Nodding syndrome phenotypes.
Nodding syndrome (NS) is a progressive encephalopathy of children and adolescents characterized by seizures, including periodic vertical head nodding. Epidemic NS, which has affected parts of East Africa, appears to have clinical overlap with sub-Saharan Nakalanga syndrome (NLS), a brain disorder associated with pituitary dwarfism that appears to have a patchy distribution across sub-Sahara. Clinical stages of NS include inattention and blank stares, vertical head nodding, convulsive seizures, multiple impairments, and severe cognitive and motorsystem disability, including features suggesting parkinsonism. Head nodding episodes occur in clusters with an electrographic correlate of diffuse high-amplitude slow waves followed by an electrodecremental pattern with superimposed diffuse fast activity. Brain imaging reveals differing degrees of cerebral cortical and cerebellar atrophy. Brains of NS-affected children with mild frontotemporal cortical atrophy display neurofibrillary pathology and dystrophic neurites immunopositive for tau, consistent with a progressive neurodegenerative disorder. The etiology of NS and NLS appears to be dominated by environmental factors, including malnutrition, displacement, and nematode infection, but the specific cause is unknown.


In vitro anthelmintic activity of the essential oils of Zanthoxylum zanthoxyloides and Newbouldia laevis against Strongyloides ratti.
The need for new anthelmintic with no chemical residues is becoming urgent. In a program aiming at the evaluation of plant as sources of new active molecules, the anthelmintic activities of the essential oils (EOs) obtained from either Zanthoxylum zanthoxyloides seeds or Newbouldia laevis leaves were evaluated against Strongyloides ratti by analyzing the results of two in vitro bioassays. These two plants and their tested parts were retained after an ethnopharmacology survey that confirmed their use by small-scale farmers for treatment of small ruminants affected by digestive helminths. The plants were harvested in Benin, and their EO were obtained by hydrodistillation. The EO yield of extraction was 0.65% (w/w) of for Z. zanthoxyloides seeds and 0.05% (w/w) for N. laevis. The chemical compositions of the two EOs were analyzed by gas chromatography coupled with mass spectrometry. The major constituents of the EO from Z. zanthoxyloides consisted of the following compounds: γ-terpinene (18 %), undecane (15 %), valencene (8.3 %), decanal (8.3 %), and 3-carene (6.7 %). In contrast, the major constituents of the EO from N. laevis leaves consisted of the following compounds: β-caryophyllene (36 %) and eugenol (5.8 %). An egg-hatching inhibition (EHI) assay was developed and a larval migration inhibition assay was used on S. ratti to examine the effects of the EOs and to evidence their inhibitory concentrations (IC(50) and IC(90)) values on this nematode. Furthermore, the toxicity of the two EOs on Vero cell line was evaluated. When tested on S. ratti egg hatching, the two EOs resulted in similar IC(50) values (19.5 and 18.2 μg/ml for Z. zanthoxyloides and N. laevis, respectively), which were about sevenfold higher than that of the control (thiabendazole, IC(50) = 2.5 μg/ml). Larval migration was inhibited at similar concentrations for: Z. zanthoxyloides (IC(50) = 46 μg/ml), N. laevis (IC(50) = 51 μg/ml), and the control [levamisole (IC(50) = 36 μg/ml)]. No cytotoxicity was found on Vero cells because both EOs had IC(50) values higher than 50 μg/ml. Therefore, we have concluded that the EOs from two plants, used in folk medicine, may contain compounds with anthelmintic activity and could be used as improved traditional medicines or, at least, as food additives in a combined treatment for the control of helminth infections.


A polyamine-centric, blood-based metabolite panel predictive of poor response to CAR-T cell therapy in large B cell lymphoma.
Anti-CD19 chimeric antigen receptor (CAR) T cell therapy for relapsed or refractory (r/r) large B cell lymphoma (LBCL) results in durable response in only a subset of patients. MYC overexpression in LBCL tumors is associated with poor response to treatment. We tested whether an MYC-driven polyamine signature, as a liquid biopsy, is predictive of response to anti-CD19 CAR-T therapy in patients with r/r LBCL. Elevated plasma acetylated polyamines were associated with non-durable response. Concordantly, increased expression of spermidine synthase, a key enzyme that regulates levels of acetylated spermidine, was prognostic for survival in r/r LBCL. A broad metabolite screen identified additional markers that resulted in a 6-marker panel (6MetP) consisting of acetylspermidine, diacetylspermidine, and lysophospholipids, which was validated in an independent set from another institution as predictive of non-durable response to CAR-T therapy. A polyamine centric metabolomics liquid biopsy panel has predictive value for response to CAR-T therapy in r/r LBCL.


[A procedure for determining the dose distribution behind block shields. II. Calculation of the dose distribution of 60Co radiation fields using a pencil beam model].
A model to calculate dose distribution behind block shielding is represented in a water equivalent medium for 60Co-radiation. The model is based on integration of spread dose distribution of a pencil beam over the total irradiation area. It is suitable to estimate dose distribution for an irregularly shaped irradiation field.


Dynamic models for the study of frailty.
Frailty can be viewed as resulting from the degradation of multiple interacting physiologic systems that are normally responsible for healthy adaptation to the daily demands of life. Mathematical models that can quantify alterations in the dynamics of physiologic systems and their interactions may help characterize the syndrome of frailty and enable investigators to test interventions to prevent its onset. One theoretical mathematical model reported by Varadhan et al. in this issue of the Journal represents one type of regulatory process that may become altered in frail individuals-the stimulus-response mechanism [Varadhan, R., Seplaki, C.S., Xue, Q.L., Bandeen-Roche, K., Fried, L.P. Stimulus-response paradigm for characterizing the loss of resilience in homeostatic regulation associated with frailty. Mech. Ageing Dev., this issue]. This model focuses on the timing of recovery from a single stimulus, rather than the full array of responses that might be altered in a complex dynamical system. Therefore, alternative models are needed to describe the wide variety of behaviors of physiologic systems over time and how they change with the onset of frailty. One such model, based on a simple signaling network composed of a lattice of nodes and the bi-directional connections between them, can reproduce the complex, fractal-like nature of healthy physiological processes. This model can be used to demonstrate how the degradation of signaling pathways within a physiologic system can result in the loss of complex dynamics that characterizes frailty.


Temporal bone and cranial nerve findings in pontine tegmental cap dysplasia.
Pontine tegmental cap dysplasia (PTCD) is a recently described brain malformation associated with multiple cranial neuropathies, most commonly congenital sensorineural hearing loss. The purpose of this study is to systematically characterize the cranial nerve and temporal bone findings in a cohort of children with this rare condition. Sixteen patients with PTCD and diagnostic quality imaging were retrospectively reviewed. All patients had high-resolution MR of the brain and/or internal auditory canals, and seven patients had additional high-resolution CT of the temporal bones. Studies were evaluated by two pediatric neuroradiologists for cranial nerve and temporal bone anomalies. Fifteen of 16 patients (94%) had duplication of one or both internal auditory canals. Of the 24 total duplicated internal auditory canals, all 24 (100%) demonstrated stenosis or atresia of the vestibulocochlear nerve canal, as well as ipsilateral vestibulocochlear nerve aplasia. Of the non-duplicated internal auditory canals, 63% (5/8) were atretic or stenotic. Thirty-eight percent (3/8) were associated with absent vestibulocochlear nerve, and 38% (3/8) demonstrated isolated cochlear nerve aplasia. Twenty-five percent (2/8) demonstrated normal vestibulocochlear nerves, both in the same patient. Fifteen of 16 patients overall (94%) demonstrated bilateral cochlear nerve aplasia. Of the 32 total temporal bones, 4 (13%) demonstrated facial nerve aplasia. Seventy-nine percent (22/28) of facial nerves that were present demonstrated an aberrant origin or course. Patients with PTCD have highly characteristic temporal bone and cranial nerve findings on both CT and MR. Recognition of these findings is important for improved diagnosis of this rare disorder, particularly by CT.


Large fibres in urinary calculi--promoters of stone formation.
Large fibres (phi 10-20 microns, length up to 5,000 microns) are sometimes imbedded in urinary calculi. It may be that these fibres can catch sediment particles and promote stone growth. By scanning electron microscopy the morphology of the fibres was studied as well as the relationship of the fibres with crystalline stone components. The reported findings suggest that the fibres are possibly formed in the tubuli as the result of an hitherto unknown defect.


A standardized extract of Centella asiatica (ECa 233) prevents temporomandibular joint osteoarthritis by modulating the expression of local inflammatory mediators in mice.
To investigate the effect of a standardized extract of Centella asiatica (ECa 233), which has anti-inflammatory properties, on the local expression of the transient receptor potential vanilloid 1 (TRPV1), the acid-sensing ion channel subunit 3 (ASIC3), and the calcitonin gene-related peptide (CGRP) in the temporomandibular joint (TMJ) structure 21 days after injecting the TMJ with complete Freund's adjuvant (CFA). A mouse model was induced by analyzing the CFA-injected TMJ on days 7, 14, and 21. We assessed TMJ histology by the osteoarthritis cartilage grade score. Then, we observed the effect of different ECa 233 concentrations (30, 100, and 300 mg/kg) and of 140 mg/kg ibuprofen doses on TRPV1, ASIC3, and CGRP local expression on day 21. Osteoarthritis cartilage scores were 1.17±0.37 and 3.83±0.68 on days 14 and 21, respectively, in the CFA group (n=5). On day 21, TRPV1, ASIC3, and CGRP expression significantly increased in the CFA group. In the ibuprofen-treated group, TRPV1 expression significantly decreased, but ASIC3 and CGRP showed no significant difference. All ECa 233 doses reduced TRPV1 expression, but the 100 mg/kg ECa 233 dose significantly decreased ASIC3 expression. TRPV1, ASIC3, and CGRP expression increased in mice with TMJ-OA on day 21. All ECa 233 and ibuprofen doses inhibited pathogenesis by modulating the local expression of TRPV1 and ASIC3. Therefore, ECa 233 was more effective than ibuprofen.


Identification of 7-(4'-Cyanophenyl)indoline-1-benzenesulfonamide as a mitotic inhibitor to induce apoptotic cell death and inhibit autophagy in human colorectal cancer cells.
Targeting cellular mitosis in tumor cells is an attractive cancer treatment strategy. Here, we report that B220, a synthetic benzenesulfonamide compound, could represent a new mitotic inhibitor for the treatment of colorectal cancer. We examined the action mechanism of B220 in the colorectal carcinoma HCT116 cell line, and found that treatment of cells with B220 caused cells to accumulate in G2/M phase, with a concomitant induction of the mitotic phase markers, MPM2 and cyclin B1. After 48 h of B220 treatment, cells underwent apoptotic cell death via caspase-3 activation and poly(ADP ribose) polymerase (PARP) cleavage. In addition, B220 inhibits autophagy by blocking conversion of microtubule-associated protein 1 light chain 3 (LC3-I) to LC3-II and inhibiting autophagic flux. Notably, blockade of autophagy by pharmacological inhibition or using an Atg5-targeting shRNA reduced B220-induced cytotoxicity. Conversely, the autophagy inducer NVP-BEZ235 shows a synergistic interaction with B220 in HCT116 cells, indicating autophagy was required for the observed cell death. In summary, these results indicate B220 combined with the induction of autophagy using the dual PI3K/mTOR inhibitor, NVP-BEZ235, might be an attractive strategy for cancer therapy, and provides a framework for further development of B220 as a new therapeutic agent for colon cancer treatment.


