as parameters related to the ultrasound imaging equipment used. The generated output is either flow-parameter values computed in regions-of-interest, or parametric flow-images (e.g., mean velocity, mean transit time, mean flow, flow variance, or skewness). This approach thus establishes a base for extracting information about the morphology of vascular beds in vivo, and could allow absolute quantification provided that appropriate instrument calibration is implemented.


[Linear measurements of the rhomboid fossa (the fourth ventricle in man].
The linear sizes of the rhombiod fossa of the human brain were studied with the help of the M. M. Sauliak-Savitskaja's device. Under study were 72 objects of the brain of humans from 20 to 78 years of age. The obtained data were statistically treated. No relationship between the sizes of the rhombiod fossa, sex and age was revealed, no statistically significant distinctions between the sizes of the right and left parts of the rhombiod fossa were revealed either. Between the length and width of the rhomboid fossa there exits a direct correlative relationship, the width of the rhomboid fossa having more close correlative relationships with the length of the superior part of the fossa rombiodea that the length of its inferior part.


Antimicrobial activity and chemical composition of white birch (Betula papyrifera Marshall) bark extracts.
Extracts from white birch have been reported to possess antimicrobial properties, but no study has linked the chemical composition of bark extract with antimicrobial activity. This study aimed to identify white birch (Betula papyrifera Marshall) bark extracts with antimicrobial activity and elucidate its composition. In order to obtain the highest extraction yield, bark residues >3 mm were retained for extraction. A total of 10 extraction solvents were used to determine the extraction yield of each of them. Methanol and ethanol solvents extracted a greater proportion of molecules. When tested on eight microorganism species, the water extract proved to have the best antimicrobial potential followed by the methanol extract. The water extract inhibited all microorganisms at low concentration with minimal inhibitory concentration between 0.83 and 1.67 mg/ml. Using ultraperformance liquid chromatography coupled to a time-of-flight quadrupole mass spectrometer, several molecules that have already been studied for their antimicrobial properties were identified in water and methanol extracts. Catechol was identified as one of the dominant components in white birch bark water extract, and its antimicrobial activity has already been demonstrated, suggesting that catechol could be one of the main components contributing to the antimicrobial activity of this extract. Thus, extractives from forestry wastes have potential for new applications to valorize these residues.


Maternal infanticides in Fiji.
This essay contributes to the cross-cultural literature on childhood homicides by examining 16 infanticidal homicides that occurred in Fiji over an 11-year period. The results are compared with infanticide studies conducted in other societies. Official police data recorded in a Homicide and Manslaughter register are analyzed. These are supplemented by newspaper reports of infanticides and semi-structured interviews conducted with key criminal justice and medical personnel intimately associated with infanticide cases. The findings show that most infanticide defendants were young, poor, Fijian, with little formal education, living with nonparental kin at the time of the crime. The infanticides were precipitated by unwanted pregnancies brought on by nonmarital and extramarital sex. Pregnancy is carried to full gestation without knowledge of family, friends and neighbors of offenders and the infant is killed immediately following birth. The current findings demonstrate that the patterns of maternal infant killings in Fiji are congruous in many significant ways with those in advanced industrialized societies. It is concluded that additional research in non-Western, nonindustrialized nations is imperative to contribute to the development of sound conclusions about, and remedies for infanticide.


Microalbuminuria and coronary heart disease in non-diabetics.
Microalbuminuria (or urinary albumin excretion rates (AER) above normal limits) is associated with coronary heart disease (CHD) particularly in diabetics. To determine the sensitivity and specificity of AER for CHD in a non-diabetic population we prospectively studied 115 consecutive patients undergoing coronary angiography and 66 undergoing exercise electrocardiography (ECG). There was no relationship between AER and the severity of CHD determined by angiography (Gensini-scored). While microalbuminuria (AER > 20 micrograms/minute) was 91% specific it had low sensitivity (12%). Microalbuminuria is not a sensitive indicator of CHD in a non-diabetic population.


