(Phosphino)(aryl)carbenes: effect of aryl substituents on their stabilization mode.
A broad range of (phosphino)(aryl)carbenes, 1b-d, 10a,b, and 14a,b, were prepared by photolysis of their diazo precursors. The influence of the steric and electronic properties of the aryl ring on the structure and stability of these carbenes was studied both experimentally and theoretically. Among the different stabilization modes investigated, those featuring an acceptor as well as a spectator aryl substituent result in stable or at least persistent carbenes that could be completely characterized by classical spectroscopic methods. In marked contrast, the new substitution pattern featuring a donor aryl ring results in a very fleeting carbene.


Drug adherence in patients taking oral anticoagulation therapy.
Oral anticoagulation has proven to reduce mortality and morbidity of thromboembolic events. One of the most important determinants of the effectiveness and safety of anticoagulation therapy is the adherence to the prescribed therapy. Vitamin K antagonists are characterized by under-utilization, a narrow therapeutic window and multiple food and drug interactions which contribute to a variable dose-response relationship with the risk of insufficient protection and/or increased bleeding risk. The "new" direct oral anticoagulants have demonstrated equal or superior protection and reduced bleeding risks compared to warfarin and are easier to use because of fixed dosing without monitoring of anticoagulation. Controlling of adherence to the direct oral anticoagulants is difficult. Therefore, continuous and regular medication intake represents a pre-requisite for achieving optimal protection. The present review aims to give an overview about the factors that affect drug adherence in patients taking oral anticoagulation drugs and discusses strategies to improve drug adherence.


Serial measurement of serum cytokines, cytokine receptors and neopterin in leprosy patients with reversal reactions.
Serum levels of cytokines (IL-4, IL-5, IFN-gamma, TNF-alpha), cytokine receptors (TNFR I and II) and one monokine (neopterin) were estimated in seven leprosy patients to establish disease associated markers for reversal reactions (RR). Sera were collected at diagnosis of leprosy, at the onset of reversal reaction and at different time points during and at the end of prednisone treatment of reactions. It was expected that the serum cytokine and monokine profile before and at different time points during reactions would provide guidelines for the diagnosis and monitoring of reversal reactions in leprosy. The cytokines and cytokine receptors were measured by ELISA, whereas a radioimmunoassay was used for neopterin measurement. Six of the seven patients showed increased levels of neopterin either at the onset of RR or 1 month thereafter, and levels declined on prednisone treatment to that seen at the time of diagnosis without reactions. No consistent disease associated cytokine profile was observed in these patients. Interestingly, serum TNF-alpha levels were increased in the same patients even after completion of prednisone treatment, indicating ongoing immune activity. In conclusion, this study demonstrates that despite cytokines levels in leprosy serum being inconsistent in relation to reversal reactions, serum neopterin measurement appears to be an useful biomarker in monitoring RR patients during corticosteroid therapy.


Treatment of chronic mandibular dislocations by bone plates: two case reports.
Various surgical procedures have been used to limit mandibular opening in patients with recurrent dislocations of the temporomandibular joint (TMJ). These include intracapsular injection of sclerosing agents and tethering of the mandible. Other methods include obstruction of the condylar translation by downfracturing the zygomatic arch or by bone graft augmentation of the tuberculum and creating a mechanical impediment using Vitallium mesh or a stainless steel pin. In this paper, two patients are described in whom the range of condylar movement was restricted by a bone plate attached to the lateral surface of the zygomatic arch. One arm of the plate was extended medially just below the articular eminence. One patient had a hypermobile joint in combination with mitral valve prolapse, and the other patient suffered mental retardation. The surgical technique is described in detail. Six months postoperatively, TMJ function was unimpeded and there was no recurrence of condylar dislocation.


Is a low dose of concomitant chemotherapy with extended-field radiotherapy acceptable as an efficient treatment for cervical cancer patients with metastases to the para-aortic lymph nodes?
Extended-field radiotherapy (EFRT) with the concomitant administration of chemotherapy for patients with advanced cervical cancer has problems regarding its feasibility. The goal of the present study was to assess the tolerability and control rate of low-dose cisplatin with EFRT in patients with imaging-confirmed positive para-aortic lymph nodes (PALs). Sixteen patients with cervical cancer metastatic to the PALs treated with EFRT were evaluated. The patients included those with stages I to III disease according to the International Federation of Gynecology and Obstetrics with positive PALs diagnosed by computed tomographic imaging. The patients were treated with 25 to 30 mg/m weekly of cisplatin concurrently with radiation therapy. Doses of 48.6 to 51.0 Gy were delivered in 1.8-Gy fractions to the pelvis and included the PALs field. In addition, boost doses for the involved nodes of PALs were delivered contiguously for a total dose of 54 to 60 Gy. All patients were treated with a high dose rate of intracavitary brachytherapy combined with external irradiation. All patients completed the radiation therapy. Grade 3 or 4 acute hematologic toxicity occurred in 7 patients, but there were no cases of grade 3 or 4 nonhematologic acute toxicity. As a late toxicity, 1 patient developed a grade 3 small bowel obstruction. No grade 4 or worse late toxicity occurred. The 4-year overall survival rate was 56.3%. The 4-year distant metastasis-free survival rate was 50%. Seven patients had no recurrence. Eight patients developed distant failures, and another had an isolated local intrapelvic recurrence. A dose greater than 54 Gy for positive PALs in EFRT, in combination with intracavitary irradiation and low-dose weekly cisplatin administration, was safely completed by all of our patients. However, half of the patients had distant failure. This study provided relatively favorable local control and survival. Further considering modifications of the treatment should therefore be encouraged.


Comparison of the secretory response of the nasal mucosa to methacholine and histamine.
To better understand the secretory response of the nasal mucosa, we must be able to accurately measure its physiological response. To this end, we developed a localized challenge technique using paper disks to stimulate the mucosa on one side and measure secretions from both sides to study both direct and reflex responses. Both methacholine and histamine induced a dose-dependent increase in secretion weights on the challenge side, whereas only histamine induced a contralateral reflex. Repeated stimulation with histamine, but not methacholine, resulted in tachyphylaxis. Pretreatment with atropine resulted in inhibition of the contralateral secretory response to histamine and the ipsilateral response to methacholine with only partial inhibition of the ipsilateral histamine response. Terfenadine pretreatment resulted in the complete inhibition of both the ipsilateral and contralateral responses to histamine with no effect on methacholine-induced secretions. Ipsilaterally applied lidocaine had no effect on the histamine response but, when applied contralaterally, partially inhibited that response. Topical diphenhydramine applied ipsilaterally led to significant inhibition of the ipsilateral and contralateral secretory responses to histamine but had no effect when applied contralaterally. We conclude that methacholine and histamine have different effects on the nasal mucosa. We speculate that methacholine stimulates glands directly, whereas histamine includes both direct and neurogenic stimulation.


Lacrimal sac lymphoma: A series of Japanese patients.
To present cases of primary lacrimal sac lymphoma in a Japanese population. In this retrospective case series, five cases (two males and three females; mean age: 49.8 years; age range: 38-62 years) were included. Clinical features, diagnostic findings, and treatment outcomes were collected and reviewed. Most patients presented with a swelling or mass in the medial canthal area. Only one patient presented with epiphora, while another patient also complained of pain which was due to inflammation. Imaging studies revealed a lacrimal sac mass with involvement of the nasolacrimal duct and variable involvement of the nasal cavity. Histopathological findings revealed three cases of diffuse large B-cell lymphoma, one case of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, and one case of follicular lymphoma. Four cases were treated with a combination of chemotherapy and immunotherapy, with one case necessitating additional radiotherapy. One case was treated with immunotherapy alone. The mean follow-up was 23 (range: 3-50) months. Four cases showed complete remission, while the remaining patient is still ongoing treatment. Diffuse large B-cell lymphoma is the most common type of lacrimal sac lymphoma in this series. Lacrimal sac tumors should be ruled out in the presence of epiphora, dacryocystitis, or a mass in the medial canthus, even in the absence of pain or bleeding. Combined chemotherapy and immunotherapy is an effective treatment for these cases.


Influenza, including the novel H1N1, in organ transplant patients.
This article will review the epidemiology, diagnosis, prevention and management of influenza in solid organ transplant recipients. A number of recent studies have documented that influenza vaccination is both well tolerated and generally effective in producing an immunologic response in most solid organ transplant (SOT) recipients. Antiviral use is associated with improved clinical outcomes, but prolonged shedding may require a longer course of therapy than what is currently approved by the FDA. Antiviral resistance emerges rarely in transplant patients and should be considered in all patients with an inadequate clinical and/or virologic response. Influenza is associated with significant morbidity and mortality, particularly in lung transplant recipients. Molecular diagnostics are preferred over other diagnostic modalities, if available. Influenza vaccination is well tolerated and provides protective benefit in most SOT recipients; in those with contraindications to vaccination or in whom responses are predicted to be poor, antivirals may be considered. Antiviral therapy is associated with improved outcomes in transplant patients and treatment should be continued until clinically and virologic response have been documented. Resistance, particularly with patients infected with the pandemic influenza A/H1N1, should be considered and treated with an antiviral with predicted activity.


The effect of sterilisation on the plasticity of multi-use Eschmann gum elastic bougies: a bench and manikin study.
We investigated the deterioration in plasticity of the multi-use Portex Tracheal Guide ('bougie') with repeated sterilisation. Six bougies were prepared by washing them between 0 and 100 times (in accordance with the manufacturer's guidelines). Two tests were employed: a bench test in which rapid serial photographs were taken of the bougies uncoiling from a preformed curve; and a manikin-based test in which the six bougies were used in a simulated difficult airway. The bench test demonstrated a progressive deterioration in plasticity with repeated washing. However, the manikin-based test showed no significant difference between bougies in the incidence of oesophageal placement (p = 0.74). Time to placement differed significantly only between the two most-washed bougies but was broadly similar. We suggest therefore that the manufacturer's limit of five washings may be unnecessarily cautious.