X-gal inhibits the swarming of Vibrio species.
The expressional levels of genes in swarmer cells can be determined by a simple method using X-gal-containing semisolid agars and lacZ-fusion transcription reporter strains of the genes concerned. However, X-gal alone inhibited the swarming of Vibrio, regardless of their ability to digest X-gal. Moreover, X-gal inhibited the growth of V. vulnificus containing functional lacZ. These effects of X-gal itself should be carefully considered when trying to determine the expression levels of genes in swarming cells using X-gal-containing semisolid agar.


Colocalization of NGF and TSH-like immunoreactivity in cultures of adult rat anterior pituitary cells.
Nerve growth factor (NGF) has been well-characterized with respect to its role as a trophic agent for various peripheral nervous system (PNS) and central nervous system (CNS) neuronal populations. Recent evidence indicates that NGF may also play a functional role in endocrine systems, although investigations in this field are only beginning to define sites of action and molecular mechanisms involved in NGF-endocrine interactions. A potential site for such an interaction to occur is within the pituitary. Previous investigations have demonstrated the presence of NGF and NGF receptors in the pituitary and our group has recently reported the presence of NGF-like immunoreactivity exclusively within the thyrotrophic cells of the anterior pituitary of the adult rat. Since many questions regarding how NGF interacts in the anterior pituitary will be more efficiently addressed using an in vitro system, it was necessary to first determine if cultured adult anterior pituitary cells retain the NGF-like staining and unique association of NGF with thyroid-stimulating hormone-producing cells seen in vivo. Results of the present investigation confirm that cultured anterior pituitary cells retain the characteristics previously observed in vivo and further demonstrate the stability of these cells and their specific NGF and pituitary hormone contents in culture for as long as 6 days.


Comparison of monometal and multimetal adsorption in Mississippi River alluvial wetland sediment: batch and column experiments.
Monometal and multimetal adsorption of selected heavy metals in a sediment from a coastal Louisiana forested swamp used for wastewater treatment was studied. Results from the batch experiments show that the maximum adsorption capacities of the metals by the sediment were in the order of Pb>>Hg>Cr>CdCuZn>>As based on monometal adsorption isotherm, and Hg>Cr>CuCd approximately Pb>>As approximately Zn based on multimetal adsorption isotherm, respectively. Batch experimental data best fit the Langmuir model rather than the Freundlich isotherms. In the column experiments, the maximum adsorption capacities of the metals were in the order of Pb>>Hg>Cr>Cd>Cu>Zn>>As in monometal conditions, and Hg>>Cr>>Pb>CuZn approximately Cd>As in multimetal conditions. The metals became more mobile in multimetal than in monometal conditions. Results from both the batch and column experiments show that competitive adsorption among metals increases the mobility of these metals. Particularly, in this study, Pb in multimetal conditions lost it adsorption capacity most significantly. In both monometal and multimetal conditions, the maximum adsorption capacity of the metals in the column experiments was higher than that in the batch experiment indicating other metal retention mechanisms rather than adsorption may be involved. Therefore, both column and batch experiments are needed for estimating retention capacities and removal efficiencies of metals in sediments.


Efficacy of intravenous vancomycin in the treatment of gram-positive peritonitis in long-term peritoneal dialysis.
Peritonitis is the major complication of long-term peritoneal dialysis. Gram-positive bacteria are responsible for two thirds of the total number of peritonitis episodes. Conventional therapy consists of daily administration of antibiotics, either parenterally or intraperitoneally. Vancomycin, an antibiotic with a prolonged half-life in renal failure, has a wide spectrum of activity against gram-positive bacteria and diffuses readily across the peritoneal membrane. In the present study, 82 percent of gram-positive peritonitis episodes were cured following the intravenous administration of vancomycin at weekly intervals. This cure rate compares favorably with that obtained following conventional therapy of peritonitis. It is concluded that intravenous vancomycin is an effective treatment for gram-positive peritonitis in patients undergoing long-term peritoneal dialysis. This form of therapy is convenient, reduces hospitalization, minimizes cost, and avoids possible contamination of the peritoneal dialysate used during the intraperitoneal administration of antibiotics.


Preclinical profiling and safety studies of ABT-769: a compound with potential for broad-spectrum antiepileptic activity.
The objective of this study was to characterize the antiseizure and safety profiles of ABT-769 [(R)-N-(2 amino-2-oxoethyl)spiro[2,5]octane-1-carboxamide]. ABT-769 was tested for protection against maximal electroshock and pentylenetetrazol-induced seizures in the mouse and for suppression of electrically kindled amygdala seizures and spontaneous absence-like seizures in the rat. The central nervous system safety profile was evaluated by using tests of motor coordination and inhibitory avoidance. The potential for liver toxicity was assessed in vitro by using a mitochondrial fatty acid beta-oxidation assay. Teratogenic potential was assessed in the mouse. ABT-769 blocked maximal electroshock, subcutaneous pentylenetetrazol and intravenous pentylenetetrazol-induced seizures with median effective dose (ED50) values of 0.25, 0.38, and 0.11 mmol/kg, p.o., respectively. No tolerance was evident in the intravenous pentylenetetrazol test after twice-daily dosing of ABT-769 (0.3 mmol/kg, p.o.) for 4 days. ABT-769 blocked absence-like spike-wave discharge (ED50, 0.15 mmol/kg, p.o.) and shortened the cortical and amygdala afterdischarge duration of kindled seizures (1 and 3 mmol/kg, p.o.). The protective indices (ED50 rotorod impairment/ED50 seizure protection) were 4.8, 3.2, and 10.9 in the maximal electroshock, subcutaneous pentylenetetrazol and intravenous pentylenetetrazol seizure tests, respectively. ABT-769 did not affect inhibitory avoidance performance (0.1-1 mmol/kg, p.o.). ABT-769 did not affect mitochondrial fatty acid beta-oxidation or induce neural tube defects. ABT-769 is an efficacious antiseizure agent in animal models of convulsive and nonconvulsive epilepsy and has a favorable safety profile. ABT-769 has a broad-spectrum profile like that of valproic acid. Its profile is clearly different from those of carbamazepine, phenytoin, lamotrigine, topiramate, vigabatrin, and tiagabine.


Tubastatin A suppresses renal fibrosis via regulation of epigenetic histone modification and Smad3-dependent fibrotic genes.
Inflammation and fibrosis are implicated in the pathogenesis of hypertensive kidney damage. We previously demonstrated that a nonspecific histone deacetylase (HDAC) inhibitor attenuates cardiac fibrosis in deoxycorticosterone acetate-salt hypertensive rats, which induces HDAC6 protein and enzymatic activity. However, the HDAC inhibitor's effect and mechanism have not yet been demonstrated. We sought to determine whether an HDAC6-selective inhibitor could treat hypertension and kidney damage in angiotensin II-infused mice. Hypertension was induced by infusion of ANG in mice. Tubastatin A, an HDAC6 selective inhibitor, did not regulate blood pressure. Hypertensive stimuli enhanced the expression of HDAC6 in vivo and in vitro. We showed that the inhibition of HDAC6 prevents fibrosis and inflammation as determined by quantitative real-time PCR, western blot, and immunohistochemistry. Small interfering RNA (siRNA) against HDAC6 or Smad3 attenuated hypertensive stimuli-induced fibrosis and inflammation, whereas Smad2 siRNA failed to inhibit fibrosis. Interestingly, the combination of the HDAC6 inhibitor and Smad3 knockdown synergistically blocked transforming growth factor β (TGF-β) or ANG-induced fibrosis. We also demonstrated for the first time, to our knowledge, that acetylation of collagen type I can be regulated by HDAC6/p300 acetyltransferase. The chromatin immunoprecipitation assay revealed that the HDAC6 inhibitor suppressed TGF-β-induced acetylated histone H4 or phospho-Smad2/3 to Smad3 binding elements in the fibrosis-associated gene promoters including collagen type I. These results suggest that HDAC6 may be a valuable therapeutic target for the treatment of hypertension-induced kidney fibrosis and inflammation.


Efficient purification of tetracycline wastewater by activated persulfate with heterogeneous Co-V bimetallic oxides.
The persistence and wide dispersion of antibiotics have a severe impact on the ecological environment. Developing an effective method with universal applicability to remove pollutants is pretty necessary. Herein, a bimetallic oxides (Co3V2O8) heterogeneous material was successfully prepared and used to activate the persulfate (PS) for purification of tetracycline (TC) wastewater. By exploring the reaction conditions and influencing factors, the removal rate of 50 mg⋅L-1 TC reached 87.1% by Co3V2O8/PS system, and the reaction rate constant was up to 0.0271 min-1. As a highly efficient catalyst for the activation of PS, Co3V2O8/PS system produces radicals of SO4•-, •OH, •O2- and 1O2 in the reaction process due to the Co(II) and V(IV) exchange electrons with S2O82- and O2. Simultaneously, the internal electron exchange occurs between Co(II)/Co(III) and V(IV)/V(V), which stabilizes the content of Co(II) and V(IV). This work provides a novel activator for PS activation to degrade contaminants and contributes to a better understanding of the PS activation mechanism by transition compound.


Menstrual and Reproductive Factors and Risk of Breast Cancer in Iranian Female Population: A Systematic Review and Meta-Analysis.
Breast cancer (BC) is the most frequent cancer in Iranian females. Due to the changes in lifestyle and reproductive risk factors, the BC incidence rate has been rapidly increasing. Knowing risk factors of BC could significantly contribute to improve preventive behaviors. To investigate the relationship between menstrual and reproductive factors and BC in Iranian female population. Web of Science, PubMed, Scopus, and SID as well as references of included studies were searched. Among relevant published observational studies, 27 studies met the inclusion criteria. Pooled risk estimates for the risk factors were determined using random-effects models due to the presence of substantial heterogeneity (P < 0.05). All of the selected studies had case-control design. There was a positive relationship between maternal age at first pregnancy and risk of BC (OR = 1.79 95% CI: 1.36-2.35). Also, menopausal status was associated with higher risk of BC (OR = 1.60 95% CI: 1.18-2.17), whereas, there was no association between menarche age and increased risk of BC (OR = 0.55 95% CI: 0.29-1.03). History of abortion (OR = 1.21 95% CI: 0.97-1.5), nulliparity (OR = 1.43 95% CI: 0.89-2.31), and breastfeeding history (OR = 0.68 95% CI: 0.42-1.09) were not associated with BC risk. Our findings suggest that age at the first pregnancy and menopausal status were significantly associated with BC risk among Iranian women, whereas menarche age, nulliparity, and history of breastfeeding were not. In regard to the history of abortion, our findings revealed no association with BC, but in high-quality studies, this relationship was significant.


