Calcium bioavailability from a calcium- and sulfate-rich mineral water, compared with milk, in young adult women.
Some mineral waters have a high calcium content and may contribute a significant part of the human daily requirements. Calcium bioavailability from a calcium- and sulfate-rich mineral water (CS-W) containing 11.2 mmol Ca/L (467 mg/L) was compared with that from milk in nine healthy young women. Calcium absorption was measured in the fasting state with a dual-label stable-isotope technique. Fractional absorption rates from milk and CS-W were 25.0 +/- 6.7% and 23.8 +/- 4.8% (means +/- SD), respectively, and did not differ significantly (P = 0.05). Urine was collected for 36 h after the administration of the oral stable isotope while the subjects consumed a controlled diet and a quantity of milk or CS-W providing 25 mmol (1000 mg) Ca. No significant difference was found in the excretion of calcium, nor in the excretion of the two stable isotopes. Mean urinary sulfate excretion was significantly increased by 35% when the CS-W was consumed. No significant correlation was found between 36-h urinary excretion of the intravenous calcium tracer and sulfate, sodium, or urine volume. Therefore, calcium from the CS-W was as well absorbed and retained as that from milk, and no calciuric effect of sulfate was found, showing that such mineral waters can be valuable dietary sources of calcium.


Ni-promoted synthesis of graphitic carbon nanotubes from in situ produced graphitic carbon for dehydrogenation of ethylbenzene.
Graphitic carbon nanotubes (GCNTs) were fabricated from in situ produced graphitic carbon by calcining biomass/melamine/Ni(NO3)2·6H2O. Ni-based hybrids (NiOx@GCNTs) displayed superior catalytic capacity in direct dehydrogenation of ethylbenzene. The specific reaction rate can reach up to 8.1 μmol m(-2) h(-1), and unprecedented stability was obtained over 165 h without any activation process.


Toll-6 and Toll-7 function as neurotrophin receptors in the Drosophila melanogaster CNS.
Neurotrophin receptors corresponding to vertebrate Trk, p75(NTR) or Sortilin have not been identified in Drosophila, thus it is unknown how neurotrophism may be implemented in insects. Two Drosophila neurotrophins, DNT1 and DNT2, have nervous system functions, but their receptors are unknown. The Toll receptor superfamily has ancient evolutionary origins and a universal function in innate immunity. Here we show that Toll paralogs unrelated to the mammalian neurotrophin receptors function as neurotrophin receptors in fruit flies. Toll-6 and Toll-7 are expressed in the CNS throughout development and regulate locomotion, motor axon targeting and neuronal survival. DNT1 (also known as NT1 and spz2) and DNT2 (also known as NT2 and spz5) interact genetically with Toll-6 and Toll-7, and DNT1 and DNT2 bind to Toll-6 and Toll-7 promiscuously and are distributed in vivo in domains complementary to or overlapping with those of Toll-6 and Toll-7. We conclude that in fruit flies, Tolls are not only involved in development and immunity but also in neurotrophism, revealing an unforeseen relationship between the neurotrophin and Toll protein families.


Antithrombotic effects of exercise.
Regular exercise appears to have antithrombotic effects on the blood. Athlete's anemia, a dilutional pseudoanemia, enhances performance and decreases blood viscosity; it may also decrease platelet adhesion to damaged arteries. Physical conditioning may decrease platelet aggregability. Exercise activates fibrinolysis, and physical fitness seems to enhance the rate of fibrinolysis. The hematologic changes of exercise may help prevent coronary heart disease.


Effects of seven antibiotics on the growth and development of Phaenicia sericata (Diptera: Calliphoridae) larvae.
Maggot therapy is used for patients with severe tissue destruction, who often receive antibiotics concurrently. Therefore, we studied the effects on maggots of ampicillin, cefazolin, ceftizoxime, clindamycin, gentamicin, mezlocillin, and vancomycin in concentrations of 1, 10, 100, and 1,000 times the average minimum bactericidal or bacteriostatic concentration against highly susceptible organisms. There was a reduction in larval survival in media with gentamicin at concentrations of 1,000 times the average pharmacologic level, or 4,000 micrograms/ml (2.7% survival), versus lower concentrations (80-88% survival). Maturation of the surviving pupae to adults also was decreased at this concentration. Media with cefazolin concentrations of 100 times the average bacteristatic level, or 800 micrograms/ml, also led to a significant decrease in larval survival (70% versus 80-88%). There were no differences in larval survival, rate of maturation, or pupal weights for organisms reared on media containing ampicillin, ceftizoxime, clindamycin, mezlocillin, or vancomycin. P. sericata matured normally--and thus can be used therapeutically--when exposed to standard pharmacologic levels of the 7 antibiotics tested. Furthermore, the methods employed herein may be helpful to forensic entomologists attempting to develop models for drug ingestion by maggots.


Use of hydrophilic hydroxypropyl methacrylate/ethylene glycol methacrylate packing material in size-exclusion chromatography.
Spherical particles of hydroxypropyl methacrylate/ethylene glycol methacrylate copolymer were synthesized in-house for use in size-exclusion chromatography. The porous hydrophilic material was packed in glass and stainless steel columns to evaluate their chromatographic performance. The support particles were small (approximately 20 A), and the average pore size was in the low range of mesopores (approximately 100 A). The packed columns were calibrated by using polysaccharide dextrans, showing a good range of separation for molecular weights between 10000 and 600000 daltons. The packing material appears to separate the large molecules through the size-exclusion mechanism. Polysaccharides and polypeptides dissolved in adequate mobile phases were injected into the packed column. The separation of the macromolecules was consistent with the size-exclusion mechanism. Application of the packing material to the separation of small molecules (alkyl alcohols) was also investigated.


RRM Transcription Factors Interact with NLRs and Regulate Broad-Spectrum Blast Resistance in Rice.
Nucleotide-binding site leucine-rich repeat (NLR) receptors perceive pathogen effectors and trigger plant immunity. However, the mechanisms underlying NLR-triggered defense responses remain obscure. The recently discovered Pigm locus in rice encodes a cluster of NLRs, including PigmR, which confers broad-spectrum resistance to blast fungus. Here, we identify PIBP1 (PigmR-INTERACTING and BLAST RESISTANCE PROTEIN 1), an RRM (RNA-recognition motif) protein that specifically interacts with PigmR and other similar NLRs to trigger blast resistance. PigmR-promoted nuclear accumulation of PIBP1 ensures full blast resistance. We find that PIBP1 and a homolog, Os06 g02240, bind DNA and function as unconventional transcription factors at the promoters of the defense genes OsWAK14 and OsPAL1, activating their expression. Knockout of PIBP1 and Os06 g02240 greatly attenuated blast resistance. Collectively, our study discovers previously unappreciated RRM transcription factors that directly interact with NLRs to activate plant defense, establishing a direct link between transcriptional activation of immune responses with NLR-mediated pathogen perception.


Anti-LYPD1/CD3 T-Cell-Dependent Bispecific Antibody for the Treatment of Ovarian Cancer.
Ovarian cancer is a diverse class of tumors with very few effective treatment options and suboptimal response rates in early clinical studies using immunotherapies. Here we describe LY6/PLAUR domain containing 1 (LYPD1) as a novel target for therapeutic antibodies for the treatment of ovarian cancer. LYPD1 is broadly expressed in both primary and metastatic ovarian cancer with ∼70% prevalence in the serous cancer subset. Bispecific antibodies targeting CD3 on T cells and a tumor antigen on cancer cells have demonstrated significant clinical activity in hematologic cancers. We have developed an anti-LYPD1/CD3 T-cell-dependent bispecific antibody (TDB) to redirect T-cell responses to LYPD1 expressing ovarian cancer. Here we characterize the nonclinical pharmacology of anti-LYPD1/CD3 TDB and show induction of a robust polyclonal T-cell activation and target dependent killing of LYPD1 expressing ovarian cancer cells resulting in efficient in vivo antitumor responses in PBMC reconstituted immune-deficient mice and human CD3 transgenic mouse models. Anti-LYPD1/CD3 TDB is generally well tolerated at high-dose levels in mice, a pharmacologically relevant species, and showed no evidence of toxicity or damage to LYPD1 expressing tissues.


Reference values for vertebral heights in Scandinavian females and males.
Vertebral heights were measured on lateral spine radiographs covering T4-L5 in 113 healthy Caucasian volunteers (73 females aged 22-80 years, and 40 males aged 22-79 years). Vertebral heights were significantly higher in men than in women (p < 0.001). In women, a significant correlation was found between the height of T4 and the heights of the other vertebrae with correlation coefficients ranging from 0.71 (T5) to 0.38 (L1) and similar figures were found in males. Both the absolute and relative vertebral heights in this series were close to those reported by others. Selection of subjects and racial, environmental, and technical factors may explain the small differences. It is concluded that vertebral heights can be predicted from vertebrae rarely affected by spinal osteoporosis. Both relative and absolute vertebral heights differed between sexes. Although the reference values in this Scandinavian population were in agreement with previously reported data, small differences between populations were found, emphasizing the need for regional normative data.


Effects of addition of nitrogen during rapid compression of baboons.
A series of dives was carried out to depths of 600 and 800 m seawater (msw) using baboons (Papio papio). Experiments were designed to study the effects of compression and the use of a He-N2-O2 gas mixture on high-pressure nervous syndrome (HPNS). When N2 was added to the He-O2 mixture at the beginning of a linear compression (200 msw/h), the symptoms associated with HPNS were still seen; in addition, the electroencephalogram (EEG) changes were more severe than those seen without N2. By use of an identical mixture, a 2-h exponential compression to 600 msw produced less severe signs of HPNS than the nonexponential profile. By use of a 2-h exponential compression to 600 msw and with addition of N2 at the end of compression, the HPNS that had been started under the He-O2 mixture decreased. Progressive addition of N2 during compression reduced the behavioral signs of HPNS without further EEG changes. These results show that the action of N2 is more complex than can be explained by a simple narcotic pressure antagonism and that the HPNS differed according to the gas mixture used.


Effect of KI/AgI on the thermal and optical properties of the GeS₂-In₂S₃ chalcogenide glasses.
GeS₂-In₂S₃-KI/AgI chalcohalide glasses were prepared by traditional melt-quenching method and the glass-forming region was determined. The dependence of glass properties on composition as formula of (100 - x)(0.75GeS₂-0.25In₂S₃) - x(In₂S₃-KI/AgI) was investigated. The allowed indirect transition of samples was calculated according to the classical Tauc equation. The results show that 50 mol% AgI can be introduced in the glassy matrix while only 40 mol% of KI can be incorporated in the GeS₂-In₂S₃-KI glass system. GeS₂-In₂ S₃-AgI glass system has larger density, higher refractive index and better thermal stability, while GeS₂-In₂S₃-KI glass system has shorter visible cut-off wavelength and higher optical band gap.


