Gonorrhea - an evolving disease of the new millennium.
Etiology, transmission and protection: Neisseria gonorrhoeae (the gonococcus) is the etiological agent for the strictly human sexually transmitted disease gonorrhea. Infections lead to limited immunity, therefore individuals can become repeatedly infected. Pathology/symptomatology: Gonorrhea is generally a non-complicated mucosal infection with a pustular discharge. More severe sequellae include salpingitis and pelvic inflammatory disease which may lead to sterility and/or ectopic pregnancy. Occasionally, the organism can disseminate as a bloodstream infection. Epidemiology, incidence and prevalence: Gonorrhea is a global disease infecting approximately 60 million people annually. In the United States there are approximately 300, 000 cases each year, with an incidence of approximately 100 cases per 100,000 population. Treatment and curability: Gonorrhea is susceptible to an array of antibiotics. Antibiotic resistance is becoming a major problem and there are fears that the gonococcus will become the next "superbug" as the antibiotic arsenal diminishes. Currently, third generation extended-spectrum cephalosporins are being prescribed. Molecular mechanisms of infection: Gonococci elaborate numerous strategies to thwart the immune system. The organism engages in extensive phase (on/off switching) and antigenic variation of several surface antigens. The organism expresses IgA protease which cleaves mucosal antibody. The organism can become serum resistant due to its ability to sialylate lipooligosaccharide in conjunction with its ability to subvert complement activation. The gonococcus can survive within neutrophils as well as in several other lymphocytic cells. The organism manipulates the immune response such that no immune memory is generated which leads to a lack of protective immunity.


A critical evaluation of the strategy project.
The STRATEGY project (sustainable restoration and long-term management of contaminated rural, urban and industrial ecosystems; www.strategy-ec.org.uk) addressed the need for a holistic decision framework for the selection of optimal remediation strategies for long-term sustainable management of contaminated areas in Western Europe. The project considered both technical and social aspects of implementing restoration strategies for urban and rural environments. The importance of considering socially relevant objectives in addition to the dose reduction was emphasised. A critical evaluation was carried out on 101 selected countermeasures, (including rural waste disposal options), a model was developed to aid optimising countermeasure strategies and a method of carrying out participatory decision-making suggested. The outputs of the project are described and critically evaluated.


Catecholaminergic A1/C1 neurons contribute to the maintenance of upper airway muscle tone but may not participate in NREM sleep-related depression of these muscles.
Neural mechanisms of obstructive sleep apnea, a common sleep-related breathing disorder, are incompletely understood. Hypoglossal motoneurons, which provide tonic and inspiratory activation of genioglossus (GG) muscle (a major upper airway dilator), receive catecholaminergic input from medullary A1/C1 neurons. We aimed to determine the contribution of A1/C1 neurons in control of GG muscle during sleep and wakefulness. To do so, we placed injections of a viral vector into DBH-cre mice to selectively express the hMD4i inhibitory chemoreceptors in A1/C1 neurons. Administration of the hM4Di ligand, clozapine-N-oxide (CNO), in these mice decreased GG muscle activity during NREM sleep (F1,1,3=17.1, p<0.05); a similar non-significant decrease was observed during wakefulness. CNO administration had no effect on neck muscle activity, respiratory parameters or state durations. In addition, CNO-induced inhibition of A1/C1 neurons did not alter the magnitude of the naturally occurring depression of GG activity during transitions from wakefulness to NREM sleep. These findings suggest that A1/C1 neurons have a net excitatory effect on GG activity that is most likely mediated by hypoglossal motoneurons. However, the activity of A1/C1 neurons does not appear to contribute to NREM sleep-related inhibition of GG muscle activity, suggesting that A1/C1 neurons regulate upper airway patency in a state-independent manner.


Algevir: An Expression System for Microalgae Based on Viral Vectors.
The use of recombinant algae for the production of valuable compounds is opening promising biotechnological applications. However, the development of efficient expression approaches is still needed to expand the exploitation of microalgae in biotechnology. Herein, the concept of using viral expression vectors in microalgae was explored for the first time. An inducible geminiviral vector leading to Rep-mediated replication of the expression cassette allowed the production of antigenic proteins at high levels. This system, called Algevir, allows the production of complex viral proteins (GP1 from Zaire ebolavirus) and bacterial toxin subunits (B subunit of the heat-labile Escherichia coli enterotoxin), which retained their antigenic activity. The highest achieved yield was 1.25 mg/g fresh biomass (6 mg/L of culture), which was attained 3 days after transformation. The Algevir system allows for a fast and efficient production of recombinant proteins, overcoming the difficulties imposed by the low yields and unstable expression patterns frequently observed in stably transformed microalgae at the nuclear level; as well as the toxicity of some target proteins.


Can MOPP be replaced in the treatment of advanced Hodgkin's disease?
MOPP (mechlorethamine, vincristine, procarbazine, prednisone) was the first successful regimen for the treatment of Hodgkin's disease. It has the longest period of follow-up and is best studied as to its benefits and acute and long-term side effects. The acute toxicity of the side effects, including nausea and/or vomiting, hair loss, and myelosuppression, may have been reason to modify doses of nitrogen mustard, an agent whose dose intensity may be critical in achieving long-term benefits. The substitution of chlorambucil and vinblastine in the ChlVPP (chlorambucil, vinblastine, procarbazine, prednisone) program has relieved all of these acute toxicities, except myelosuppression. The long-term toxicity of sterility, especially in males, and myelodysplasia is most likely due to alkylating-agent toxicity and would not be influenced by the various MOPP variants, such as MVPP (mechlorethamine, vinblastine, procarbazine, prednisone), ChlVPP, and COPP (chlorambucil-vincristine, procarbazine, prednisone). Doxorubicin-containing regimens, such as ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and ABDIC (doxorubicin, bleomycin, dacarbazine, lomustine, prednisone), have been second-line treatments that have significant antitumor effect and, as such, have resulted in few, if any, long-term cures in most series. ABVD has been incorporated into alternating MOPP/ABVD schemes or in hybrids that attempt to offer all active agents, such as MOPP/ABV. The initial experience has been encouraging with high and durable complete remissions (CRs). MOPP/ABVD x 12(1) and MOPP-2/ABVD-2(2) have been compared with MOPP alone with a significant superiority for the alternating regimens. Other randomized trials have not shown any superiority for the alternating program. The Cancer and Leukemia Group B (CALGB) has compared MOPP with MOPP/ABVD given with a third arm of ABVD alone. The complete response and time-to-treatment failure rates for MOPP/ABVD and ABVD alone were superior to those for MOPP. Significant modifications of MOPP doses may explain the differences, since only 20% of patients were receiving full doses of nitrogen mustard by the sixth dose. ABVD has unique toxicity, and myelodysplasia and sterility are not seen. Pulmonary fibrosis with radiation and bleomycin is unique to ABVD, as shown in the ABVD experience at the NCl (Milan). Can ABVD be improved? The demonstrated single-dose activity of etoposide in Hodgkin's disease has prompted its inclusion in second-line programs, such as EVA (etoposide, vincristine or vinblastine, doxorubicin). The second-line response rates in the St Bartholomew's (London, England) series (where vincristine was used) was 11 of 19 patients (58%);3 in the ongoing CALGB trial of EVA (vinblastine combination), the response rate is 67%. (ABSTRACT TRUNCATED AT 400 WORDS)


Measurements of heat production for estimation of maintenance energy requirements of Hereford steers.
This study aimed to test the hypothesis that maintenance energy requirement (MEm) can be estimated from continuous heat production measurements during a change from a near maintenance feeding level to far below maintenance for two consecutive days. The MEm of eight Hereford steers weighing 286 +/- 5 kg (mean +/- SE) was determined in a balance trial. In addition, during the 10-d collection period, the animals were kept in open-circuit respiration chambers to measure 24-h gas exchange continuously at 10-min intervals. During the balance trial, the animals were fed dried chopped grass twice daily at an estimated level of 1.2 x MEm. After termination of the collection period on the 11th d of the balance trial, the steers were offered 2 kg/d of wheat straw while only gas exchange was measured. Estimates of MEm were derived from heat production (HP) data. The analyses included values of 24-h HP, HP of the nocturnal period (0000 to 0630), HP of the nocturnal period (excluding HP caused by standing) during the grass-feeding period and 24-h HP, nocturnal HP, and nocturnal HP (excluding HP caused by standing) during the straw feeding period. The MEm predicted from estimates of HP measurements were 536 +/- 9, 470 +/- 8, 441 +/- 8, 435 +/- 8, 393 +/- 9, and 373 +/- 9 kJ.kg of BW(-0.75).d(-1), respectively, whereas MEm calculated from data of the balance trial were 416 +/- 9 kJ.kg of BW(-0.75).d(-1). Values predicted for nocturnal HP (excluding HP caused by standing) of grass fed animals, 24-h HP, and nocturnal HP during straw feeding did not differ significantly from MEm. The differences in MEm among animals were reflected by all estimates of HP, whereas the correlation with the 24-h HP during straw feeding reached 0.9 (P = 0.002). We conclude that the method described is adequate to determine MEm with a sufficient degree of accuracy.


Breakdown of mucin and plant polysaccharides in the human colon.
To obtain an estimate of the extent to which complex carbohydrates are degraded by bacteria in the human colon, aqueous extracts of colon contents from four human subjects were separated into high and low molecular weight fractions by chromatography on a Sephadex G-100 column. The composition of these fractions was compared with the composition of similar fractions from ileal contents, i.e., from material entering the colon. In all four subjects, high molecular weight carbohydrate concentrations were lower in the colon than in the ileum, indicating that breakdown of complex carbohydrate occurs in the colon. The high molecular weight carbohydrate fraction contained sugars characteristic of plant polysaccharides (arabinose, xylose, mannose, rhamnose) as well as sugars characteristic of mucin (fucose, hexosamines, sialic acids). Concentrations of most of these sugars were uniformly lower in the colon than in the ileum. Since high molecular weight protein concentrations were lower in the colon than in the ileum of two of the four subjects tested, some degradation of protein may also occur in the colon.


Different Clinical Presentations of Brucellosis.
Brucellosis is one of the important multi-organ zoonotic infectious diseases. The forms of the clinical course of brucellosis in humans are acute, sub-acute and chronic. The present study aimed to retrospectively analyze the clinical characteristics and complications in the clinical forms of human brucellosis in Iran. The population included 957 patients admitted in the infectious diseases clinic affiliated to Babol University of Medical Sciences, Babol, Iran, within the past two decades. Data for the patients were obtained and documented in questionnaires. Patients were divided into three groups according to their history, symptoms and clinical presentation time: acute (0 - 2 months), sub-acute (3 - 12 months), and chronic (> 1 year). Most of the patients (73.8%) were in the acute stages of brucellosis, 22.6% had sub-acute brucellosis and 3.7% had chronic brucellosis. The most frequently observed symptoms were arthralgia (71%), sweating (66.7%), fever (57.2%) and backache (39.3%). The most common complication was arthritis (13.2%) in this study. This infection was observed with a diversity of clinical manifestations. Therefore, diagnostic difficulty because of the various clinical presentations and the way to find undiagnosed complications should be investigated in the differential diagnosis of other diseases.


