Health literacy and health risk behaviors among older adults.
Limited health literacy is associated with poorer physical and mental health, although the causal pathways are not entirely clear. In this study, the association between health literacy and the prevalence of health risk behaviors was examined among older adults. A cross-sectional survey of 2923 new Medicare, managed-care enrollees was conducted in four U.S. metropolitan areas (Cleveland OH; Houston TX; Tampa FL; Fort Lauderdale-Miami FL). Health literacy was measured using the short form of the Test of Functional Health Literacy in Adults. Behaviors investigated included self-reported cigarette smoking, alcohol consumption, physical activity, body mass index, and seat belt use. Individuals with inadequate health literacy were more likely to have never smoked (46.7% vs. 38.6, p =0.01); to completely abstain from alcohol (75.6% vs. 57.9, p <0.001); and to report a sedentary lifestyle (38.2% vs. 21.6%, p <0.001) compared to those with adequate health literacy. No significant differences were noted by mean body mass index or seat belt use. In multinomial logistic regression models that adjusted for relevant covariates, inadequate health literacy was not found to be significantly associated with any of the health risk behaviors investigated. Among community-dwelling elderly, limited health literacy was not independently associated with health risk behaviors after controlling for relevant covariates.


Extended HLA haplotypes in Japanese homozygous typing cells.
We have defined extended HLA haplotypes including the HLA class II genes, the non-HLA genes such as TAP1, TAP2 and LMP2, and the (CTG)n microsatellite repeats within the NOTCH4 gene between DRA and 21OH in 33 Japanese HLA homozygous typing cells (HTC). These conserved haplotypes characterized by unique linkage might be maintained as a result of functional co-operation among them in the antigen presentation pathway. These HTCs can be served as an original and ethnic-specific standard panel, providing useful genetic markers in haplotypic diversity, disease association, and anthropology studies.


[MINI TITANIUM PLATE FOR TREATMENT OF INTRACAPSULAR CONDYLAR FRACTURES].
To investigate the effectiveness of mini titanium plate for the treatment of intracapsular condylar fractures-type A. Between March 2013 and July 2015, 22 cases (26 sides) of intracapsular condylar fractures-type A were treated with mini titanium plate through anterior auricular approach. There were 13 males and 9 females, aged from 16 to 32 years (mean, 22.7 years). The disease causes were traffic accident injury in 17 cases, falling injury in 4 cases, and heavy impact injury in 1 case. Five cases had intracapsular condylar fractures-type A only, and the other cases were accompanied with fractures of mandible, maxillary, or other part of jaw. All patients had different degrees of limitation of opening mouth, occlusal disorder, and joint pain, and the maximum opening was 5-16 mm (mean, 8.6 mm). All patients received surgical treatment within 2 to 9 days after injury (mean, 4 days). The clinical dysfunction index (DI) of Helkimo index was used to evaluate the mandibular motor function postoperatively. According to the 4 basic criterion of cure about mandibular condylar fractures by the international consensus conference in 1999, and maximal mouth opening by HE Dongmei et al., the surgical treatment effectiveness was evaluated. All wounds healed at stage I, with no infection or other complications. All 22 cases were followed up 5-8 months (mean, 6 months). At 1 week after operation, the coronal spiral CT and three-dimensional reconstruction showed that contraposition of fractures was good, and the condyles located in the articular fossa. At 6 months after operation, the maximum opening was 33-42 mm (mean, 35.7 mm). After operation, 3 cases showed the mandible deflected to the affected side when opening, and limited lateral motion. According to the DI evaluation method in Helkimo index, there were 7 sides of DI grade 0, 18 sides of DI grade I, and 1 side of DI grade II. Based on surgical treatment effect of intracapsular condylar fractures-type A, occlusion recovery was obtained in 19 cases (86.36%), maximum opening degree of ≥ 35 mm in 20 cases (90.91%), no symptoms of joint injury in 19 cases (86.36%), and no serious postoperative complications in 22 cases (100%); 17 cases (77.27%) were in accordance with the above 4 items. Mini titanium plate is one of the most effective approaches to treat intracapsular condylar fractures-type A.


Occupational Therapy's Role in Addressing the Psychological and Social Impact of COVID-19.
During the coronavirus disease 2019 (COVID-19) pandemic, health care practitioners' primary focus has been on its physical consequences. Yet, the emotional strain of the pandemic exposed the mental health needs of survivors and society as a result of forced changes in occupational choices, habits, and roles. These forced changes caused a collective confusion, fear, loss, and grief. This column focuses on occupational therapy's critical contributions to supporting society's mental health and wellness. Occupational therapy has a unique opportunity to provide interventions to address population-wide mental health and wellness, targeted prevention of mental health concerns for people at risk, and intensive intervention for people with COVID-19-induced mental health diagnoses.


MyD88 Adaptor Protein Is Required for Appropriate Hepcidin Induction in Response to Dietary Iron Overload in Mice.
Iron homeostasis is tightly regulated to provide virtually all cells in the body, particularly red blood cells, with this essential element while defending against its toxicity. The peptide hormone hepcidin is central to the control of the amount of iron absorbed from the diet and iron recycling from macrophages. Previously, we have shown that hepcidin induction in macrophages following Toll-like receptor (TLR) stimulation depends on the presence of myeloid differentiation primary response gene 88 (MyD88). In this study, we analyzed the regulation of iron metabolism in MyD88-/- mice to further investigate MyD88 involvement in iron sensing and hepcidin induction. We show that mice lacking MyD88 accumulate significantly more iron in their livers than wild-type counterparts in response to dietary iron loading as they are unable to appropriately control hepcidin levels. The defect was associated with inappropriately low levels of Smad4 protein and Smad1/5/8 phosphorylation in liver samples found in the MyD88-/- mice compared to wild-type mice. In conclusion, our results reveal a previously unknown link between MyD88 and iron homeostasis, and provide new insights into the regulation of hepcidin through the iron-sensing pathway.