[Multidisciplinary consultation meetings: decision-making in palliative chemotherapy].
Multidisciplinary consultation meetings provide an opportunity for specialists from different disciplines to engage in formal discussions over diagnostic and therapeutic strategies in oncology. In complex clinical situations, specialists discuss medical decisions collectively, particularly in cases involving palliative chemotherapy. The purpose of this study was to identify the factors considered in multidisciplinary consultation meetings in deciding whether palliative chemotherapy is needed. A study was conducted over a three-month period in an adult hematology department in order to identify the criteria used in weekly multidisciplinary consultation meetings to determine whether palliative chemotherapy is required. The study only included patients who were confirmed to be in the palliative phase by all the doctors present at the multidisciplinary consultation meetings. The criteria cover 5 areas related to patient's characteristics, patients'environment, the disease, scientific data and the objectives of palliative chemotherapy. The criteria considered in 100% of cases were related to the disease, the expected benefits of chemotherapy with palliative intent and patients' characteristics. The least important criteria were related to the patients' environment. Scientific data were not discussed during the multidisciplinary consultation meetings. The results show that the criteria used to determine whether chemotherapy with palliative intent is required are essentially of a medical nature. However, in palliative situations, factors related to patients' environment must be taken into account. In order to meet this requirement, it may be necessary to increase the participation of paramedical professionals and palliative care teams in multidisciplinary consultation meetings and to promote dialogue and collaboration with doctors and coordinating nurses.


Incidence and clinical significance of late right heart failure during continuous-flow left ventricular assist device support.
Right heart failure (RHF) is an unresolved issue during continuous-flow left ventricular assist device (LVAD) support. Little is known about the incidence and clinical significance of late RHF during LVAD support. Between May 2004 and December 2013, 336 patients underwent continuous-flow LVAD implantation. Of these, 293 patients (87%) discharged with isolated LVAD support were included in this study. Late RHF was defined as HF requiring re-admission and medical or surgical intervention after initial surgery. Late RHF occurred in 33 patients (11%) at a median of 99 days after discharge (range 19 to 1,357 days). Freedom from late RHF rates were 87%, 84% and 79% at 1, 2 and 3 years, respectively. RHF recurred in 15 patients. Three patients required right ventricular assist device insertion. Univariable Cox proportional hazards regression model showed diabetes mellitus (HR 2.05, 95% CI 1.03 to 4.06, p = 0.04), body mass index >29 (HR 2.47, 95% CI 1.24 to 4.94, p = 0.01) and blood urea nitrogen level >41 mg/dl (HR 2.19; 95% CI 1.10 to 4.36; p = 0.025) as significant predictors for late RHF. Estimated on-device survival rates at 2 years were 73% in the RHF group and 82% in the non-RHF group (p = 0.20). However, overall survival at 2 years was significantly worse in patients who developed late RHF (60% vs 85%, p = 0.016). This reduction was mostly attributed to worse overall outcomes in the bridge-to-transplant (BTT) population. Late RHF is common after continuous-flow LVAD implantation, but does not affect survival during LVAD support. However, it is associated with worse overall outcomes in the BTT population.


A novel zinc-binding motif revealed by solution structures of DNA-binding domains of Arabidopsis SBP-family transcription factors.
SQUAMOSA promoter binding proteins (SBPs) form a major family of plant-specific transcription factors related to flower development. Although SBPs are heterogeneous in primary structure, they share a highly conserved DNA-binding domain (DBD) that has been suggested to be zinc binding. Here we report the NMR solution structures of DBDs of two SBPs of Arabidopsis thaliana, SPL4 and SPL7. The two share essentially the same structural features. Each structure contains two zinc-binding sites consisting of eight Cys or His residues in a Cys3HisCys2HisCys or Cys6HisCys sequence motif in which the first four residues coordinate to one zinc and the last four coordinate to the other. These structures are dissimilar to other known zinc-binding structures, and thus represent a novel type of zinc-binding motif. The electrostatic profile on the surface suggested that a continuous region, including all the conserved basic residues, is involved in the DNA binding, the mode of which is likely to be novel as well.


The first complete genomic characterization of an Amur virus isolate from China.
Amur virus (AMRV) is a member of the genus Hantavirus in the family Bunyaviridae. In this study, we determined for the first time the complete genome sequence of the AMRV H8205 strain, which was isolated from a patient with hemorrhagic fever with renal syndrome (HFRS) in China. The complete nucleotide sequence of the S segment of AMRV H8205 is 1699 nt long, with a 5' noncoding region (5'NC) of 36 nt, followed by a coding sequence of 1290 nt and a 3'NC of 373 nt. The complete sequence of the M segment is 3615 nt long, with a 5'NC of 40 nt, followed by a coding sequence of 3408 nt and a 3'NC of 167 nt. The complete sequence of the L segment is 6536 nt long, with a 5'NC of 37 nt, followed by a coding sequence of 6453 nt and a 3'NC of 40 nt. The major open reading frame (ORF) of each of the three segments (S, nt 37-1326; M, nt 41-3445; L, nt 38-6490) has a coding capacity of 430 aa, 1135 aa, 2151 aa, respectively. Phylogenetic analysis of the nucleotide sequences using the NJ method indicated that H8205 virus, together with the Amur strains isolated from Far-Eastern Russia and Korea, forms a well-supported lineage. Our results will provide insights into the genetic diversity of hantaviruses (HNTV).


Effects of thyroid hormones on liver binding sites for human growth hormone, as studied in the rat.
Several weeks after thyroidectomy (T), female rats stopped growing, and their pituitary GH content had decreased to less than 2--3% of the values found for age-matched controls (C). The liver membranes of such animals were explored with human GH (hGH). It was found that in the severely hypothyroid T rat, the number, but not the affinity, of the lactogenic binding sites was markedly reduced. Treatment of these rats for 3 weeks with 1.75 micrograms or T4 or 0.5 micrograms T3/100 g body weight/day restored growth, increased pituitary GH content and restored the number of liver lactogenic binding sites were practically to normal. As regards the lactogenic binding sites, similar results were obtained when the severely hypothyroid rats were treated with a much lower T4 dose (0.2 microgram/100 g/day): this dose was clearly growth promoting, and restored to normal both the low circulating GH levels and the pituitary PRL content of the severely hypothyroid rat. The changes in plasma PRL were not clear. The lactogenic binding sites on liver membranes from rats which were both thyroidectomized and hypophysectomized were decreased in number. Treatment with 0.5 microgram T3/100 g/day for 30 days (but not for 12 days) resulted in an increase in the number of lactogenic binding sites, though it did not affect growth or the undetectable plasma GH levels. The effect on the lactogenic binding sites was less marked than in T rats with an intact pituitary. It would appear that minute amounts of thyroid hormones are needed for maintenance of liver lactogenic binding sites; it is possible that this not only occurs through mechanism(s) which involve the pituitary, but also through others which do not. The possible role of these receptors in growth processes is not yet clearly understood.


Cancer stem cells revisited.
The cancer stem cell (CSC) concept was proposed four decades ago, and states that tumor growth, analogous to the renewal of healthy tissues, is fueled by small numbers of dedicated stem cells. It has gradually become clear that many tumors harbor CSCs in dedicated niches, and yet their identification and eradication has not been as obvious as was initially hoped. Recently developed lineage-tracing and cell-ablation strategies have provided insights into CSC plasticity, quiescence, renewal, and therapeutic response. Here we discuss new developments in the CSC field in relationship to changing insights into how normal stem cells maintain healthy tissues. Expectations in the field have become more realistic, and now, the first successes of therapies based on the CSC concept are emerging.


Gas5 Exerts Tumor-suppressive Functions in Human Glioma Cells by Targeting miR-222.
Aberrant expression of noncoding RNAs in glioma cells, including long noncoding RNAs (lncRNAs) and microRNAs, may participate in the progression of glioma. Encoded by Growth Arrest-Specific 5 (GAS5) gene, lncRNA Gas5 was reported to be a negative regulator for survival and proliferation of several cancers. Here, Gas5 is found to be downregulated in glioma specimens and U87 and U251 glioma cell lines. We showed that the introduction of Gas5 by plasmid transfection increased the expression of tumor suppressor Bcl-2-modifying factor (bmf) and Plexin C1 via directly targeting and reducing the expression of miR-222. Downregulated expression of miR-222 inhibited U87 and U251 cell proliferation and promoted the apoptosis by upregulating bmf. As downstream signaling molecules of bmf, Bcl-2 and Bax were involved in the process. Meanwhile, knockdown of miR-222 attenuated U87 and U251 cell migration and invasion by upregulating Plexin C1, and cofilin was a crucial regulator targeted by Plexin C1. Gas5 combined with the knockdown of miR-222 resulted in the smallest tumor volumes and the longest survivals of nude mice in vivo. In summary, we show that Gas5 suppresses tumor malignancy by downregulating miR-222, which may serve as a promising therapy for glioma.


Washington Poison Center as perceived by our state's emergency physicians.
In 1986, we conducted the first survey of Washington emergency physicians about their perceptions of the performance of the Washington Poison Center (WPC); the results were summarized and published. The exercise was repeated in 1993, 1997 and in 2005. The original conventional 2-page survey was updated and distributed with an explanatory letter and return envelope to a mailing list obtained from the state chapter of the American College of Emergency Physicians. Responses were tallied, summarized and compared to prior surveys. For 2005, 612 surveys were distributed; 221 were returned. The average respondent had been in practice for 14 years, with more than 50% functioning in "urban" communities. They reported calling the WPC an average of 19 times per year, and particularly valued being able to consult with a board-certified medical toxicologist in a virtually "STAT'' manner. In more than 80% of calls, the information played a positive role in management of the patient. Washington's emergency physicians continue to highly value the WPC's services, with increasing numbers in favor of governmental support of the operation.


The use of radioactive oxygen to study muscle function in peripheral vascular disease.
We have use 15O to study the relationship between blood flow and oxygen utilization in the limbs of patients with peripheral vascular diseases. This technique is noninvasive and provides a useful method of studying the function of ischemic limbs.