Ontogeny of swim performance and mechanics in bottlenose dolphins (Tursiops truncatus).
Morphological and physiological development impacts swimming performance throughout ontogeny. Our investigation of the ontogeny of swim performance (mean and maximum swim speed) and swim effort (stroke amplitude and tailbeat frequency) of independently swimming bottlenose dolphins (Tursiops truncatus) demonstrated that swimming capabilities are extremely limited in calves. Mean and maximum swim speeds of 0-1-month-old calves were only 37% and 52% of that for adults, respectively, and levels similar to those of adults were not achieved until one year post-partum. Limitations in swim speed were associated with an inability to achieve mature thrusting capabilities, as stroke amplitude and distance covered per stroke remained significantly lower than adult levels during the first-year post-partum. Although calves were expected to require less thrusting power to propel their smaller bodies through water, size-specific stroke amplitudes of 0-3-month-olds (23-26% of body length) were smaller than those of dolphins >or=10 months post-partum (29-30% of body length). As a result, swim speed standardized by body length was significantly slower for 0-3-month-old dolphins compared with dolphins >or=10 months post-partum. These results suggest that other factors, such as underdeveloped physiology, act synergistically with small body size to limit independent swim performance in dolphins during ontogeny.


Single-molecule sensing using carbon nanotubes decorated with magnetic clusters.
First-principles and nonequilibrium Green's function techniques are used to investigate magnetism and spin-polarized quantum transport in metallic carbon nanotubes (CNT) decorated with transition metal (Ni(13), Pt(13)) magnetic nanoclusters (NC). For small cluster sizes, the strong CNT-NC interaction induces spin-polarization in the CNT. The adsorption of a benzene molecule is found to drastically modify the CNT-NC magnetization. Such a magnetization change should be large enough to be detected via magnetic-AFM or SQUID magnetometry, hence suggesting a novel approach for single-molecule gas detection.


Potential protective effects of oral administration of allicin on acrylamide-induced toxicity in male mice.
Acrylamide (AA) forms during the heating of starchy foods at high temperature, and is regarded as a potential genotoxic carcinogen. However, with the worldwide concern about the carcinogenicity of AA, how to reduce the toxicity of AA has become a hot research topic. In this study, we further discussed the effects of oral administration of allicin on AA-induced toxicity by determining the hematological, biochemical and immunological parameters in the serum, kidney, liver, and brain of male mice. Our data showed that the orally administered allicin of 5, 10, and 20 mg kg⁻¹ bw d⁻¹ could significantly decrease thiobarbituric reactive substances (TBARS) and myeloperoxidase (MPO) levels, and simultaneously remarkably increased the superoxide dismutase (SOD) activity, glutathione S-transferase (GST) and glutathione (GSH) levels in the kidney, liver, and brain of the AA-treated mice. Furthermore, oral administration of allicin not only significantly decreased aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), tumor necrosis factor α (TNF-α), interleukin (IL)-1β, interleukin (IL)-6, reactive oxygen species (ROS), and 8-hydroxy-desoxyguanosine (8-OHdG), but also increased interleukin (IL)-10 in the serum of AA-treated mice. Therefore, it was concluded that oral administration of allicin had a significant in vivo protective effect against the AA induced toxicity.


Using triaxial magnetic fields to create high susceptibility particle composites.
We report on the use of triaxial magnetic fields to create a variety of isotropic and anisotropic magnetic particle/polymer composites with significantly enhanced magnetic susceptibilities. A triaxial field is a superposition of three orthogonal ac magnetic fields, each generated by a Helmholtz coil in series resonance with a tunable capacitor bank. Field frequencies are in the range of 150-400 Hz. Because both the field amplitudes and frequencies can be varied, a rich variety of structures can be created. Perhaps the most unusual effects occur when either two or three of the field components are heterodyned to give beat frequencies on the order of 1 Hz. This leads to a striking particle dynamics that evolves into surprising structures during resin gelation. These structures are found to have perhaps the highest susceptibility that a particle composite can have. The susceptibility anisotropy of these composites can be controlled over a wide range by judicious adjustment of the relative field amplitudes. These experimental data are supported by large-scale Brownian dynamics simulations of the complex many-body interactions that occur in triaxial magnetic fields. These simulations show that athermal three-dimensional field heterodyning leads to structures with a susceptibility that is as high as that achieved with thermal annealing. Thus with coherent particle motions we can achieve magnetostatic energies that are quite close to the ground state.


Development of Betalain Producing Callus Lines from Colored Quinoa Varieties (Chenopodium quinoa Willd).
Betalains are water-soluble plant pigments of hydrophilic nature with promising bioactive potential. Among the scarce edible sources of betalains is the grain crop quinoa (Chenopodium quinoa Willd), with violet, red, and yellow grains being colored by these pigments. In this work, callus cultures have been developed from differently colored plant varieties. Stable callus lines exhibited color and pigment production when maintained on Murashige and Skoog medium supplemented with the plant growth regulators 6-benzylaminopurine (8.88 μM) and 2,4-dichlorophenoxyacetic acid (6.79 μM) with a reduction of the nitrogen source to 5.91 mM. Pigment analysis by HPLC-DAD and ESI-MS/MS fully describes the content of individual pigments in the cell lines and allows the first report on the pigments present in quinoa seedlings. Phyllocactin and vulgaxanthin I are described as novel pigments in the species and show the potential of C. quinoa culture lines in the production of compounds of nutritional value.


The "stomatin" gene and protein in overhydrated hereditary stomatocytosis.
In overhydrated hereditary stomatocytosis (OHSt), Coomassie- and silver-stained polyacrylamide gels show an apparently complete deficit of the 32-kDa membrane protein, stomatin. We have used an antistomatin antibody to examine peripheral blood films, bone marrow, splenic tissue, and hepatic tissue from these patients by immunocytochemistry. This technique revealed that, in fact, some red cells did show positive stomatin immunoreactivity; and consistent with this result, Western blot analysis of the red cell membranes confirmed that about one twentieth to one fiftieth of the normal amount of stomatin was in fact present. Flow cytometry, combining immunoreactive quantitation of stomatin expression with thiazole orange staining for reticulocytes, showed that in OHSt, it was the young cells that had more stomatin. Magnetic-activated cell separation studies, using beads to which an anti-transferrin receptor antibody was conjugated, confirmed that in OHSt there was a correspondence between expression of stomatin and the transferrin receptor. Immunocytochemistry and Western blotting revealed that in OHSt patients, the protein was present in spleen, liver, neutrophils, platelets, monocytes, and about 50% of the peripheral lymphocytes, with the same distribution as in healthy controls. Neither Southern blots, nor direct sequencing of multiple subclones of the cDNA, nor sequencing of amplicons from genomic DNA revealed any significant abnormality in stomatin gene sequence in these patients. The deficiency of stomatin from red cells appears to be due to a loss of stomatin from these red cells on maturation in the bone marrow and in the circulation.


Quantitative analysis of T-wave morphology increases confidence in drug-induced cardiac repolarization abnormalities: evidence from the investigational IKr inhibitor Lu 35-138.
This study investigates repolarization changes induced by a new candidate drug to determine whether a composite electrocardiographic (ECG) measure of T-wave morphology could be used as a reliable marker to support the evidence of abnormal repolarization, which is indicated by QT interval prolongation. Seventy-nine healthy subjects were included in this parallel study. After a baseline day during which no drug was given, 40 subjects received an I(Kr)-blocking antipsychotic compound (Lu 35-138) on 7 consecutive days while 39 subjects received placebo. Resting ECGs were recorded and used to determine a combined measure of repolarization morphology (morphology combination score [MCS]), based on asymmetry, flatness, and notching. Replicate measurements were used to determine reliable change and study power for both measures. Lu 35-138 increased the QTc interval with corresponding changes in T-wave morphology as determined by MCS. For subjects taking Lu 35-138, T-wave morphology was a more reliable indicator of I(Kr) inhibition than QTcF (chi(2) = 20.3, P = .001). At 80% study power for identifying a 5-millisecond placebo-adjusted change from baseline for QTcF, the corresponding study power for MCS was 93%. As a covariate to the assessment of QT interval liability, MCS offered important additive information to the effect of Lu 35-138 on cardiac repolarization.


Is insulin growth factor-1 (IGF-1) playing a role for aneurysm formation in patients with pituitary gland tumor?
The combination of pituitary gland tumor and aneurysmal disease has previously been described. Most of these aneurysms have affected intracranial arteries. The purpose is to present 2 patients with thoracoabdominal aortic aneurysm and pituitary gland tumor and further to discuss the mechanism behind this combination of diseases. A 59-year-old male patient was admitted with abdominal pain and a 120 mm thoracoabdominal aortic aneurysm type III. He was operated with resection and graft replacement. During the operation, it was noted that his intra-abdominal arteries were extremely enlarged. The diagnosis acromegaly was confirmed in the late 50's and he had received irradiation therapy and underwent partial trans-sphenoidal hypophysectomy. His growth hormone values eventually declined while he had elevated insulin growth factor-1 (IGF-1) levels. The patient died from stroke 6 years after operation. Patient n. 2 is a 73-year-old female with a type II thoracoabdominal aortic aneurysm. She was operated for a pituitary adenoma in 1988. There were no clinical or biochemical signs of acromegaly. However, she had elevated serum values of IGF-1. The maximum diameter of the aneurysm was 60 mm. Because of comorbidity the patient has been followed at the outpatient clinic. The mechanism behind the combination of pituitary gland tumor and aneurysm is obscure. One of our patients had classical acromegaly. Growth hormone decreased over the years, while his IGF-1 values were normal or elevated. The other patient had increased levels of IGF-1 without typical acromegaly. This might indicate that IGF-1 could play a role in the development of aneurysm in patients with pituitary tumor. This combination of diagnoses should be kept in mind when dealing with patients having aneurysmal disease.


Health effects guidance for uranium in drinking water.
The interim regulations for radioactivity in drinking water were promulgated in 1976 (Federal Register, Friday, 9 July, 1976, p. 28402). These regulations specifically excluded uranium because of uncertainties concerning its toxicology, treatment technology and occurrence. At this time, EPA's Office of Drinking Water is considering proposing a health effects guidance level of 10 pCi/l. (0.37 Bq/l.) for uranium in drinking water. This paper describes the approach that EPAs Office of Drinking Water is considering in developing the guidance level. This value has not yet been officially determined to be EPA's formal guidance, but is presented as a working hypothesis for review and comments. Included here is a discussion of occurrence, pharmacokinetics and health effects. The calculation of doses uses the ICRP 30 model and the risk determination uses EPA's newly developed life table approach. The risk level from ingesting drinking water with a uranium content of 10 pCi/l. is estimated to be about 3 X 10(-5) excess cancers/lifetime.