Disturbed sensorimotor and electrophysiological patterns in lead intoxicated rats during development are restored by curcumin I.
Lead poisoning is one of the most significant health problem of environmental origin. It is known to cause different damages in the central and peripheral nervous system which could be represented by several neurophysiological and behavioral symptoms. In this study we firstly investigated the effect of lead prenatal exposure in rats to (3g/L), from neonatal to young age, on the motor/sensory performances, excitability of the spinal cord and gaits during development. Then we evaluated neuroprotective effects of curcumin I (Cur I) against lead neurotoxicity, by means of grasping and cliff avoidance tests to reveal the impairment of the sensorimotor functions in neonatal rats exposed prenatally to lead. In addition, extracellular recordings of motor output in spinal cord revealed an hyper-excitability of spinal networks in lead treated rats. The frequency of induced fictive locomotion was also increased in treated rats. At the young age, rats exhibited an impaired locomotor gait. All those abnormalities were attenuated by Cur I treatment at a dose of 16g/kg. Based on our finding, Cur I has shown features of a potent chemical compound able to restore the neuronal and the relative locomotor behaviors disturbances induced by lead intoxication. Therefore, this chemical can be recommended as a new therapeutic trial against lead induced neurotoxicity.


Antioxidant status of patients after on-pump and off-pump coronary artery bypass grafting.
It has been convincingly established that cardiopulmonary bypass routinely used in cardiac surgery induces an oxidative stress. The extensive production of reactive oxygen species occurring during cardiopulmonary bypass has a deleterious effect on the endogenous antioxidant defense pool. The recovery of antioxidant enzyme activities as well as other antioxidatively substances is one of the important tasks for the effective defense of patients in the postoperative period. Oxidative stress markers and the antioxidant status and the activities of some antioxidant enzymes were studied in patients during one-week period after cardiac revascularization performed using cardiopulmonary bypass and the results were compared with patients operated by off-pump technique. Thirty-nine patients undergoing elective surgical revascularization (coronary artery bypass grafting) were divided in two groups: twenty-two patients operated using cardiopulmonary bypass (group A) and a group B of seventeen patients undergoing pump-off surgery. Blood samples were drawn before operation and then in course of the first week after surgery. The following biochemical parameters were estimated: plasma levels of total antioxidant status (TAS) and of thiobarbituric acid reactive substances (TBARS) as well as erythrocyte activities of two antioxidant enzymes--superoxide dismutase (SOD) and glutathione peroxidase (GPx). There was a significantly decreased preoperative and also postoperative levels of TAS associated with a preoperatively increased level of TBARS in group A only. In both groups of patients (especially in group B), markedly decreased activity of SOD was observed. The increase of GPx activity--especially on the third postoperative day--was not significant. Regardless of the surgical technique, both groups of patients had a markedly decreased antioxidant capacity with a significantly increased production of lipid peroxides especially in patients operated with cardiopulmonary bypass. The decreased antioxidant status was connected with decreased erythrocyte activity of SOD. Therefore, we recommend the regular supply of antioxidant acting substances (antioxidant vitamins and coenzyme Q10) be included in their standard therapeutic strategy especially in the preoperative period. (Tab. 2, Fig. 4, Ref: 22.)


Exosomes-Small Players, Big Sound.
Incipiently named extracellular vesicles, exosomes are forming now a separate class of cellular mediators with important functions in physiological and pathological states. Their ability to transfer information between cells through encapsulation of proteins, nucleic acids and lipids for the preservation of the homeostatic equilibrium is translated also in pathological conditions. The recipient cells react to the reception of foreign molecules adjusting their molecular state according to the enclosed message. Cancer cells, in order to influence the microenvironment and facilitate the malignant expanding, exploit this intercellular trafficking. Immune cells are also producing exosomes that ensure the transportation of immune mediators and signaling molecules between cells. Current experimental attempts are concentrated on the adjustment of exosomes level for therapeutic purposes, enrolment of these vesicles as diagnosis or prognosis tools and also exosomes' use as drug delivery vehicles or immune stimulatory agents.


Plasmon-Enhanced Energy Transfer in Photosensitive Nanocrystal Device.
Förster resonance energy transfer (FRET) interacted with localized surface plasmon (LSP) gives us the ability to overcome inadequate transfer of energy between donor and acceptor nanocrystals (NCs). In this paper, we show LSP-enhanced FRET in colloidal photosensors of NCs in operation, resulting in substantially enhanced photosensitivity. The proposed photosensitive device is a layered self-assembled colloidal platform consisting of separated monolayers of the donor and the acceptor colloidal NCs with an intermediate metal nanoparticle (MNP) layer made of gold interspaced by polyelectrolyte layers. Using LBL assembly, we fabricated and comparatively studied seven types of such NC-monolayer devices (containing only donor, only acceptor, Au MNP-donor, Au MNP-acceptor, donor-acceptor bilayer, donor-Au MNP-acceptor trilayer, and acceptor-Au MNP-donor reverse trilayer). In these structures, we revealed the effect of LSP-enhanced FRET and exciton interactions from the donor NCs layer to the acceptor NCs layer. Compared to a single acceptor NC device, we observed a significant extension in operating wavelength range and a substantial photosensitivity enhancement (2.91-fold) around the LSP resonance peak of Au MNPs in the LSP-enhanced FRET trilayer structure. Moreover, we present a theoretical model for the intercoupled donor-Au MNP-acceptor structure subject to the plasmon-mediated nonradiative energy transfer. The obtained numerical results are in excellent agreement with the systematic experimental studies done in our work. The potential to modify the energy transfer through mastering the exciton-plasmon interactions and its implication in devices make them attractive for applications in nanophotonic devices and sensors.


Formation of doubly positively charged diatomic ions of Mo2(2+) produced by Ar+ sputtering of an Mo metal surface.
Long-lived metastable doubly positively charged diatomic ions of Mo2(2+) have been produced by Ar+ bombardment of a molybdenum metal surface. These exotic molecular dications, such as for example 92,95Mo2(2+) at m/z 93.5, could be observed in positive ion mass spectra for ion flight times of approximately 17 micros in a Cameca IMS-3f secondary ion mass spectrometer, when the ion extraction field was adjusted for detection of ions that are formed in the gas phase several micrometers in front of the sputtered surface. Mo2(2+) was observed at high primary current densities for projectile ions of Ar+, but could not be detected under very similar bombarding conditions for projectile ions of Xe+. Such a dependence of ion production by inert gas sputtering on the primary ion species [ionization energies: IP1(Ar) = 15.76 eV and IP1(Xe) = 12.13 eV] is unusual. It is shown that formation of Mo2(2+) dications takes place by resonant charge transfer in grazing gas-phase collisions between incoming projectile ions of Ar+ and sputtered molecular ions of Mo2+. The efficiency for such a resonant electron capture (Mo2+ + Ar+ --> Mo2(2+) + Ar) is of the order of 10(-5) for the bombarding conditions in our mass spectrometer and corresponds to a cross section of a few 10(-15) cm2.


Alternative lengthening of telomeres is induced by telomerase inhibitors in Barrett's esophageal cells.
A crucial step in the path to the malignant transformation of cells and tumor formation is immortalization, which essentially depends on telomere maintenance. The aim of this study was to investigate the role of telomerase in the progression of Barrett's esophagus. Telomerase activity was measured in Barrett's cells using terminal restriction fragment (TRF) analysis. Telomere length was measured using Q-FISH analysis. Furthermore, the telomere recombination events were detected between sister chromatids using chromosome orientation FISH (CO-FISH). There was a reduction in telomerase activity in the CP-A cells transduced with MT-hTER/47A+siRNA, which led to an almost complete disappearance of telomerase activity. The telomere length of the CP-A cells transduced with MT-hTER/47A+siRNA was slightly shorter compared to that of the untransduced cells. The telomerase-inhibited cells were morphologically indistinguishable from those untransduced and WT-hter-transduced cells. In the control cells, the growth rate was between 0.9 to 1.1 with the population doubling per day. Although the transduction of the telomerase inhibitors in the CP-A cells did not cause a significant reduction in cell growth, these transduced cells grew generally slower compared with the control cells. The heterogeneous telomere length was also be detected in the telomerase-inhibited CP-A cells. However, the telomere length remained homogeneous in the control cells. The metaphase of the CP-A cells transduced with MT-hTER/47A+siRNA demonstrated 70% heterogeneous telomeres. In addition, no increased recombination was observed between sister chromatids in the transduced CP-A cells compared with the control cells. Our findings suggest that an alternative lengthening of telomeres (ALT) may be induced by telomerase inhibitors in CP-A cells. Therefore, telomerase inhibitors may exhibit high potency in the treatment of esophageal adenocarcinoma arising from Barrett's esophagus.


Specular-reflection contributions to static and dynamic radiation forces on circular cylinders.
Interest in the response of highly reflecting objects in water to modulated acoustical radiation forces makes it appropriate to consider contributions to such forces from perfectly reflecting objects to provide insight into radiation forces. The acoustic illumination can have wavelengths much smaller than the object's size, and objects of interest may have complicated shapes. Here, the specular contribution to the oscillating radiation force on an infinite circular cylinder at normal incidence is considered for double-sideband-suppressed carrier-modulated acoustic illumination. The oscillatory magnitude of the specular force decreases monotonically with increasing modulation frequency, and the phase of the oscillating force depends on the relative phase of the sidebands. The phase dependence on the modulation frequency can be reduced with the appropriate selection of a sideband relative-phase parameter. That is a consequence of the significance of rays that are incident on the cylinder having small impact parameters that are nearly backscattered. For one choice of a relative sideband phase, a prior partial wave series (PWS) solution is available, which supports the specular analysis when the PWS is evaluated for a rigid cylinder. The importance of specular contributions for aluminum cylinders in water is noted. A specular analysis for an analogous spherical reflector is also summarized.