Rural patients highly satisfied with gynaecological oncology care via telehealth.
Introduction of telehealth for gynaecological oncology consultations aims to improve access to specialised care for rural and remote Queensland women with gynaecological malignancies. This survey examines patient satisfaction with gynaecological oncology consultations via telehealth after introduction of the service in Far North Queensland in 2017. Patients who accessed the gynaecological oncology telehealth service at Cairns Hospital from January 2019 to June 2020 were invited to participate in the study. Demographic details and results of a satisfaction survey were investigated. The questionnaire included 16 statements measured on a five-point Likert scale and three open-ended questions, which were coded into related responses and predominant themes developed. Fifty-three patients completed the study. The mean satisfaction score across all questions was 90.5% (standard deviation 8.7%). The lowest overall patient score was 77.5% and the highest was 100%. Themes emerging from the open questions were emotions experienced by women, communication, relationship building and acceptability of the service. Patients were highly satisfied with the telehealth service. Our findings encourage further development and research into telehealth care models for surgical disciplines such as gynaecological oncology.


The use of a low dose hydrocortisone to prevent pulmonary embolism in patients with multiple trauma.
Venous thromboembolism events are common in trauma patients. Immediate acute inflammation following injury triggers coagulation cascade and may increase the risk of pulmonary embolism (PE) in this population. We aimed to evaluate whether early low-dose steroids prevent symptomatic PE onset in multiple trauma patients. The medical surgical intensive care unit of Habib Bourguiba University Hospital (Sfax--Tunisia). Comparative study of two cohorts: a retrospective cohort of patients who didn't receive early low-dose steroids (steroid (-) group) and a prospective cohort of patients who received hydrocortisone with a dose of 100 mg/8 h for a scheduled period of 7 days (steroid (+) group). All adult patients admitted in our intensive care unit (ICU) for multiple trauma with predicted duration of mechanical ventilation over 48 h were included. Evaluation of the impact of low-dose steroids on the incidence of symptomatic PE. We included 175 patients: 92 in the steroids (-) group and 83 in the steroids (+) group. PE was diagnosed in 15 patients (8.5 %). The incidence of PE was significantly lower in steroid (+) group (3.6 vs 13 %; p = 0.013). In multivariate analysis, independent factors predicting PE onset were meningeal hemorrhage [OR = 14.7; 95 % CI (2.2-96.3); p = 0.013] and pelvic ring trauma [OR = 8; 95 % CI (1.8-36.4); p = 0.007] whereas low-dose steroids were significantly associated with a protective effect [OR = 0.2; 95 % CI (0.05-0.77); p = 0.019]. There was no significant difference between steroids (+) and steroids (-) groups neither in terms of mean ICU length of stay (LOS) (respectively 11 ± 9.7 and 12.3 ± 10.7 days; p = 0.372) nor in terms of ICU mortality (respectively 29.3 and 24.1 %; p = 0.434). Steroids are effective in reducing the incidence of PE in multiple trauma patients. However, no significant benefice was found on ICU mortality.


Inverse association between statin use and head and neck cancer: Population-based case-control study in Han population.
This case-control study aimed to find the relationship between prior statin use and head and neck cancer occurrence using a large population-based database. This study used claims data from the Taiwan Longitudinal Health Insurance Database. We included 5515 patients with head and neck cancer as cases and 5515 propensity score-matched patients without head and neck cancer as controls. Conditional logistic regressions were performed to investigate the relationship between head and neck cancer and prior statin exposure. Of the 11 030 total sampled patients, 16.95% had previously received prescriptions for statins. In addition, statin exposure was found in 15.99% of cases and 17.91% of controls. The logistic regression also revealed that the adjusted odds ratio of prior statin exposure for cases was 0.86 (95% confidence interval: 0.77-0.95) compared to propensity score-matched controls. This study found an inverse association between statin usage and head and neck cancer occurrence.


Thymosin beta4 is released from human blood platelets and attached by factor XIIIa (transglutaminase) to fibrin and collagen.
The beta-thymosins constitute a family of highly conserved and extremely water-soluble 5 kDa polypeptides. Thymosin beta4 is the most abundant member; it is expressed in most cell types and is regarded as the main intracellular G-actin sequestering peptide. There is increasing evidence for extracellular functions of thymosin beta4. For example, thymosin beta4 increases the rate of attachment and spreading of endothelial cells on matrix components and stimulates the migration of human umbilical vein endothelial cells. Here we show that thymosin beta4 can be cross-linked to proteins such as fibrin and collagen by tissue transglutaminase. Thymosin beta4 is not cross-linked to many other proteins and its cross-linking to fibrin is competed by another family member, thymosin beta10. After activation of human platelets with thrombin, thymosin beta4 is released and cross-linked to fibrin in a time- and calcium-dependent manner. We suggest that thymosin beta4 cross-linking is mediated by factor XIIIa, a transglutaminase that is coreleased from stimulated platelets. This provides a mechanism to increase the local concentration of thymosin beta4 near sites of clots and tissue damage, where it may contribute to wound healing, angiogenesis and inflammatory responses.


Active versus receptive group music therapy for major depressive disorder-A pilot study.
To compare the effects of 1) active group music therapy and 2) receptive group music therapy to group counseling in treatment of major depressive disorder (MDD). On top of standard care, 14 MDD outpatients were randomly assigned to receive 1) active group music therapy (n=5), 2) receptive group music therapy (n=5), or 3) group counseling (n=4). There were 12 one-hour weekly group sessions in each arm. Participants were assessed at baseline, 1 month (after 4 sessions), 3 months (end of interventions), and 6 months. Primary outcomes were depressive scores measured by Montgomery-Åsberg Depression Rating Scale (MADRS) Thai version. Secondary outcomes were self-rated depression score and quality of life. At 1 month, 3 months, and 6 months, both therapy groups showed statistically non-significant reduction in MADRS Thai scores when compared with the control group (group counseling). The reduction was slightly greater in the active group than the receptive group. Although there were trend toward better outcomes on self-report depression and quality of life, the differences were not statistically significant. Group music therapy, either active or receptive, is an interesting adjunctive treatment option for outpatients with MDD. The receptive group may reach peak therapeutic effect faster, but the active group may have higher peak effect. Group music therapy deserves further comprehensive studies.


Infrared thermal imaging-based research on the intermediate structures of the lung and large intestine exterior-interior relationship in asthma patients.
By observing body surface temperature variation of the intermediate structures of the Lung (Fei) and Large Intestine (Dachang) exterior-interior relationship in asthmatic patients, to investigate the pathological response on the pathway of channels and to substantiate the objective existence of the intermediary structures. The study included 60 subjects meeting the bronchial asthma inclusion criteria (experimental group) and 60 healthy subjects (normal control group). ATIR-M301 infrared thermal imaging device was used for detecting body surface temperature of the subjects and collecting the infrared thermal images. The temperature values of the intermediate structures of Lung and Large Intestine exterior-interior relationship [throat, Quepen, elbow, nose, Lieque (LU 7), Pianli (LI 6)], control areas (0.2 cm lateral to the above structures) and Yintang (EX-HN 3) were measured on the infrared thermal image by infrared imaging system. Then, the above temperature values were compared and analyzed within and between two groups. There were insignificant differences between the temperature on the left and right sides of the intermediate structures (Quepen, elbow, LU 7, LI 6) in normal control group (P>0.05). Except for that of Quepen, there were insignifificant differences between the temperature of the intermediate structures and their corresponding control areas in normal control group (P>0.05). In the experimental group, the temperature on the left and right sides of the intermediate structures (Quepen, elbow, LU 7, LI 6) showed statistically signifificant differences (P<0.05 or P<0.01); the temperature difference between intermediate structure (throat, Quepen, elbow, nose, LI 6) and their respective control areas were also significant (P<0.05 or P<0.01). The temperature of the intermediate structures (throat, Quepen, elbow, LU7, LI 6) between the experimental group and normal control group showed signifificant differences (P<0.05 or P<0.01). This study is an initial step to validate the objective existence of Lung and Large Intestine exterior-interior relationship intermediate structures, as described in the Chinese classical medical literatures, through the functional imaging angle. The intermediate structures are the pathological reaction areas of the bronchial asthmatic patients.


Role of endocannabinoids in the progression of diabetic retinopathy.
In the past decades, the role of numerous factors in the pathophysiology of diabetic retinopathy has been explored, following which marked progress has been made in developing several novel therapeutic options, such as anti-vascular endothelial growth factor, anti-tumor necrosis factor-alpha and various other anti-inflammatory and anti-angiogenic agents, for the treatment of diabetic retinopathy. However, the involvement of endocannabinoid system in its pathogenesis has not been much explored. This review aims at unveiling every aspect of association of the endocannabinoid system and its interactions with various physiological and pathological pathways to induce disease progression. The various alterations induced by endocannabinoids, such as anandamide and 2-arachidonylglycerol, in retina during hyperglycaemia clearly demonstrate and verify their involvement in aggravating the pathological conditions, hence leading to the progression of diabetic retinopathy. Exploring this involvement furthermore, in greater depths, might be beneficial in acknowledging and understanding the hidden aspects of the pathogenesis of this complication even better and might provide a therapeutically beneficial alternative target to combat and restrict its progression amongst diabetic patients.


Care management and 90-day post discharge mortality in patients hospitalized for myocardial infarction and COVID-19: A French nationwide observational study.
Concomitant or cured coronavirus disease 2019 (COVID-19) in patients with myocardial infarction (MI) may lead to difficulties in acute care management and impair prognosis. To describe and compare the characteristics, care management and 90-day post discharge outcomes of patients hospitalized for MI who did not have COVID-19 with those of patients with concomitant or previous hospital-diagnosed COVID-19. This population-based French study included all patients hospitalized for MI in France (30 December 2019 to 04 October 2020) from the French National Health Data System. Outcomes were described for each COVID-19 group and compared using adjusted logistic regression analysis. Among 55,524 patients hospitalized for MI, 135 had previous hospital-diagnosed COVID-19 and 329 had concomitant COVID-19. Patients with previous hospital-diagnosed COVID-19 had more personal history of cardiovascular diseases than those without concomitant/previous confirmed COVID-19. In-hospital and 90-day post discharge mortality rates of patients with previous COVID-19 were 8.1% and 4.0%, respectively, compared with 3.5% and 3.0% in patients without concomitant/previous confirmed COVID-19 (odds ratio [OR]adjin-hospital 1.83, 95% confidence interval [CI] 0.97-3.46; ORadjpostdischarge 0.77, 95% CI 0.28-2.13). Patients with concomitant COVID-19 had more personal history of cardiovascular diseases, but also a poorer prognosis than their no concomitant/no previous confirmed COVID-19 counterparts; they presented excess cardiac complications during hospitalization (ORadj 1.62, 95% CI 1.29-2.04), in-hospital mortality (ORadj 3.31, 95% CI 2.32-4.72) and 90-day post discharge mortality (ORadj 2.09, 95% CI 1.24-3.51). In-hospital and 90-day post discharge mortality of patients hospitalized for MI who had previous hospital-diagnosed COVID-19 did not seem to differ from those hospitalized for MI alone. Conversely, concomitant COVID-19 and MI carried a poorer prognosis extending beyond the hospital stay. Special attention should be given to patients with simultaneous COVID-19 and MI, in terms of acute care and secondary prevention.