Highly selective recognition of adenine nucleobases by synthetic hosts with a linked five-six-five-membered triheteroaromatic structure and the application to potentiometric sensing of the adenine nucleotide.
A new structure for an adenine-selective host molecule, featuring the pertinent link of five-six-five-membered heteroaromatic rings and two carbamoyl NH sites, was developed. This structure provides a correctly oriented array of complementary hydrogen bonding sites for the adenine nucleobase, which exploits both Watson-Crick and Hoogsteen-type interactions. The complexation with adenine nucleobases by multiple hydrogen bonding was supported by (1)H NMR spectroscopy. This type of host displayed high selectivity in complexation, with an accompanying fluorescent response to lipophilized adenosine in CHCl(3). Furthermore, a remarkably selective potentiometric response was attained for adenosine 5'-monophosphate over 5'-GMP, 5'-CMP, and 5'-UMP by using an ion-selective electrode with a PVC-supported solvent polymeric membrane. This indicates recognition of water-soluble nucleotide guests through the membrane-water interface. These findings are expected to form a reliable basis for the development of artificial sensing systems for mononucleotides in biological systems.


Bilateral superior cerebellar artery infarcts: unusual presentation in two patients of stroke in young.
Stroke or cerebrovascular disease is one of the most important causes of high morbidity and mortality throughout the world. Stroke in young individuals poses a major problem as these individuals are bread earners of the family. Ischaemic strokes are increasingly being attributed to causes other than atherothrombotic disease. Disorders of coagulation leading to thrombotic disorders are relatively uncommon conditions which are implicated in approximately 1% of all ischaemic strokes and 4-8% of young strokes. Bilateral superior cerebellar infarcts due to hypercoagulable state are extremely rare situations. Here we present two patients with unusual presentation of stroke in young due to hypercoagulable state.


Ca(2+)-activated K+ channel is present in guinea-pig but lacking in rat hepatocytes.
The mechanisms of norepinephrine-induced membrane responses in isolated hepatocytes from guinea-pigs and rats were compared using the suction-pipette, patch-clamp method, and intracellular Ca2+ concentration ([Ca2+]i) was measured using the Ca2+ fluorescent dye, Quin 2. The resting membrane potentials of isolated guinea-pig hepatocytes were -50 +/- 1 mV (mean +/- SD; n = 38), which is similar to that previously reported in rat hepatocytes by Sawanobori et al. (J Cell Physiol 139: 580-585, 1989). In guinea-pig hepatocytes, norepinephrine (6 microM) caused a membrane hyperpolarization, and norepinephrine (6 microM) or Ca(2+)-ionophore (A23187) (0.4 microM) caused a corresponding outward current. The sensitive current produced by norepinephrine and Ca(2+)-ionophore reversed its polarity at -74 +/- 9 mV (n = 7). The single channel recorded by cell-attached patch and inside-out patch had mean conductance of around 20 + 1 pS and was activated by 1 microM [Ca2+]i. On the other hand, neither norepinephrine (6-20 microM) nor Ca(2+)-ionophore (A 23187) (0.4 microM) caused any change in membrane potential and current in rat hepatocytes, whereas norepinephrine increased [Ca2+]i both in rat and guinea-pig hepatocytes to a similar degree. In the single-channel recording, we recorded single channels that had a mean conductance of 109.8 +/- 17.7 pS different from around 20 pS in guinea-pig. In inside-out patches, increased Ca2+ concentration from 10(-6) to 10(-3) M at the intracellular face of the membrane did not modify the single channel of rat hepatocytes. These results indicate that increased [Ca2+]i activates this channel in guinea-pigs, but that the channel activated by increased [Ca2+]i is lacking in rat hepatocytes membrane. Therefore, different mechanism operates in different species of liver cells to keep the constant state.


[Changes in the kallikrein-kinin system of the blood following hypothalamo-hypophyseal stimulation of animals of different ages].
Changes occurring in the formation and synthesis of kinins become irregular with ageing: the content of kallikreinogenes decreases, the activity of kininase and inhibitors of trypsin falls, and total blood activity of hydrolysis of ethyl--N--benzoil--L--arginine ether rises. Stimulation of the hypothalamus causes an obvious activation of the kalikrein--kinin system in adult animals: the contents of kallikreinogenes and kininogenes fall, the kallikrein activity sharply increases, whereas the kininase activity decreases. Both single and repeated administrations of vasopressin induce the same shifts of kallikrein--kinin system as the stimulation of hypothalamus. On repeated administrations of vasopressin the kininase activity rises.


Myelinated nerve fibers and refractory amblyopia: a case report.
We describe the case of a 3.5-year-old boy who had myelinated retinal nerve fibers and ipsilateral amblyopia refractory to occlusion therapy and simple myopic astigmatic correction. We suggest that myelinated nerve fibers may result in organic amblyopia with a resultant poor visual prognosis.


Vertically Grown Few-Layer MoS2 Nanosheets on Hierarchical Carbon Nanocages for Pseudocapacitive Lithium Storage with Ultrahigh-Rate Capability and Long-Term Recyclability.
Molybdenum disulfide (MoS2 ) is an intensively studied anode material for lithium-ion batteries (LIBs) owing to its high theoretical capacity, but it is still confronted by severe challenges of unsatisfactory rate capability and cycle life. Herein, few-layer MoS2 nanosheets, vertically grown on hierarchical carbon nanocages (hCNC) by a facile hydrothermal method, introduce pseudocapacitive lithium storage owing to the highly exposed MoS2 basal planes, enhanced conductivity, and facilitated electrolyte access arising from good hybridization with hCNC. Thus, the optimized MoS2 /hCNC exhibits reversible capacities of 1670 mAh g-1 at 0.1 A g-1 after 50 cycles, 621 mAh g-1 at 5.0 A g-1 after 500 cycles, and 196 mAh g-1 at 50 A g-1 after 2500 cycles, which are among the best for MoS2 -based anode materials. The specific power and specific energy, which can reach 16.1 kW kg electrode - 1 and 252.8 Wh kg electrode - 1 after 3000 cycles, respectively, indicate great potential in high-power and long-life LIBs. These findings suggest a promising strategy for exploring advanced anode materials with high reversible capacity, high-rate capability, and long-term recyclability.


[Laryngeal papillomatosis: A rare cause of dysphonia in the child. Case series].
Juvenile laryngeal papillomatosis is an uncommon disease caused by human papilloma virus, mainly types 6 and 11. It is the most common benign laryngeal tumor in children. This condition should be suspected in any children with persistent and progressive dysphonia with or without stridor and respiratory distress. Flexible laryngoscopy under local anesthesia allows to visualize the typical wart-like lesions. The diagnosis is confirmed by pathological anatomy. Existing treatment is palliative and consists mainly of the surgical excision of the papillomas to maintain the airway without obstruction and to improve the quality of the voice, but it has a high rate of relapse. We present 20 patients with juvenile laryngeal papillomatosis. We describe the clinical manifestations, the diagnostic methods and the treatment of this pathology.


Maternal febrile illnesses, medication use, and the risk of congenital renal anomalies.
Renal anomalies occur in about three infants per 1000 live births and have been associated with several environmental risk factors. Researchers have yet to assess the effect of maternal febrile illnesses on renal anomalies, even though febrile illnesses have been associated with other birth defects. Our objective was to determine whether maternal illness, fever, or medication use during the first trimester of pregnancy is associated with the occurrence of renal anomalies. In this population-based case-control study, we evaluated 192 infants with renal anomalies (renal agenesis [n = 44], obstructive defects [n = 134], and renal duplication defects [n = 14]) and 3029 infant without birth defects, all of whom were born in metropolitan Atlanta, Georgia, from 1968 through 1980. Maternal illness was defined as reported flu-like illness and/or episodic illness during the first trimester. Our adjusted multivariate analyses showed that among the 192 case-infants, 38 had mothers with an illness (adjusted odds ratio [AOR], 1.71; 95% confidence interval [CI], 1.15-2.52), 20 had mothers who reported a fever (AOR, 1.80; 95% CI, 1.07-3.02) and 26 had mothers who reported taking medication (AOR, 1.69; 95% CI, 1.07-2.68). Fifteen mothers reported a fever and medication use (AOR, 1.90; 95% CI, 1.05-3.45). Nonprescription aspirin-containing medication use showed the strongest association (AOR, 3.45; 95% CI, 1.36-8.75) with renal anomalies. Our data suggest that maternal exposure to illness, fever, and medication (particularly aspirin) may increase the risk of congenital renal anomalies.


Brain tissue pH, oxygen tension, and carbon dioxide tension in profoundly hypothermic cardiopulmonary bypass. Pulsatile assistance for circulatory arrest, low-flow perfusion, and moderate-flow perfusion.
The brain tissue pH, oxygen tension, and carbon dioxide tension were experimentally examined during profoundly hypothermic cardiopulmonary bypass with core cooling and core rewarming. Sixty-minute circulatory arrests (n = 28, group I), 120-minute low-flow perfusions (25 ml/kg/min; n = 16, group II), and 120-minute moderate-flow perfusions (50 ml/kg/min; n = 16, group III) were accomplished with and without pulsatile flow. In group I, progressive brain tissue acidosis and hypercapnia were recovered with pulsatile assistance. In group II, brain tissue acidosis and hypercapnia were recovered completely with pulsatile assistance but incompletely without it. In group III mild acidosis was eliminated with pulsatile assistance where the pH was significantly higher than in groups I and II, and brain tissue carbon dioxide pressure was significantly lower than in groups I and II with and without pulsatile assistance. Brain tissue hypoxia was severe in group I, slight in group II, but not found in group III. We concluded that a perfusion flow rate will decide the safe period, and a pulsatile assistance will promote brain protection at any flow rate in profoundly hypothermic cardiopulmonary bypass.


[Late results of radical surgery of stomach cancer. Study of 380 patients from 1967 to 1977].
The report is based on the analysis of 380 cases. There was an absolute 5-year-survival rate of 12.6%, and a relative 5-year-survival rate of 25.3%. The dependence of late results on factors characterizing the tumorous process has been analysed and the modalities for improving the results are discussed.


A patient with acute myeloid leukemia who developed fatal pneumonia caused by carbapenem-resistant Bacillus cereus.
Bacillus cereus is known as a serious bacterial pathogen in neutropenic patients. B. cereus is often resistant to beta-lactams, including penicillins and cephalosporins. We report a case of fatal pneumonia caused by B. cereus in a patient with newly diagnosed acute myeloid leukemia (AML) during remission induction therapy. Cefepime was started for febrile neutropenia (FN) initially and was switched to panipem/betamipron, when fulminant pneumonia supervened. The isolated strain was resistant not only to cefepime but also to panipenem/betamipron. This is the first report of fulminant infection caused by carbapenem-resistant B. cereus in a neutropenic patient. B. cereus should be kept in mind as a target of empirical treatment when neutropenic patients develop pneumonia.