Neoplastic transformation of osteogenic cells: quantitative morphometric analysis of an in vitro model for osteosarcoma.
Previously we have reported the development of a model in vitro system for the study of osteosarcoma. In this system, when chick periosteal explants are infected with Fujinami sarcoma virus (FSV), osteosarcoma-like tissue is formed. In the present study, a series of histopathologic parameters of neoplastic transformation and osteogenesis were quantitated, at a single cell level, by computer-assisted morphometry. Most significantly, it was found that compared to uninfected (control) cultures, in the FSV-infected (experimental) cultures, the bone to osteoid ratio per unit area was decreased due to a relative decrease in the area of bone and an increase in the area of osteoid. The cellularity of the FSV-infected tissues was significantly increased due to an increase in the number of unlabeled and [3H]thymidine-labeled cells, while the proportion of alkaline phosphatase (AP) positive cells decreased. Double-label immunohistochemistry (with anti-P140gag-fps) and histochemistry for AP activity was performed, to demonstrate production of the oncogene-encoded protein, and osteoblastic differentiation respectively. In an in vitro transformation assay, single cells derived from control, uninfected cultures did not grow, while those derived from FSV-infected cultures formed colonies in semisolid medium. Some of these colonies demonstrated AP staining. Taken together these data show that in this in vitro system (i) neoplastic transformation of osteogenic cells does occur, (ii) changes in osteoid and bone production are related to neoplastic transformation, and (iii) osteosarcoma-like changes can be quantitated at the individual cell level.


Downregulation of Brassica napus MYB69 (BnMYB69) increases biomass growth and disease susceptibility via remodeling phytohormone, chlorophyll, shikimate and lignin levels.
MYB transcription factors are major actors regulating plant development and adaptability. Brassica napus is a staple oil crop and is hampered by lodging and diseases. Here, four B. napus MYB69 (BnMYB69s) genes were cloned and functionally characterized. They were dominantly expressed in stems during lignification. BnMYB69 RNA interference (BnMYB69i) plants showed considerable changes in morphology, anatomy, metabolism and gene expression. Stem diameter, leaves, roots and total biomass were distinctly larger, but plant height was significantly reduced. Contents of lignin, cellulose and protopectin in stems were significantly reduced, accompanied with decrease in bending resistance and Sclerotinia sclerotiorum resistance. Anatomical detection observed perturbation in vascular and fiber differentiation in stems, but promotion in parenchyma growth, accompanied with changes in cell size and cell number. In shoots, contents of IAA, shikimates and proanthocyanidin were reduced, while contents of ABA, BL and leaf chlorophyll were increased. qRT-PCR revealed changes in multiple pathways of primary and secondary metabolisms. IAA treatment could recover many phenotypes and metabolisms of BnMYB69i plants. However, roots showed trends opposite to shoots in most cases, and BnMYB69i phenotypes were light-sensitive. Conclusively, BnMYB69s might be light-regulated positive regulators of shikimates-related metabolisms, and exert profound influences on various internal and external plant traits.


Long-term efficacy and safety of once-daily enoxaparin plus warfarin for the outpatient ambulatory treatment of lower-limb deep vein thrombosis in the TROMBOTEK trial.
The present study was designed to evaluate the long-term efficacy and safety of once-daily enoxaparin plus warfarin for the outpatient ambulatory treatment of lower-limb deep venous thrombosis (DVT). A total of 246 patients, comprising 128 men (mean age, 54.28±16.48 years) and 118 women (mean age, 50.11±16.47 years) with symptomatic lower extremity DVT, were included in this open-label, single-arm, multicenter, phase IV clinical trial conducted at 14 centers in Turkey. All patients were administered subcutaneous enoxaparin (1.5 mg/kg, once-daily) until international normalized ratio (INR) levels reached to 2 to 3, followed by oral warfarin (5 mg/d) for at least 3 months and elastic compression stockings (30-40 mm Hg). Clinical signs (leg circumference), symptoms (edema, pain, tenderness), recanalization rates upon duplex ultrasound examination, laboratory findings (D-dimer and INR levels), and postthrombotic syndrome status with CEAP classification were the efficacy parameters evaluated every 3 months during 18 months of follow-up. Safety end points included minor and major bleeding as well as serious adverse events. Ambulatory treatment with enoxaparin plus warfarin significantly reduced physical symptoms, including tenderness, edema, pain (P<.001), and the circumference of the affected leg (P<.001). The leg circumference difference in almost all patients was <1.5 cm at the end of 18 months (P<.001). Recanalization rates for occluded iliofemoral vein were 76.1% at 3 months and 86.5% at 18 months (P<.001). An early and significant decrease obtained in D-dimer levels on day 10 continued to decline significantly until month 6 and remained unchanged afterwards (P<.001). Of four patients diagnosed with major bleeding during oral anticoagulant use, three recovered with conservative treatment (reduction in hemoglobin levels in 2 developed at visit 2 [day 10] and intracranial bleeding in 1 developed at visit 3 [day 30]), and one patient required a hysterectomy after menorrhagia developed at visit 7 (month 18). Two of the 65 (9.9%) adverse events documented were serious adverse events, but none of the serious adverse events leading to death were related to the study medications. Ambulatory treatment with enoxaparin plus warfarin seems to be effective in symptomatic healing and in clinical improvement by reducing thrombus formation and organization at all levels of lower extremity venous system with DVT, without a significant major bleeding risk. Therefore, the results of our conventional conservative treatment are in line with 1A level evidence reported in the recent American College of Chest Physicians guideline.


Variable responsiveness of hormone-inducible hybrid genes in different cell lines.
Altered steroid responsiveness leads to various pathological conditions and is a particular problem for the treatment of cancers arising in steroid-sensitive cells. To develop cellular model systems for the analysis of the molecular mechanisms mediating altered steroid responses, we have analyzed the inducibility of a steroid-responsive promoter in different cell lines. In vitro constructs containing the mouse mammary tumor virus promoter fused to the herpes simplex virus thymidine kinase gene or the bacterial neo gene were transfected into four different cell lines [Rat-2, CHO chinese hamster ovary cells, F9, and T47D). Thymidine kinase+ clones and neo-resistant clones were selected in the presence of dexamethasone (dex) and/or other steroid hormones. We find that the mouse mammary tumor virus promoter activity is completely dependent on the presence of dex in Rat-2 cells but is constitutively active in CHO cells and is inactive in F9 teratocarcinoma cells in the presence and absence of dex. In the human breast cancer cell line T47D, we observe no response to dex but do observe an inducibility by progesterone. Examination of glucocorticoid receptors in these cell lines showed that Rat-2, CHO, and F9 cells contain sufficient receptors to allow a hormonal response, whereas in T47D cells several glucocorticoid binding activities appear to be present. Our results indicate that the presence of receptor in cells is not always sufficient to allow hormonal activation and that, in some cell lines, like CHO, other factors are present that can substitute for an activated steroid hormone receptor complex.(ABSTRACT TRUNCATED AT 250 WORDS)


Structurally Analogous Degradable Version of Fluorene-Bipyridine Copolymer with Exceptional Selectivity for Large-Diameter Semiconducting Carbon Nanotubes.
Separation of electronically pure, narrowly dispersed, pristine, semiconducting single-walled carbon nanotubes (CNTs) from a heterogeneous as-synthesized mixture is essential for various semiconducting technologies and biomedical applications. Although conjugated polymer wrappers are often utilized to facilitate electronic-type sorting, it is highly desirable to remove organic residues from the resulting devices. We report here the design and synthesis of a mild acid-degradable π-conjugated polyimine polymer, poly[(9,9-di-n-octyl-2,7-fluoren-dinitrilomethine)-alt-co-(6,6'-{2,2'-bipyridyl-dimethine})] (PFO-N-BPy), that is structurally analogous to the commonly used and commercially available poly[(9,9-dioctylfluorenyl-2,7-diyl)-alt-co-(6,6'-(2,2'-bipyridine))] (PFO-BPy). An acid cleavable imine link (-HC═N-) was introduced in the PFO-N-BPy backbone to impart degradability, which is absent in PFO-BPy. PFO-N-BPy was synthesized via a metal catalyst-free aza-Wittig reaction in high yields. PFO-N-BPy with a degree of polymerization of just ∼10 showed excellent (>99% electronic purity) selectivity for both large-diameter (1.3-1.7 nm) arc-discharge semiconducting CNTs (S-CNTs) and smaller diameter (0.8-1.2 nm) high-pressure carbon monoxide disproportionation reaction S-CNTs. Overall, the selectivity for the semiconducting species is similar to that of PFO-BPy but with an advantage of complete depolymerization under mild acidic conditions into recyclable monomers. We further show by ultraviolet-visible spectroscopy, X-ray photoelectron spectroscopy, and scanning electron microscopy that the PFO-N-BPy-wrapped S-CNTs can be aligned into a monolayer array on gate dielectrics using a floating evaporative self-assembly process from which the polymer can be completely removed. Short channel field effect transistors were fabricated from the polymer-stripped aligned S-CNT arrays, which further confirmed the semiconducting purity on the order of 99.9% or higher.


Role of MicroRNAs in Insect Host-Microorganism Interactions.
MicroRNAs (miRNAs) have appeared as important regulators of various biological processes including development, cancer, immunity, and host-microorganism interactions. Accumulating evidence demonstrates the differential expression of host miRNAs upon infection by various microorganisms and the involvement of microorganism-encoded miRNAs in host manipulation. Some of these alterations could be part of a host response to an infection to limit replication and dissemination of the microorganism or, conversely, due to manipulation of the host miRNA pathway by the microorganism to facilitate its replication. Insights into the role of miRNAs in host defense responses and host manipulation by microorganisms will enable a better understanding of host-microorganism interactions.


Intra-abdominal desmoid tumors: a case report.
Desmoid tumors are defined as a rare fibroblastic proliferative disease and may occur in any musculoaponeurotic or fascial tissue . A 54-year-old man with FAP referred to our institution presenting fever and abdominal pain. Four years before a prophylactic colectomy with ileal-rectal anastomosis was done. Three years later a wide intraabdominal mass with desmoid characteristics was detected. In spite of therapy with tamoxifene the RM control showed an increase of mass dimension. Few days later the patient arrived in our istitute with fever and abdominal pain. Medical therapy didn't improve clinical symptoms and the patient underwent surgery. Desmoid tumors are benign tumors, but not a benign disease. Most of these tumors occur sporadically, but about 5% arise in association with familial adenomatous polyposis. Intra-abdominal desmoid tumors remain asymptomatic until their growth and infiltration causes visceral compression. They can cause serious complications and treatment is often unsuccessful. Aggressive fibromatosis treatment should be evaluated and managed by a multidisciplinary team with expertise and experience in sarcoma, prior to initiation of therapy. In FAP, surgery has been recommended for abdominal wall tumors but there are only few indications for intra-abdominal disease like pain, bowel obstruction and desmoids perforation.