Patterns of care in two HIV continuity clinics in Uganda, Africa: a time-motion study.
The study objectives were to identify opportunities to improve the quality of care in resource-limited settings by examining the workflow and patient activities at two large outpatient HIV clinics in Uganda. Using time motion study techniques, we collected detailed data on all activities of patients and clinicians in two government-sponsored HIV clinics in Uganda. Processes measured included amount of time clinicians (physicians, nurse practitioners and clinical officers) spend in clinic, the daily patient census and patient visit-length. We also recorded the time spent on various activities by providers and patients. We found that the mean time in clinic per workday at Masaka was 5.5 hours and at Mbarara 4.9 hours, with about 60% of this time spent in direct and indirect care of patients at both sites. Workday start-times varied by two hours in Masaka and one-and-a half hours in Mbarara and end-times by five and three hours respectively. One-hundred-and-nineteen patients (SD 34) visited Masaka each day and 107 (SD 45) visited Mbarara. The mean duration of the patient visit was 77 minutes at Masaka and 196 minutes at Mbarara, with 66% and 62% of the time spent at respective sites waiting for care. We conclude that clinicians in resource-poor settings spend limited amounts of time at the clinic site, with a large portion of the clinic-time taken up by tasks that do not require specialized patient-care skills. This study demonstrates that opportunities exist to improve clinic productivity and visit experience for patients, and provides a baseline for designing and evaluating the impact of process improvement interventions.


Safety and one-year efficacy of intrathecal baclofen therapy in children with intractable spastic cerebral palsy.
Prospective studies that address both efficacy and safety of continuous infusion of intrathecal baclofen (CITB) in children with spastic cerebral palsy (CP), and that use outcome measures beyond muscle tone are lacking. To study the efficacy at 12 months and safety up to 24 months after start of CITB in children with intractable spastic CP. Nine girls and eight boys, aged 13.7 years (SD 2.9), received a SynchroMed pump for CITB. We prospectively recorded effects and adverse events at regular follow-up visits up to 24 months. Outcome measures included the 0-10 visual analogue scale (VAS) for individual problems, Gross Motor Function Measure (GMFM) and health related quality of life as measured with the Child Health Questionnaire-PF50. CITB for 12 months significantly improved the VAS for individual problems with 4.7 (SD 2.0; p=0.000), VAS for ease of care with 5.2 (SD 2.1; p=0.000), VAS for pain with 5.4 (SD 2.7; p=0.002); GMFM sitting dimension with 3.3 (range -4.0 to 22.0; p=0.022), GMFM goal dimension with 4.0 (range 0.0-26.0; p=0.007); and Child Health Questionnaire-PF50 domains of bodily pain/discomfort with 25.6 (SD 35.9; p=0.016) and mental health with 9.8 (SD 11.3; p=0.007). During a mean follow-up of 18.4 months (range 12-24), we recorded 80 adverse events. Eight adverse events were serious, but not life-threatening. CITB was effective at 12 months and safe up to 24 months for carefully selected children with intractable spastic CP. CITB relieved pain, facilitated ease of care and improved mental health. The majority of children could extend their activities and participation.


Koumiss promotes Mycobacterium bovis infection by disturbing intestinal flora and inhibiting endoplasmic reticulum stress.
Mycobacterium bovis is the causative agent of bovine tuberculosis and also responsible for serious threat to public health. Koumiss is a fermented mare's milk product, used as traditional drink. Here, we explored the effect of koumiss on gut microbiota and the host immune response against M bovis infection. Therefore, mice were treated with koumiss and fresh mare milk for 14 days before M bovis infection and continue for 5 weeks after infection. The results showed a clear change in the intestinal flora of mice treated with koumiss, and the lungs of mice treated with koumiss showed severe edema, inflammatory infiltration, and pulmonary nodules in M bovis-infected mice. Notably, we found that the content of short-chain fatty acids was significantly lower in the koumiss-treated group compared with the control group. However, the expression of endoplasmic reticulum stress and apoptosis-related proteins in the lungs of koumiss-treated mice were significantly decreased. Collectively, these findings suggest that koumiss treatment disturb the intestinal flora of, which is associated with disease severity and the possible mechanism that induces lungs pathology. Our current findings can be exploited further to establish the "gut-lung" axis which might be a novel strategy for the control of tuberculosis.


Mated pairs of owl monkeys (Aotus nancymaae) exhibit sex differences in response to unfamiliar male and female conspecifics.
In socially monogamous species, mate-guarding could be a reproductive strategy that benefits both males and females, especially when males contribute to parental care. By actively guarding mates, males may reduce their chances of being cuckolded, whereas females that mate-guard may reduce the likelihood that their mates will desert them or acquire additional mates, and hence limit or reduce paternal care of offspring. Owl monkeys (Aotus spp.) are socially monogamous with biparental care of young and, hence, potential beneficiaries of mate-guarding. We presented mated pairs of captive owl monkeys (A. nancymaae) with unfamiliar male and female conspecifics, to determine if either member of the pair exhibits intraspecific aggression toward an intruder or stays close to its mate, behaviors indicative of mate-guarding. Male mates were more responsible for the maintenance of close proximity between mates than females. Male mates also exhibited elevated levels of behavior that signify arousal when presented with a male conspecific. These responses by mated male owl monkeys are consistent with patterns that may help prevent cuckoldry.