Broadly tunable dual-wavelength light source for coherent anti-Stokes Raman scattering microscopy.
The signal and idler beams from a picosecond, synchronously pumped optical parametric oscillator (OPO) provide the two colors necessary for coherent anti-Stokes Raman scattering (CARS) microscopy. The OPO provides a continuously tunable frequency difference between the two beams over a broad range of Raman shifts (100-3700 cm(-1)) by varying the temperature of a single nonlinear crystal. The near-infrared output (900-1300 nm) allows for deep penetration into thick samples and reduced nonlinear photodamage. Applications of this light source to in vivo cell and ex vivo tissue imaging are demonstrated.


[Comparative study of diffuse intimal thickening of the coronary arteries in infants in the 1st year of life in Moscow, Frunze and Yakutsk].
The frequency and degree of the intima diffuse thickening (IDT) of heart coronary arteries from 186 autopsy cases--newborns and children of the first year of life of both sexes in the cities of Moscow, Frunze and Yakutsk, were studied. The higher incidence and higher degree of intensity is noted in Moscow as compared to Frunze and Yakutsk. Statistically significant differences are found between male infants in Moscow as compared to indigenous (p less than 0.001) and non-indigenous male infants in Frunze and Yakutsk; in female infants such differences (p less than 0.002) are found between those in Moscow on the one hand and indigenous female infants in Frunze and Yakutsk. In Frunze and Yakutsk the incidence and degree of intensity of IDT was somewhat higher in non-indigenous population of both sexes. The highest incidence and degree of intensity of IDT of coronary arteries were in children of both sexes whose mothers suffered from arterial hypertension.


A preliminary analysis of preparation strategies and other correlates to performance on a basic science qualifying exam in chiropractic.
Due to the high-stakes nature of board exams, students who enroll in chiropractic and other healthcare educational programs spend a significant amount of time and money on preparation strategies including: commercial coaching courses, course notes, commercial note sets, old test questions, online resources, text books and small group study sessions. However, whether such strategies help predict academic performance on the National Board exams has received little attention by researchers in chiropractic education. The purpose of this study is to evaluate the effects of study strategies, student demographics, prepared materials and other measures of general academic preparedness on the National Board of Chiropractic Examiners (NBCE) Part I exam performance. A Student survey utilizing descriptive statistics was used and multivariable analysis was performed. Two hundred twenty-nine subjects completed a 52-item survey. Participants were asked to describe their study preparation for the NBCE Part I exam. Survey responses were then examined with composite NBCE Part I scores, selected demographics, pre-chiropractic cumulative grade point average (GPA), and in-program chiropractic college GPA. Pre-chiropractic GPA and in-program GPA correlated significantly to the response variable (NBCE Part I Scores). Using multiple regression, the paired variables of past education and in-program GPA accounted for a significant portion (R(2) = .638, P < .001) of the total variance in NBCE Part I scores. Further, the in-program GPA variable alone accounted for significant unique explanation (change R(2) =.368, P < .001). Demographics, employment status, preparation strategies, and prepared materials were considerably less potent predictors of performance on Part I of the NBCE exam. This study raises questions concerning the effectiveness of preparation strategies including commercial coaching courses on the National Board examination scores. Further, the results suggest that short-term preparation strategies and study efforts immediately before the NBCE Part I exam (as well as other factors) have a minimal correlation to exam scores. In this study, pre-chiropractic GPA, in-program GPA, and post-secondary education completed before matriculation into chiropractic college were the best predictors of performance on NBCE Part I.


Effect of divalent versus monovalent cations on the MS2 retention capacity of amino-functionalized ceramic filters.
Ceramic capillary membranes conditioned for virus filtration via functionalization with n-(3-trimethoxysilylpropyl)diethylenetriamine (TPDA) are analyzed with respect to their virus retention capacity when using feed solutions based on monovalent and divalent salts (NaCl, MgCl2). The log reduction value (LRV) by operating in dead-end mode using the model bacteriophage MS2 with a diameter of 25 nm and an IEP of 3.9 is as high as 9.6 when using feeds containing MgCl2. In contrast, a lesser LRV of 6.4 is observed for feed solutions based on NaCl. The TPDA functionalized surface is simulated at the atomistic scale using explicit-solvent molecular dynamics in the presence of either Na+ or Mg2+ ions. Computational prediction of the binding free energy reveals that the Mg2+ ions remain preferentially adsorbed at the surface, whereas Na+ ions form a weakly bound dissolved ionic layer. The charge shielding between surface and amino groups by the adsorbed Mg2+ ions leads to an upright orientation of the TPDA molecules as opposed to a more tilted orientation in the presence of Na+ ions. The resulting better accessibility of the TPDA molecules is very likely responsible for the enhanced virus retention capacity using a feed solution with Mg2+ ions.


National Databases in Pediatric Orthopaedic Surgery: A Comparison of Demographics, Procedures, and Outcomes.
Large national databases have been increasingly used in recent years to determine the rate of adverse events and identify factors associated with altered surgical outcomes. This can be especially useful to evaluate rare events such as 30-day mortality. Despite differences between national pediatric databases, there have been no comparison studies in the pediatric orthopaedic population. The Healthcare Cost and Utilization Project's Kids' Inpatient Database (KID) along with the American College of Surgeons National Surgical Quality Improvement Program Pediatric (NSQIP Pediatric) databases were queried to identify common pediatric orthopaedic procedures for humeral fractures, scoliosis, slipped capital femoral epiphysis, and femoral fractures during a single year. Clinical characteristics and complications in the 2 databases were compared using Student t test, χ, or Fisher' exact test. In total, 26,978 patients in the KID and 5186 patients in the NSQIP Pediatric databases were identified. Large differences were observed between the databases in identical procedure categories with respect to age, race, sex, and length of stay. Regardless of procedure, NSQIP Pediatric had statistically higher reported rates of cumulative complications. Surgical site infections and sepsis were consistently observed to be at least twice as common in the NSQIP Pediatric database in comparison to the KID. Overall, complication rates ranged from <1% in humeral fractures to >100% in neuromuscular scoliosis. Clinically and statistically significant differences exist between the KID and NSQIP Pediatric databases. Clinicians and researchers who utilize large databases must understand the differences in data import, quality control, and population sampling in order to provide adequate representation of the population as a whole. Level III, prognostic study.


Detection and transmission of infectious hematopoietic necrosis virus in rainbow trout.
Detection and transmission of Infectious Hematopoietic Necrosis Virus in rainbow trout (Salmo gairdneri) was studied at a commercial trout hatchery. Transmission of virus was demonstrated via water, feed and contaminated eggs. If eggs from carrier females were incubated several weeks in virus-free water, the resulting fry did not become infected. However, if fry subsequently became infected they were lifetime carriers. Infectious virus was readily detectable in most tissues of moribund fish; in carriers it was detected in sex products of spawning fish, and in samples from the intestine of post-spawning fish, but not in samples from blood, feces, kidney, or liver. The carrier rate was not significantly different between sexes. It was concluded that adult carriers are the reservoir of infection and that transmission occurs primarily when carriers shed virus and expose susceptable fish or eggs.


Hyperargininemia due to liver arginase deficiency.
The urea cycle is a series of six reactions necessary to rid the body of the nitrogen generated by the metabolism, primarily of amino acids, from the diet or released as the result of endogenous protein catabolism. Arginase is the sixth and final enzyme of this cycle. Arginase catalyzes the conversion of arginine to urea and ornithine, the latter recycled to continue the cycle. Hyperargininemia due to arginase deficiency is inherited in an autosomal recessive manner and gene for arginase, designated AI, has been cloned. Unlike the other urea cycle enzymes, a second gene encoding arginase, with similar structural properties and enzyme characteristics, exists and has been named Arginase II (AII). Comprehensive histories and physical examinations confirm a strikingly uniform clinical picture and one notably different from patients with other urea cycle disorders. This condition rarely presents in the neonatal period and first symptoms typically present in children between 2 and 4 years of age. First symptoms are often neurologically based. If untreated, symptoms are progressive with a gradual loss of developmental milestones. With adherence to a dietary and drug regimen, a favorable outcome can be expected, with cessation of further neurological deterioration and in some instances, of improvement. This article summarizes the clinical course of selected patients who represent the full spectrum of presentations of arginase deficiency. In addition to the clinical characterization of this disorder; the biochemical, enzymatic, and molecular evidence of disease is summarized. Treatment and prenatal diagnosis are also discussed.


[Examination of visual evoked potentials in persons exposed to prolonged contact with ethyl benzene vapors].
The aim of this study is an estimation of the visual evoked potentials (VEP) of persons exposed to prolonged contact with leaded petrol. A group of 90 males aged between 22 and 53, exposed to prolonged contact with leaded petrol for the period of between a few months to 30 years, was examined. Those examined were divided into three groups depending on the length of exposure: group 1 up to 10 years, group II-11-20 years, group III-20 years and more. The results were compared with those obtained from a group of 40 healthy age-matched males, not exposed to leaded petrol. In neurological and ophthalmological examinations no pathological symptoms were detected in both groups. The VEP examination was executed using pattern reversal (pr) and pattern flash (pf) stimulation. The frequent pathological record of VEP was an elongation in the latency of P-100 and reduction of response amplitude. Using pr stimulation, the reduction of the mean value of the amplitude for group III was found statistically significant (p < 0.01). In pf examination in group III mean latency of the P-100 was significantly statistically (p < 0.01) longer than in the control group. Significant reduction of the response amplitude in groups II (p < 0.01) and III (p < 0.001) was found in this type of stimulation. The results of studies indicate subclinical damage of the visual pathway particularly of persons exposed to leaded petrol vapour during work for longer than 20 years.


Body masses, functional responses and predator-prey stability.
The stability of ecological communities depends strongly on quantitative characteristics of population interactions (type-II vs. type-III functional responses) and the distribution of body masses across species. Until now, these two aspects have almost exclusively been treated separately leaving a substantial gap in our general understanding of food webs. We analysed a large data set of arthropod feeding rates and found that all functional-response parameters depend on the body masses of predator and prey. Thus, we propose generalised functional responses which predict gradual shifts from type-II predation of small predators on equally sized prey to type-III functional-responses of large predators on small prey. Models including these generalised functional responses predict population dynamics and persistence only depending on predator and prey body masses, and we show that these predictions are strongly supported by empirical data on forest soil food webs. These results help unravelling systematic relationships between quantitative population interactions and large-scale community patterns.