A comparative study of combined intravenous and topical administration of tranexamic acid with topical tranexamic acid alone for blood loss reduction after primary uncemented total hip arthroplasty.
The aim of the present study was to evaluate the efficacy of topical versus combined (intravenous + topical) tranexamic acid (TXA) to reduce perioperative blood loss after uncemented primary total hip arthroplasty (THA). Seventy-five patients were randomized in three comparable experimental groups: 1) topical TXA (3 g in 50 ml of saline solution); 2) intravenous + topical TXA (3 g topical + 2 g in 100 ml of saline solution intravenously); 3) controls. Pre- and post-operative hemoglobin (Hb) levels and hematocrit (Hct) values along with the rate of blood transfusion in the 3 groups were compared. The intravenous + topical TXA group demonstrated higher Hb levels and Hct values at postoperative day one (Hb = p <0.05, Hct = p <0.001), postoperative day three (Hb = p <0.05, Hct = p <0.001), and discharge (Hct = p <0.01) compared to the control group. The intravenous + topical group had a lower transfusion rate compared to the control group (0% vs 20%, p = 0.014). With the numbers available, no difference in postoperative Hb level and transfusion rate emerged between topical TXA and control group.


Peptide receptor radionuclide therapy with ¹⁷⁷Lu-DOTATATE: the IEO phase I-II study.
Peptide receptor radionuclide therapy (PRRT) is used in tumours expressing type 2 somatostatin receptors (sst(2)), mainly neuroendocrine. The aim of this prospective phase I-II study was to evaluate the toxicity and efficacy of (177)Lu-DOTATATE in multiple cycles. Fifty-one consecutive patients with unresectable/metastatic sst(2)-positive tumours, divided into two groups, received escalating activities (3.7-5.18 GBq/cycle, group 1; 5.18-7.4 GBq/cycle, group 2) of (177)Lu-DOTATATE. Cumulative activities ranged from 3.7 to 29.2 GBq (median 26.4 GBq in median 6 cycles, group 1, 21 patients) and 5.55 to 28.9 GBq (median 25.2 GBq in 4 cycles, group 2, 30 patients), based on dosimetry. No major acute or delayed renal or haematological toxicity occurred (one grade 3 leukopenia and thrombocytopenia). Cumulative renal absorbed doses were 8-37 Gy (9-41 Gy bioeffective doses). A median decrease of creatinine clearance of 21.7% 6 months after PRRT, 23.9% after 1 year and 27.6% after 2 years was observed. Higher losses (>20%) occurred in patients with risk factors for renal toxicity, particularly hypertension and diabetes. Cumulative bone marrow doses were <1.5 Gy. Blood elements showed a progressive mild drop during cycles and recovered during follow-up (median 30 months). Thirty-nine patients were progressive at enrolment. Partial and complete responses occurred in 15 of 46 (32.6%) assessable patients. The median time to progression was 36 months. Overall survival was 68% at 36 months. Non-responders and patients with extensive tumour involvement had lower survival. (177)Lu-DOTATATE was well tolerated up to 29 GBq cumulative activity (up to 7.4 GBq/cycle). The maximum tolerated dose/cycle was not reached. However, considering the individual bone marrow function and the presence of risk factors for kidney toxicity, it seems safer to divide cumulative activities into lower activity cycles.


Ixodes dammini (Acari: Ixodidae) infestation on medium-sized mammals and blue jays in northwestern Illinois.
High prevalence of infestation of five species of medium-sized mammals and blue jays, Cyanocitta cristata (L.), by immature Ixodes dammini Spielman, Clifford, Piesman and Corwin was found in Castle Rock State Park in northwestern Illinois during May-August 1991. Raccoons, Procyon lotor L., and opossums, Didelphis virginiana Kerr, were infested with the highest larval densities and were trapped primarily in bottomland forest and ecotone habitats. All species had similar nymphal densities, except the eastern cottontails, Sylvilagus floridanus Allen, which were infested with fewer nymphs. Infestation by I. dammini is reported for the first time for fox squirrels, Sciurus niger E. G. St. Hilaire, and for the first time in the midwestern United States for blue jays, C. cristata. These two species were hosts for nymphs in upland forest habitat. Molting rates varied among ticks that fed on different host species and among larvae that fed on individuals of the same species. Molting rate is proposed as an important factor in determining the relative importance of a host species to I. dammini population dynamics.


Clinical and microbiological characteristics of Flavobacterium indologenes infections associated with indwelling devices.
Clinical infections caused by Flavobacterium indologenes have never been documented. Thirteen isolates derived from seven patients with indwelling device-associated F. indologenes infections were identified from 1 April through 30 November 1995. The antimicrobial susceptibilities to 20 antimicrobial agents of the isolates, the cellular fatty acid chromatograms for the isolates, and the random amplified polymorphic DNA (RAPD) patterns generated by arbitrarily primed PCR of the isolates were studied. The antibiotypes and RAPD patterns differed among the isolates recovered from different patients. However, both antibiotypes and RAPD patterns were identical among the five isolates from one patient with multiple episodes of central venous catheter-associated bacteremia within a 1.5-month period and between the two isolates from another patient suffering from two episodes of catheter-related bacteriuria at an interval of 14 days. It is documented that the recurrent infections in each of these two patients were caused by a single F. indologenes clone, respectively. Identical antibiotypes and RAPD patterns were also demonstrated between two isolates from a patient with ventilator-associated pneumonia, one recovered from an endotracheal aspirate and the other derived from a blood specimen 10 days later, indicating the invasive nature of F. indologenes. Two cellular fatty acid chromatograms were identified among these isolates. All of the isolates showed in vitro resistance to cephalothin, cefotaxime, ceftriaxone, moxalactam, aztreonam, aminoglycosides, erythromycin, clindamycin, vancomycin, and teicoplanin. F. indologenes should be included as an etiologic agent of infections associated with the use of indwelling devices.


Nasal eosinophilic inflammation contributes to bronchial hyperresponsiveness in patients with allergic rhinitis.
There are increasing evidences that allergic rhinitis (AR) may influence the clinical course of asthma. We conducted methacholine challenge test and nasal eosinophils on nasal smear to patients with allergic rhinitis in order to investigate the mechanism of connecting upper and lower airway inflammation in 35 patients with AR during exacerbation. The methacholine concentration causing a 20% fall in FEV1 (PC20) was used as thresholds of bronchial hyperresponsiveness (BHR). Thresholds of 25 mg/dL or less were assumed to indicate BHR. All patients had normal pulmonary function. Significant differences in BHR were detected in the comparison of patients with cough or postnasal drip and without cough or postnasal drip. There were significant differences of PC20 between patients with cough or postnasal drip and those without cough or postnasal drip (3.41+/-3.59 mg/mL vs 10.2+/-1.2 mg/mL, p=0.001). The levels of total IgE were higher in patients with seasonal AR than in patients with perennial AR with exacerbation (472.5+/-132.5 IU/L vs. 389.0+/-70.9 IU/L, p<0.05). Nasal eosinophils were closely related to log PC20 (r=-0.65, p<0.01). These findings demonstrated that nasal eosinophilic inflammation might contribute to BHR in patients with AR.


Oscillatory growth in lily pollen tubes does not require aerobic energy metabolism.
Oscillatory tip growth in pollen tubes depends on prodigious amounts of energy. We have tested the hypothesis that oscillations in the electron transport chain lead to growth oscillations in lily (Lilium formosanum). Using three respiratory inhibitors, oligomycin, antimycin A, and cyanide, we find that pollen tube growth is much less sensitive to respiratory inhibition than respiration is. All three block respiration at concentrations severalfold lower than necessary to inhibit growth. Mitochondrial NAD(P)H and potentiometric JC-1 fluorescence, employed as markers for electron transport chain activity, rise rapidly in response to oligomycin, as expected. Pollen tube growth stops for several minutes before resuming. Subsequent growth has a lower mean rate, but continues to oscillate, albeit with a longer period. NAD(P)H fluorescence no longer exhibits coherent oscillations, and mitochondria no longer congregate directly behind the apex: they distribute evenly throughout the cell. Postinhibition growth relies on aerobic fermentation for energy production as revealed by an increase in ethanol in the media. These data suggest that oscillatory growth depends not on a single oscillatory pacemaker but rather is an emergent property arising from a number of stable limit cycles.


Natural history and risk factors of long-term mortality in acute coronary syndrome patients with cardiogenic shock.
Cardiogenic shock (CS) is a severe complication of acute coronary syndromes (ACS). Intra-aortic balloon pump (IABP) is considered important mechanical therapy for acute CS. We aimed to analyze the natural history and possible prognostic factors in patients with CS complicating ACS. All 126 patients (mean age 65.8 ± 12.5 years), who were hospitalized in single center due to an episode of CS in the course of ACS, had IABP and were scheduled for coronary angiography. The assessed end-point was 5-year death from any cause. Median left ventricle ejection fraction (LVEF) 28% (interquartile range (IQR) 23-35%), 39 patients (31%) were female, in 91 (72%) the initial diagnosis was ST-elevation myocardial infarction (STEMI). Mean time on the IABP was 3.8 ± 3 days. During index hospitalization there were 56 deaths (44%). Other 27 patients (out of 70 discharged - 38.5%) died during 5-year follow-up. In univariate logistic regression, the significant effect on long term mortality had age, female gender, reduced ejection fraction below 31% and hypotension on admission. The out of hospital survival was also determined by age, gender and hypotension, while LVEF lost its predictive value The multivariate survival analysis both in whole group and in patients discharged from hospital was independently affected by age and hypotension on the admission. The mortality of patients with CS despite treatment with IABP remains very high, especially during the in-hospital period and early after discharge. Among assessed parameters age and hypotension on the admission are the most important predictors of adverse long term prognosis.