Hepatitis E infection with a benign course during vedolizumab treatment for Crohn's disease: A case report.
We present a 49 year old female patient with Crohn's disease (CD) in remission on vedolizumab therapy who experienced a symptomatic, though benign, course of acute hepatitis E. Routine blood tests showed substantial elevation of liver enzymes and polymerase chain reaction (PCR) testing confirmed hepatitis E virus (HEV) infection. Vedolizumab therapy was paused, liver enzymes improved three weeks after infection and normalized after six months. The patient recovered completely from mild symptoms. This case shows that hepatitis E is a potential cause of acute hepatitis during vedolizumab therapy, and in this case the infection has run a benign course.


Comparison of keratometric measurements obtained by the Verion Image Guided System with optical biometry and auto-keratorefractometer.
The aim of this study was to compare the keratometric measurements of Verion Image Guided System with an optical biometer (Zeiss IOLMaster 500, Carl Zeiss Meditec, Jena, Germany) and an automated keratorefractometer (AKR) (Topcon KR-8900, Topcon, Japan). In this prospective clinical trial, the right eyes of 52 patients with cataract were examined (mean age 62.25 ± 12.16 years). The measurements were taken by the three systems in a random order. Keratometric data, magnitude of astigmatism, and astigmatic axis measurements from all three instruments were compared. The results were evaluated using, intraclass correlation coefficients (ICC), Bland-Altman plots, and paired samples t tests. The mean flat/steep K of Verion, IOLMaster, and AKR were 43.22 ± 1.38D/44.23 ± 1.46D, 43.07 ± 1.26D/44.05 ± 1.34D, and 43.07 ± 1.31D/43.89 ± 1.42D, respectively. Flat K readings of Verion were higher than IOLMaster and AKR (p < 0.05 for both). Steep K readings were different for all three (p < 0.05). The magnitude of astigmatism by Verion and IOLMaster were 0.98 ± 0.65D and 0.98 ± 0.59D (p = 0.88). The mean astigmatism measured by the AKR was 0.82 ± 0.62D, less than the other two instruments (p < 0.001). Astigmatic axis measurements of Verion and AKR differed <10° in 38, between 10° and 20° in 5, and >20° in 9 eyes; the same difference was 30, 11, and 11 eyes, respectively, between Verion and IOLMaster. Although, keratometric and astigmatic results obtained from Verion were not completely interchangeable with IOLMaster and AKR, especially the agreement between Verion and IOLMaster was excellent with ICCs close to one. However, there were pronounced astigmatic axis measurement differences between three instruments.


Binding of human IgA1 and IgA1 fragments to jacalin.
Interaction of jacalin, an N-terminal galactose specific lectin, with human IgA1 and IgA1 fragments was investigated. IgA1 and all galactose containing fragments bound to jacalin-Sepharose, including Fab fragments containing only the galNac linked to serine-224 and Fc fragments containing four gal-galNac sequences. These data indicate that both the galNac and gal-galNac sequences can interact with jacalin. Jacalin precipitated IgA1 and the fragments F(abc)2, F(ab')2 and Fc in agar gel and from solutions. It also precipitated Fab' fragments in agar gel. Jacalin did not precipitate Fab fragments significantly. This suggests that, except for the single binding site on the Fab fragments containing the galNac linked to serine-224, jacalin itself also has a limited number of sites to interact with N-terminal galactose residues. ELISA studies revealed that intact IgA1 had a lower jacalin binding capacity than F(abc)2 fragments which lack CH3 domains, than F(ab')2 which lack the CH2 and CH3 domains, and than Fc fragments containing four gal-galNac sequences. This led to the conclusion that part of the galNac or gal-galNac sequences in intact IgA1 molecules are inaccessible to interaction with jacalin. Cleaving the C-terminal domains off may have induced a reorientation of the hinge region structure, including the orientation of the carbohydrate units.


Molecular basis of Mg2+ permeation through the human mitochondrial Mrs2 channel.
Mitochondrial RNA splicing 2 (Mrs2), a eukaryotic CorA ortholog, enables Mg2+ to permeate the inner mitochondrial membrane and plays an important role in mitochondrial metabolic function. However, the mechanism by which Mrs2 permeates Mg2+ remains unclear. Here, we report four cryo-electron microscopy (cryo-EM) reconstructions of Homo sapiens Mrs2 (hMrs2) under various conditions. All of these hMrs2 structures form symmetrical pentamers with very similar pentamer and protomer conformations. A special structural feature of Cl--bound R-ring, which consists of five Arg332 residues, was found in the hMrs2 structure. Molecular dynamics simulations and mitochondrial Mg2+ uptake assays show that the R-ring may function as a charge repulsion barrier, and Cl- may function as a ferry to jointly gate Mg2+ permeation in hMrs2. In addition, the membrane potential is likely to be the driving force for Mg2+ permeation. Our results provide insights into the channel assembly and Mg2+ permeation of hMrs2.


Image enhancement for increased dot-counting efficiency in FISH.
The most commonly used molecular cytogenetic technique is fluorescence in situ hybridization (FISH). It has been widely applied in many areas of diagnosis and research, including pre-natal and post-natal screening of chromosomal aberrations, pre-implantation genetic diagnosis, cancer cytogenetics, gene mapping, molecular pathology and developmental molecular biology. The analysis of FISH images consists of detecting fluorescent dots, after which the number of dots per cell can be counted or their relative positions can be measured. A major impediment in the analysis of FISH specimens is signal (dot) quality, which is influenced by the hybridization efficiency and/or the sensitivity of the camera that records the images. In this paper, we present an approach to improve the efficiency of detecting fluorescent signals in FISH images by recovering the radiance map of the camera. This allows us to generate a high-dynamic-range image wherein an extended range of the sample radiance captured by the camera can be visualized at distinct intensity values. The resulting higher-order numeric complexity of the transformed image is adjusted (or simplified) by examining the intensity distribution in each of the three colour channels (red, green and blue), and remapping the intensity values to generate a high-contrast image with a lower-order (compressed) dynamic range. The remapping is based on a criterion that optimizes the detection of the hybridized signals, allowing attenuation of saturated intensity values while amplifying low-intensity signals. A simple dot-counting algorithm is used to automatically process 2000 FISH images. The images are taken for lymphocytes from cultured blood specimens for cytogenetic testing. Images are manually analyzed by an expert to obtain ground truth for dot counts. A quantitative analysis is performed by comparing results of automated dot detection on images before and after enhancement with the developed algorithms. In addition, common errors in dot counting due to split dots, dust, poor segmentation and overlapping signals are analyzed and the robustness of the developed approach against these errors evaluated. It is observed that dot-detection efficiency is increased by an average of 9% across all colour channels while reducing errors in missed and false dot counts. Our proposed method and results demonstrate that dot-counting specificity and sensitivity can be improved by pre-processing and enhancing the image using the radiance curve of the camera and generating a high-contrast, remapped high-dynamic-range image prior to using any algorithm for dot counting.


Restrictions in quality of life in colorectal cancer patients over three years after diagnosis: a population based study.
Despite the burden and prevalence of colorectal cancer (CRC), there is only limited information regarding quality of life of patients who have survived beyond the first year post treatment. We assessed quality of life in a population-based cohort of 309 patients with CRC from Saarland (Germany) one and three years after diagnosis using the QLQ-C30 questionnaire and the tumour specific module QLQ-CR38. When compared with reference data from the general population, most patients with CRC reported high overall quality of life and only small deficits in physical functioning but deficits in emotional and social functioning persist over years in patients with colorectal cancer. Improvements in quality of life from the first to the third year after diagnosis in patients who remained free of disease were very modest and limited to less financial difficulties, a better future perspective and fewer stoma-related problems.


Ginsenoside Rg1 promotes browning by inducing UCP1 expression and mitochondrial activity in 3T3-L1 and subcutaneous white adipocytes.
Panax ginseng Meyer is known as a conventional herbal medicine, and ginsenoside Rg1, a steroid glycoside, is one of its components. Although Rg1 has been proved to have an antiobesity effect, the mechanism of this effect and whether it involves adipose browning have not been elucidated. 3T3-L1 and subcutaneous white adipocytes from mice were used to access the thermogenic effect of Rg1. Adipose mitochondria and uncoupling protein 1 (UCP1) expression were analyzed by immunofluorescence. Protein level and mRNA of UCP1 were also evaluated by Western blotting and real-time polymerase chain reaction, respectively. Rg1 dramatically enhanced expression of brown adipocyte-specific markers, such as UCP1 and fatty acid oxidation genes, including carnitine palmitoyltransferase 1. In addition, it modulated lipid metabolism, activated 5' adenosine monophosphate (AMP)-activated protein kinase, and promoted lipid droplet dispersion. Rg1 increases UCP1 expression and mitochondrial biogenesis in 3T3-L1 and subcutaneous white adipose cells isolated from C57BL/6 mice. We suggest that Rg1 exerts its antiobesity effects by promoting adipocyte browning through activation of the AMP-activated protein kinase pathway.


Ni-doped Bi2O2CO3 nanosheet with H+/Zn2+ co-insertion for "rocking chair" zinc-ion battery.
Developing insertion-type anode is key to advancing "rocking chair" zinc-ion batteries, though there are few reported insertion-type anodes. Herein, the Bi2O2CO3 is a high-potential anode, with a special layered structure. A one-step hydrothermal method was used to prepare Ni-doped Bi2O2CO3 nanosheet, and also a free-standing electrode consisting of Ni-Bi2O2CO3 and CNTs was designed. Both cross-linked CNTs conductive networks and Ni doping improve charge transfer. Ex situ tests (XRD, XPS, TEM, etc.) reveal the H+/Zn2+ co-insertion mechanism of Bi2O2CO3 and that Ni doping improves its electrochemical reversibility and structural stability. Therefore, this optimized electrode offers a high specific capacity of 159 mAh g-1 at 100 mA g-1, a suitable average discharge voltage of ≈0.400 V, and a long-term cycling stability of 2200 cycles at 700 mA g-1. Besides, the Ni-Bi2O2CO3//MnO2 "rocking chair" zinc-ion battery (based on the total mass of cathode and anode) delivers a high capacity of ≈100 mAh g-1 at 50.0 mA g-1. This work provides a reference for designing high-performance anode in zinc-ion batteries.