Efficient genome engineering approaches for the short-lived African turquoise killifish.
A central challenge in experimental aging research is the lack of short-lived vertebrate models for genetic studies. Here we present a comprehensive protocol for efficient genome engineering in the African turquoise killifish (Nothobranchius furzeri), which is the shortest-lived vertebrate in captivity with a median life span of 4-6 months. By taking advantage of the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 nuclease (CRISPR/Cas9) system and the turquoise killifish genome, this platform enables the generation of knockout alleles via nonhomologous end joining (NHEJ) and knock-in alleles via homology-directed repair (HDR). We include guidelines for guide RNA (gRNA) target design, embryo injection and hatching, germ-line transmission and for minimizing off-target effects. We also provide strategies for Tol2-based transgenesis and large-scale husbandry conditions that are critical for success. Because of the fast life cycle of the turquoise killifish, stable lines can be generated as rapidly as 2-3 months, which is much faster than other fish models. This protocol provides powerful genetic tools for studying vertebrate aging and aging-related diseases.


Interleukin-8 derived from local tissue-resident stromal cells promotes tumor cell invasion.
The aim of this study is to evaluate the role of adipose tissue resident stromal cells on tumor cell invasion. Our data show that a subpopulation of adipose tissue derived stromal cells expressing Nestin, NG2, α-smooth muscle actin and PDGFR-α migrate toward the cancer cells. Microarray analysis revealed the upregulation of IL-8 in the migrated cells. We demonstrated that stromal cell derived IL-8 promote the invasion and the anchorage-independent growth of cancer cells. We conclude that human breast cancer cells attract a subpopulation of stromal cells that secrete IL-8 to promote tumor cell invasion in a paracrine fashion.


Does Lung Compliance Optimization Through PEEP Manipulations Reduce the Incidence of Postoperative Hypoxemia in Laparoscopic Bariatric Surgery? A Randomized Trial.
In obese patients (OP), the best intraoperative ventilation strategy remains to be defined. Dynamic lung compliance (Cdyn) and dead space fraction are indicators of efficient ventilation at an optimal positive end-expiratory pressure (PEEP). Herein, we investigated whether intraoperative dynamic lung compliance optimization through PEEP manipulations affects the incidence of postoperative hypoxemia (SpO2 < 90%) in OP undergoing laparoscopic bariatric surgery (LBS). This was a single-center, prospective, randomized controlled study conducted from July 2013 to December 2015. After obtaining institutional review board approval and informed consent, 100 OP undergoing LBS under volume-controlled ventilation (tidal volume 8 mL/kg of ideal body weight) were randomized according to the PEEP level maintained during the surgery. In the control group, a PEEP of 10 cm H2O was maintained, while in the intervention group, the PEEP was adapted to achieve the best dynamic lung compliance. Anesthesia and analgesia were standardized. The patients received supplemental nasal oxygen on the first postoperative day and were monitored up to the second postoperative day with a portable pulse oximeter. Demographics were similar between groups. There was no difference in the incidence of hypoxemia during the first 2 postoperative days (control: 1.3%; intervention: 2.1%; p = 0.264). The incidence of postoperative hypoxemia was not reduced by an open-lung approach with protective ventilation strategy in obese patients undergoing LBS. A pragmatic application of a PEEP level of 10 cm H2O was comparable to individual PEEP titration in these patients. Clinicaltrials.gov identifier, NCT02579798; https://clinicaltrials.gov/ct2/show/NCT02579798.


The relationship between intraoperative contamination of the lower respiratory tract and postoperative chest infection.
The relationship between intraoperative contamination of the lower respiratory tract and postoperative chest infection was studied in 193 patients undergoing biliary tract surgery. During surgery, sputum was obtained from the lower respiratory tract for bacteriological culture. The diagnosis of postoperative pulmonary complications was based on clinical criteria, supported by the pattern of sequential blood gas changes in the postoperative period. Chest infection was present in 30% of patients who harboured Haemophilus species in their sputum at the time of surgery compared with 10% of those with negative cultures. Contamination of the lower respiratory tract at operation by Haemophilus sp. is associated with development of postoperative chest infection.


Genomic expression profiling of peripheral blood leukocytes of pigs infected with highly virulent classical swine fever virus strain Shimen.
Classical swine fever (CSF), caused by a virus of the same name (CSFV), is a highly contagious swine pyrexic disease featuring extensive haemorrhagic lesions and leukopenia, but little is known about the molecular mechanisms of its pathogenesis. To gain insight into the interaction between the virus and host cells, microarray analyses were performed to detect alterations in genomic expression of pig peripheral blood leukocytes (PBLs) following CSFV infection. Three healthy pigs were inoculated with a lethal dose of highly virulent CSFV strain Shimen. PBLs were isolated at the onset of typical clinical signs and total RNA was subjected to microarray analyses with Affymetrix Porcine Genome Array GeneChips. Of all 20,201 pig genes arrayed in the chip, 1745 showed altered expression (up- or downregulation) after infection. These were classified into eight functional groups, relating to cell proliferation (3.6%), immune response (2.1%), apoptosis (1.4%), kinase activity (1.4%), signal transduction (1.4%), transcription (0.7%), receptor activity (0.7%) and cytokines/chemokines (0.4%). The remaining 88.3% of genes had unknown functions. Alterations in genomic expression were confirmed by real-time RT-PCR of selected cellular genes and Western blotting of annexin 2, a cellular protein relating to virus infection. The observed expression changes of numerous genes involved in immune and inflammatory responses and in the apoptosis process indicate that CSFV has developed sophisticated mechanisms to cause leukopenia in infected pigs. These data provide a basis for exploring the molecular pathogenesis of CSFV infection through an understanding of the interaction between viral and cellular components.


Detection of human influence on twentieth-century precipitation trends.
Human influence on climate has been detected in surface air temperature, sea level pressure, free atmospheric temperature, tropopause height and ocean heat content. Human-induced changes have not, however, previously been detected in precipitation at the global scale, partly because changes in precipitation in different regions cancel each other out and thereby reduce the strength of the global average signal. Models suggest that anthropogenic forcing should have caused a small increase in global mean precipitation and a latitudinal redistribution of precipitation, increasing precipitation at high latitudes, decreasing precipitation at sub-tropical latitudes, and possibly changing the distribution of precipitation within the tropics by shifting the position of the Intertropical Convergence Zone. Here we compare observed changes in land precipitation during the twentieth century averaged over latitudinal bands with changes simulated by fourteen climate models. We show that anthropogenic forcing has had a detectable influence on observed changes in average precipitation within latitudinal bands, and that these changes cannot be explained by internal climate variability or natural forcing. We estimate that anthropogenic forcing contributed significantly to observed increases in precipitation in the Northern Hemisphere mid-latitudes, drying in the Northern Hemisphere subtropics and tropics, and moistening in the Southern Hemisphere subtropics and deep tropics. The observed changes, which are larger than estimated from model simulations, may have already had significant effects on ecosystems, agriculture and human health in regions that are sensitive to changes in precipitation, such as the Sahel.


[A case report of cystic fibrosis and review of 16 cases of cystic fibrosis in Chinese patients].
To report a case of cystic fibrosis (CF) in a Chinese and to review the clinical features, gene mutations, diagnosis and outcome of CF in Chinese patients. A 14-year-old Chinese girl presenting with recurrent productive cough since birth with parasinusitis and otitis media was confirmed to have CF in Peking University First Hospital. Chest CT scan showed bronchiectasis, more severe in the right upper lobe. Sweat tests were taken three times, and the values of Na(+) and Cl(-) were (126.6 +/- 5.4) mmol/L and (108.9 +/- 3.3) mmol/L, respectively. The examination of the pancreas showed no remarkable cystic changes on CT scan and there was no pancreatic insufficiency. Sixteen patients with CF in Chinese reported from 1974 to 1999 were reviewed. Sixteen of the 17 patients (7 males and 9 females, aged from 6 months to 25 years) had clinical data available for analysis. Eleven of them had died, nine before the age of 13. They all suffered from frequent episodes of pneumonia, while 14 had malnutrition and 4 had jaundice. The diagnostic procedures included clinical features, sweat test and autopsy. Four of them had DNA screened and four kinds of novel mutations in the cystic fibrosis transmembrane conductance regulator gene were found. Chinese patients with CF show similar clinical manifestations to patients in the European and North American populations, but the CFTR mutation was different.