Magnocellular nuclei of the basal forebrain: substrates of sleep and arousal regulation.
Magnocellular regions of the basal forebrain (BF) are recognized as important sites of sleep-wake regulation. Evidence is reviewed for the coexistence within the BF of mechanisms that regulate neocortical and limbic system arousal along with mechanisms that promote sleep. Arousal-related functions are mediated by a system of magnocellular cholinergic neurons. BF cholinergic neurons project monosynaptically to the entire neocortex and limbic telencephalon, exert excitatory effects on target cells and participate in the regulation of activated EEG patterns characteristic of waking and REM sleep. Evidence suggests that, within the waking state, the BF cholinergic system modulates processing of sensory information in the neocortex and is involved in cognitive processes. One or more noncholinergic cell types are responsible for the sleep-promoting functions of the BF. Neurons that display elevated discharge rates during transitions from waking to sleep and during nonREM sleep have been recorded in BF sites were electrical stimulation evokes sleep and experimental lesions cause insomnia. BF neurons function to promote sleep, in part, via descending inhibition of caudal hypothalamic and brainstem activating systems. GABAergic neurons located within magnocellular regions of the BF are hypothesized to mediate sleep-promoting actions. Afferents to the BF from hypothalamic and brainstem regions are functionally important for sleep-wake regulation. Thermosensitive inputs from the anterior hypothalamus modulate the activity of BF sleep- and arousal-related cell types. Excitatory effects of brainstem inputs to BF arousal-related cells have been documented. Additional evidence supports a critical role for GABAergic-cholinergic interactions, both within the magnocellular BF and at cortical and diencephalic sites, in the regulation of behavioral state.


Evolutionary mode and functional divergence of vertebrate NMDA receptor subunit 2 genes.
Ionotropic glutamate receptors in the central nervous system play a major role in numerous brain functions including learning and memory in many vertebrate species. NR2 subunits have been regarded as rate-limiting molecules in controlling the optimal N-methyl-D-aspartate (NMDA) receptor's coincidence-detection property and subsequent learning and memory function across multi-species. However, its evolutionary mode among vertebrate species remains unclear. With extensive analysis of phylogeny, exon structure, protein domain, paralogon and synteny, we demonstrated that two-round genome duplication generated quartet GRIN2 genes and the third-round fish-specific genome duplication generated extra copies of fish GRIN2 genes. In addition, in-depth investigation has enabled the identification of three novel genes, GRIN2C_Gg, GRIN2D-1_Ol and GRIN2D-2_Tr in the chicken, medaka and fugu genome, respectively. Furthermore, we showed functional divergence of NR2 genes mostly occurred at the first-round duplication, amino acid residues located at the N-terminal Lig_chan domain were responsible for type I functional divergence between these GRIN2 subfamilies and purifying selection has been the prominent natural pressure operating on these diversified GRIN2 genes. These findings provide intriguing subjects for testing the 2R and 3R hypothesis and we expect it could provide new insights into the underlying evolution mechanisms of cognition in vertebrate.


The ratio of serum des-gamma-carboxy prothrombin to tumor volume as a new biomarker for early recurrence of resected hepatocellular carcinoma.
Early recurrence (ER) of hepatocellular carcinoma (HCC) (within 1 year after resection) is known to be a poor prognostic factor. The aim was to identify the risk factors associated with ER after HCC resection. Data were analyzed retrospectively from patients who underwent primary resection for HCC from two hospitals. For cross-validation, HCC resection cases were divided into the training and testing cohort. The clinicopathological factors between the ER and non-ER groups and factors for predicting ER and prognosis after HCC resection were compared. Out of 173 patients in the training dataset, 33 patients had ER and the ER group showed larger tumor size, more intrahepatic metastasis (IM), and a higher ratio of serum des-gamma-carboxy prothrombin (DCP) to tumor volume (TV) (DCP/TV) than the non-ER group. Out of 203 patients in the testing dataset, 30 patients had ER and the ER group demonstrated larger tumor size, more IM, and higher serum alpha-fetoprotein, AFP/TV, DCP/TV, AFP/tumor maximum diameter (TMD), and DCP/TMD than the non-ER group. The patients were divided into high and low DCP/TV groups and high serum DCP/TV was associated with unfavorable overall survival in the training and testing dataset. Multivariate analysis confirmed that high serum DCP/TV and IM were independently associated with ER. Preoperative high serum DCP/TV may be useful for stratifying patients at risk of early HCC recurrence after curative resection.


Effectiveness of strategies for recruiting overweight and obese Generation Y women to a clinical weight management trial.
Limited research in young overweight and obese women indicates that they are difficult to recruit to weight management trials, with attrition higher and weight loss success lower than middle to older age participants. This study aimed to evaluate the effectiveness of different recruitment strategies for a clinical weight loss trial in overweight and obese Generation Y women. Overweight and obese (BMI >=27.5 kg/m-2) women aged 18-25 years (n=70) were required for a 12 month clinical weight management trial including diet, exercise and behaviour modification. Contact with researchers and eventual recruitment are reported for the various strategies employed to engage participants. Data reported as % or mean±SE. Recruitment was challenging with only 50 of the total 70 participants recruited within the scheduled time frame (24 months). Just over one quarter (27%) of volunteers assessed were recruited. Flyers posted around local tertiary education campuses were the most successful method, yielding 36% of included participants. This was followed by advertisements on the local area health service intranet (26%) and in local and metropolitan newspapers (16%). Recruitment of overweight and obese Generation Y women for a clinical weight loss trial was difficult. Multiple strategies targeted at this age and gender group were required. Less rigorous selection criteria and reduced face-to-face intervention time may improve recruitment and retention rates into clinical trials for this age group.


[Study on the relationship between hypertension management and the risk of stroke at community level].
To observe whether the community-based management for patients with hypertension can reduce the incidence of stroke. Sample of this study included 36 863 people aged 35 years or more who came from a cohort consisting three communities from Tiantan Hospital, Puren Hospital and the Gymnasium Road Hospital in Beijing, based on the surveys on the Integrated Community Intervention Measures of Cerebro-vascular Diseases. Some patients with hypertension in this cohort were followed up and under management. First-ever stroke was considered as the end-point event. In both groups diagnosed as borderline hypertension or definite hypertension group, the rates of management and control showed an annual increase. The management rate for women was higher, but the control rate was lower (P < 0.05) than that for men. In the third year of this study, the control rate was nearly 18%. With the qualification of control rate, the risk factors of overall stroke, ischemic stroke or hemorrhagic stroke reduced gradually, and the qualification of control rate showed more effects on hemorrhagic stroke. The qualification of control rate in the three years could cause the risk factors of total stroke, ischemic stroke or hemorrhagic stroke to reduce by 25.7%, 19.1%, 27.4%, respectively. When comparing with blood pressure level at < 160/95 mm Hg (1 mm Hg = 0.133 kPa), the level of < 140/90 mm Hg could reduce the risk factors as: 12.3% to total stroke, 12.8% to ischemic stroke and 14.9% to hemorrhagic stroke. Programs as long-term followed-up and management for patients with hypertension, and control the blood pressure at low level etc. could significantly reduce the incidence of stroke.


Early use of mammalian target of rapamycin inhibitors is an independent risk factor for incisional hernia development after liver transplantation.
Incisional hernias (IHs) are common complications after liver transplantation (LT) with a reported incidence of 1.7% to 34.3%. The purpose of this retrospective study was to evaluate the risk factors for IH development after LT with a focus on the role of immunosuppressive therapy during the first month after LT. We analyzed 373 patients who underwent LT and divided them into 2 groups according to their postoperative course: an IH group (121 patients or 32.4%) and a no-IH group (252 patients or 67.6%). A univariate analysis demonstrated that the following were risk factors related to IH development: male sex (P = 0.03), a body mass index ≥ 29 kg/m(2) (P = 0.005), LT after 2004 (P = 0.02), a Model for End-Stage Liver Disease (MELD) score ≥ 22 (P = 0.01), and hepatitis B virus infection (P = 0.01). The highest incidence of IHs was found in patients treated with mammalian target of rapamycin (mTOR) inhibitors (54.5%, P = 0.004). A multivariate analysis revealed male sex (P = 0.03), a pretransplant MELD score ≥ 22 (P = 0.04), and the use of mTOR inhibitors (P = 0.001) to be independent risk factors for IHs after LT. In conclusion, immunosuppressive therapy with mTOR inhibitors is an important independent risk factor for IH development after LT. To reduce the incidence of IHs, mTOR inhibitors should be avoided until the fourth month after LT unless their use is deemed to be strictly necessary.


A qualitative study of microaggressions against African Americans on predominantly White campuses.
Pierce's (The Black seventies: an extending horizon book, 1970) conception of "subtle and stunning" daily racial offenses, or microaggressions, remains salient even 50 years after it was introduced. Microaggressions were defined further by Sue and colleagues (Am Psychol 62:271, 2007), and this construct has found growing utility as the deleterious effects of microaggressions on the health of people of color continues to mount. Microaggressions are common on campuses and contribute to negative social, academic, and mental health outcomes. This paper explores how Black college students' experiences correspond to or differ from the microaggression types originally proposed by Sue et al. (Am Psychol 62:271, 2007). Themes were identified from focus group data of students of color (N = 36) from predominately White institutions (PWIs) of higher learning (N = 3) using interpretative phenomenological analysis. We identified 15 categories of racial microaggressions, largely consistent with the original taxonomy of Sue et al. but expanded in several notable ways. New categories in our data and observed by other researchers, included categories termed Connecting via Stereotypes, Exoticization and Eroticization, and Avoidance and Distancing. Lesser studied categories identified included Sue et al.'s Denial of Individual Racism, and new categories termed Reverse Racism Hostility, Connecting via Stereotypes, and Environmental Attacks. While previous literature has either embraced the taxonomy developed by Sue and colleagues or proposed a novel taxonomy, this study synthesized the Sue framework in concert with our own focus group findings and the contributions of other researchers. Improving our understanding of microaggressions as they impact people of color may better allow for improved understanding and measurement of this important construct.


An Examination of the Effectiveness of Child Endangerment Laws in Preventing Child Fatalities in Alcohol-Involved Motor Vehicle Crashes.
The aim of this study was to assess the impact of U.S. child-endangerment laws on the prevalence of child passengers fatally injured in motor vehicle crashes in which the adult driver was drinking. We used data from the 2002-2012 Fatality Analysis Reporting System. We conducted both bivariate and multivariate analyses using Heckman selection models. After adjusting for several cofactors, including driver demographics and blood alcohol concentration, child seat positioning, and seat belt laws, we found that passing a DUI child-endangerment law may have no impact at all on the likelihood of finding impaired drivers among those driving with children. There are a number of reasons why DUI child-endangerment laws have not been effective in saving the lives of young passengers who are driven by adult drinking drivers. These reasons include lack of publicity and education, as well as issues related to enforcement. Potential solutions are suggested that include examining sanctions and strengthening of DUI child endangerment laws.