Effects on cement after partial replacement with burned joss paper ash.
In the last ten years, as international environmental protection consciousness has increased, the study and applications of green building, green construction materials and energy savings as well as reduction of carbon dioxide have become urgent issues for governments. In Taiwan, joss papers are burned in more than 11,731 registered shrines or temples in traditional Chinese deity or ancestor worship ceremonies during special holidays or occasions. Instead of placing this large amount of burned joss paper ash (BJPA) in landfills, this study proposes recycling BJPA by replacing some cement with calcined BJPA (CBJPA) in mortar specimens. After BJPA samples were calcined at a high kiln temperature, mortar samples were created using CBJPA to replace cement at seven different levels: 0%, 5%, 10%, 15%, 20%, 25% and 30%. Tests like setting time and compressive strength were performed for macro-analyses; scanning electron microscopy-energy dispersive spectroscopy, X-ray diffraction and thermal gravimetric analysis/differential thermal analysis were carried out for the microstructure and chemical composition analyses. The test results showed that the compressive strengths of specimens with different levels of CBJPA replacement were apparently less than those of the control group (0% CBJPA) at all curing times. The compressive strength and setting time both decreased as the fraction of CBJPA in the mortar increased. Furthermore, because the hydration product did not cement and the mortar specimen structure was loose, the expected strength improvement from the pozzolanic reaction provided by the CBJPA was not clearly observed.


Influence of two-stage anatomic correction on size and distensibility of the anatomic pulmonary/functional aortic root in patients with simple transposition of the great arteries.
To evaluate the results of the two-stage anatomic correction of simple transposition of the great arteries the size, distensibility, and histologic characteristics of the anatomic pulmonary root, which arises from the anatomic left ventricle and which we termed the functional aortic root after anatomic correction, were determined in seven patients before and twice after anatomic correction (mean 43 and 671 days) and the results were compared with those in normal control subjects. The diameter of the systolic sinus of the anatomic pulmonary root increased after banding on the average to 140% of normal, whereas the diameter of the diastolic sinus of the functional aortic root increased after anatomic correction on the average to 150% of normal. Diameters of both the systolic and diastolic sinuses of the functional aortic root remained 30% to 55% larger than normal after anatomic correction. Growth potential of the functional aortic root after anatomic correction was normal, whereas its distensibility, as assessed by determination of the percent change in radius and pressure-strain elastic modulus (stiffness index), was decreased after anatomic correction. This pressure-strain elastic modulus was directly related to the corresponding body surface area and age at banding. In four of five specimens of the anatomic pulmonary arterial wall that were obtained at the time of anatomic correction, fragmentation and shortening of elastic fibers were observed. The histologic characteristics of the pulmonary root in the patient with the smallest body surface area at banding and normal distensibility of the anatomic pulmonary/functional aortic root before and after anatomic correction revealed normal aortic configuration of the elastic tissue.(ABSTRACT TRUNCATED AT 250 WORDS)


Incidence and 10-year survival of intracerebral hemorrhage in a population-based registry.
The purpose of this study was to evaluate the incidence and prognosis of intracerebral hemorrhage. We analyzed data referring to our prospective population-based registry, including patients with a first-ever stroke followed up to 10 years. In a 5-year period, we included 549 patients (247 men and 302 women; mean age+/-SD, 73.6+/-12.5 years) with an intracerebral hemorrhage. The crude annual incidence rate was 36.9 per 100000 (95% CI, 33.8 to 40.0), 32.9 per 100000 when standardized to the 2006 European population, and 15.9 per 100000 when standardized to the world population. The case-fatality rate was 34.6% (95% CI, 30.6 to 38.6) at 7 days; it increased to 50.3% (95% CI, 46.1 to 54.5) at 30 days and to 59.0% (95% CI, 54.9 to 63.1) at 1 year. Diabetes mellitus and posterior fossa hemorrhage were associated with an increased risk of 7- and 30-day mortality, whereas older age was associated with an increased risk of 30-day mortality only. At the Kaplan-Meier analysis, the 10-year survival rate was 24.1% (95% CI, 20.1 to 28.1). Intracerebral hemorrhage is characterized by a severe prognosis, mostly in the short term. Because of the high proportion of fatal events that occurs early after the stroke, it is mandatory to identify and apply specific therapeutic strategies for patients with intracerebral hemorrhage.


Completion Rate and Safety of Tuberculosis Infection Treatment With Shorter Regimens.
The traditional treatment of tuberculosis (TB) infection (9 months of daily isoniazid [9H]) is safe but completion rates of <50% are reported. Shorter regimens (3 months of once-weekly isoniazid and rifapentine [3HP] or 4 months of daily rifampin [4R]) are associated with improved adherence in adults. This was a retrospective cohort study (2014-2017) of children (0-18 years old) seen at a children's TB clinic in a low-incidence nation. We compared the frequency of completion and adverse events (AEs) in children receiving 3HP, 4R, and 9H; the latter 2 regimens could be administered by families (termed self-administered therapy [SAT]) or as directly observed preventive therapy (DOPT); 3HP was always administered under DOPT. TB infection treatment was started in 667 children: 283 (42.4%) 3HP, 252 (37.8%) 9H, and 132 (19.8%) 4R. Only 52% of children receiving 9H via SAT completed therapy. Children receiving 3HP were more likely to complete therapy than the 9H (SAT) group (odds ratio [OR] 27.4, 95% confidence interval [CI]: 11.8-63.7). Multivariate analyses found receipt of medication under DOPT (OR: 5.72, 95% CI: 3.47-9.43), increasing age (OR: 1.09, 95% CI: 1.02-1.17), and the absence of any AE (OR: 1.70, 95% CI: 0.26-0.60) to be associated with completing therapy. AEs were more common in the 9H group (OR: 2.51, 95% CI: 1.48-4.32). Two (0.9%) children receiving 9H developed hepatotoxicity; no child receiving 3HP or 4R developed hepatotoxicity. Shorter regimens are associated with increased completion rates and fewer AEs than 9H.


Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus.
Three new neurofibromatosis type 1 (NF1) mutations have been detected and characterized. Pulsed-field gel and Southern blot analyses reveal the mutations to be deletions of 190, 40, and 11 kb of DNA. The 11 kb deletion does not contain any of the previously characterized genes that lie between two NF1 translocation breakpoints, but it does include a portion of a rodent/human conserved DNA sequence previously shown to span one of the translocation breakpoints. By screening cDNA libraries with the conserved sequence, we identified a number of cDNA clones from the translocation breakpoint region (TBR), one of which hybridizes to an approximately 11 kb mRNA. The TBR gene crosses at least one of the chromosome 17 translocation breakpoints found in NF1 patients. Furthermore, the newly characterized NF1 deletions remove internal exons of the TBR gene. Although these mutations might act by compromising regulatory elements affecting some other gene, these findings strongly suggest that the TBR gene is the NF1 gene.


Causal relationship between genetically predicted depression and cancer risk: a two-sample bi-directional mendelian randomization.
Depression has been reported to be associated with some types of cancer in observational studies. However, the direction and magnitude of the causal relationships between depression and different types of cancer remain unclear. We performed the two-sample bi-directional mendelian randomization with the publicly available GWAS summary statistics to investigate the causal relationship between the genetically predicted depression and the risk of multiple types of cancers, including ovarian cancer, breast cancer, lung cancer, glioma, pancreatic cancer, lymphoma, colorectal cancer, thyroid cancer, bladder cancer, and kidney cancer. The total sample size varies from 504,034 to 729,150. Causal estimate was calculated by inverse variance weighted method. We also performed additional sensitivity tests to evaluate the validity of the causal relationship. After correction for heterogeneity and horizontal pleiotropy, we only detected suggestive evidence for the causality of genetically predicted depression on breast cancer (OR = 1.09, 95% CI: 1.03-1.15, P = 0.0022). The causal effect of depression on breast cancer was consistent in direction and magnitude in the sensitivity analysis. No evidence of causal effects of depression on other types of cancer and reverse causality was detected. The result of this study suggests a causative effect of genetically predicted depression on specific type of cancer. Our findings emphasize the importance of depression in the prevention and treatment of breast cancer.


Supporting Team Reflexivity During the COVID-19 Lockdown: A Qualitative Study of Multi-Vision Groups In-person and Online.
Introduction: The professional self is often hindered by a lack of self-care and poor work-life balance, and cannot be considered an unlimited resource. Given this, the reflexive team is an important organizational tool for protecting workers' well-being. The non-profit organization Maestri di Strada (MdS) ("Street Teachers") conducts action research (AR) in the area of socio-education. The main tool used by the group to protect the well-being of its members is a guided reflexivity group, inspired by the Balint Group and termed the Multi-Vision Group (MG). In March 2020, because of the COVID-19 lockdown, the MdS team had to quickly revamp its working model, and MGs were held online for the first time. Aim: Through qualitative research that takes a longitudinal approach, the aim of this study is to evaluate the efficacy of the MG in supporting the team's reflexivity in this new online format. Methods: This article considers MGs during two different time periods: pre-pandemic (T1) and early pandemic (T2). During T1, the MdS team met 18 times in person, while during T2 the team met 12 times through an online platform (always under the guidance of a psychotherapist). During all sessions in both time periods, a silent observer was present in the meetings, and they subsequently compiled narrative reports. The textual corpora of the reports were submitted for a Thematic Analysis of Elementary Contexts through T-Lab Plus, in order to examine the main content of the groups' discourse. Results: The results (five clusters in T1; and five in T2) show that, during T2, the group devoted considerable time to experiences tied to the pandemic (T21: schools facing the pandemic crisis; T2.2: the pandemic: death, inner worlds, and thought resistance; T2.3: kids' stories involving physical distancing and emotional proximity). The group also came up with innovative educational initiatives that defied the lockdown (T2.4: fieldwork: the delivery of "packages of food for thought"; T2.5: the MdS group: identity and separation). Based on these findings, the MG most likely contributed to the emergence of MdS as a "resilient community," capable of absorbing the shock of the pandemic and realizing a fast recovery response.


Onset of anomalous diffusion from local motion rules.
Anomalous diffusion processes, in particular superdiffusive ones, are known to be efficient strategies for searching and navigation in animals and also in human mobility. One way to create such regimes are Lévy flights, where the walkers are allowed to perform jumps, the "flights," that can eventually be very long as their length distribution is asymptotically power-law distributed. In our work, we present a model in which walkers are allowed to perform, on a one-dimensional lattice, "cascades" of n unitary steps instead of one jump of a randomly generated length, as in the Lévy case, where n is drawn from a cascade distribution p_{n}. We show that this local mechanism may give rise to superdiffusion or normal diffusion when p_{n} is distributed as a power law. We also introduce waiting times that are power-law distributed as well and therefore the probability distribution scaling is steered by the two local distributions power-law exponents. As a perspective, our approach may engender a possible generalization of anomalous diffusion in context where distances are difficult to define, as in the case of complex networks, and also provide an interesting model for diffusion in temporal networks.