[Lipids, depression and suicide].
Polyunsatured fatty acids are made out of a hydrocarbonated chain of variable length with several double bonds. The position of the first double bond (omega) differentiates polyunsatured omega 3 fatty acids (for example: alpha-linolenic acid or alpha-LNA) and polyunsatured omega 6 fatty acids (for example: linoleic acid or LA). These two classes of fatty acids are said to be essential because they cannot be synthetised by the organism and have to be taken from alimentation. The omega 3 are present in linseed oil, nuts, soya beans, wheat and cold water fish whereas omega 6 are present in maize, sunflower and sesame oil. Fatty acids are part of phospholipids and, consequently, of all biological membranes. The membrane fluidity, of crucial importance for its functioning, depends on its lipidic components. Phospholipids composed of chains of polyunsatured fatty acids increase the membrane fluidity because, by bending some chains, double bonds prevent them from compacting themselves perfectly. Membrane fluidity is also determined by the phospholipids/free cholesterol ratio, as cholesterol increases membrane viscosity. A diet based on a high proportion of essential polyunsatured fatty acids (fluid) would allow a higher incorporation of cholesterol (rigid) in the membranes to balance their fluidity, which would contribute to lower blood cholesterol levels. Brain membranes have a very high content in essential polyunsatured fatty acids for which they depend on alimentation. Any dietary lack of essential polyunsatured fatty acids has consequences on cerebral development, modifying the activity of enzymes of the cerebral membranes and decreasing efficiency in learning tasks. The prevalence of depression seems to increase continuously since the beginning of the century. Though different factors most probably contribute to this evolution, it has been suggested that it could be related to an evolution of alimentary patterns in the Western world, in which polyunsatured omega 3 fatty acids contained in fish, game and vegetables have been largely replaced by polyunsatured omega 6 fatty acids of cereal oils. Some epidemiological data support the hypothesis of a relation between lower depression and/or suicide rates and a higher consumption of fish. These data do not however prove a relation of causality. Several cohort studies (on nondepressed subjects) have assessed the relationship between plasma cholesterol and depressive symptoms with contradictory results. Though some results found a significant relationship between a decrease of total cholesterol and high scores of depression, some other did not. Studies among patients suffering from major depression signalled more constantly an association between low cholesterol and major depression. Besides, some trials showed that clinical recovery may be associated with a significant increase of total cholesterol. The hypothesis that a low cholesterol level may represent a suicidal risk factor was discovered accidentally following a series of epidemiological studies which revealed an increase of the suicidal risk among subjects with a low cholesterol level. Though some contradictory studies do exist, this relationship has been confirmed by several subsequent cohort studies. These findings have challenged the vast public health programs aimed at promoting the decrease of cholesterol, and even suggested to suspend the administration of lipid lowering drugs. Recent clinical studies on populations treated with lipid lowering drugs showed nevertheless a lack of significant increase of mortality, either by suicide or accident. In addition, several controlled studies among psychiatric patients revealed a decrease of the concentrations of plasma cholesterol among patients who had attempted suicide in comparison with other patients. In major depression, all studies revealed a significant decrease of the polyunsaturated omega 3 fatty acids and/or an increase of the omega 6/omega 3 ratio in plasma and/or in the membranes of the red cells. In addition, two studies found a higher severity of depression when the level of polyunsaturated omega 3 fatty acids or the ratio omega 3/omega 6 was low. Parallel to these modifications, other biochemical perturbations have been reported in major depression, particularly an activation of the inflammatory response system, resulting in an increase of the pro-inflammatory cytokines (interleukins: IL-1b, IL-6 and interferon g) and eicosanoids (among others, prostaglandin E2) in the blood and the CSF of depressed patients. These substances cause a peroxidation and, consequently a catabolism of membrane phospholipids, among others those containing polyunsaturated fatty acids. The cytokines and eicosanoids derive from polyunsaturated fatty acids and have opposite physiological functions according to their omega 3 or omega 6 precursor. Arachidonic acid (omega 6) is, among others, precursor of pro-inflammatory prostaglandin E2 (PGE2), whereas polyunsaturated omega 3 fatty acids inhibit the formation of PGE2. It has been shown that a dietary increase of polyunsaturated omega 3 fatty acids reduced strongly the production of IL-1 beta, IL-2, IL-6 and TNF-alpha (tumor necrosis factor-alpha). In contrast, diets with a higher supply of linoleic acid (omega 6) increased significantly the production of pro-inflammatory cytokines, like TNF-alpha. Therefore, polyunsaturated omega 3 fatty acids could be associated at different levels in the pathophysiology of major depression, on the one hand through their role in the membrane fluidity which influences diverse steps of neurotransmission and, on the other hand, through their function as precursor of pro-inflammatory cytokines and eicosanoids disturbing neurotransmission. In addition, antidepressants could exhibit an immunoregulating effect by reducing the release of pro-inflammatory cytokines, by increasing the release of endogenous antagonists of pro-inflammatory cytokines like IL-10 and, finally, by acting like inhibitors of cyclo-oxygenase. Data available concerning the administration of supplements of DHA (docosahexanoic acid) or other polyunsaturated fatty acids omega 3 are limited. In a double blind placebo-controlled study on 30 patients with bipolar disorder, the addition of polyunsaturated omega 3 fatty acids was associated with a longer period of remission. Moreover, nearly all the other prognosis measures were better in the omega 3 group. Very recently, a controlled trial showed the benefits of adding an omega 3 fatty acid, eicosopentanoic acid, among depressed patients. After 4 weeks, six of the 10 patients receiving the fatty acid were considered as responders in comparison with only one of the ten patients receiving placebo. Some epidemiological, experimental and clinical data favour the hypothesis that polyunsaturated fatty acids could play a role in the pathogenesis and/or the treatment of depression. More studies however are needed in order to better precise the actual implication of those biochemical factors among the various aspects of depressive illness.


Genital asymmetry in men.
This study examined genital asymmetry in a large sample of men. The probands were 6544 non-delinquent men who were interviewed by the Kinsey Institute for Research in Sex, Gender and Reproduction from 1938 to 1963. The measures were four indicators of penile and scrotal asymmetry, along with self-reported handedness, from Kinsey's interview protocol. Most men reported some degree of lateral asymmetry in their flaccid penis and in their testicles; less asymmetry was reported for their erect penis. The asymmetry typically occurred in the left direction, and this pattern occurred in both right- and nonright-handers. However, this 'leftward' pattern was significantly less pronounced in nonright-handers. The results are discussed in relation to previous findings of genital asymmetry in men, the possible relationship of genital asymmetry to functional cerebral asymmetry, and recent data suggesting genital asymmetry may predict patterns of cognitive performance and genital/sexual organ cancers.


Alzheimer beta protein mediated oxidative damage of mitochondrial DNA: prevention by melatonin.
Most contemporary progress in Alzheimer's disease (AD) stems from the study of a 42 43 amino acid peptide. called the amyloid beta protein (Abeta), as the main neuropathologic marker of the disorder. It has been demonstrated that Abeta has neurotoxic properties and that such effects are mediated by free-radicals. Exposure of neuronal cells to Abeta results in a spectrum of oxidative lesions that are profoundly harmful to neuronal homeostasis. We had previously shown that Abeta25-35 induces oxidative damage to mitochondrial DNA (mtDNA) and that this modality of injury is prevented by melatonin. Because Abeta25 35 does not occur in AD and because the mode of toxicity by Abeta25-35 may be different from that of Abeta1-42 (the physiologically relevant form of Abeta), we extended our initial observations to determine whether oxidative damage to mtDNA could also be induced by Abeta1-42 and whether this type of injury is prevented by melatonin. Exposure of human neuroblastoma cells to Abeta1-42 resulted in marked oxidative damage to mtDNA as determined by a quantitative polymerase chain reaction method. Addition of melatonin to cell cultures along with Abeta completely prevented the damage. This study supports previous findings with Abeta25-35, including a causative role for Abeta in the mitochondrial oxidative lesions present in AD brains. Most important, the data confirms the neuroprotective role of melatonin in Abeta-mediated oxidative injury. Because melatonin also inhibits amyloid aggregation, lacks toxicity, and efficiently crosses the blood-brain barrier, this hormone appears superior to other available antioxidants as a candidate for pharmacologic intervention in AD.


The Medicago truncatula reference accession A17 has an aberrant chromosomal configuration.
Medicago truncatula (barrel medic) has emerged as a model legume and accession A17 is the reference genotype selected for the sequencing of the genome. In the present study we compare the A17 chromosomal configuration with that of other accessions by examining pollen viability and genetic maps of intraspecific hybrids. Hybrids derived from crosses between M. truncatula accessions, representative of the large genetic variation within the germplasm collection, were evaluated for pollen viability using Alexander's stain. Genetic maps were generated for the following crosses: SA27063 x SA3054 (n = 94), SA27063 x A17 (n = 92), A17 x Borung (n = 99) and A17 x A20 (n = 69). All F(1) individuals derived from crosses involving A17 showed 50% pollen viability or less. Examination of the recombination frequencies between markers of chromosomes 4 and 8 revealed an apparent genetic linkage between the lower arms of these chromosomes in genetic maps derived from A17. Semisterility and unexpected linkage relationship are both good indicators of a reciprocal translocation. The implications of the A17 distinctive chromosomal rearrangement on studies of genetic mapping, genome sequencing and synteny between species are discussed.


PSA-use in a Spanish industrial area.
To document the extent of prostate-specific antigen (PSA)-testing in the general population at Getafe (Spain) outside our prostate cancer (PC) screening program, and to check its performance in terms of PC detection. A total of 5371 PSA-test records (1997-1999) were reviewed and testing rates estimated per 1000 person-years. The extent of patient referral (men referred to our facilities) was calculated adjusting for PSA levels. To approach the performance of testing in the general population, our PC screening program acted as a standard for comparison. The probability of missing one PC in the general population was estimated in terms of number of men necessary to screen (NNS). Calculations were made adjusting for PSA levels. PSA-testing rate in the general population was 21.6/1000 person-years. In the age-group 55-69 years, this rate was 86.8/1000 (152.6 in men >70 years). Referral rates were 67.9 and 39.5% for men with PSA 4-10 and >10 ng/ml, respectively. Overall PC detection rate was 1.76%. Detection rates for PSA 4-10 and >10 ng/ml were 4.66 and 12.94%, respectively. When compared with the performance of the screening program, for every 17 men with a PSA in the range 4-10 ng/ml one cancer was missed (95% confidence interval (CI), 9-580). Similarly, one cancer was lost for every four men with a PSA >10 ng/ml (95% CI, 2-8). The extent of opportunistic testing in our setting is very high, particularly in the older age groups. Opportunistic screening renders PC detection rates lower than expected for every PSA level and cannot be encouraged.


Principal component analysis suggests subtle changes in glutamate receptor subunit expression in the rat hippocampus following bilateral vestibular deafferentation.
Previous studies have shown that lesions of the peripheral vestibular system result in electrophysiological dysfunction in the hippocampus. Given the importance of glutamate as a neurotransmitter in the hippocampus, it was predicted that bilateral vestibular deafferentation (BVD) would alter the expression of NMDA and AMPA receptors in this area of the brain. However, the results of studies conducted to date are inconsistent. In this study, we performed principal component analysis (PCA) on the expression of the NR1, NR2B, GluR1, GluR2 and GluR3 glutamate receptor subunits, as well as calmodulin kinase IIα (CaMKIIα) and phosphorylated CaMKIIα (pCaMKIIα), in the rat CA1, CA2/3 and dentate gyrus (DG) subregions of the hippocampus, at 6 months following BVD, using western blotting. The expressions of the different glutamate receptor subunits, in terms of NMDA versus AMPA receptor subunits, as well as CaMKIIα and pCaMKIIα, were tightly correlated, and this was shown again the loading plots. However, the pattern of the contributions of each protein to the first 2 principal components appeared to be inverted for the BVD group compared to the sham group.