Toughening of Epoxy Resin: The Effect of Water Jet Milling on Worn Tire Rubber Particles.
In this work a cycloaliphatic amine-cured epoxy (EP) resin was modified by micron-scale rubber particles (RP). Nominal RP, in sizes of 200 and 600 µm respectively, were produced using worn truck tires and ultra-high-pressure water jet cutting. The RP were dispersed into the EP resin using different mixing techniques (mechanical, magnetic, and ultrasonic stirring) prior to the introduction of the amine hardener. The dispersion of the RP was studied using optical light microscopy. A longer mixing time reduced the mean size of the particles in the EP compounds. Static (tensile and flexural), dynamic (unnotched Charpy impact), and fracture mechanical (fracture toughness and strain-energy release rate) properties were determined. The incorporation of the RP decreased the stiffness and strength values of the modified EPs. In contrast, the irregular and rough surface of the RP resulted in improved toughness. The fracture toughness and strain-energy release rate were enhanced up to 18% owing to the incorporation of 1% by weight (wt%) RP. This was traced to the effects of crack pinning and crack deflection. Considerably higher improvement (i.e., up to 130%) was found for the unnotched Charpy impact energy. This was attributed to multiple cracking associated with RP-bridging prior to final fracture.


Antihelper T cell autoantibody in acquired agammaglobulinemia.
A patient with acquired agammaglobulinemia had an antihelper T cell factor that was identified as an immunoglobulin of the IgG class. The factor specifically bound to the TH2- T cell subset and, in the presence of complement, abolished the helper effect of normal T cells. The antihelper T cell antibody preceded by several years the appearance of suppressor TH2+Ia+ T cells, at which time the clinical course rapidly deteriorated. Plasmapheresis resulted in lymphocytosis and reappearance of a functionally intact helper T cell population. It did not affect the suppressor cells. Conversely, total thymectomy resulted in a temporary disappearance of the TH2+Ia+ suppressor cells, but did not decrease the levels of the autoantibody to helper T cells. Neither of these treatments reversed the state of agammaglobulinemia.


Luminescence performance and vibronic behavior of Mn4+-activated Ca14-xKxAl10Zn6O35 deep-red phosphor.
In this study, a significant improvement of deep-red luminescence was successfully achieved via the substitution approach in the Mn4+-activated Ca14-xKxAl10Zn6O35 phosphor. The optimal Mn4+ doping level x was determined by studying luminescence concentration quenching behavior. The measured photoluminescence (PL) spectrum showed five distinct vibronic structures with the main peak centered at 712 nm. A theoretical simulation work was conducted for comparison, and the predominant phonon mode involving in the vibronic transition process was revealed. From the temperature-dependent PL spectra, an abnormal luminescence enhancement was observed at the temperature rising from T=100 to 340 K, and the underlying phonon-assisted luminescence mechanism was theoretically disclosed. Finally, we studied the temperature-dependent luminescence lifetime, and the primary phonon energy in the vibronic behavior was identified from the fitting work.


Navigational bronchoscopy specimens and PD-L1 expression: a retrospective study.
Additional data regarding the ability of navigational bronchoscopy (NB) to provide sufficient material for programmed death-ligand 1 (PD-L1) expression is needed. We performed a retrospective study of NB cases at our institution to determine performance of NB in providing adequate samples for PD-L1. We conducted a retrospective review of all consecutive NB procedures performed at our institution from January 1, 2018 to August 4, 2020 that involved biopsies of a lung nodule/mass with a diagnosis of non-small cell lung cancer (NSCLC). The primary outcome was adequacy of material for PD-L1 testing. All procedural, demographic, and diagnostic data were collected. The association of factors with PD-L1 adequacy was evaluated with rate ratios (RR) using modified Poisson regression models with robust standard errors. A total of 102 NB procedures with a diagnosis of NSCLC were performed over a 2-year period. The mean [standard deviation (SD)] nodule size was 25.0 [interquartile range (IQR), 18.0-32.0] mm and 57.8% (59/102) had a bronchus sign; 73% (68/93, 9 missing data) of samples were adequate for PD-L1 testing. Radial endobronchial ultrasound (REBUS) was utilized in 99% (101/102) of biopsies; a concentric or eccentric view was observed in 78.2% (79/101) and 16.8% (17/101), respectively. Transbronchial biopsy (TBBX) was performed in 92.2% (94/102). Only 4% (4/102) of cases required additional biopsies with either computed tomography (CT) guided transthoracic or surgical biopsies due to insufficient bronchoscopy tissue. No factors were predictive of PD-L1 adequacy in regression models. NB demonstrated good performance in obtaining adequate samples for PD-L1 testing. Only 4% of patients required additional procedures for more tissue when clinically indicated. However, additional study is needed to validate these results against surgical resection specimens.


Policy, toxicology and physicochemical considerations on the inhalation of high concentrations of food flavour.
Food flavour ingredients are required by law to obtain prior approval from regulatory bodies, such as the U.S. Food and Drug Administration (FDA) or the European Food Safety Authority (EFSA) in terms of toxicological data and intended use levels. However, there are no regulations for labelling the type and concentration of flavour additives on the product, primarily due to their low concentration in food and generally recognised as safe (GRAS) status determined by the flavour and extract manufacturers' association (FEMA). Their status for use in e-cigarettes and other vaping products challenges these fundamental assumptions, because their concentration can be over ten-thousand times higher than in food, and the method of administration is through inhalation, which is currently not evaluated by the FEMA expert panel. This work provides a review of some common flavour ingredients used in food and vaping products, their product concentrations, inhalation toxicity and aroma interactions reported with different biological substrates. We have identified several studies, which suggest that the high concentrations of flavour through inhalation may pose a serious health threat, especially in terms of their cytotoxicity. As a result of the wide range of possible protein-aroma interactions reported in our diet and metabolism, including links to several non-communicable diseases, we suggest that it is instrumental to update current flavour- labelling regulations, and support new strategies of understanding the effects of flavour uptake on the digestive and respiratory systems, in order to prevent the onset of future non-communicable diseases.


Residual platelet reactivity is preferred over platelet inhibition rate in monitoring antiplatelet efficacy: insights using thrombelastography.
Although thrombelastography (TEG) has been widely implemented in the clinical setting of endovascular intervention, consensus on the optimal parameter for defining high ischemic risk patients is lacking due to the limited data about the relationship between various TEG parameters and clinical outcomes. In this article, we report a post hoc analysis of a prospective, single-center cohort study, including 447 patients with acute coronary syndrome (ACS). Arachidonic acid (AA)- or adenosine diphosphate (ADP)-induced platelet-fibrin clot strength (MAAA or MAADP) was indicative of the net residual platelet reactivity after the treatment with aspirin or clopidogrel, respectively. AA% or ADP% was indices of the relative platelet inhibition rate on AA or ADP pathway. We found that each parameter alone was predictive of the risk of 6-month ischemic event, even after adjusting for confounding factors. However, the association between AA% and clinical outcome disappeared when further adjusted for MAAA. Likewise, inclusion of MAADP changed the significant relation between ADP% and clinical outcome. MAADP > 47.0 mm and MAAA > 15.1 mm were identified as the optimal cutoffs by receiver operating characteristic analysis. High MAAA (HR = 3.963; 95% CI: 1.152-13.632; P = 0.029) and high MAADP (HR = 5.185; 95% CI: 2.228-12.062; P < 0.001) were independent predictors when both were included in multivariable Cox regression hazards model. Interestingly, an even higher risk was found for the coexisting high MAAA and high MAADP (HR = 7.870; 95% CI: 3.462-17.899; P < 0.001). We conclude that when performing TEG to predict clinical efficacy, residual platelet reactivity has superiority over platelet inhibition rate as a measure of thrombotic risk in patients treated with aspirin and clopidogrel after ACS.


Laparoscopic cholecystectomy in the third trimester of pregnancy.
Laparoscopic cholecystectomy has become the method of choice for symptomatic cholelithiasis. Laparoscopic cholecystectomy during pregnancy is also becoming more accepted, as illustrated by several recent publications on this subject. In the third trimester, however, laparoscopic cholecystectomy has been less commonly attempted, with only a few case reports. We present a series of four patients who underwent laparoscopic cholecystectomy during the third trimester of pregnancy without complication. We describe a safe and effective technique for this procedure, and review the literature on this topic.


The NIP7 protein is required for accurate pre-rRNA processing in human cells.
Eukaryotic ribosome biogenesis requires the function of a large number of trans-acting factors which interact transiently with the nascent pre-rRNA and dissociate as the ribosomal subunits proceed to maturation and export to the cytoplasm. Loss-of-function mutations in human trans-acting factors or ribosome components may lead to genetic syndromes. In a previous study, we have shown association between the SBDS (Shwachman-Bodian-Diamond syndrome) and NIP7 proteins and that downregulation of SBDS in HEK293 affects gene expression at the transcriptional and translational levels. In this study, we show that downregulation of NIP7 affects pre-rRNA processing, causing an imbalance of the 40S/60S subunit ratio. We also identified defects at the pre-rRNA processing level with a decrease of the 34S pre-rRNA concentration and an increase of the 26S and 21S pre-rRNA concentrations, indicating that processing at site 2 is particularly slower in NIP7-depleted cells and showing that NIP7 is required for maturation of the 18S rRNA. The NIP7 protein is restricted to the nuclear compartment and co-sediments with complexes with molecular masses in the range of 40S-80S, suggesting an association to nucleolar pre-ribosomal particles. Downregulation of NIP7 affects cell proliferation, consistently with an important role for NIP7 in rRNA biosynthesis in human cells.


[Modern requirements of data processing in nuclear medicine (author's transl)].
Having used a computer system for nuclear medicine for a period of seven years, our experience in its routine use has been evaluated. From this experience, and the present state of computer technique, the demands placed on the computer by scanners, gamma cameras and dynamic measurements have been assessed. Although available hardware meets the demands of present techniques in nuclear medicine, the corresponding software has not yet reached a satisfactory stage of development. There is still a lack of generally recognised, tested and standardised basic principles.


Ca2+ channel blockers distinguish between G protein-coupled pharmacomechanical Ca2+ release and Ca2+ sensitization.
The effects of Ca2+ channel blockers on two modes of G protein-mediated pharmacomechanical coupling, Ca2+ release and modulation of Ca2+ sensitivity of the contractile apparatus, were investigated. Smooth muscles were permeabilized with Staphylococcal alpha-toxin or with beta-escin to avoid effects due to block of sarcolemmal Ca2+ channels, while retaining receptor/G protein coupling. In permeabilized portal vein smooth muscle, verapamil and nifedipine inhibited Ca2+ release induced by an alpha 1-adrenergic agonist (phenylephrine) and by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), but not that induced by inositol 1,4,5-trisphosphate (InsP3). These Ca2+ channel blockers also did not block the phenylephrine- or GTP gamma S-induced force development at constant cytoplasmic Ca2+ ("Ca2+ sensitization"). An alpha 1-blocker (prazosin) inhibited both the Ca2(+)-releasing and Ca2(+)-sensitizing effects of phenylephrine, but not those of GTP gamma S, nor did it block InsP3-induced Ca2+ release. We conclude that Ca2+ channel blockers selectively uncouple the Ca2(+)-releasing, but not the Ca2(+)-sensitizing, component of pharmacomechanical coupling. These findings raise the possibility that pharmacomechanical Ca2+ release may be modulated by dihydropyridine binding proteins at the level of G proteins/phospholipase C and also indicate a divergence of the Ca2(+)-releasing and Ca2(+)-sensitizing effects at some step prior to phospholipase C.