Temporal change in IL-6 mRNA and protein expression produced by cyclic stretching of human pulmonary artery endothelial cells.
The time courses of interleukin (IL)-6 gene expression and protein production were examined in human pulmonary artery endothelial cells (HPAECs) subjected to cyclic stretching. IL-6 protein was increased even in cells without stretching. Fold changes determined by dividing the level of IL-6 protein in stretched cells by that in unstretched cells at the same sampling times indicated that IL-6 protein was increased by stretching. At least 1 h of stretching was necessary to elicit an increase of IL-6 protein, and the levels peaked at 3 h after the start of stretching. After withdrawal of stretching, there was no further increase of IL-6 protein. The expression levels of the IL-6 gene were significantly increased by stretching and peaked at 30 min after the start of stretching. The difference in the peak times of IL-6 gene and protein expression likely reflects the process of protein synthesis after the appearance of IL-6 mRNA.


The types and timing of the degenerative changes seen in the cysts during and after benzimidazole treatment of cystic echinococcosis.
In a large-scale Bulgarian study, 122 patients with abdominal and/or lung echinococcosis were randomly selected for treatment with albendazole or mebendazole. The main aims were to evaluate the effect of each drug on the hydatid cysts, to follow the changes in cyst morphology during and after treatment, and to determine how quickly each drug produced the first, detectable, degenerative changes in the cysts. Follow-up was based on periodic ultrasonography, chest radiography and computed tomography. The abdominal cysts were categorised as small (<5 cm in diameter) or large. As albendazole treatment had effects that were almost identical to those of mebendazole treatment, the results for the two drugs were combined. In the lungs and, particularly, in the abdomen, the size of the cysts being treated influenced the character and timing of the degenerative changes seen in them. The initial change seen in each abdominal cyst was detachment of the endocyst, which occurred 1-3 months (small cysts) or 2-5 months (large cysts) after the initiation of treatment (P<0.05). The abdominal cysts then developed a hyper-echoic/hyper-dense appearance, became smaller, and finally disappeared 3.3-9.3 months (small cysts) or 5.6-13.9 months (large cysts) after treatment began (P<0.05). The first degenerative change noted in the lung cysts was cyst rupture, which occurred as early as day 10 of therapy but was generally observed 1 or 2 months after treatment began. After their complete evacuation, the ruptured lung cysts shrank and became deformed, some disappearing within 5-9 months of the initiation of treatment. The degenerative changes recorded, which began significantly earlier in the lung cysts than in abdominal cysts, indicate serious damage to the cysts and the parasiticidal, curative effect of each of the two benzimidazoles employed.


Solid-state photopolymerization of a shape-persistent macrocycle with two 1,8-diazaanthracene units in a single crystal.
A macrocyclic monomer with two opposing 1,8-diazaanthracene units is polymerized in a single crystal by a photochemically induced [4 + 4] cycloaddition reaction between neighboring monomers in which the anthracene units are stacked face-to-face at the critical Schmidt distance. The severe structural changes associated with this are minimized by the monomer design, wherein the linkers between the two opposing photoreactive 1,8-diazaanthracene units are connected to the 4 and 5 positions of the latter, whose spatial positioning is changed the least during dimerization. This helps to keep the monomer's overall shape basically unchanged during the polymerization. The resulting new rigid-rod polymer is soluble in its protonated form, and after counterion exchange with a surfactant, it can be depolymerized back into monomer upon relatively mild thermal treatment (120 °C) in an organic solvent.


Effects of 3 Different Methods of Care on the Peristomal Skin Integrity of Children with Percutaneous Endoscopic Gastrostomy Tubes: A Prospective Randomized Controlled Trial.
There are a limited number of studies examining the effects of products used in stoma care. This study compares the effects of 3 different methods of care on the peristomal skin integrity of children with percutaneous endoscopic gastrostomy (PEG) tubes. In this randomized controlled study, 60 children were allocated to the 3 study groups (group 1: hydrogel, group 2: soap and water, group 3: saline solution). Dressings were changed daily for all groups during the first week, then weekly for group 1 and daily for groups 2 and 3. The evaluations were performed using a PEG Region Peristomal Skin Integrity Observation Form and devices measuring stoma region pH, moisture, and temperature. One evaluation was performed in a hospital and 4 during home visits in the first month after PEG insertion. Moisture levels in the stoma region were normal in the saline solution group, high in the hydrogel group, and low in the soap and water group (P < .05). Complications potentially affecting peristomal skin integrity in the stoma region (erythema, drainage, hemorrhage, hypergranulation tissue) were observed most frequently in the soap and water group (5%-45%) and least frequently in the hydrogel group (15%-25%). However, there was no statistically significant difference among the groups with respect to these complications (P > .05). Because the dressing requires 6 times fewer changes per month, and wound site infection in the stoma site is minimized, the use of glycerin hydrogel should be considered for inclusion in pediatric stoma care procedures.


CAR T-cell treatment during the COVID-19 pandemic: Management strategies and challenges.
The pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly across the world. Currently, the COVID-19 pandemic is affecting the continuity of essential routine healthcare services and procedures, including chimeric antigen receptor T-cell (CAR-T) therapy, a life-saving option for patients with relapsed/refractory (R/R) hematologic malignancies. Due to the rapid disease progression of hematological malignancies, there is an urgent need to manufacture and utilize CAR T-cells. However, CAR-T treatment has become extraordinarily challenging during this COVID-19 pandemic. Thus, many medical and technical factors must now be taken into consideration before, during, and after CAR-T therapy. The purpose of this review is to provide brief suggestions for rational decision-making strategies in evaluating and selecting CAR T-cell treatment and appropriate CAR T-cell products, and protective strategies for medical staff and patients to prevent infection in the midst of the current COVID-19 pandemic.


New SHH and Known SIX3 Variants in a Series of Latin American Patients with Holoprosencephaly.
Holoprosencephaly (HPE) is the failure of the embryonic forebrain to develop into 2 hemispheres promoting midline cerebral and facial defects. The wide phenotypic variability and causal heterogeneity make genetic counseling difficult. Heterozygous variants with incomplete penetrance and variable expressivity in the SHH, SIX3, ZIC2, and TGIF1 genes explain ∼25% of the known causes of nonchromosomal HPE. We studied these 4 genes and clinically described 27 Latin American families presenting with nonchromosomal HPE. Three new SHH variants and a third known SIX3 likely pathogenic variant found by Sanger sequencing explained 15% of our cases. Genotype-phenotype correlation in these 4 families and published families with identical or similar driver gene, mutated domain, conservation of residue in other species, and the type of variant explain the pathogenicity but not the phenotypic variability. Nine patients, including 2 with SHH pathogenic variants, presented benign variants of the SHH, SIX3, ZIC2, and TGIF1 genes with potential alteration of splicing, a causal proposition in need of further studies. Finding more families with the same SIX3 variant may allow further identification of genetic or environmental modifiers explaining its variable phenotypic expression.


Influence of inositol 1,4,5-trisphosphate and guanine nucleotides on intracellular calcium release within the N1E-115 neuronal cell line.
The Ca2+ accumulating properties of a nonmitochondrial intracellular organelle within cultured N1E-115 neuroblastoma cells containing an (ATP + Mg2+)-dependent Ca2+ pump were recently described in detail (Gill, D. L., and Chueh, S. H. (1985) J. Biol. Chem. 260, 9289-9297). Using both saponin-permeabilized N1E-115 cells and microsomal membranes from cells, this report describes the effectiveness of both inositol 1,4,5-trisphosphate (IP3) and guanine nucleotides in mediating Ca2+ release from this internal organelle, believed to be endoplasmic reticulum. Using permeabilized N1E-115 cells, 2 microM IP3 effects rapid release (t1/2 less than 20 s) of approximately 40% of accumulated Ca2+ releasable with 5 microM A23187. Half-maximal Ca2+ release occurs with 0.5 microM IP3, and maximal release with 3 microM IP3. Using a frozen microsomal membrane fraction isolated from lysed cells, 2 microM IP3 rapidly releases (t1/2 less than 30 s) 10-20% of A23187-releasable Ca2+ accumulated within nonmitochondrial Ca2+-pumping vesicles, although only in the presence of 3% polyethylene glycol (PEG). 10 microM GTP, but not guanosine 5'-(beta, gamma-imido)triphosphate (GMPPNP), increases the extent of release in the presence of IP3. Importantly, however, GTP alone induces a substantial release of Ca2+ (up to 40% of releasable Ca2+) with a t1/2 value (60-90 s) slightly longer than that for IP3. The effects of IP3 and GTP are approximately additive, and both effects require 3% PEG. Half-maximal Ca2+ release occurs with 1 microM GTP, with maximal release at 3-5 microM GTP; 20 microM GMPPNP has no effect on release and only slightly inhibits 5 microM GTP; 20 microM GDP promotes full release, but only after a 90-s lag, and initially inhibits the action of 5 microM GTP. Using permeabilized N1E-115 cells, 5 microM GTP with 3% PEG releases greater than 50% of releasable Ca2+; without PEG, GTP still mediates approximately 30% release of Ca2+ from cells. Neither IP3, GTP, or both together (with or without PEG) effects release of Ca2+ accumulated within synaptic plasma membrane vesicles. The profound effectiveness of GTP on Ca2+ release has important implications for intracellular Ca2+ regulation and is probably related to Ca2+ release mediated by IP3.


Massive Osteochondral Lesion of the Talus in a Skeletally Immature Patient Associated With a Tarsal Coalition and Valgus Hindfoot.
Rarely, osteochondral lesions of the talus occur without a history of trauma. Accurate interpretation of the mechanical load distributions onto the ankle leading to potential atraumatic cartilage damage must always be studied. The published data on the optimal treatment of talar osteochondral lesions in skeletally immature patients are scarce, especially when the lesions are associated with hindfoot malalignment. We describe the case of a pediatric female with an atraumatic osteochondral lesion of the talus associated with a talocalcaneal coalition and a valgus hindfoot, which we consider the first case to be reported. She presented with prolonged bilateral ankle pain and catching during gait of approximately 2 years' duration with a restricted range of motion, with the pain more excruciating in the right ankle. Radiographs revealed a large osteochondral lesion located at the lateral talar dome. The patient underwent partial osteochondral allograft transplantation, together with hindfoot realignment and coalition resection with a fat graft interposition. At the 2-year follow-up examination, the patient was free of pain in her right foot and ankle, with no signs of radiologic failure.