Peripheral blood lymphocyte cell subsets in subjects with chronic obstructive pulmonary disease: association with smoking, IgE and lung function.
In contrast to the numerous studies which show that lymphocytes play an important role in the pathogenesis of asthma, few studies have investigated the role of lymphocytes in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate lymphocyte subsets in peripheral venous blood of smoking and non-smoking COPD patients and healthy controls. The interaction of smoking and IgE has also been assessed, and it was investigated whether a lower level of FEV1 was associated with changes in lymphocyte subsets. In the present study, peripheral venous blood lymphocyte subsets were investigated in 42 smoking and non-smoking, non-atopic subjects with a clear diagnosis of COPD (43-74 years) who all used bronchodilator therapy only, and in 24 normal, healthy control subjects (40-72 years). No significant differences in lymphocyte subsets were found when either total groups or smoking subjects of both groups were compared. However, the percentage of CD8+ lymphocytes (suppressor/ cytotoxic T-cells) was significantly higher in the non-smoking COPD subjects compared with the non-smoking, healthy control subjects (P < 0.05). In addition, within the group of non-smoking COPD subjects, a higher CD4:CD8 ratio was associated with a higher FEV1 as a percentage of predicted (% pred.) (r = 0.55, P = 0.01) and a lower total serum IgE (r = -0.45, P = 0.04). Within the group of smoking COPD subjects, a higher FEV1 % pred. was associated with a higher percentage of CD19+ lymphocytes (B-cells) (r = 0.65, P < 0.01). The present study provides further evidence that the changes in the balance of T-cell subsets and IgE synthesis possibly plays a role in the pathogenesis of COPD.


Proximal hip geometry and hip fracture risk assessment in a Korean population.
The association between proximal femoral geometry and hip fracture risk were investigated. The risk of intertrochanteric fractures increased 1.64-fold and 2.32-fold with 1 standard deviation (sd) increase of hip axis length and neck-shaft angle, respectively, while the risk of femur neck fracture 2.03-fold with 1 sd decrease in femoral head offset. The purpose of this study was to determine the association between proximal femoral geometry (PFG) and the risk of hip fracture in femur neck (FN) and intertrochanteric (IT) fractures in a Korean population. The study included 151 patients (57 patients with IT fractures, 43 patients with FN fractures, and 51 control patients). Data on BMD, PFG parameters (hip axis length [HAL], neck-shaft angle [NSA], neck length, femoral head offset, neck diameter, shaft diameter (SD), and demographics [age, gender, height, and body weight]) were collected. Descriptive statistics and odds ratios of PFG parameters corrected with demographic variables were obtained using logistic regressions. HAL (p = 0.046) and NSA (p = 0.003) were significantly greater in the patients with IT fracture than in the control patients, while neither parameter was significantly greater in patients with FN fractures than the control patients. The femoral head offset was significantly shorter in the patients with FN fractures (p = 0.003) compared with the control patients. In patients with IT fractures, the fracture risk increased 1.64-fold (p = 0.048) with a 1 sd increase of the HAL, while it increased 2.32-fold (p = 0.003) with a 1 sd increase of the NSA. In FN fractures, the fracture risk increased 2.03-fold (p = 0.012) with a 1 sd decrease in femoral head offset. Our study showed that some PFG parameters as well as BMD values predict hip fractures in a Korean population, and their evaluation may be useful in the understanding of the biomechanics of hip fractures.


Characterization of cell deformation and migration using a parametric estimation of image motion.
This paper deals with the spatio-temporal analysis of two-dimensional deformation and motion of cells from time series of digitized video images. A parametric motion approach based on an affine model has been proposed for the quantitative characterization of cellular movements in different experimental areas of cellular biology including spontaneous cell deformation, cell mitosis, individual cell migration and collective migration of cell populations as cell monolayer. The accuracy and robustness of the affine model parameter estimation, which is based on a multiresolution algorithm, has been established from synthesized image sequences. A major interest of our approach is to follow with time the evolution of a few number of parameters characteristic of cellular motion and deformation. From the time-varying eigenvalues of the affine model square matrix, a precise quantification of the cell pseudopodial activity, as well as of cell division has been performed. For migrating cells, the motion quantification confirms that cell body deformation has a leading role in controlling nucleus displacement, the nucleus itself undergoing a larger rotational motion. At the cell population level, image motion analysis of in vitro wound healing experiments quantifies the heterogeneous cell populations dynamics.


Serum concentrations of fluoxetine in the clinical treatment setting.
This article discusses fluoxetine serum concentrations as displayed in a clinical setting. A racemic serum fluoxetine and norfluoxetine high-performance liquid chromatography method, including ultraviolet light detection, was used for routine therapeutic drug monitoring (TDM) purposes. In all, 508 samples were analyzed. For the scientific investigation, predefined inclusion and exclusion criteria were applied and 150 samples representative of trough values in steady-state conditions with essential clinical information provided on the assay request forms were evaluated. Fluoxetine plus norfluoxetine concentration-to-dose (C/D) ratio showed Gaussian distribution. Interindividual coefficients of variation of fluoxetine and norfluoxetine serum concentrations after different doses were found to be 40-63%. Intraindividual fluoxetine TDM variability was low. The Spearman rank correlation coefficient for fluoxetine and norfluoxetine C/D ratios in first and second samples was 0.68. Minor increases in norfluoxetine C/D and fluoxetine plus norfluoxetine C/D ratios were found in elderly patients compared with younger adult patients. A higher body-mass index was associated with minor decreases in fluoxetine and fluoxetine plus norfluoxetine C/D ratios. New fluoxetine pharmacokinetic data are added to the results from earlier phases of drug development. Moreover, the results of this study support the usefulness of a fluoxetine TDM procedure for individual dose optimization, detection of drug interactions, and assessments of patient compliance.


Temporary feed restriction partially protects broilers from necrotic enteritis.
The objective of this study was to investigate the effect of feed restriction on the intestinal ecosystem and on the pathogenesis of experimental necrotic enteritis in broiler chicks. To induce subclinical necrotic enteritis, an experimental challenge model using a specific diet formulation, Gumboro vaccination, oral inoculation of broilers with a 10-fold dose of attenuated anticoccidial vaccine and multiple oral inoculations with a specific strain of Clostridium perfringens was adopted. Two hundred and forty 1-day-old Cobb 500 broilers were randomly allocated to four groups: feed restricted, challenged, both feed restricted and challenged, and negative control. At 21, 22, 23 and 24 days of age, the intestines, gizzard and liver were collected from 15 birds in each group and scored for gross lesions. The intestinal digesta was collected for pH and viscosity determination. One caecum from each bird was taken for microbiological analysis. The application of feed restriction in birds challenged with C. perfringens reduced the necrotic enteritis lesion score significantly (P ≤ 0.05) and feed restriction significantly reduced (P ≤ 0.05) pH in the small intestine, the viscosity of the jejunum digesta as well as the C. perfringens counts in the caeca compared with the controls. In conclusion, feed restriction of broilers has a positive effect on the intestinal ecosystem and a significant protective effect against necrotic enteritis in the subclinical experimental model.


The regulatory effect of substances released from porcine bronchial epithelial cells on hypoxic pulmonary vasoconstriction.
In this study, porcine pulmonary artery segments (intact or denuded) and bronchial segments (with or without epithelium) were tested in organ bath. Hypoxia caused a bronchial epithelium dependent relaxation of intact or denuded pulmonary artery preconstricted with phenylephrine. Constriction in intact pulmonary artery coated with epithelium denuded bronchus was observed during hypoxia. The bronchial epithelium-dependent relaxation could be inhibited by indomethacin but not be blocked by the following agents: atropine, propranolol, gossypol, methylene blue and chlorpheniramine. The results suggested that HPV was endothelium-dependent. Hypoxia could cause the production of an epithelium-derived relaxing factor (EpDRF), which acted directly on smooth muscle. The effect of EpDRF was not mediated by pulmonary endothelium, but might be related to arachidonic acid cyclooxygenase pathway.


[Use of various preparations with beta-adrenergic blocking action in the overall therapy of thyrotoxicosis].
Three beta-adrenoblockers (trasicor, alpheprol, isoptin) were used in 68 patients with thyrotoxicosis in the complex therapy of the disease. Their effect on hemodynamic indices, urinary catecholamine excretion were studied, and the results of investigation were compared with the data obtained earlier with the use of anaprylin. The action of the latter on the thyroid metabolism was ascertained. Anaprylin proved to be the most effective of the aforementioned preparations. Trasicor, which was somewhat less effective, could be used in patients with thyrotoxicosis complicated by cardiovascular insufficiency due to its less pronounced inotropic action. Isoptin may be recommended as an anti-arrhythmic agent in thyrotoxicosis. The action mechanism of beta-adrenoblockers in thyrotoxicosis is suggested.


Caries prevention by CO2 laser treatment: dependency on the number of pulses used.
The aim of this study was to assess the caries-preventive potential of various carbon dioxide laser conditions and to explore the effect of the number of laser pulses used. The authors irradiated unerupted human molars at two wavelengths--10.6 or 9.6 micrometers--and at 1, 5, 25 or 100 pulses. All teeth were then subjected to pH cycling simulating the conditions for caries progression. Pulsed CO2 laser-preventive treatment inhibited caries-like lesion progression by up to 87 percent. This effect was dependent on the number of pulses used, but there was no correlation between caries resistance and enamel surface morphological changes.


To study the incidence, etiology and EEG profile of neonatal seizures: a prospective observational study from India.
To study the incidence, etiology and electroencephalography (EEG) profile of neonatal seizures and also to study the correlation between clinical picture and EEG appearance. Prospective observational cohort study. Study duration: September 2011 to April 2013. Inclusion and exclusion: Seizures within first 28 d of life and seizures documented by doctors. Neonates admitted in intensive care unit: intramural (4412) and extramural (1900) admissions (all together 6312). One hundred and seventy-two neonates with seizures were enrolled. All the neonates were evaluated with necessary investigation, ultrasound head and CT scan. All the neonates underwent EEG as early as possible with neonatal stabilization. The etiology of neonatal seizures, CT scan and ultrasound head, characteristic of the EEG and neonatal mortality were noted. The incidence of neonatal seizure was 0.77% in the intramural and 7.3% among the extramural neonates. The incidence of seizures in term newborn was 0.7% and in preterm was 1.1%. The most common cause of neonatal seizure was hypoxic ischemic encephalopathy (HIE) followed by hypocalcemia. The predominant seizure type was multifocal (51%) followed by subtle seizure (43%). There was an EEG abnormality in 72% of the total EEG with varied patterns. The mortality rate in the cohort was 15% with HIE being the most common cause. Most common cases of neonatal seizure were HIE and with the most common type being multifocal. EEG was abnormal in the majority of the neonates with various pattern of abnormality.