Prevalences and characteristics of cultivable nasal bacteria isolated from preclinical medical students.
Commensal bacteria in the nasal cavity may act as opportunistic pathogens that cause infections under certain conditions. Screening for commensal bacteria in the nasal cavity may aid in understanding their roles in microbiota balance and preventing potential infections. Nasal samples were collected from healthy preclinical medical students and used to inoculate various bacterial culture media, by means of the WaspLab microbiology automated system. Bacterial colonies were then identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Antibiotic resistance phenotypes of Staphylococcus aureus were determined by antibiotic susceptibility tests. In total, 549 bacterial strains were isolated from 161 participants. These strains included the following genera: Staphylococcus, Streptococcus, Corynebacterium, Dolosigranulum, Bacillus, Micrococcus, Haemophilus, Neisseria, Moraxella, Pseudomonas, and members of Enterobacteriaceae (e.g., Escherichia, Klebsiella, Citrobacter, Enterobacter, and Serratia). Approximately 25.5% of students were carriers of S. aureus; most S. aureus isolates were resistant to penicillin, erythromycin, and clindamycin. The prevalence of methicillin-resistant S. aureus in nasal samples was 4.3%. A diverse group of nasal commensal bacteria inhabited our population of healthy volunteers. These data can improve comprehension of the potential roles of these nasal commensal bacteria in regulating microbiota balance and promoting or mitigating potential future infections.


Can Voice Pitch Be Preserved in Patients after Transoral Endoscopic Thyroidectomy Vestibular Approach?
Transoral endoscopic thyroidectomy vestibular approach (TOETVA) has become increasingly popular. Several reports have emphasized the safety and efficacy of this new approach. However, there is no report on functional voice outcomes, including voice pitch change after TOETVA. The functional voice outcomes of patients undergoing TOETVA were compared with those of patients undergoing conventional thyroidectomy. A total of 82 consecutive patients were included in the study: 44 underwent thyroid lobectomy via TOETVA (transoral group) and 38 underwent thyroid lobectomy via the classic cervical approach (open group). Thyroidectomy-related voice questionnaire (TVQ), perceptual voice analysis, fiberoptic laryngoscopic and videolaryngostroboscopic examinations, and acoustic analysis were carried out before and one month after surgery. The changes in these values after surgery and the differences between the transoral and open groups were analyzed. We found no significant postoperative change in voice workups in either group. The mean high pitch decreased (from 367.91 ± 120.98 to 325.80 ± 100.86 Hz, p = 0.069) in the transoral group, but statistical significance was not attained. Clinically significant changes in pitch (postoperative change in speaking fundamental frequency, ΔSFF ≥ 12) after surgery were evident in seven (15.91%) patients in the transoral group and eight (21.05%) patients in the open group without significant difference (p = 0.579). This is the first study to assess functional voice outcomes (including pitch) after TOETVA compared with conventional open surgery. TOETVA was associated with good voice outcomes without any significant drop in pitch.


Determinants of late initiation for antenatal care follow up: the case of northern Ethiopian pregnant women.
Early antenatal care follow-up is the main strategy of preventing pregnancy related adverse outcomes; in which World Health Organization recommends first antenatal care visit should be offered within the first trimester. However, Low utilization and late booking is the predominant problem in most developing countries including Ethiopia. This study aimed to determine the prevalence of late initiation for antenatal care follow-up and associated factors among pregnant women. Institutional based cross-sectional study was conducted among 423 pregnant mothers using systematic sampling technique. Multivariable logistic regression analysis was performed at the level of significance of p-value ≤ 0.05. The findings showed 59.4% of pregnant women started their first visit after first trimester. Having age ≥ 25 years (AOR = 1.62, CI 1.1, 2.49), recognition of pregnancy by missed period (AOR = 2.54 CI 1.63, 3.96), pregnant mother who were not advised to start antenatal-care (AOR = 3.36, CI 1.74, 6.5) and primary educational level (AOR = 2.22, CI 1.16, 4.25) were found to be significantly associated with late initiation for antenatal care. The prevalence of late antenatal care follow-up is high. Multidisciplinary approaches to keep empowering women through education are recommended for early initiation of antenatal care.


An Inactivated Influenza Virus Vaccine Approach to Targeting the Conserved Hemagglutinin Stalk and M2e Domains.
Universal influenza virus vaccine candidates that focus on the conserved hemagglutinin (HA) stalk domain and the extracellular domain of the matrix protein 2 (M2e) have been developed to increase the breadth of protection against multiple strains. In this study, we report a novel inactivated influenza virus vaccine approach that combines these two strategies. We inserted a human consensus M2e epitope into the immunodominant antigenic site (Ca2 site) of three different chimeric HAs (cHAs). Sequential immunization with inactivated viruses containing these modified cHAs substantially enhanced M2e antibody responses while simultaneously boosting stalk antibody responses. The combination of additional M2e antibodies with HA stalk antibodies resulted in superior antibody-mediated protection in mice against challenge viruses expressing homologous or heterosubtypic hemagglutinin and neuraminidase compared to vaccination strategies that targeted the HA stalk or M2e epitopes in isolation.


The health care crisis--how we got there.
There are upward pressures on the medical economy that we can do little to control. Among these are general inflationary factors, high technology costs, and care for a population ever increasing in age. Nothing in the way of reform is likely to come out of Washington other than another bureaucratic scheme which will add further confusion and put in place another multilayered system. Many of the wrongs I have cited can and should be corrected. By changing those wrongs into rights we can preserve the best of our present system, including two American icons: fee-for-service and freedom-of-choice of physician. Let us not swap the devil for the witch.


Berberine enhances chemosensitivity to irinotecan in colon cancer via inhibition of NF‑κB.
Previous studies have shown that irinotecan (CPT‑11) impairs chemotherapy‑induced apoptosis by activating nuclear factor‑κB (NF‑κB) and a number of strategies have been employed to augment chemosensitivity through the suppression of NF‑κB activation. Berberine, a botanical alkaloid, was reported to enhance chemosensitivity to 5‑fluorouracil and doxorubicin by suppressing NF‑κB activation. In the present study, the effect of berberine on CPT‑11‑induced apoptosis was investigated through the inhibition of NF‑κB. Inhibition of NF‑κB activation by p65 small interfering RNA was shown to potentiate apoptosis induced by CPT‑11. Berberine suppressed CPT‑11‑induced NF‑κB activation in a dose‑dependent manner and enhanced chemosensitivity to CPT‑11 by downregulating NF‑κB activation of antiapoptotic genes, c‑IAP1, c‑IAP2, survivin and Bcl‑xL. The current observations indicate that berberine inhibits NF‑κB activation and may be used to enhance CPT‑11‑induced apoptosis in colon cancer.


Secondary cluster headache responsive to sumatriptan.
A patient was seen with secondary cluster headache whose acute pain responded promptly to sumatriptan. The headaches started after injury to the vertebral artery. This finding provides clinical affirmation of the existence of the trigeminal/cervical nuclear overlap that is central to this condition.


Fine needle aspirate cell blocks are reliable for detection of hormone receptors and HER-2 by immunohistochemistry in breast carcinoma.
To evaluate the reliability of fine needle aspirate cell blocks in the assessment of oestrogen receptor (ER), progesterone receptor (PR) and HER-2/neu proteins by immunohistochemistry in comparison with surgical specimens. This is a retrospective study of 62 cases of breast carcinoma diagnosed by fine needle aspiration cytology (FNAC) and confirmed using the surgical specimen. Immunohistochemical tests were performed to assess the presence of oestrogen receptor (ER), progesterone receptor (PR) and HER-2/neu proteins in cell blocks and the corresponding surgical specimens. The cell block method used alcohol prior to formalin fixation. Cases with 10% or more stained cells were considered positive for ER and PR. Positivity for HER-2/neu was assessed on a scale of 0-3+. The criterion for positivity was a score of 3+. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of the cell blocks in the investigation of ER, PR and HER-2/neu protein (3+) were (%): ER, 92.7, 85.7, 92.7, 85.7 and 90.3; PR, 92.7, 94.7, 97.4, 87.0 and 93.5; HER-2/neu, 70.0, 100.0, 100.0, 94.5 and 95.2. Discrepancies were seen in cell blocks in the 1+ and 2+ HER-2/neu staining scores: two of 12 cases scoring 2+ and one case of 26 scoring 1+ on cell blocks scored 3+ on surgical specimens. The correlation index between cell block and corresponding surgical specimen varied from 90% to 94%. Cell blocks provide a useful method of assessing ER, PR and HER-2/neu, mainly for inoperable and recurrent cases, but consideration should be given to carrying out FISH analysis on 1+ as well as 2+ HER-2/neu results.


Bio-Guided Isolation of Acetogenins from Annona cherimola Deciduous Leaves: Production of Nanocarriers to Boost the Bioavailability Properties.
Annonaceous acetogenins (ACGs) are lipophilic polyketides isolated exclusively from Annonaceae. They are considered to be amongst the most potent antitumor compounds. Nevertheless, their applications are limited by their poor solubility. The isolation of ACGs from Annona cherimola leaves, an agricultural waste, has not been reported to date. Molvizarin (1) cherimolin-1 (2), motrilin (3), annonacin (4) and annonisin (5) are isolated for the first time from A. cherimola deciduous leaves. Annonacin was found to be four- and two-times more potent in tumoral cells (HeLa, 23.6% live cells; IGROV-1, 40.8% live cells for 24 h) than in HEK-293 at 50 µM (24 h, 87.2% live cells). Supramolecular polymer micelles (SMPMs) were synthesized to encapsulate the major ACG isolated, annonacin, in order to improve its solubility in aqueous media. The bioavailability of this compound was increased by a factor of 13 in a simulated human digestive system when compared with free annonacin and an encapsulation efficiency of 35% was achieved. In addition, the cytotoxic activity of SMPMs that hosted annonacin (100 µM, 24 h, 5.8% live cells) was increased compared with free annonacin in water (100 µM, 24 h, 92% live cells). These results highlight the use of by-products of A. cherimola, and their pure compounds, as a promising source of anticancer agents. The use of SMPMs as nanocarriers of ACGs could be an alternative for their application in food field as nutraceutical to enhance the administration and efficacy.