Evaluation of a multi-agent chemotherapy protocol combining dexamethasone, melphalan, actinomycin D, and cytarabine for the treatment of resistant canine non-Hodgkin high-grade lymphomas: a single centre's experience.
The DMAC protocol (dexamethasone, melphalan, actinomycin-D, cytarabine) has been evaluated in American studies for the treatment of relapsed canine lymphoma, comparing similarly to other rescue protocols. The aim of this study was to evaluate efficacy and toxicity of DMAC, in a larger UK cohort of resistant canine lymphomas. Medical records of dogs with resistant non-Hodgkin high-grade lymphomas that received DMAC as a rescue protocol were reviewed from 2007 to 2017. Response, time from initiation to discontinuation (TTD) and toxicity (Veterinary Cooperative Oncology Group criteria) were assessed. One hundred dogs were included; 86 received CEOP (modified CHOP including epirubicin) as first-line treatment. Thirty-five dogs (35%) responded: 21 complete responders (CRs) and 14 partial responders (PRs). Responders had significantly longer TTD (P < 0.001) compared with non-responders: 62 days (range 28-952) for CR vs 32 days (range 20-70) for PR. Six CR received more than six cycles of DMAC (range 7-36 cycles) and experienced a longer TTD (median 508, range 126-952 days). Thrombocytopenia occurred in 45% (24 grade 1-2, 21 grade 3-4) and neutropenia in 36% of cases (29 grade 1-2, 7 grade 3-4). Gastrointestinal toxicity occurred in 42% of dogs (40 grade 1-2, 2 grade 3-4). Owing to chemotherapy toxicity, treatment was discontinued in five, and hospitalization required in six cases. In this study, response to DMAC was lower and of generally shorter duration than previously reported. Toxicity was high, but infrequently led to hospitalization or discontinuation of treatment.


Repression of bone morphogenetic protein 4 by let-7i attenuates mesenchymal migration of head and neck cancer cells.
The movement modes of epithelial cancer cells in three-dimensional (3D) environments include the mesenchymal mode, which is associated with local invasion, and the amoeboid mode, which facilitates distant metastasis. The migratory behavior of individual cancer cells is critical for tumor dissemination; however, the mechanism underlying regulation of the switch between movement modes is not clearly understood. For head and neck squamous cell carcinoma (HNSCC), local invasion is the major route of dissemination. We previously demonstrated that, in HNSCC cells, Twist1 represses let-7i expression to elicit mesenchymal-mode movement through activation of Ras-related C3 botulinum toxin substrate 1 (RAC1). In this study, we discover another important target gene of let-7i for regulating HNSCC migration. Using bioinformatic tools, we identified bone morphogenetic protein 4 (BMP4) as a candidate target of let-7i. Further experiments, including 3'-untranslated region (UTR) reporter assays, quantitative RT-PCR and western blotting, confirmed that BMP4 is a bona fide target repressed by let-7i. In the HNSCC cell line OECM-1, knockdown of BMP4 reduced mesenchymal-mode migration and invasion in 3D culture. In clinical HNSCC samples, let-7i expression was inversely correlated with BMP4 expression. Our results revealed that let-7i attenuates mesenchymal-mode migration of HNSCC cells through repression of a novel target, BMP4.


Mutational Profiling of Driver Tumor Suppressor and Oncogenic Genes in Brazilian Malignant Pleural Mesotheliomas.
Malignant pleural mesothelioma (MPM) is a highly lethal disease comprising a heterogeneous group of tumors with challenging to predict biological behavior. The diagnosis is complex, and the histologic classification includes 2 major subtypes of MPM: epithelioid (∼60% of cases) and sarcomatous (∼20%). Its identification depends upon pathological investigation supported by clinical and radiological evidence and more recently ancillary molecular testing. Treatment options are currently limited, with no known targeted therapies available. To elucidate the mutation profile of driver tumor suppressor and oncogenic genes in a cohort of Brazilian patients. We sequenced 16 driver genes in a series of 43 Brazilian malignant mesothelioma (MM) patients from 3 distinct Brazilian centers. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor tissue blocks, and the TERT promoter region was amplified by PCR followed by direct capillary sequencing. The Illumina TruSight Tumor 15 was used to evaluate 250 amplicons from 15 genes associated with solid tumors (AKT1, GNA11, NRAS, BRAF, GNAQ, PDGFRA, EGFR, KIT, PIK3CA, ERBB2, KRAS, RET, FOXL2, MET,and TP53). Library preparation with the TruSight Tumor 15 was performed before sequencing at the MiSeq platform. Data analysis was performed using Sophia DDM software. Out of 43 MPM patients, 38 (88.4%) were epithelioid subtype and 5 (11.6%) were sarcomatoid histotype. Asbestos exposure was present in 15 (39.5%) patients with epithelioid MPM and 3 (60%) patients with sarcomatoid MPM. We found a TERT promoter mutation in 11.6% of MM, and the c.-146C>T mutation was the most common event. The next-generation sequencing was successful in 33 cases. A total of 18 samples showed at least 1 pathogenic, with a median of 1.8 variants, ranging from 1 to 6. The most mutated genes were TP53 and ERBB2 with 7 variants each, followed by NRAS BRAF, PI3KCA, EGFR and PDGFRA with 2 variants each. KIT, AKT1, and FOXL2 genes exhibited 1 variant each. Interestingly, 2 variants observed in the PDGFRA gene are classic imatinib-sensitive therapy. We concluded that Brazilian MPM harbor mutation in classic tumor suppressor and oncogenic genes, which might help in the guidance of personalized treatment of MPM.


Tooth auto-transplantation with double periodontal ligament stimulation to replace periodontally compromised teeth.
The healing process of autotransplantation puts 2 different tissues in competition: the ligament on the root surface and the bone tissue of the alveolus. This study shows the effects of a protocol with 2 surgical stages, which promote ligament repair, inhibit adhesion between bone and dental root, and reduce the occurrence of the ankylosis-root resorption phenomenon. Forty-three patients, 33 to 73 years old, received 47 transplantations of mature teeth (including retained teeth) during a 5-year period. During the first surgical step, the transplanted tooth is extracted, measured, immediately replaced in its origin site, and maintained with an original suture technique. The alveolus to which the tooth will be transplanted is adapted after extraction of the periodontally compromised tooth. The second surgery occurs at day 14, when regeneration of periodontal ligament (PDL) is at a maximum (first stimulation). The tooth is transplanted in its new alveolus and retained using the same suture technique to avoid a rigid splint and to create mechanical stimulation of the PDL (second stimulation). The results were 95.75% positive with normal PDL, with a 4.25% failure rate (transplant loss) and no ankylosis. Mean probing reduction was 8.37 +/- 3.0 mm. Mean radiographic bone gain was 7.73 +/- 4.32 mm. This study suggests that auto-transplantation with double PDL stimulation can be a viable treatment in clinical practice, especially to replace teeth with large periodontal lesions, deep furcation defects, and/or root fractures. This study shows the high potential of stimulated PDL to regenerate alveolar bone and periodontal structures in severe destruction sites.


Serum concentration of penicillin in the horse after repeated intramuscular injections of procaine penicillin G alone or in combination with benzathine penicillin and/or phenylbutazone.
Twenty-one adult horses were randomly assigned into 7 groups of 3 and were treated for 5 days with procaine penicillin G, benzathine penicillin , or phenylbutazone in various combinations and dosage schedules. Serum concentration of penicillin was measured serially over a 7-day period. The highest mean peak serum concentration was 2.06 micrograms/ml. Comparable peak values were seen 2 to 4 hours after administration of 22,000 IU of procaine penicillin G/kg of body weight given once or twice daily. A minimum serum concentration of 0.25 micrograms/ml was selected as adequate for efficacy against organisms that can be considered sensitive to penicillin. Once daily administration of procaine penicillin G and, although peak concentrations were lower, some regimens of procaine and benzathine penicillin G did maintain this concentration. Concurrent phenylbutazone administration did not affect serum concentration of penicillin appreciably.


[Associated factors for the infection of Beijing genotype Mycobacterium tuberculosis].
to analyze the risk factors for the infection of Beijing genotype Mycobacterium tuberculosis (MTB) and the relationship to drug resistance and clinical symptoms. sputum samples were collected from patients with pulmonary tuberculosis who were admitted to the hospital during July, 2007 to March, 2008. The sputum was cultured with L-J method, and then the bacterial DNA was isolated and genotyped with VNTR-7 (variable-number tandem repeats, VNTR) and RD105 deletion method respectively. The association between different genotypes and risk factors was analyzed. a hundred and sixteen clinical sputum isolates were obtained from 172 positive sputum cases. There were 112 isolates of MTB, and isolates of non-tuberculosis mycobacterium (NTM). Among the 97 isolates from Shanghai, Zhejiang and Jiangsu areas, Beijing genotype accounted for 86.6% (84/97), and non-Beijing genotype for 13.4% (13/97). The rates of MDR (multi-drug resistance), PDR (poly-drug resistance) and single drug resistance in Beijing genotype were not significantly higher than those in non-Beijing genotype. Among the risk factors, female gender, and CD(4)/CD(8)< 1 in patients with newly-treated tuberculosis, were associated with higher rate of Beijing genotype, chi(2) = 4.436, 4.494 and all P < 0.05, respectively. The Beijing genotype isolates were subdivided into 31 VNTR-7 types, and the distribution of quantity and resistance among different VNTR-7 genotypes was not even. A large number of MTB isolates (47.6%, 40/84) and drug resistant isolates (43.6%, 17/39) were among four VNTR-7 genotypes. Beijing genotype is the most prevalent MTB in Shanghai, Zhejian and Jiangsu areas. Female gender and low CD(4)/CD(8) ratio in patients with newly-treated TB are risk factors for infecting Beijing genotype MTB, which may have no relationship with drug resistance and clinical symptoms.


Long-term soft-tissue effects of biliary extracorporeal shock waves: an animal study.
Although delayed effects of renal extracorporeal shock-wave lithotripsy (ESWL) have been reported, the long-term soft-tissue effects after biliary ESWL have not been investigated. We report soft-tissue effects seen up to 1 year after biliary extracorporeal shock waves were administered to 18 Yucatan pigs. The gallbladder received 4000 electromagnetic shock waves from a Siemens Lithostar overhead module. Blood samples were drawn from each pig for hematologic, coagulation, and biochemical profiles immediately before and then at prescribed time intervals after administration of shock waves. Autopsy and histopathologic examination of the gallbladder and surrounding organs were performed. Kidneys and adrenal glands also were examined in five pigs followed up for 1 year. There were no gross or microscopic abnormalities in 11 animals, including all five animals in the 1-year group in which kidneys and adrenal glands also were normal. One animal (3-week group) had two 2-mm foci of parenchymal necrosis in the right lobe of the liver, probably related to ischemia after shock-wave therapy. Transient rise in liver and pancreatic enzyme levels was seen in most animals after administration of shock waves. The levels returned to normal within 2 months in all but one animal. We conclude that biliary ESWL with the Lithostar Plus does not produce long-term histologic evidence of organ damage in Yucatan pigs.