Antigenicity of the new quinolone antibacterial agent levofloxacin.
An antigenicity study of a new quinolone antibacterial agent, (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo- 7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid hemihydrate (lefovloxacin, DR-3355, CAS 100986-85-4), was carried out in mice, guinea pigs and rabbits with passive cutaneous anaphylaxis (PCA), systemic anaphylaxis (SA) and enzyme linked immunosorbent assay (ELISA). Mice were sensitized with DR-3355 (1-100 mg/kg) or DR-3355-ovalbumin (OA) conjugate (DR-3355-OA; 500 micrograms/kg). No IgE antibodies to DR-3355 were detected in the sera obtained from the DR-3355-sensitized mice, indicating that DR-3355 has no immunogenicity in mice. By using DR-3355-OA as a sensitizing antigen, DR-3355-specific IgE was produced successfully in 7 out of 10 sera, and 4 sera showed positive responses in 24-h PCA on intravenous injection of DR-3355 (40 mg/kg). These responses disappeared on challenge with a dose of 2.5 mg/kg. Guinea pigs or rabbits were sensitized with DR-3355 (2-100 or 2-20 mg/kg) or DR-3355-OA (2 mg/kg). No SA was observed in the sensitized guinea pigs after the intravenous injection of DR-3355 (40 mg/kg). No antibodies to DR-3355 were detected in the sera obtained from the sensitized guinea pigs and rabbits by PCA or ELISA. These results suggest that DR-3355 may not possess antigenicity in guinea pigs and rabbits. On the other hand, the results of PCA in mice suggest that DR-3355 may have eliciting antigenicity potential.


Did the assumed partial skeleton LB1 (aka Homo floresiensis) really have long feet?
About 100 hominin bones were found during excavations at the Liang Bua cave on the island of Flores, Indonesia. More than 60 of them were assigned to the partial skeleton LB1 which was designated as the holotype of a new species, Homo floresiensis. Analyses of skeletal proportions of LB1 led to the conclusion that its foot was exceptionally long relative to femur and tibia, respectively. This ratio was considered a unique feature that contributes to the definition of the new species. The published illustrations of the in situ-situation and the published inventory of the bones suggest a high degree of commingling rather than the presence of larger anatomically joining units that was asserted in the publications on the findings. The available information further suggests that hand and foot bones of several individuals were found commingled as well. Here I argue, based on the published data, that certain problems exist regarding the correct anatomical identification of some of the phalangeal bones that contributed to the results on which the conclusions about skeletal proportions in LB1 were based. It is further suggested that the assignment of bones to specific individuals is debatable. Conclusions on the taxonomic status of the Liang Bua hominins and their pattern of bipedalism based on these data therefore need to be substantiated by further studies. Specifically, on the basis of the available information, a large relative foot length should no longer be claimed as a unique feature of the presumed new species H. floresiensis.


[Strategy for laboratory tests of thyroid function (author's transl)].
Clinical findings suggesting hyperthyroidism should be confirmed by the following basic tests of thyroid function: serum T3 and T4, and iFT4. In the case where there is contradiction between the T3 and T4 values, hyperthyroidism may be confirm by the absence of effect of TRH on serum TSH level. Clinical findings suggesting hypothyroidism should be confirmed by the following basic tests: serum T3 and T4, iFT4, and serum TSH which also will be greatly helpful in the differentiation of primary or secundary hypothyroidism. When there is an absence of parallelism between total and free T3 and T4 determinations, it is necessary to look for a possible abnormality in the binding protein. In vivo explorations (radio-iodine uptake, scintigraphy) and other assays should be proposed in view of clinical findings but should not be systematically prescribed.


Crystal structure of the gold nanoparticle [N(C8H17)4][Au25(SCH2CH2Ph)18].
We report the crystal structure of the thiolate gold nanoparticle [TOA+][Au25(SCH2CH2Ph)18-], where TOA+ = N(C8H17)4+. The crystal structure reveals three types of gold atoms: (a) one central gold atom whose coordination number is 12 (12 bonds to gold atoms); (b) 12 gold atoms that form the vertices of an icosahedron around the central atom, whose coordination number is 6 (five bonds to gold atoms and one to a sulfur atom), and (c) 12 gold atoms that are stellated on 12 of the 20 faces of the Au13 icosahedron. The arrangement of the latter gold atoms may be influenced by aurophilic bonding. Together they form six orthogonal semirings, or staples, of -Au2(SCH2CH2Ph)3- in an octahedral arrangement around the Au13 core.


Differences between posttraumatic stress disorder patients with delayed and undelayed onsets.
In an effort to determine whether they differ from one another in important ways, the authors compared posttraumatic stress disorder (PTSD) victims who reported delayed onsets with those who claimed undelayed onsets of PTSD symptom self-ratings, MMPI clinical and validity scale scores, stress histories, and repression measures. The number and the sizes of the differences did not exceed chance expectations and did not support the establishment of separate delayed- and undelayed-onset PTSD categories in the diagnostic manual, nor did they support the hypotheses that the delay, when it appears, is attributable to the magnitude of the trauma, the severity of the symptoms, repression, or a limited stress history.


Determinants of HIV infection among female sex workers in two cities in the Republic of Moldova: the role of injection drug use and sexual risk.
In 2009-2010, females who reported having vaginal, anal or oral sex in exchange for money in the previous year, ≥16 years, and living in either Chisinau (n = 299) or Balti (n = 359), Moldova, were recruited into a respondent driven sampling survey. One fifth reported ever injecting drugs and over 30 % ever had sexual intercourse with men who inject drugs. In both cities, condom use with permanent and casual partners was much lower than condom use with commercial partners. In Chisinau, 6.9 % and in Balti, 24.7 % tested positive for HIV; 18 and 23.7 % had antibodies to hepatitis C; 9.1 and 8.9 % had antibodies to HBV; and, 8.4 and 6.1 % tested positive for syphilis. HIV seropositive FSW in either city were more likely to have ever injected drugs and to be infected with HCV. Limited government initiative and drastic reductions in international funding will likely impact urgently needed HIV prevention and harm reduction services targeting FSW in Moldova.


Acid- and base-catalyzed hydrolysis of chloroacetamide herbicides.
Despite the prevalence of chloroacetamides as herbicides, little is known about the rates or products of acid- or base-catalyzed hydrolysis of these compounds. Mechanisms of acid-catalyzed reactions may parallel those catalyzed by (hydr)oxide minerals, while base-catalyzed processes have as important counterparts reactions with environmental nucleophiles (such as reduced sulfur species). The current study systematically investigates how the structure of nine chloroacetamides affects their reactivity in 2 N NaOH, 2 N HCl, or 6 N HCl at 25 or 85 degrees C. Base-catalyzed hydrolysis proceeds either through an intermolecular SN2 reaction to hydroxy-substituted derivatives or (in a few cases) through amide cleavage, while both amide and ether group cleavages are observed under acidic conditions. Our results reveal that subtle differences in chloroacetamide structure [notably the type of (alkoxy)alkyl substituent] can dramatically influence reactivity and reaction mechanism. Hydroxy-substituted, morpholinone, and secondary aniline derivatives were identified upon reaction for several years in deionized water at circumneutral pH.


After early release of tourniquet in total knee arthroplasty, should it be reinflated or kept deflated? A randomized trial.
This study was undertaken to determine the efficacy of reinflation of the tourniquet after its early release in TKA compared to early release alone, in terms of surgical field visualization and operative time. We also questioned whether tourniquet reinflation after its early release is safe, with respect to post-operative blood loss, post-operative pain and other tourniquet-related complications. Two hundred and six patients undergoing TKA were randomly allocated to either the early release (deflation) group (n = 105) or reinflation after early release (reinflation) group (n = 101). Efficacy was measured in terms of surgical field visualization, specifically the number of wound clearances, and operative time. Safety outcomes were drained volume, decline in haemoglobin on post-operative days 2 and 5, the frequency of transfusion, knee and thigh pain visual analog scale, local wound complications, tourniquet site complications and other complications, including infection, deep vein thrombosis and pulmonary embolism. Surgical field visualization was better in the reinflation group; however, the operative time did not differ between the two groups. There were no differences between the two groups in post-operative blood loss, decline in haemoglobin on days 2 and 5, transfusion rate, pain level, local complications and other complications. Reinflation of tourniquet is a safe alternative to its early release after deflation in that it improves surgical field visualization during TKA. Therapeutic study, Level I.


Cross-Presentation Assay for Human Dendritic Cells.
The presentation of exogenous antigens on major histocompatibility complex (MHC) class I molecules, termed cross-presentation, is essential for the initiation of cytotoxic immune responses. Numerous studies in mice and human have shown that dendritic cells are the best cross-presenting cells. The protocol described here allows the assessment of the cross-presentation by human dendritic cells of a model antigen (either soluble or cell associated) to antigen-specific CD8 T cells.


Endorectal sonography.
Endorectal sonography is a technique that has been developed recently to visualize the rectal wall and perirectal tissues with a high degree of clarity. Studies utilizing endorectal sonography in the preoperative staging of rectal carcinoma have reported an accuracy of between 67 and 92% in the visualization of the depth of tumor invasion in the rectal wall. This surpasses the accuracy reported for digital exam and other preoperative imaging methods such as CT and MRI. Perirectal lymphadenopathy is also well visualized by this method and guided biopsy of perirectal nodes has been reported. Precise preoperative staging of rectal carcinoma by endorectal sonography is an important technique that can: (1) improve surgical planning, (2) provide prognosis in nonsurgical candidates, and (3) select patients suitable for local excision therapy.


Limitations of urinary telomerase activity measurement in urothelial cancer.
The reported frequency of detectable telomerase activity in spontaneously voided urine samples from patients with urothelial cancer varied from 0 to 85%. We examined stasis in the bladder and specimen storage as interfering conditions in this assay. Telomerase activity in exfoliated cells was measured by a polymerase-chain-reaction-based assay in spontaneously voided urine from urothelial cancer patients. Effects of retention in the bladder and specimen storage from voiding to measurement of telomerase activity were modeled by suspending 10(6) cells from the cancer-derived T24 line in normal urine (pH 6.5) at 37 degrees C and 25 degrees C, respectively. Hematuria was modeled by adding hemoglobin. In T24 cells suspended in urine at 37 degrees C, telomerase activity had decreased to approximately 20% of preincubation activity after 1 h, and had disappeared after 3 h. In urine at 25 degrees C, telomerase activity in T24 cells had decreased to approximately 40% of preincubation activity at 1 h and to <10% at 6 h. When we examined telomerase activity in exfoliated cells in spontaneously voided urine from urothelial cancer patients (excluding first-voided morning specimens), telomerase activity was detected in only 21% of samples (four of 19) despite measurement with 1 h of voiding and steps to avoid hemoglobin interference. Measurement of telomerase activity in spontaneously voided urine is insufficiently sensitive and reliable for the diagnosis of urothelial cancer.