Diagnostic performance of microRNA-133a in acute myocardial infarction: A meta-analysis.
The aim of this study was to evaluate the diagnostic performance of microRNA-133a in the diagnosis of acute myocardial infarction (AMI). Major databases including PubMed, Embase and the Cochrane Library were searched for case-controlled studies comparing AMI and non-AMI patients. The outcome was evaluated by the relative expression of microRNA-133a in plasma or serum. The Mantel-Haenszel odds ratio (OR) was calculated using a fixed-effects model meta-analysis for the outcome. The primary outcomes of interest were pooled sensitivity, specificity and diagnostic accuracy of microRNA-133a for AMI. Out of 137 identified related articles, 10 were found to conform with the inclusion and ex-clusion criteria of the study. The 10 case-controlled studies contained complete data for 1,074 patients (with no restrictions of race, age or sex), and a database containing 137 patients from the registry of each study. In addition to low heterogeneity, a statistically significant increase was found in overall microRNA-133a expression between AMI vs. non-AMI; the pooled OR was 22.84 (95% confidence interval [CI] 13.87-37.63), sensitivity was 0.84 (95% CI 0.75-0.90), specificity was 0.82 (95% CI 0.74-0.89) and area under curve (AUC) was 0.90 (95% CI 0.87-0.92). Based on the meta-analysis of ten case-controlled studies including 1,074 patients,it was found that the level of microRNA-133a in blood serum or plasma maybe used as a diagnostic biomarker of AMI.


Nonlinear kernels, dominance, and envirotyping data increase the accuracy of genome-based prediction in multi-environment trials.
Modern whole-genome prediction (WGP) frameworks that focus on multi-environment trials (MET) integrate large-scale genomics, phenomics, and envirotyping data. However, the more complex the statistical model, the longer the computational processing times, which do not always result in accuracy gains. We investigated the use of new kernel methods and modeling structures involving genomics and nongenomic sources of variation in two MET maize data sets. Five WGP models were considered, advancing in complexity from a main-effect additive model (A) to more complex structures, including dominance deviations (D), genotype × environment interaction (AE and DE), and the reaction-norm model using environmental covariables (W) and their interaction with A and D (AW + DW). A combination of those models built with three different kernel methods, Gaussian kernel (GK), Deep kernel (DK), and the benchmark genomic best linear-unbiased predictor (GBLUP/GB), was tested under three prediction scenarios: newly developed hybrids (CV1), sparse MET conditions (CV2), and new environments (CV0). GK and DK outperformed GB in prediction accuracy and reduction of computation time (~up to 20%) under all model-kernel scenarios. GK was more efficient in capturing the variation due to A + AE and D + DE effects and translated it into accuracy gains (~up to 85% compared with GB). DK provided more consistent predictions, even for more complex structures such as W + AW + DW. Our results suggest that DK and GK are more efficient in translating model complexity into accuracy, and more suitable for including dominance and reaction-norm effects in a biologically accurate and faster way.


Vascular surgery resident training in Canada.
The training of vascular surgeons in Canada has evolved over the past decade. Direct entry into a vascular surgery training program after medical school has been offered since 2012. At some institutions, it is the only option for surgery training. The smaller population of Canada and a single-payer health care system has resulted in unique opportunities and challenges for the training of vascular surgeons and providing opportunities for trainees to transition into clinical practice.


Cardiovascular outcomes of pregnancy in Marfan's syndrome patients: A literature review.
Pregnancy in patients with Marfan's syndrome (MFS) carries an increased risk of cardiovascular complications, resulting in increased maternal and fetal mortality and morbidity. Literature on MFS pregnant patients is relatively sparse, and there has yet to be a concrete consensus on the management of this unique patient population. The purpose of our paper is to provide a literature review of case reports and studies on MFS during pregnancy (published between 2005 and 2015) and to explore cardiovascular outcomes of patients with MFS. Of the 852 women in our review, there were 1112 pregnancies, with an aortic dissection rate of 7.9% and mortality of 1.2%. Data demonstrated a trend that patients whose aortic diameter ≥40 mm had a greater rate of dissection than MFS patients whose aortic diameter <40 mm (Fisher's exact test, P = .0504). Fetal outcome included a 5.6% mortality rate and 41% of births were cesarean deliveries and of those reported, 75% secondary to cardiac emergencies. Patients with MFS, especially those whose initial aortic diameters ≥40 mm, planning a pregnancy or currently pregnant should be carefully counseled about the maternal and fetal risks throughout pregnancy. MFS patients whose aortic diameters ≥40 mm should be advised to ideally await pregnancy until prophylactic aortic surgery. As MFS varies in its phenotypic expression, each patient's risk of adverse cardiac events should be assessed individually through a joint Maternal Fetal Medicine and Cardiology Center.


Convention on Consent to Marriage, Minimum Age for Marriage and Registration of Marriages, 25 October 1988.
The Government of Antigua and Barbuda succeeded to this Convention on Consent to Marriage, Minimum Age for Marriage and Registration of Marriages on 25 October 1988.


A transcription map for the rabbit beta-globin gene.
We have characterized the transcripts of the beta-globin gene in RNA isolated from rabbit bone marrow using the S1 mapping procedure of Berk and Sharp (1977). The largest beta-globin-specific RNA that we have detected is a transcript, colinear with the gene, that contains the mRNA coding sequences plus both intervening sequences but does not extend into the extragenic DNA sequences. The 5' and 3' ends of this pre-mRNA maps at the same position as those of mature globin mRNA. Several partially spliced RNAs are described that are probably intermediates in the pathway from the colinear transcript to mature mRNA. The largest spliced pre-mRNA has lost only about 40 of the 126 nucleotides of the small intervening sequence and contains the entire large intervening sequence together with the coding sequences. A second major intermediate pre-mRNA lacks only the entire small intervening sequence. Finally, a pre-mRNA is described in which all but approximately 90 nucleotides of the large intervening sequence have been excised. Thus both intervening sequences appear to be able to be excised in a stepwise fashion. Removal of the small intervening sequence seems to precede the removal of the large intervening sequence.


The interplay of DNA methyltransferases and demethylases with tuberization genes in potato (Solanum tuberosum L.) genotypes under high temperature.
Potato is a temperate crop consumed globally as a staple food. High temperature negatively impacts the tuberization process, eventually affecting crop yield. DNA methylation plays an important role in various developmental and physiological processes in plants. It is a conserved epigenetic mark determined by the dynamic concurrent action of cytosine-5 DNA methyltransferases (C5-MTases) and demethylases (DeMets). However, C5-MTases and DeMets remain unidentified in potato, and their expression patterns are unknown under high temperatures. Here, we performed genome-wide analysis and identified 10 C5-MTases and 8 DeMets in potatoes. Analysis of their conserved motifs, gene structures, and phylogenetic analysis grouped C5-MTases into four subfamilies (StMET, StCMT3, StDRM, and StDNMT2) and DeMets into three subfamilies (StROS, StDML, and StDME). Promoter analysis showed the presence of multiple cis-regulatory elements involved in plant development, hormone, and stress response. Furthermore, expression dynamics of C5-MTases and DeMets were determined in the different tissues (leaf, flower, and stolon) of heat-sensitive (HS) and heat-tolerant (HT) genotypes under high temperature. qPCR results revealed that high temperature resulted in pronounced upregulation of CMT and DRM genes in the HT genotype. Likewise, demethylases showed strong upregulation in HT genotype as compared to HS genotype. Several positive (StSP6A and StBEL5) and negative (StSP5G, StSUT4, and StRAP1) regulators are involved in the potato tuberization. Expression analysis of these genes revealed that high temperature induces the expression of positive regulators in the leaf and stolon samples of HT genotype, possibly through active DNA demethylation and RNA-directed DNA methylation (RdDM) pathway components. Our findings lay a framework for understanding how epigenetic pathways synergistically or antagonistically regulate the tuberization process under high-temperature stress in potatoes. Uncovering such mechanisms will contribute to potato breeding for developing thermotolerant potato varieties.


The effect of pause time upon the communicative interactions of young people who use augmentative and alternative communication.
This study investigated the effect of variation in partner-initiated pause time on the expressive communication of young people who use Augmentative and Alternative Communication (AAC). Eight participants aged 8;11-20;08 years (mean 16;02 years) participated in the study. Three pause time conditions (2, 10, and 45 seconds) were trialled during a scripted shared storybook reading task. A total of 27 turn opportunities were provided for participants during the task. Participant interactions were analysed for the percentage of responses made to a turn opportunity, mean length of utterance in words (MLU), percentage of assertive conversational acts made, and the modes of communication used. Findings indicated that participants were more likely to respond to a turn opportunity when their communication partner provided a longer pause time. Additionally, a longer pause time resulted in longer MLUs. Participants did not use more assertive conversational acts and continued to use a variety of communication modes when provided with a longer pause time. Results indicate that increasing pause time is an effective strategy to support the development of expressive communication for young people who use AAC. This suggests the need for professionals providing AAC services to encourage communication partners to provide extended pauses during interactions.


Ubiquitination and down-regulation of gap junction protein connexin-43 in response to 12-O-tetradecanoylphorbol 13-acetate treatment.
Gap junctions are specialized plasma membrane domains enriched in connexin proteins that form channels between adjacent cells. Gap junctions are highly dynamic, and modulation of the connexin turnover rate is considered to play an important role in the regulation of gap junctional intercellular communication. In the present study, we show that the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) induces ubiquitination of connexin-43 (Cx43) in IAR20 rat liver epithelial cells. The accelerated ubiquitination of Cx43 in response to TPA occurred concomitantly with Cx43 hyperphosphorylation and inhibition of cell-cell communication via gap junctions. The TPA-induced ubiquitination of Cx43 was mediated via protein kinase C and partly involved the mitogen-activated protein kinase pathway. Following ubiquitination, Cx43 was internalized and degraded. The loss of Cx43 protein was counteracted by ammonium chloride, indicating that acidification of internalized Cx43 gap junctions is a prerequisite for its degradation. Furthermore, the Cx43 degradation was partly counteracted by leupeptin, an inhibitor of cathepsin B, H, and L. Cx43 internalization and subsequent degradation were blocked by inhibitors of the proteasome. Evidence is provided that Cx43 is modified by multiple monoubiquitins rather than a polyubiquitin chain in response to TPA. Moreover, the TPA-induced ubiquitination of Cx43 was blocked by proteasomal inhibitors. Taken together, the data indicate that Cx43 ubiquitination is a highly regulated process. Moreover, the results suggest that the proteasome might play an indirect role in Cx43 degradation by affecting the level of monoubiquitin conjugation and trafficking of Cx43 to endosomal compartments.