Effect of polychlorinated biphenyl on viral infections in mice.
Mice that were fed a diet containing 400, 200 or 100 microgram of polychlorinated biphenyls (PCB) per g were significantly more susceptible to Herpes simplex virus than mice that were fed a PCB-free diet. The mortality of mice that were fed a diet containing 400 or 200 microgram of PCB per g and infected with ectromelia virus was higher than that of normal control mice infected with virus. There was no significant difference in inducibility of interferon by polyinosinic acid-polycytoidylic acid between PCB-fed mice and control mice.


Study on the digitized and quantified evaluating method for super information characteristics of herbal preparation by infrared spectrum fingerprints.
This paper aims to establish the infrared spectrum fingerprint (IRFP) in the absorbing region of 4,000-400 cm(-1) and its first derivative infrared spectrum fingerprints (d-IRFP) of ginkgo tablet (GT). And set up theories of the digitized and quantified evaluating method for super information characteristics by IRFPs of traditional Chinese medicine (TCM) which consists of the IRFP index, information index, fluctuation index, information fluctuation index and the quantified infrared fingerprint method (QIFM). Direct tabletting method was applied during the data collection of the IRFPs of 14 batches of GTs by Fourier transform infrared spectrometer. In terms of the digitized features, QIFM and similarity analysis of d-IRFP, sample S4 and S7 were evaluated as suspected outliers while the qualities of S1, S2, S6 and S12 were less well and the rests were relatively good. The assessing approach makes the expression and processing of superposed information in IRFP of TCM digitized simple and effective. What's more, an approach which can test total chemical contents in the complex system of TCM rapidly, simply and accurately was achieved by the application of QIFM based on IR technique. Finally, the quantitative and digitized infrared fingerprinting method was established as a novel approach to evaluate the quality of TCM.


Finnish adolescents' perceptions of their health choices: A qualitative study.
This study described adolescents' perceptions of the aims of their daily health choices and how they make them. We used a qualitative, explorative design, with 67 adolescents aged 15-16 years taking part in semi-structured focus groups in Finland in 2016. We analyzed the data with qualitative inductive content analysis. Adolescents perceived their health choices as automatic and driven by knowledge and mistakes, and these decisions reflected their values and feelings. Their health choices were based on immediate and long-term goals and they reported that making good choices improved their self-confidence and enhanced their individuality. Adolescents also used health choices to promote other people's health. Health choices were linked to parental help and restrictions, and seeking acceptance from friends. Adolescents' health choices were also enabled and limited by society and the environment that they lived in. In conclusion, adolescents' health choices were an integral part of their daily decision-making, reflected the environment they lived in, and aimed to promote their health and express their individuality.


Atopic dermatitis in a chimpanzee (pan troglodytes verus)-A diagnostic and therapeutic challenge.
Diagnosis and treatment of atopic dermatitis (AD) in chimpanzees are challenging. Validated allergy tests specific for chimpanzees are not available. A multifactorial management of atopic dermatitis is important. Successful management of AD has, to the best knowledge of the authors, not been described in chimpanzees.


Intermolecular forces and correlations mediated by a phonon bath.
Inspired by the possibility to experimentally manipulate and enhance chemical reactivity in helium nanodroplets, we investigate the effective interaction and the resulting correlations between two diatomic molecules immersed in a bath of bosons. By analogy with the bipolaron, we introduce the biangulon quasiparticle describing two rotating molecules that align with respect to each other due to the effective attractive interaction mediated by the excitations of the bath. We study this system in different parameter regimes and apply several theoretical approaches to describe its properties. Using a Born-Oppenheimer approximation, we investigate the dependence of the effective intermolecular interaction on the rotational state of the two molecules. In the strong-coupling regime, a product-state ansatz shows that the molecules tend to have a strong alignment in the ground state. To investigate the system in the weak-coupling regime, we apply a one-phonon excitation variational ansatz, which allows us to access the energy spectrum. In comparison to the angulon quasiparticle, the biangulon shows shifted angulon instabilities and an additional spectral instability, where resonant angular momentum transfer between the molecules and the bath takes place. These features are proposed as an experimentally observable signature for the formation of the biangulon quasiparticle. Finally, by using products of single angulon and bare impurity wave functions as basis states, we introduce a diagonalization scheme that allows us to describe the transition from two separated angulons to a biangulon as a function of the distance between the two molecules.


Microtubules and early stages of cell-plate formation in the endosperm of Haemanthus katherinae Baker.
A fine structure study of the phragmoplast and developing cell plate has been made on glutaraldehyde-osmium tetroxide-fixed, dividing, cultured cells of the liquid endosperm of Haemanthus katherinae Baker. The phragmoplast arises between the telophase nuclei, usually in association with a remnant strand of spindle elements, and consists of an accumulation of microtubules oriented at right angles to the plane of the future cell plate. The microtubules, which are 200-240 A in diameter, occur in small clusters spaced at approximately 0.2-0.3 micro intervals along the plate. Short interconnections interpreted as "cross-bridges" have been observed between individual microtubules. Within each cluster there is an electron-opaque zone about 0.3 micro in width which can be attributed in part to an overlap of microtubules from both sides of the plate and in part to a local accumulation of an amorphous electron-opaque material. During development these dense zones become aligned in a plane which itself defines the plane of the plate. Vesicles, commonly observed in long files, are derived from a cytoplasmic matrix rich in elements of the endoplasmic reticulum and sparse in dictyosomes. They aggregate between the clusters of microtubules and eventually coalesce to form the cell plate.


Effectiveness of a video intervention on fertility knowledge among university students: a randomised pre-test/post-test study.
Recent evidence has shown that young adults have poor knowledge about reproductive health and fertility, and that interventions are needed to increase fertility awareness. The aim of this study was to assess the effectiveness of a brief video in increasing knowledge about fertility and infertility in young adults. We carried out a two-arm, parallel-group, randomised controlled trial with a pre-test/post-test design (NCT02607761, ClinicalTrials.gov). The sample was composed of 173 undergraduates who completed a self-report questionnaire. Participants were randomly assigned to exposure or no exposure to an educational video about reproductive health and infertility (intervention group, n = 89; control group, n = 84). At baseline, participants revealed poor knowledge of infertility risk factors and fertility issues, and average knowledge of the definition of infertility. Interaction effects between group and time were found for all variables targeted in the video. Participants in the intervention group significantly increased their knowledge of fertility issues, infertility risk factors and the definition of infertility. No significant differences in post-test knowledge were observed in the control group, except for the age at which there is a marked decrease in female fertility. A short video intervention is effective in increasing short-term knowledge about reproductive health and infertility. If future research using longer intervals corroborates our findings, video intervention could be a useful tool in public health prevention campaigns.


Comparative effects of antidepressants, amitriptyline, and maprotiline on intraventricular conduction, effective refractory period, and incidence of ventricular arrhythmias induced by programmed stimulation in dog hearts after myocardial infarction.
The effects of amitriptyline and maprotiline, standard tricyclic and tetracyclic antidepressants, on intraventricular conduction, the effective refractory period (ERP), and the incidence of ventricular arrhythmias induced by programmed stimulation were studied and compared in dog hearts after myocardial infarction. Amitriptyline at doses of 1-3 mg/kg significantly slowed ventricular conduction of the infarcted zones in a frequency-dependent and dose-dependent manner. Amitriptyline at doses of 2 and 3 mg/kg slowed conduction slightly in normal zones. The ERP was prolonged by amitriptyline at a dose of 2 mg/kg. Amitriptyline increased the incidence of ventricular arrhythmias induced by programmed stimulation. Maprotiline at doses of 1-3 mg/kg slowed conduction in infarcted zones to a lesser extent as compared with amitriptyline, although severely depressed conduction in the infarcted zone was obviously slowed by maprotiline. Maprotiline did not increase the incidence of ventricular arrhythmias significantly. From the present results, maprotiline appears to have less cardiac toxicity than amitriptyline, although maprotiline produces a slight decrease in conduction of infarcted zones.


[Magnetic resonance in the diagnosis, characterization, and assessment of renal carcinoma extension].
Many authors discussed the reliability of MR imaging in the diagnosis of small tumoral masses (less than 1.5 cm) affecting the kidney, and stressed its low diagnostic power. On the other hand, MR imaging is a useful technique in the study of renal masses, for its capability in the differentiation of adipose tissue (angiomyolipomas), fluid content (cystic lesions), parenchymatous tissues (neoplastic lesions). The distinction between malignant and benign masses is often impossible on the basis of MR except in the cases of invasion of the adjacent structures. MR imaging is, at present, the most accurate method in the staging of neoplastic masses of the kidney.


Acute myelogenous leukemia with eosinophilic differentiation and trisomy-1.
A 50-year-old woman presented with anemia and eosinophilia. Her bone marrow biopsy, peripheral blood, and clinical features were consistent with a diagnosis of an evolving acute myelogenous leukemia. Striking dysplastic eosinophilic differentiation associated with trisomy-1 was evident, and eosinophil granule major basic protein was detected in involved tissue. Trisomy-1 has not been previously reported in association with acute myelogenous leukemia showing eosinophilic differentiation. Intensive cytotoxic chemotherapy produced a short-lived clinical and cytogenetic remission. At autopsy multiple tumor nodules composed of dysplastic eosinophil precursors and myeloblasts were evident in multiple organs.


Seroconversion from HBs-Ag to anti-HBs in a case of liver cirrhosis associated with hepatocellular carcinoma.
This paper reports a case of liver cirrhosis associated with hepatocellular carcinoma (HCC) of a woman who was converted from hepatitis B surface antigen (HBs-Ag) positive to antibody against HBs-Ag (anti-HBs) positive in the serum through an immunoregulatory steroid rebound phenomenon. The histology of the biopsy specimen taken before the seroconversion showed an early stage of liver cirrhosis with moderate infiltration of mononuclear cells. At autopsy about 3 years after the seroconversion, the liver tissue free of the tumor was in an early stage of liver cirrhosis. Fibrosis did not advance as compared with the biopsy specimen. In addition, mononuclear cell infiltration decreased remarkably and piecemeal necrosis disappeared after the seroconversion. The immunohistologic examination of hepatocytes demonstrated that positive stainings for HBs-Ag and for hepatitis B core antigen (HBc-Ag) in the biopsy specimen turned to be negative in the autopsy specimen. These facts indicate that the steroid rebound phenomenon eliminated free hepatitis B virus (HBV) in the hepatocytes in the absence of massive necrosis of hepatocytes. HBV-DNA integration was proved in the genome of HCC by molecular hybridization method.