Heart Rate Response to Exercise and Recovery: INDEPENDENT PROGNOSTIC MEASURES IN PATIENTS WITHOUT KNOWN MAJOR CARDIOVASCULAR DISEASE.
Heart rate response during exercise testing (ET) provides valuable prognostic information. Limited data are available regarding the prognostic interplay of heart rate (HR) measured at rest, exercise and recovery phases of ET, and its ability to predict risk beyond exercise capacity. Retrospective analysis of treadmill ETs was performed by the Bruce protocol in patients aged 35-75 yr without known cardiovascular disease (CVD; n = 13 887; 47% women). Heart rate recovery at 2 min (HRR2; defined abnormal <42 beats) and chronotropic index (CI; defined abnormal <80%, determined as age-predicted HR reserve) were analyzed in association with the risk of developing myocardial infarction, stroke, or death (major adverse cardiovascular event [MACE]) during median follow-up of 6.5 yr. The HRR2 <42 beats and CI <80% were each associated with increased risk of MACE: adjusted hazard ratios with 95% confidence interval 1.47: 1.27-1.72 and 1.66: 1.42-1.93, P < .001, respectively, evident also when analyzed as continuous variables. Strength of association of HRR2 and CI with outcome was attenuated but remained significant with further adjustment for exercise duration and metabolic equivalents. Having both HRR2 and CI abnormal compared with only one measure abnormal was associated with hazard ratios with 95% confidence interval of 1.66: 1.38-2.00 and 1.48: 1.22-1.79 for MACE, before and after adjustment for cardiorespiratory fitness (CRF). The degree of CRF (low vs mid/high) did not modify the prognostic effect of HRR2 and CI (P-for-interaction nonsignificant). Both HRR2 and CI provide independent prognostic information beyond CRF in patients without CVD referred for ET. The predictive ability is more pronounced when both abnormal HR measures coexist.


The complex relationship between lung tumor volume and survival in patients with non-small cell lung cancer treated by definitive radiotherapy: a prospective, observational prognostic factor study of the Trans-Tasman Radiation Oncology Group (TROG 99.05).
To investigate the hypothesis that primary tumor volume is prognostic independent of T and N stages in patients with non-small cell lung cancer (NSCLC) treated by definitive radiotherapy. Multicenter prospective observational study. Patient eligibility: pathologically proven stage I-III non-small cell lung cancer planned for definitive radiotherapy (minimum 50 Gy in 20 fractions) using CT-based contouring. Volumes of the primary tumor and enlarged nodes were measured according to a standardized protocol. Survival was adjusted for the effect of T and N stage. There were 509 eligible patients. Five-year survival rates for tumor volume grouped by quartiles were, for increasing tumor volume, 22%, 14%, 15% and 21%. Larger primary tumor volume was associated with shorter survival (HR=1.060 (per doubling); 95% CI 1.01-1.12; P=0.029). However, after adjusting for the effects of T and N stage, there was no evidence for an association (HR=1.029, 95% CI, 0.96-1.10, P=0.39). There was evidence, however, that larger primary tumor volume was associated with an increased risk of dying, independently of T and N stage, in the first 18 months but not beyond. In patients treated by non-surgical means we were unable to show that lung tumor volume, overall, provides additional prognostic information beyond the T and N stage (TNM, 6th edition). There is evidence, however, that larger primary tumor volume adversely affects outcome only within the first 18 months. Larger tumor size alone should not by itself exclude patients from curative (chemo)radiotherapy.


Mitral valve regurgitation assessed by intraventricular CMR 4D-flow: a systematic review on the technological aspects and potential clinical applications.
Cardiac magnetic resonance (CMR) four-dimensional (4D) flow is a novel method for flow quantification potentially helpful in management of mitral valve regurgitation (MVR). In this systematic review, we aimed to depict the clinical role of intraventricular 4D-flow in MVR. The reproducibility, technical aspects, and comparison against conventional techniques were evaluated. Published studies on SCOPUS, MEDLINE, and EMBASE were included using search terms on 4D-flow CMR in MVR. Out of 420 screened articles, 18 studies fulfilled our inclusion criteria. All studies (n = 18, 100%) assessed MVR using 4D-flow intraventricular annular inflow (4D-flowAIM) method, which calculates the regurgitation by subtracting the aortic forward flow from the mitral forward flow. Thereof, 4D-flow jet quantification (4D-flowjet) was assessed in 5 (28%), standard 2D phase-contrast (2D-PC) flow imaging in 8 (44%) and the volumetric method (the deviation of left ventricle stroke volume and right ventricular stroke volume) in 2 (11%) studies. Inter-method correlations among the 4 MVR quantification methods were heterogeneous across studies, ranging from moderate to excellent correlations. Two studies compared 4D-flowAIM to echocardiography with moderate correlation. In 12 (63%) studies the reproducibility of 4D-flow techniques in quantifying MVR was studied. Thereof, 9 (75%) studies investigated the reproducibility of the 4D-flowAIM method and the majority (n = 7, 78%) reported good to excellent intra- and inter-reader reproducibility. Intraventricular 4D-flowAIM provides high reproducibility with heterogeneous correlations to conventional quantification methods. Due to the absence of a gold standard and unknown accuracies, future longitudinal outcome studies are needed to assess the clinical value of 4D-flow in the clinical setting of MVR.


The O-chain structure from the LPS of marine halophilic bacterium Pseudoalteromonas carrageenovora-type strain IAM 12662T.
The O-chain polysaccharide of the lipopolysaccharide from the halophilic marine bacterium Pseudoalteromonas carrageenovora IAM 12662T was characterized. The structure was studied by means of chemical analysis and 2D NMR spectroscopy of the de-O-acylated lipopolysaccharide and shown to be the following:Col is colitose, 3,6-di-deoxy-L-xylo-hexose.


Status epilepticus and anti-NMDA receptor encephalitis after resection of an ovarian teratoma.
Anti-N-methyl-D-aspartate receptor encephalitis is a recently recognised autoimmune, paraneoplastic syndrome that typically presents with psychiatric disturbance, reduced conscious level and seizures. The disorder has been previously associated with ovarian teratomas. We present the case of a 35-year-old female, with a previous surgical history for resection of an ovarian teratoma, who later developed status epilepticus and anti-N-methyl-D-aspartate receptor encephalitis requiring intensive care management. Her presentation, treatment and early follow-up are described, alongside an overview of anti-N-methyl-D-aspartate receptor encephalitis pathophysiology and intensive care management.


Fine resolution analysis of bacterial communities associated with Neochloris oleoabundans culture and insights into terpenes as contamination control agents.
Biological contamination is one of the main bottlenecks in microalgae production, reducing quality and productivity and sometimes leading to the complete loss of the cultures. Selecting terpenes can be a pathway toward eco-friendly contamination control in microalgae cultures. This work evaluated the presence of bacterial contaminants in N. oleoabundans cultures through HTS and 16 S analysis and their susceptibility to six natural terpenes (α-pinene, β-pinene, limonene, trans-cinnamaldehyde, linalool, and eugenol). The principal phyla identified were Proteobacteria, Bacteroidetes, and Actinobacteria, and based on these data, 89 bacterial isolates of seven genera were obtained (36 Aureimonas sp., 27 Microbacterium sp., 5 Pseudomonas sp., 9 Bacillus sp., 14 Shinella sp., 1 Brevundimonas sp., and 1 Exiguobacterium sp.) at 25ºC in the presence of light. It was possible to observe that Beta-pinene 50 mg L- 1 only inhibited Bacillus sp. In contrast, Alpha-pinene, Linalool, and Trans-cinnamaldehyde, at a concentration of 6.25 mg L- 1 efficiently inhibited most isolates. The inhibition percentages found were 79-99%.


Pre- and postnatal MR imaging of an asymptomatic giant hypothalamic hamartoma.
Hypothalamic hamartomas are rare tumors that are most often diagnosed in early childhood. These lesions are classified as giant hypothalamic hamartomas when they exceed 4 cm in any 1 dimension. The most common presenting symptoms associated with these lesions are precocious puberty, gelastic seizures, and (less commonly) syndromic conditions such as Pallister-Hall syndrome. We present a unique case of an asymptomatic giant hypothalamic hamartoma diagnosed prenatally by fetal magnetic resonance imaging and followed throughout infancy. This case demonstrates the utility of multimetric analysis using difference sequences, including diffuse-weighted imaging, to assess specific properties of intracranial lesions detected in utero and to aid in accurate diagnosis prior to birth.


RAPID PENTOSAN POLYSULFATE SODIUM MACULOPATHY PROGRESSION.
The purpose of this study was to report a unique case of pentosan polysulfate sodium (PPS) maculopathy with remarkable rapid progression over 2 years. These findings show the importance of early detection of macular disease to limit toxic exposure and reduce the risk of progression. Multimodal retinal imaging including fundus autofluorescence, near-infrared reflectance with pseudocolor, and spectral domain optical coherence tomography was performed in an elderly patient with a history of PPS therapy (cumulative dose of 1,205 g) at baseline and 2 years later. Baseline multimodal retinal imaging failed to show significant macular findings of PPS toxicity in either eye, but on repeat evaluation 2 years later, advanced features of PPS maculopathy were detected in both eyes with fundus autofluorescence, near-infrared reflectance, pseudocolor, and spectral domain optical coherence tomography. This report describes a remarkable case of rapid progression of PPS maculopathy as documented with multimodal retinal imaging. The dramatic progression of macular findings over just 2 years underscores the importance of early detection and prompt withdrawal of therapy, if systemically feasible, to retard the development and rate of progression of PPS maculopathy.


Comparison of vitrified outcomes between human early blastocysts and expanded blastocysts.
We compared the vitrified outcomes between early and expanded blastocysts with or without laser drilling. The grade III embryos from the patients undergoing in vitro fertilization-embryo transfer (IVF-ET) in our reproductive center from September 2009 to February 2015 were incubated into early blastocysts and expanded blastocysts. The early blastocysts and expanded blastocysts were, respectively, divided into laser group (vitrification after laser drilling), non-laser group (direct vitrification), and control group (fresh non-vitrified blastocysts). After thawing, the blastular anabiosis rate, expansion rate, hatching rate, and apoptosis were observed in each group and then were compared amongst groups. This study indicated that the blastular expansion rate (all P < 0.01) and hatching rate (all P < 0.01) were significantly lower, but the blastular apoptosis (all P < 0.05) was significantly higher in both laser and non-laser groups than in the control group in the early blastocysts. In the expanded blastocysts, the blastular anabiosis rate was significantly higher in the laser group than in the non-laser group (P < 0.01), and the blastular expansion rate was significantly higher, but the blastular apoptosis was significantly lower in both laser group and control group than in the non-laser group (all P < 0.05). The blastular expansion rate (all P < 0.01) and hatching rate (all P < 0.01) were significantly higher, but the blastular apoptosis (all P < 0.05) was significantly lower in the expanded laser group than in both early laser and early non-laser groups. We conclude that vitrification for laser-drilling expanded blastocysts can achieve the best outcomes.