Prevention programmes of progressive renal disease in developing nations.
Development of strategies for the early detection and prevention of non-communicable diseases, including kidney disease, is the only realistic strategy to avert an imminent global health and economic crisis and enhance equity in health care worldwide. In this article, we briefly examine the burden of non-communicable diseases, including diabetes, hypertension, cardiovascular disease and how chronic kidney disease (CKD) represents a key integrated element in the setting, even in developing countries. A possible explanation of the increasing number of people who have or are at risk to develop CKD in poor countries is also given. A survey of major screening and intervention programmes performed or ongoing globally is then presented, highlighting differences and hurdles of projects planned in developed or developing nations as well as in unprivileged communities in developed countries. Finally, some recommendations on future steps to implement prevention programmes in emerging worlds are provided.


Somatic chromosomal aberrations and male infertility.
A significant correlation was found between the frequency of chromosomally aberrant peripheral lymphocytes and a low frequency of morphologically normal spermatozoa in men. No correlation was found between increased chromosomal breakage, other sperm parameters and density, motility or agglutination of spermatozoa. Smokers had significantly more cells with aberrations than nonsmokers. The significance of induced lesions in peripheral lymphocytes and their relationship to reproduction was discussed.


Modulation of intestinal barrier properties by miltefosine.
Miltefosine (hexadecylphosphocholine, HePC) is the first effective oral agent for the treatment of visceral leishmaniasis. This study aimed to determine whether this oral administration alters the integrity and transport capacities of the intestinal barrier. The objectives of this study were: (i) to evaluate the cytotoxicity of HePC, (ii) to investigate the effects of HePC on paracellular and transcellular transport and (iii) to investigate the influence of HePC on three major transporters of the intestinal barrier, namely, P-glycoprotein, the human intestinal peptide transporter (PepT-1) and the monocarboxylic acid transporter (MCT-1) in Caco-2 cell monolayers, used as an in vitro model of the human intestinal barrier. We show that HePC reduced the transepithelial electrical resistance and increased D-[14C]mannitol permeability in a dose-dependent manner but had no effect on [3H]testosterone permeability, demonstrating that HePC treatment enhances paracellular permeability via an opening of the tight junction complex without affecting the transcellular route. Morphological studies using confocal fluorescence microscopy showed no perturbation of the normal distribution of ZO-1, occludin or E-cadherin but revealed a redistribution of the tight junction-associated protein claudin-1 and the perijunctional actin after incubation with HePC. Finally, HePC was found to inhibit the intestinal P-glycoprotein in the Caco-2 cell model after a single short exposure. These results suggest that HePC could modify the oral bioavailability of other therapeutic compounds absorbed via the paracellular route or which are substrates of the intestinal P-glycoprotein.


Specific apoptosis induction by the dual PI3K/mTor inhibitor NVP-BEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells.
NVP-BEZ235 is a dual PI3K/mTOR inhibitor currently in phase I clinical trials. We profiled this compound against a panel of breast tumor cell lines to identify the patient populations that would benefit from such treatment. In this setting, NVP-BEZ235 selectively induced cell death in cell lines presenting either HER2 amplification and/or PIK3CA mutation, but not in cell lines with PTEN loss of function or KRAS mutations, for which resistance could be attributed, in part to ERK pathway activity. An in depth analysis of death markers revealed that the cell death observed upon NVP-BEZ235 treatment could be recapitulated with other PI3K inhibitors and that this event is linked to active PARP cleavage indicative of an apoptotic process. Moreover, the effect seemed to be partly independent of the caspase-9 executioner and mitochondrial activated caspases, suggesting an alternate route for apoptosis induction by PI3K inhibitors. Overall, this study will provide guidance for patient stratification for forthcoming breast cancer phase II trials for NVP-BEZ235.


Expression of endothelin-2 (ET-2) gene in a human renal adenocarcinoma cell line: purification and cDNA cloning of ET-2.
It has been found that human renal adenocarcinoma ACHN cells synthesize and secrete immunoreactive endothelin (ir-ET) in the culture medium. Partial characterization of this material with reverse-phase high-performance liquid chromatography (RP-HPLC) suggested that ACHN cells synthesized only human endothelin-2 (ET-2). Isolation and characterization of this ir-ET-2 has revealed that this peptide has almost the same amino acid sequence and molecular weight as that of human ET-2 deduced from the nucleotide sequence of cloned human ET-2 gene. To delineate the precise structure of human ET-2 precursor, ET-2 cDNAs were cloned from a cDNA library constructed with mRNA derived from the ACHN cells, and the nucleotide and deduced amino acid sequences were determined. The ET-2 cDNA that has the longest open reading frame encodes prepro-ET-2 protein, consisting of 178 amino acid residues. The ET-like sequence found in the prepro-ET-1 and -ET-3 was also conserved in this prepro-ET-2. The Northern blot analysis of mRNA revealed that the transcript of the human ET-2 gene was 1.4 kb.


Effect of decentration on the optical performance in multifocal intraocular lenses.
To evaluate the influence of decentration on optical performance in multifocal intraocular lenses (IOLs) using eye models. This study evaluated 4 types of multifocal IOLs (ReSTOR SA60D3, Alcon; TECNIS Multifocal ZM900, AMO; ReZoom, AMO; SFX-MV1, Hoya). The evaluations were based on measurements of the near and far modulation transfer function (MTF) and visualized actual near images (newspaper) using eye models with the IOL horizontally displaced 0, 0.25, 0.5, 0.75 and 1.0 mm from the center. For the diffractive ReSTOR the near MTF decreased with increasing decentration. The near images (newspaper characters) became difficult to distinguish at a decentration of 1.0 mm. For the diffractive ZM900, the near and far MTFs gradually decreased with increasing decentration. For the refractive ReZoom and SFX-MV1, we observed almost no change in the near MTF from a decentration of 0-1.0 mm. However, the far MTF clearly decreased starting at a decentration of 1.0 mm for ReZoom and 0.75 mm for SFX-MV1. The MTFs and near images are affected to a different extent depending on the design of multifocal IOLs; clinically relevant effects are not to be expected up to a decentration of 0.75 mm.


[Adverse effects of longterm, continual administration of high doses of albendazole in the treatment of echinococcal disease].
Modern treatment of cystic echinococcosis, except for surgical treatment and percutaneous drainage of cyst considers also administration of albendazole as a type of individual therapy. However, clinicians fear of the serious adverse effects of high doses of albendazole, first of all the elevation of serum transaminases activity, very frequently results in subdosing of albendazole and wrong conclusions its efficacy and safety. The aim of this study was to investigate adverse effects of a longterm, continual administration of high doses of albendazole in the treatment of patients with echinococcal disease. A total of 42 patients (mean age 40.4 +/- 18.3 years) with echinococcal disease were included in the study. They were treated with continual administration of high doses of albendazole within the period of 4 to 6 months. The subgroups of 27 and 15 patients were treated with 15-20 mg/kg/day and with 21-25 mg/kg/day albendazole, respectively. The patients in the control group (18 with surgical treatment, 6 with percutaneous drainage of cyst) were treated with 800 mg albendazole per day (< 15 mg/kg body weight) in the cycles of 28 days (1-3 cycles) and a two-week pause between them. In the study group adverse effects of albendazole were registered in 20 (47.6%), whereas in the control group in 6 (30.0%) of the patients. In both subgroups elevated activity of serum transaminases were found more frequently in the study group compared to the control one (35.7% vs 25%, p < 0.05), especially in the patients who were treated with higher doses of albendazole. The patients in the study group, compared to the patients in the control group had significantly higher mean activity of serum alanin aminotransferase in the course of the second and third month of the therapy (p < 0.05). Administration of albendazole due to adverse effects was stopped in 3 (7.1%) of the patients in the study group. Two (4.8%) of them had a very high activity of serum transaminases and one had a muscle pains and high activity of serum creatine kinase. After the interruption of the therapy we documented a nonnalization of serum enzyme levels in all the patients. Longterm, continual administration of high doses of albendazole in the patients with echinococcal disease results in significant elevation of serum transaminases activity, compared to the patients treated with albendazole in the cycles, but in the majority of the patients serum transaminases activity was normalizated by the end of a 6-month period.


Synthesis and structures of one- and two-electron oxidized forms of bis(acetylene)tetrairon clusters Cp'(4)Fe(4)(HCCH)(2) (Cp' = Cp, eta5-C(5)H(4)Me).
Air-oxidation of Cp'(4)Fe(4)(HCCH)(2) (Cp' = Cp (1a), C(5)H(4)Me (1b)) in an NH(4)PF(6)/CH(3)CN solution afforded the one-electron oxidized clusters [Cp'(4)Fe(4)(HCCH)(2)](PF(6)). Oxidation of 1a with excess AgBF(4) in THF afforded [1a](BF(4)), while that of 1b with excess AgBF(4) gave [1b](BF(4))(2). The X-ray crystal structure analysis of [1a](BF(4)) revealed that the monocationic cluster retains the butterfly-type Fe(4)(mu4-eta(2):eta(2):eta(1):eta(1)-HCCH)(2) framework similar to that of the neutral cluster. The average Fe-Fe bond length is shorter by 0.029 A than that in the neutral cluster. Electrochemical oxidation of 1a and 1b in 0.1 M NH(4)PF(6)/CH(3)CN solution at +0.30 and +0.25 V versus Ag/10 mM AgNO(3), respectively, afforded the two-electron oxidized clusters [1a](PF(6))(2) and [1b](PF(6))(2). The X-ray crystal structure analysis for [1b](BF(4))(2) shows that the butterfly-type cluster core is retained but shrinks more of those of neutral and monocationic clusters. The four Fe-Fe bonds in [1b](BF(4))(2) are unequivalent: one Fe-Fe bond (2.397(1) A) is apparently shorter than the others (2.439(2)-2.461(2) A).


Assessment of Trace Elements Supply in Canned Tuna Fish Commercialized for Human Consumption in Brazil.
This study evaluates the elemental content in 4 types of canned tuna fish groups, each with 4 brands that are commercialized for human consumption in Brazil. The results are based on trace elements in canned tuna fish quantified by ICP OES and a comparison to limit levels set by the FAO/WHO. We also checked the carcinogenic risk (CR), non-carcinogenic risk (Hazard Index (HI) and Hazard Quotient (HQ)), and pollution index (PI) for the studied canned tuna samples. As and Se concentrations in all groups are above the intake values set by FAO/WHO considering specific groups. The carcinogenic risk values for arsenic (As) in groups are considerably unacceptable (≥10-4). Hazard quotients (HQ) were >1 for As in all groups, while no sample was below 1 for HI. The pollution index (PI) results show that the main canned tuna fish contaminant is aluminum, then selenium and arsenic, respectively. Only half of the samples did not present elemental contaminant levels. All studied brands of canned tuna presented elemental concentrations that could pose a health risk to human consumption, that could be from CR, HQ, HI, or PI. The contaminant levels are alarming and should raise a red flag for the intake of these products, especially a long-term one. These results urge the authorities to supervise and enforce better practices for this type of food, protecting their population from health hazards.