[Optimization of culture measure for bovine-bovine and goat-bovine cloned embryos in vitro].
This study is conducted to explore an effective culture method for supporting the embryo development. The cattle fetal ear fibroblasts and the goat fetal ear fibroblasts are transplanted into the enucleated cattle oocytes separately by oocyte intraplasmic nuclear injection method to construct bovine cloned embryos and goat-bovine cloned embryos. The embryos are first cultivated in modified charles rosenkrans 2 amino acid medium (mCR2aa) and modified synthetic oviduct fluid medium (mSOF) separately. Then BSA (8 mg/mL) or FBS (10%) can be added to mSOF according to the different culture period. The supplements and orders, added during the first three days and after three days are as follow: BSA and BSA, BSA and FBS, FBS and BSA, FBS and FBS. On the basis of the cleavage rate, 8/16-cell rate, blastocysts rate and total cell number of blastocysts, the best culture way can be screened out. First, cleavage rate, 8/16-cell rate, blastocysts rate and total cell number of blastocysts, cultivated in mSOF solution are all higher than those cultivated in mCR2aa( P < 0.05). Second, the cleavage rate and 8/16-cell rate, adding BSA and FBS into mSOF, are in turn 79.8% +/- 7.1%, 49.7% +/- 3.5%, 21.5% +/- 1.8%, and 115.2 +/- 4.3 in bovine cloned embryo, and 40.1% +/- 6.3%, 29.2% +/- 2.0%, 13.4% +/- 2.1% and 100.1 +/- 3.0 in goat-bovine cloned embryo, which are significant higher than other culture groups (P < 0.05). The goat-bovine cloned embryo can be cultivated by the optimized culture measure of bovine cloned embryo. The best culture ways of bovine cloned embryo and goat-bovine cloned embryo are all to use mSOF supplemented BSA in the first three days and then use mSOF supplemented FBS in the next five days.


Khellactone Derivatives and Other Phenolics of Phlojodicarpus sibiricus (Apiaceae): HPLC-DAD-ESI-QQQ-MS/MS and HPLC-UV Profile, and Antiobesity Potential of Dihydrosamidin.
With obesity, the consumption of phenolic-enriched food additives as a part of traditional nutrition avoids the negative implications of eating high-calorie products. This study investigated the new herbal food additive, Phlojodicarpus sibiricus roots and herb, ubiquitously used in Siberia as a spice. Chromatographic techniques such as HPLC-DAD-ESI-QQQ-MS/MS and microcolumn HPLC-UV were the basic instruments for component profiling and quantification, and antiobesity potential was investigated using a differentiated 3T3-L1 adipocytes assay. We found that the roots and herb of P. sibiricus were high-coumarin-containing additives inhibiting triacylglycerol accumulation in 3T3-L1 preadipocytes. Forty-one phenolics were detected in P. sibiricus extracts, and 35 were coumarins, including 27 khellactone derivatives present as esters and glucosides. Total coumarin content varied from 36.16 mg/g of herb to 98.24 mg/g of roots, and from 0.32 mg/mL to 52.91 mg/mL in P. sibiricus preparations. Moreover, Siberian populations of P. sibiricus were characterised by a different HPLC-based coumarin profile. The most pronounced inhibiting effect on triacylglycerol accumulation in 3T3-L1 preadipocytes was shown for dihydrosamidin (khellactone 3'-O-isovaleroyl-4'-O-acetyl ester), which was more active than other khellactone esters and glucosides. The results demonstrated that if used as a food additive Phlojodicarpus sibiricus could be a source of bioactive coumarins of the khellactone group with high antiobesity potential.


Emerging Potential of Exosomal Non-coding RNA in Parkinson's Disease: A Review.
Exosomes are extracellular vesicles that are released by cells and circulate freely in body fluids. Under physiological and pathological conditions, they serve as cargo for various biological substances such as nucleotides (DNA, RNA, ncRNA), lipids, and proteins. Recently, exosomes have been revealed to have an important role in the pathophysiology of several neurodegenerative illnesses, including Parkinson's disease (PD). When secreted from damaged neurons, these exosomes are enriched in non-coding RNAs (e.g., miRNAs, lncRNAs, and circRNAs) and display wide distribution characteristics in the brain and periphery, bridging the gap between normal neuronal function and disease pathology. However, the current status of ncRNAs carried in exosomes regulating neuroprotection and PD pathogenesis lacks a systematic summary. Therefore, this review discussed the significance of ncRNAs exosomes in maintaining the normal neuron function and their pathogenic role in PD progression. Additionally, we have emphasized the importance of ncRNAs exosomes as potential non-invasive diagnostic and screening agents for the early detection of PD. Moreover, bioengineered exosomes are proposed to be used as drug carriers for targeted delivery of RNA interference molecules across the blood-brain barrier without immune system interference. Overall, this review highlighted the diverse characteristics of ncRNA exosomes, which may aid researchers in characterizing future exosome-based biomarkers for early PD diagnosis and tailored PD medicines.


Overactive bladder in special patient populations.
It is now well accepted that overactive bladder (OAB) negatively affects the quality of life of a large number of persons and that the primary mode of therapy is the use of medication-currently antimuscarinic agents. However, it is also important for physicians to understand how the use of these drugs affects specific groups of patients. Most of the concern in this area focuses on the potential for these populations to experience certain adverse events or side effects from the use of antimuscarinic agents; this has prevented these drugs from being prescribed in these populations to the same degree as in the general population of OAB sufferers. The purpose of this article is to review these specific populations of OAB patients, including pediatric, geriatric, and pregnant patients, men with prostate problems, and patients in whom OAB is of neurogenic origin, and to discuss what is currently known about the use of antimuscarinic agents in these groups.


The C-type lectin MGL expressed by dendritic cells detects glycan changes on MUC1 in colon carcinoma.
The epithelial mucin MUC1 is a high molecular weight membrane glycoprotein frequently overexpressed and aberrantly glycosylated in adenocarcinoma. Mucins normally contain high amounts of O-linked carbohydrate structures that may influence immune reactions to this antigen. During malignant transformation, certain glyco-epitopes of MUC1, such as Tn-antigen, TF-antigen and their sialylated forms become exposed. The role of these glycan structures in tumor biology is unknown, but their presence is known to correlate with poor prognosis in several adenocarcinomas. We analyzed the potency of MUC1 containing Tn-antigens (MUC1-Tn) to target C-type lectins that function as carbohydrate recognition and uptake molecules on dendritic cells (DC). We identified the macrophage galactose type C-type lectin (MGL), expressed by both DC and macrophages, as the receptor for recognition and binding of MUC1-Tn. To validate the occurrence of MGL-MUC1 interactions in situ, we studied the binding of MGL to MUC1 in primary colon carcinoma tissue. Isolation of MUC1 out of colon carcinoma tissue showed strong binding activity to MGL. Interestingly, MGL binding to MUC1 was highly correlated to binding by the lectin Helix pomatia agglutinin (HPA), which is associated with poor prognosis in colorectal cancer. The detection of MGL positive cells in situ at the tumor site together with the modified glycosylation status of MUC1 to target MGL on DC suggests that MGL positive antigen presenting cells may play a role in tumor progression.


Plasma gonadotropins after administration of LH-releasing hormone in patients with renal or hepatic failure.
The pituitary gonadotropin response to the administration of synthetic LH-releasing hormone (LH RH) in 10 patients with renal failure and 5 patients with hepatic insufficiency was determined. The basal plasma LH and FSH levels were either normal or slightly elevated in both groups compared with the controls, but after the administration of LHRH, the peak levels (mean +/- SE mIU/ml) of LH (72.0 +/- 16.6) and FSH (18.7 +/- 4.4) in the patients with renal failure, and of LH (61.5 +/- 20.8) and FSH (13.2 +/- 2.8) in patients with hepatic insufficiency, were not significantly different from those in 11 normal controls (LH, 75.6 +/- 12.0; FSH, 12.4 +/- 2.9). However, significant elevations in plasma gonadotropin levels persisted in these patients during the second and third hours after the administration of LHRH. These studies do not resolve the question of whether the prolonged elevation in plasma LH and FSH levels after LHRH administration is due to enhanced secretion, to a diminished rate of metabolic clearance of LHRH, and/or to the gonadotropins, or both. Evidence from this and previous studies suggests that there may be defects in the secretory functions of both the hypothalamus and pituitary gland in some of these patients.


[Unacceptable quality in certain sectors of medical research].
Errors have become so common in certain sectors of medical research that the situation has been described as a scandal. The criticism applies in particular to research based on measurements, where incorrect application of mathematical and statistical methods has become accepted as the correct approach. This has had unacceptable practical consequences, and the situation requires immediate steps to raise the level of quality. The author discusses some basic aspects of measurements in general, and serious errors associated with bone mineral measurements in particular.


[Essential role of pikachurin, a novel dystroglycan-binding protein, in bipolar dendrite connection to photoreceptor ribbon synapse in the retina].
Photoreceptor cells with bipolar cells and horizontal cells form a specialized synapse, the ribbon synapse. We identified the novel retinal extracellular matrix protein pikachurin, and observed that it is localized in the synaptic cleft of the photoreceptor ribbon synapse. In order to investigate the biological functions of pikachurin, we generated a pikachurin knock-out mouse. These mice showed improper apposition of the bipolar cell dendritic tips to the photoreceptor ribbon synapses, alterations of ERG b waves both under scotopic and photopic conditions and attenuation of optokinetic responses. Using immunohistochemistry and pull-down assay, we showed that pikachurin is a novel ligand of alpha-dystroglycan. Our results indicate that the abnormality of interaction between dystrophin and dystroglycan-pikachurin complex may be one cause of the retinal electrophysiological abnormalities observed in Duchenne and Becker muscular dystrophy patients.


Toxicity of dimethoate and fenoxycarb to honey bee brood (Apis mellifera), using a new in vitro standardized feeding method.
A new in vitro method was devised to assess the effects of pesticides on honey bee brood. The method allowed the quantification of doses ingested by larvae and the assessment of larval and pupal mortality. Larval mortality in control samples was lower than 10%. Two active substances were tested: dimethoate and fenoxycarb. The LD(50) of dimethoate was 1.9 microg larva(-1) 48 h after oral exposure of larvae at day 4. Additional dose-related effects on pupal mortality were noted. After a chronic intoxication, the NOAEC (No Observed Adverse Effect Concentration) for larval mortality at day 7 was 2.5 mg kg(-1), whereas a NOAEC of 5 mg kg(-1) was found at day 22 for delayed effects on the reduction of adult emergence. Fenoxycarb applied at day 4 showed no effect on larvae, whereas emergence of adults was affected at doses higher than 6 ng larva(-1).