Reliability and validity of the dynamic gait index in persons with chronic stroke.
To establish the test-retest and interrater reliability as well as the concurrent construct validity of the Dynamic Gait Index (DGI) as a measure for dynamic balance in people with chronic stroke. Cohort study. Day hospital and ambulatory care at a rehabilitation center. A consecutive sample of 25 participants, at least 3 months poststroke and able to walk at least 10m with or without a walking aid, participated in the study. Two independent raters rated performances on the DGI. Not applicable. The DGI was administered in 2 testing sessions 3 days apart. In the second session, the participants were rated by 2 raters. Intraclass correlation coefficients (ICCs), model 2,1, and the Bland and Altman method were used to analyze total scores and item scores. Concurrent construct validity was tested by correlating results to the Berg Balance Scale, the timed walking test, the Timed Up & Go test, and the Activities-specific Balance Confidence Scale. ICCs for test-retest and interrater reliability of total scores were good (.96, .96, respectively) whereas reliability for single item scores was moderate to good (range, .55-.93). The hypotheses for concurrent construct validity were confirmed with all measures (range, .68-.83). The DGI showed high reliability and showed evidence of concurrent validity with other balance and mobility scales. It is a useful clinical tool for evaluating dynamic balance in ambulatory people with chronic stroke.


ACTH-like immunoreactivity in the gastrin cell. Independent changes in gastrin and ACTH-like immunoreactivity during ontogeny.
Rat antral gastrin cells have been shown to contain ACTH-like immunoreactivity. Studies on the ontogeny of the antral gastrin cells reveal that these cells start to store gastrin before they contain detectable quantities of ACTH-like immunoreactivity. At no stage studied were duodenal gastrin cells found to contain ACTH-like peptides. The data indicate that the G cells synthetizes and/or releases the two hormonal peptides independently.


Actinomycetoma caused by Rhodococcus spp.
We report a case of mycetoma caused by Rhodococcus in a 62-year-old man who presented with multiple draining sinuses of the left foot. Biopsy specimen showed granulomatous reaction and microabcesses contained granules. These granules were composed by rod and coccoid Gram-positive and partially acid-fast elements. Culture grew a 'Nocardia-like organism', confirmed at the Center for Disease Control as Rhodococcus spp.


Differential expression of metalloproteinase and tissue inhibitor of metalloproteinase genes in aged human fibroblasts.
The basal levels of mRNAs encoding two metalloproteinases, collagenase and stromelysin, were increased as a function of in vitro serial subcultivation (cellular aging) of human fibroblasts. Procollagenase and prostromelysin synthesis and secretion were also greater in the old cultures (late passage). In contrast, the steady-state expression of mRNA for an inhibitor of metalloproteinases, tissue inhibitor of metalloproteinase-1 (TIMP-1), in late-passage cultures was lower than that in young cell cultures (early passage). Each mRNA was analyzed using total RNA preparations isolated from normal fibroblast cultures at different phases of the in vitro life span and from cultures derived from donors with the premature senescence syndromes characterized as Werner syndrome, progeria (Hutchinson-Gilford) syndrome, or Cockayne syndrome. In normal cell cultures expression of metalloproteinase mRNAs was increased after the culture had completed greater than 90% of the in vitro life span, and the reduction in TIMP-1 mRNA expression occurred after the culture had completed greater than 74% of the in vitro lifespan. In Werner syndrome cultures expression of metalloproteinase and TIMP-1 mRNAs was similar to the level of expression observed in late-passage cell cultures. Levels of metalloproteinase and TIMP-1 mRNA expression in progeria and Cockayne syndromes were similar to those of early-passage cell cultures. To determine if young and old cells were each responsive to mediators of metalloproteinase synthesis, cultures were treated with phorbol ester or cytokines. 12-O-tetradecanoylphorbol-13-acetate treatment increased the steady-state levels of all three mRNAs in young, old, and Werner syndrome cultures and increased procollagenase levels in all cultures. Early- and late-passage cell cultures also responded to cytokines. Interleukin-1 alpha treatment increased collagenase and stromelysin mRNA levels while transforming growth factor-beta reduced the steady-state levels of both transcripts. Neither cytokine affected the steady-state level of TIMP-1 mRNA. The results indicate that in vitro cellular aging is associated with changes in expression of mRNAs encoding proteins that mediate inflammatory responses and connective tissue remodeling.


Cardiovascular risk assessment in the metabolic syndrome: results from the Prospective Cardiovascular Munster (PROCAM) Study.
We aimed (1) to construct a modified PROCAM risk algorithm, which incorporates BMI/waist circumference in a model for predicting coronary events; (2) to evaluate how accurate this and the previously established PROCAM risk algorithm predict coronary risk in individuals with metabolic syndrome. Prospective Cardiovascular Münster (PROCAM) Study, a prospective study of men and women at work in the northwest of Germany. A total of 7134 men aged 35-65 years at study entry. On the basis of 404 major coronary events (defined as nonfatal MI and coronary deaths), which occurred within 10 years of follow-up, a modified PROCAM risk algorithm was constructed by incorporating BMI/waist circumference as fixed variable in a Cox proportional hazards model for predicting coronary events. The metabolic syndrome was defined according to the latest recommendations proposed by the NCEP-ATP III Panel. Men who were classified as having the metabolic syndrome (n=2325, prevalence: 32.6%) were 2.59-fold more likely to experience a major coronary event within 10 years of follow-up than men not having the metabolic syndrome. In men with metabolic syndrome, the observed major coronary event rate of 9.6% corresponded well with their estimated global risk according to the modified BMI-based PROCAM risk algorithm (10.2%). Comparative calculations performed with the previously published fully adjusted PROCAM algorithm yielded very similar results. Both PROCAM algorithms provide very accurate means to ascertain coronary risk in male patients with metabolic syndrome.


Transcriptional insights into key genes and pathways controlling muscle lipid metabolism in broiler chickens.
Intramuscular fat (IMF) is one of the most important factors positively associated with meat quality. Triglycerides (TGs), as the main component of IMF, play an essential role in muscle lipid metabolism. This transcriptome analysis of pectoralis muscle tissue aimed to identify functional genes and biological pathways likely contributing to the extreme differences in the TG content of broiler chickens. The study included Jingxing-Huang broilers that were significantly different in TG content (5.81 mg/g and 2.26 mg/g, p < 0.01) and deposition of cholesterol also showed the same trend. This RNA sequencing analysis was performed on pectoralis muscle samples from the higher TG content group (HTG) and the lower TG content group (LTG) chickens. A total of 1200 differentially expressed genes (DEGs) were identified between two groups, of which 59 DEGs were related to TG and steroid metabolism. The HTG chickens overexpressed numerous genes related to adipogenesis and lipogenesis in pectoralis muscle tissue, including the key genes ADIPOQ, CD36, FABP4, FABP5, LPL, SCD, PLIN1, CIDEC and PPARG, as well as genes related to steroid biosynthesis (DHCR24, LSS, MSMO1, NSDHL and CH25H). Additionally, key pathways related to lipid storage and metabolism (the steroid biosynthesis and peroxisome proliferator activated receptor (PPAR) signaling pathway) may be the key pathways regulating differential lipid deposition between HTG group and LTG group. This study showed that increased TG deposition accompanying an increase in steroid synthesis in pectoralis muscle tissue. Our findings of changes in gene expression of steroid biosynthesis and PPAR signaling pathway in HTG and LTG chickens provide insight into genetic mechanisms involved in different lipid deposition patterns in pectoralis muscle tissue.


Nuclear binding of cell cycle-related proteins: cyclin A versus proliferating cell nuclear antigen (PCNA).
We have investigated the cell cycle-dependent nuclear binding of cyclin A and of the proliferating cell nuclear antigen (PCNA) in asynchronously growing human fibroblasts. To this purpose, we have applied flow cytometry immunofluorescence, a powerful technique for elucidating the cell cycle phase during which the nuclear binding occurs. We have observed that, in striking contrast with the distribution of nuclear-bound PCNA which is restricted to S phase, the immunofluorescence signal of the nuclear-bound form of cyclin A is high in the G1 and G2 phases of the cell cycle. These results suggest the involvement of nuclear-bound cyclin A in the G1/S and G2/M phase transitions.


Enhanced recovery pathways in abdominal gynecologic surgery: a systematic review and meta-analysis.
Enhanced recovery pathways have been widely accepted and implemented for different types of surgery. Their overall effect in abdominal gynecologic surgery is still underdetermined. A systematic review and meta-analysis were performed to provide an overview of current evidence and to examine their effect on postoperative outcomes in women undergoing open gynecologic surgery. Searches were conducted using Embase, Medline, CINAHL, and the Cochrane Library up to 27 June 2014. Reference lists were screened to identify additional studies. Studies were included if at least four individual items of an enhanced recovery pathway were described. Outcomes included length of hospital stay, complication rates, readmissions, and mortality. Quantitative analysis was limited to comparative studies. Effect sizes were presented as relative risks or as mean differences (MD) with 95% confidence intervals (CI). Thirty-one records, involving 16 observational studies, were included. Diversity in reported elements within studies was observed. Preoperative education, early oral intake, and early mobilization were included in all pathways. Five studies, with a high risk of bias, were eligible for quantitative analysis. Enhanced recovery pathways reduced primary (MD -1.57 days, 95% CI CI -2.94 to -0.20) and total (MD -3.05 days, 95% CI -4.87 to -1.23) length of hospital stay compared with traditional perioperative care, without an increase in complications, mortality or readmission rates. The available evidence based on a broad range of non-randomized studies at high risk of bias suggests that enhanced recovery pathways may reduce length of postoperative hospital stay in abdominal gynecologic surgery.


Synthesis of 2-sulfanyl-6-methyl-1,4-dihydropyrimidines as a new class of antifilarial agents.
A series of 2-sulfanyl-6-methyl-1,4-dihydropyrimidines (8-21) were synthesized in good yields by alkylation of 5-methyl-6-phenyl-2-thioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid ethyl esters (2-7) with different alkyl or aralkyl halides in the presence of a combination of anhydrous K(2)CO(3) and catalytic amount of tetrabutyl ammonium bromide. The title compounds were evaluated for their antifilarial activity against adult parasites of human lymphatic filarial parasite Brugia malayi (sub-periodic strain) in vitro and in vivo at various concentrations. One of the compounds (18) showed promising antifilarial activity.


Recurrent myocarditis--an important mimic of ischaemic myocardial infarction.
Patients presenting with a syndrome of chest pain, elevated cardiac enzyme levels with or without electrocardiogram changes are a common diagnostic and management problem in cardiology. Most commonly, this is due to ischaemic myocardial infarction secondary to coronary artery disease. However, when coronary angiography does not demonstrate any obstructive coronary artery lesion, the diagnosis of myocarditis should be considered. Cardiac magnetic resonance imaging is helpful towards making this diagnosis. Here, we describe the first reported Australian cases of recurrent myocarditis presenting with ischaemic chest pain and elevated cardiac enzyme levels. These cases serve as an important reminder to clinicians that myocarditis is an important mimic of ischaemic myocardial infarction.