Maintenance of potassium balance during long-term diuretic therapy in chronic heart failure patients with thiazide-induced hypokalemia: comparison of potassium supplementation with potassium chloride and potassium-sparing agents, amiloride and triamterene.
The relative efficacy of potassium chloride, amiloride and triamterene in maintaining potassium and magnesium balance was evaluated in 23 hypokalemic (S-K less than or equal to 3.5 mmol/l) patients with chronic heart failure receiving diuretic therapy. Amiloride and triamterene were administered in a randomized, crossover manner, followed by potassium chloride in an open manner. During a 5-month treatment with hydrochlorothiazide 50 mg twice/day, potassium chloride 1 g twice/day was not as effective as amiloride 5 mg or triamterene 75 mg twice/day in maintaining serum potassium and magnesium and total-body potassium, while amiloride and triamterene seemed to be equally effective. During all three supplementations, a decrease in serum potassium to a hypokalemic level was observed in some patients. The need for higher doses of potassium chloride, amiloride and triamterene was clearly concentrated to the same patients, and correction was easily reached by increasing the respective doses.


Fragments of bovine serum albumin produced by limited proteolysis. Isolation and characterization of peptic fragments.
Five new fragments of bovine serum albumin have been isolated following limited peptic hydrolysis. These fragments, and the two peptic fragments previously described by King (King, T.P. (1973), Arch. Biochem. Biophys. 156, 509), were positioned within the albumin sequence published by Brown (Brown, J.R. (1975), Fed. Proc., Fed. Am. Soc. Exp. Biol. 34, 591) on the basis of molecular weight, amino acid composition, and amino- and carboxyl-terminal sequences. The fragments correspond to residues 1-385, 1-306, 307-581, 49-185, 186-306, 307-385, and 353-503 in the albumin sequence. These peptides are likely to be native in structure since disulfide bonds were not cleaved during their preparation. In each case the amino acid composition and terminal sequences have confirmed the bovine serum albumin sequence and disulfide bridging pattern proposed by Brown, and the offer further proof that bovine albumin is composed of a series of nine independent loops. These fragments should be useful in elucidating the structure-function relationships of albumin.


A generalized right truncated bivariate Poisson regression model with applications to health data.
A generalized right truncated bivariate Poisson regression model is proposed in this paper. Estimation and tests for goodness of fit and over or under dispersion are illustrated for both untruncated and right truncated bivariate Poisson regression models using marginal-conditional approach. Estimation and test procedures are illustrated for bivariate Poisson regression models with applications to Health and Retirement Study data on number of health conditions and the number of health care services utilized. The proposed test statistics are easy to compute and it is evident from the results that the models fit the data very well. A comparison between the right truncated and untruncated bivariate Poisson regression models using the test for nonnested models clearly shows that the truncated model performs significantly better than the untruncated model.


Polo-like kinase 2 phosphorylation of amyloid precursor protein regulates activity-dependent amyloidogenic processing.
Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive deficits. Amyloidogenic processing of amyloid precursor protein (APP) produces amyloid β (Aβ), the major component of hallmark AD plaques. Synaptic activity stimulates APP cleavage, whereas APP promotes excitatory synaptic transmission, suggesting APP participates in neuronal homeostasis. However, mechanisms linking synaptic activity to APP processing are unclear. Here we show that Polo-like kinase 2 (Plk2), an activity-inducible regulator of homeostatic plasticity, directly binds and phosphorylates threonine-668 and serine-675 of APP in vitro and associates with APP in vivo. Plk2 accelerates APP amyloidogenic cleavage by β-secretase at synapses and is required for neuronal overactivity-stimulated Aβ secretion. These findings implicate Plk2 as a novel mediator of activity-dependent APP amyloidogenic processing.


Identification of a macromolecular factor in the ileum which binds intrinsic factor and immunologic identification of intrinsic factor in ileal extracts.
The precipitate which resulted when (57)CoB(12) bound to normal human gastric juice was subjected to a 15% concentration of Na(2)SO(4) contained virtually no radioactivity. However, after in vivo incubation of the gastric juice-(57)CoB(12) mixture in the distal ileum of the guinea pig, the dialyzed extract of the washed mucosa contained a fraction of (57)CoB(12) which was precipitated at 15% Na(2)SO(4). In addition, in vitro incubation of gastric juice-(57)CoB(12) with an extract of the ileal mucosa or brush border membranes also resulted in the formation of a 15% Na(2)SO(4)-insoluble fraction which contained (57)CoB(12). The formation of this (57)CoB(12)-containing insoluble fraction did not occur or was diminished by (a) addition of an excess of B(12)-free normal human gastric juice. (b) reducing the incubation pH to 2, (c) incubating the mixture at 4 degrees C, (d) pretreating the ileal extract at 56 degrees C for 30 min, (e) incubating the reaction in sodium EDTA but not calcium EDTA, (f) incubating gastric juice-(57)CoB(12) with an extract of jejunal mucosa. Sephadex gel filtration was used to demonstrate that the factor in the ileal extract which reacted with the gastric juice-(57)CoB(12) filtered through G-100 and G-200 columns in the excluded volume. When the ileal extract obtained after in vivo incubation with gastric juice-(57)CoB(12) was subjected to starch gel electrophoresis one peak of radioactivity remained at the origin and another moved anodally. Eluates of each peak reacted with anti-intrinsic factor antibody indicating that at least the immunologically reacting portion of the intrinsic factor molecule was present in two fractions with different electrophoretic mobility.These studies indicate that immunologically intact intrinsic factor can be extracted from the ileum after in vivo incubation with gastric juice-(57)CoB(12), and that a macromolecular factor is present in the distal ileal mucosa which binds intrinsic factor both in vitro and in vivo, changing its solubility and electrophoretic properties. It is suggested that this ileal binding factor is the previously postulated intestinal receptor for intrinsic factor.


Mononuclear and dinuclear ruthenium complexes of 2,3-Di-2-pyridyl-5,6-diphenylpyrazine: synthesis and spectroscopic and electrochemical studies.
Reported here are a new bridging ligand, 2,3-di-2-pyridyl-5,6-diphenylpyrazine (dpdpz), and its complexation with one or two ruthenium atoms. This ligand was designed so that it could bind to metal species in either a N(∧)N bidentate fashion or a C(∧)N(∧)N tridentate mode to form a metallacycle. The reaction between dpdpz and (tpy)RuCl3 (tpy = 2,2':6',2''-terpyridine) afforded C(∧)N(∧)N-type mono- and dinuclear cyclometalated complexes in moderate yields. On the other hand, N(∧)N-type mono- and dinuclear noncyclometalated complexes could be isolated from the reaction of dpdpz with (bpy)2RuCl2 (bpy = 2,2'-bipyridine). An asymmetric diruthenium complex, bridged by dpdpz, was prepared with one ruthenium atom cyclometalated and another one noncyclometalated. The electronic properties of these complexes were probed by electrochemical and spectroscopic techniques. They exhibited multiple reversible redox processes. However, the formal potentials and electrochemical energy gap are greatly dependent on the binding nature and number of ruthenium atoms. As indicated by electrochemical and spectroelectrochemical studies, diruthenium complexes bridged by dpdpz exhibited electronic coupling between the two metal centers. A comparison of the electronic absorption and emission properties of these complexes is also presented.


Mind over matter: exploring job stress among female blue-collar workers.
Although overall health has been defined holistically as the integration of a person's optimal mental, physical, social, intellectual, and spiritual well-being, a mental health focus remains on the fringe of many public health efforts. This report describes recent efforts by the Centers for Disease Control and Prevention (CDC) to explore job stress among female blue-collar workers. Using a more holistic approach to understand its impact on blue-collar women's overall health, health-related quality of life (HRQOL) was used to assess optimal human performance. Attempting to encapsulate how overall health affects one's ability to participate and fulfill daily personal/professional tasks, HRQOL yields a broader understanding of the interaction between psychological well-being (mind) and physical functioning (matter). Embedding CDC HRQOL-4 measures into a questionnaire used as part of a larger mixed methods project, blue-collar women responded to questions about their health, including both mental and physical. For these female workers, mental health appeared to be of greater consequence, which could be interpreted as mind being more significant than matter. This paper highlights the findings related to HRQOL issues experienced by these female blue-collar workers and summarizes recommendations for effective individual and organizational approaches to address job stress.


[Outpatient excision of low grade cervical intraepithelial lesions using loop diathermy].
Twenty five years after the introduction of outpatient treatment for cervical precancers, several cases of invasive cancer after laser, cryotherapy or electrocautery have been described. As a consequence, the diathermy loop excision has recently been proposed for the treatment of cervical intraepithelial neoplasia. The new generators seem to assure a high quality of cut and allow the histological analysis of all the lesional tissue excised as deep as the laser vaporisation usually goes (7 mm). We have tested this treatment on a series of CIN I on an outpatient basis and our results confirm that loop excision can replace destructive treatments for CIN I. As for high grade lesions, we still think that laser conisation under general anesthesia remains the best choice.


Independent Predictors of the Duration and Overall Burden of Postoperative Delirium After Cardiac Surgery in Adults: An Observational Cohort Study.
Postoperative delirium (POD) is a common complication after cardiac surgery and is associated with increased patient morbidity and mortality. The objective of this study was to identify risk factors for long duration and overall burden of POD after cardiac surgery. One-year, single-center, retrospective, observational cohort study. University hospital. Adult patients undergoing cardiac surgery with cardiopulmonary bypass in 2013. None. Patients were screened for POD using the Intensive Care Delirium Screening Checklist. The primary outcome measure was the incidence of POD. Secondary outcome measures were the duration of POD and the area under the curve determined using the Intensive Care Delirium Screening Checklist score over time. Independent predictors of POD were estimated in multivariable logistic regression models. Hospital length of stay, medications, and outcome data also were analyzed. Among the 656 patients included in the cohort, 618 were analyzed. The overall incidence of POD was 39%. Older patient age (odds ratio [95% confidence interval]) 1.06 [1.04-1.09] for an increase of 1 year, p < 0.001); low preoperative serum albumin (1.08 [1.03-1.13] for a decrease of 1 g/L, p < 0.001); a history of atrial fibrillation (2.30 [1.30-4.09], p = 0.004); perioperative stroke (6.27 [1.54-43.64], p = 0.008); ascending aortic replacement surgery (2.99 [1.50-6.05], p = 0.002); longer duration of procedure (1.37 [1.16-1.63] for an increase of 1 hour, p < 0.001); and increased postoperative C-reactive protein concentration (2.16 [1.49-3.16] for a 2-fold increase, p < 0.001) were associated with higher odds of POD. Among patients affected by POD, older age, perioperative stroke, longer procedure time, and increased postoperative C-reactive protein were consistently predictive of longer duration of POD and greater area under the curve. Known risk factors for the development of POD after cardiac surgery also are predictive of prolonged duration and high overall burden of POD.