Immunocytochemical and radioautographic study of serotonin projections to cerebral ventricles of perinatal rats.
Anatomical relationships between serotoninergic (5-HT) fibers and cerebral ventricles were studied in rats from the 16th fetal day until the 9th postnatal day with immunocytochemistry and radioautography. In the last case, 5-HT neuronal elements were detected according to their specific uptake of intraventricularly injected [3H]5-HT. At the 16th fetal day, occasional 5-HT fibers first spread from the main place of their origin in the raphe nuclei to the dorsocaudal portion of the 3rd ventricle and aqueduct. Two days later, a more extensive network of 5-HT fibers appeared around the dorsal portion of the 3rd ventricle whereas fibers only rarely penetrated toward its ventral portion. By the 9th postnatal day, extensive networks of supraependymal fibers became noticeable in the lateral ventricles and in the dorsal portion of the 3rd ventricle. In addition, a number of 5-HT fibers surrounded the infundibular and preoptic recesses and sometimes penetrated to the ventricular cavity. The functional significance of hypothalamic and ventricular 5-HT as a modulator of either the growth and differentiation of the developing brain or of some specific neuroendocrine functions is discussed.


Size-dependent oxygenation and energy status in multicellular tumor spheroids.
To evaluate interrelationships among the oxygenation, the energy status, and the development of necrosis in tumor microregions, oxygen tensions were measured with microelectrodes, and ATP distributions were determined with a quantitative imaging technique using multicellular spheroids as in vitro tumor models. The results obtained show a positive correlation between central oxygen tensions and ATP concentrations in spheroids. During spheroid growth, both quantities decrease from rather high values to recordings close to or at the background level within similar ranges of spheroid size. Since the emergence of central necroses precedes this drop in energy-rich phosphate, the data may suggest that energy metabolism is not directly involved in the development of necrosis in the spheroids investigated.


Examining central biases in somatosensory localization: Evidence from brain-damaged individuals.
How does the brain localize touch under conditions of uncertainty caused by brain damage? By testing single cases, previous work found mislocalization of touch toward the center of the hand. We investigated whether such central bias changes as a function of uncertainty in somatosensory system. Fifty-one brain-damaged individuals were presented with a tactile detection task to establish their tactile threshold, and a tactile localization task in which they localized suprathreshold stimuli presented at different locations on the hand. We predicted that with increased somatosensory uncertainty, indexed by higher detection thresholds, participants would more likely to localize the stimuli toward the center of the hand. Consistent with this prediction, participants' localization errors were biased towards the center of the hand and, importantly, this bias increased as detection threshold increased. These findings provide evidence that instead of showing random errors, uncertainty leads to systematic localization errors toward the center of the hand or the center of the stimulus distribution, which overlapped in the present study. We discuss these findings under different frameworks as potential mechanisms to explain biases in tactile localization subsequent to brain damage.


Hydroxyapatite coatings produced on commercially pure titanium by micro-arc oxidation.
A porous hydroxyapatite (HA) coating on commercially pure titanium was prepared by micro-arc oxidation (MAO) in electrolytic solution containing calcium acetate and beta-glycerol phosphate disodium salt pentahydrate (beta-GP). The thickness, phase, composition morphology and biocompatibility of the oxide coating were characterized by x-ray diffraction (XRD), electron probe microanalysis (EPMA), scanning electron microscopy (SEM) with an energy dispersive x-ray spectrometer (EDS) and cell culture. The thickness of the MAO film was about 20 microm, and the coating was porous and uneven without any apparent interface to the titanium substrates. The result of XRD showed that the porous coating was made up of HA film. The favorable osteoblast cell affinity gives HA film good biocompatibility. HA coatings are expected to have significant uses for medical applications such as dental implants and artificial bone joints.


Identification and computational analysis of USH1C, and SLC26A4 variants in Pakistani families with prelingual hearing loss.
Hearing loss (HL) is clinically and genetically heterogeneous disorder and is the most frequent occurring sensory deficit in humans. This study was conducted to decipher the genetic cause of HL occurring in two large consanguineous Pakistani families (GCNF-01, GCNF-03). Family history and pure tone audiometry of both families suggested prelingual HL, while the affected individuals of GCNF-01 also had low vision and balance problems, consistent with cardinal features of Usher syndrome type I (USH1). Exome sequencing followed by segregating analysis revealed a novel splice site variant (c.877-1G > A) of USH1C occurring with USH1 phenotype in family GCNF01. While the affected individual of family GCNF-03 were homozygous for the c.716 T > A, p.(Val239Asp) previously reported pathogenic variant of SLC26A4. Both variants have very low frequencies in control database. In silico mutagenesis and 3-dimensional simulation analyses revealed that both variants have deleterious impact on the proteins folding and secondary structures. Our study expands the mutation spectrum of the HL genes and emphasizes the utility of exome sequencing coupled with bioinformatics tools for clinical genetic diagnosis, prognosis, and family counseling.


Sorption of Perfluorooctane sulfonate (PFOS) including its isomers on hydrargillite as a function of pH, humic substances and Na2SO4.
Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant (POP) and emergent contaminant that are widespread in the environment. Understanding the mechanisms controlling the distribution of PFOS and its isomers between hydrargillite and the water phase is important in order to study their redistribution and mobility in the environment. This study investigated the effects of pH, humic acid, fulvic acid and Na2SO4 on sorption of PFOS isomers to hydrargillite. A mixture of PFOS isomers was spiked into water and hydrargillite was added to the system and shaken for one day; the system was tested with different aqueous composition. Concentrations of PFOS isomers in the aqueous phase were quantified using an ultra-performance liquid chromatograph coupled to a triple quadrupole mass spectrometer. Our results showed that the distribution coefficients of PFOS isomers were found to be 0.76, 0.71, 0.93 and 0.90 at pH 6.5, for 3-/4-/5- PFOS, 6-/2-PFOS, L-PFOS and total PFOS respectively. The distribution coefficients increased at lower pH and decreased at alkaline conditions. The presence of humic substances (HS) increased the sorption slightly at the environmental pH of 6.5, although a competition effect was observed during acidic conditions. A tendency of PFOS distribution to hydrargillite in the presence of Na2SO4 was like its behavior in the presence of HS although the mechanisms behind the sorption were interpreted differently. This study revealed that L-PFOS was readily sorbed when no other chemicals were added or in 20 mg/L FA or 100 mg/L Na2SO4. We suggest that an increase in PFOS sorption in the presence of HS may be due to hydrophobic mechanisms while Na2SO4 contributed to increased sorption through ionic strength effects.


Neuronal sodium channels in ventricular heart cells are localized near T-tubules openings.
Cardiac voltage-dependent sodium channels (VDSC) are known to be tetrodotoxin (TTX)-resistant. However, recent immunochemical studies suggest the presence of TTX-sensitive neuronal-type VDSC in the heart. Scanning ion conductance microscopy (SICM) coupled to electrophysiology was used to obtain more direct functional evidence. TTX sensitivities of whole-cell sodium currents (I(Na)) in control and detubulated cells were compared. Addition of 200 nM TTX decreased I(Na) of control cells by 20%, whereas detubulated cells were hardly effected. The remaining current peaked slightly earlier and inactivation decay was faster (as in neuronal VDSC) than in detubulated cells. Single-channel activity was first assayed at random on the plasmalemma, and after topography had been revealed by SICM, at patched T-tubules openings. In the latter case, a single-channel conductance of 11-12pS was observed with a higher rate of success. This study provides independent evidence for neuronal VDSC in cardiomyocytes where they could rapidly and synchronously couple T-tubule and cell surface depolarizations.


Identification and cloning of rat galectin-2: expression is predominantly in epithelial cells of the stomach.
A complementary DNA clone preferentially expressed in the gastrointestinal tract was obtained from a rat stomach library. The protein coded by the clone had a single carbohydrate recognition domain having conserved motifs for beta-galactoside binding and showed 67% amino acid identity with human galectin-2. The recombinant protein synthesized in Escherichia coli could bind to an asialofetuin column and was eluted with beta-galactopyranoside. From these observations, we named the protein rat galectin-2 coded by the cDNA. The rat galectin-2 was predominantly expressed in the epithelial cells of stomach. Thus this protein may form a mucin layer cross-linking with the beta-galactoside moiety of glycoproteins.


Significance of Cox-2 expression in rectal cancers with or without preoperative radiotherapy.
Radiotherapy has reduced local recurrence of rectal cancers, but the result is not satisfactory. Further biologic factors are needed to identify patients for more effective radiotherapy. Our aims were to investigate the relationship of cyclooxygenase-2 (Cox-2) expression to radiotherapy, and clinicopathologic/biologic variables in rectal cancers with or without radiotherapy. Cox-2 expression was immunohistochemically examined in distal normal mucosa (n = 28), in adjacent normal mucosa (n = 107), in primary cancer (n = 138), lymph node metastasis (n = 30), and biopsy (n = 85). The patients participated in a rectal cancer trial of preoperative radiotherapy. Cox-2 expression was increased in primary tumor compared with normal mucosa (p < 0.0001), but there was no significant change between primary tumor and metastasis. Cox-2 positivity was or tended to be related to more p53 and Ki-67 expression, and less apoptosis (p < or = 0.05). In Cox-2-negative cases of either biopsy (p = 0.01) or surgical samples (p = 0.02), radiotherapy was related to less frequency of local recurrence, but this was not the case in Cox-2-positive cases. Cox-2 expression seemed to be an early event involved in rectal cancer development. Radiotherapy might reduce a rate of local recurrence in the patients with Cox-2 weakly stained tumors, but not in those with Cox-2 strongly stained tumors.


Comprehensive oral-health assessment of individuals with acquired brain-injury in neuro-rehabilitation setting.
To perform a detailed clinical oral health assessment and oral-health-related social and behavioural aspect assessment in individuals with acquired brain injury (ABI). Prospective observational study. Thirteen individuals with ABI were recruited. Individual's social and behavioural history, bed-side oral examination score (BOE), tooth condition and periodontal status (bleeding, plaque and clinical attachment loss) were thoroughly examined. The entire examination took up to 60 minutes, using proper dental armamentarium. All evaluated individuals were diagnosed with chronic generalized periodontitis. A relationship between active periodontal disease and severe BOE score was observed (p = 0.01). Significant interaction between severe BOE scores (≥ 15 or ≥ 14) and periodontal disease severity of ≥ 2 mm (p = 0.01) was observed. The same interaction was seen between severe BOE scores and the combination of 75% extent and 2 mm severity (p = 0.01). Severity and activity of periodontitis showed dependence on individual brushing frequency (p = 0.03 and p = 0.05, respectively). Individuals with ABI had a poor status across a range of oral-, dental- and periodontal-related parameters. Further structured studies are required to define evidence-based assessment approaches for such clinical reality.