Matrix metalloproteinase-8 levels in peri-implant sulcus fluid adjacent to titanium and zirconium nitride surfaces.
During host interaction against oral biofilm, matrix metalloproteinase-8 (MMP-8) is activated, leading to collagenolytic destruction of host tissues. In periimplantitis patients, the active form of MMP-8 is elevated in peri-implant sulcus fluid (PISF). In this study, MMP-8 in PISF from titanium abutments and those coated with zirconium nitride (ZrN) was compared in vivo in a split-mouth design in 60 patients at 6 weeks, 6 months, and 12 months after prosthetic restoration. At each time point, MMP-8 values in PISF differed significantly between titanium and ZrN abutment surfaces. For example, mean MMP-8 values reached 10 to 12 ng/mL in titanium and only 6.6 to 7.5 ng/mL with ZrN. Similarly, the 75th percentile MMP-8 concentrations were 12 to 15 ng/mL and 8 to 9 ng/mL for titanium and ZrN, respectively. Based on this finding, ZrN-coated abutments seem to exert a beneficial effect regarding collagenolytic tissue destruction driven by MMP-8 in situ.


[Coprological evaluation of refugees in Strasbourg between January 1986 and December 1990].
1,000 refugees living in Strasbourg have had a stoll parasitologic exam between 1986 and 1990. We have not retained results of South America and other areas of Asia subjects because of their scarce total number. Proportionally, the most numerous are the South East Asia Nationals (51.7%); followed by those from Middle East and Africa (20 and 15.5%) and more recently by those from East of Europe (5.2%). Their parasitic infestation's rate remains important (60.9%) but variable depending on their origin. Thus, people coming from Middle East and Africa are parasited mainly by protozoan, although those from South East Asia are parasited by helminths. It's interesant to notify that the prevalence of D. fragilis is ten times higher among East European people than in the common people.


Nitrile imines and nitrile ylides: rearrangements of benzonitrile N-methylimine and benzonitrile dimethylmethylide to azabutadienes, carbodiimides, and ketenimines. Chemical activation in thermolysis of azirenes, tetrazoles, oxazolones, isoxazolones, and oxadiazolones.
Flash vacuum thermolysis (FVT) of 1-methyl-5-phenyltetrazole (5b), 2-methyl-5-phenyltetrazole (1b), and 3-methyl-5-phenyl-1,3,4-oxadiazol-2(3H)-one (3b) affords the nitrile imine (2b), which rearranges in part to N-methyl-N'-phenylcarbodiimide (7b). Another part of 2b undergoes a 1,4-H shift to the diazabutadiene (13). 13 undergoes two chemically activated decompositions, to benzonitrile and CH2═NH and to styrene and N2. FVT of 2,2-dimethyl-4-phenyl-oxazol-5(2H)-one (16) at 400 °C yields 3-methyl-1-phenyl-2-azabutadiene (18) in high yield. In contrast, FVT of 3,3-dimethyl-2-phenyl-1-azirene (21) at 600 °C or 4,4-dimethyl-3-phenyl-isoxazolone (20) at 600 °C affords only a low yield of azabutadiene (18) due to chemically activated decomposition of 18 to styrene and acetonitrile. There are two reaction paths from azirene (21): one (path a) leading to nitrile ylide (17) and the major products styrene and acetonitrile and the other (path b) leading to the vinylnitrene (22) and ketenimine (23). The nitrile ylide PhC(-)═N(+)═C(CH3)2 (17) is implicated as the immediate precursor of azabutadiene (18). FVT of either 3-phenylisoxazol-5(4H)one (25) or 2-phenylazirene (26) at 600 °C affords N-phenylketenimine (28). The nitrile ylide PhC(-)═N(+)═CH2 (30) is postulated as a reversibly formed intermediate. N-Phenylketenimine (28) undergoes chemically activated free radical rearrangement to benzyl cyanide. The mechanistic interpretations are supported by calculations of the energies of key intermediates and transition states.


[Epidemiological analysis of malaria prevalence in Sichuan Province, 2012-2014].
To understand the characteristics of malaria prevalence in Sichuan Province from 2012 to 2014, so as to provide evidences for improving the work of malaria elimination. The epidemiological data of malaria cases in Sichuan Province were collected from the Disease Surveillance Information Reporting System of Chinese Center for Disease Control and Prevention, and analyzed with the descriptive epidemiological method. A total of 690 imported malaria cases were reported in Sichuan Province from 2012 to 2014. In detail, 54.49% (376/690) were falciparum malaria cases, 42.03% (290/690) were vivax malaria cases, 0.58% (4/690) were malariae malaria cases, 1.88% (13/690) were ovale malaria cases, and 1.01% (7/690) were mixed infection cases with Plasmodium vivax and P. falciparum. Among them, five cases died. Totally 671 malaria cases were infected overseas, accounting for 97.25% of the total cases. Among which, 517 patients returned from Africa and 138 patients returned from Southeast Asia. There were malaria cases reported in the whole year, and 185 cases were reported in May and June, accounting for 26.81% of the total cases. The cases distributed in 20 prefecture-level cities in the whole province, and there were 137 and 105 ones reported in Guangan and Chengdu, respectively, which accounted for 35.07% of the total cases. The number of patients with overseas imported malaria in Sichuan Province increases year by year, and therefore effective measures should be carried out to control the overseas imported malaria.


Inhibition of oral carcinogenesis by a protease inhibitor.
The effect of the Bowman-Birk inhibitor (BBI) and soybean trypsin inhibitor (SBTI) on experimental 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6]-induced oral carcinogenesis in Syrian male hamsters was examined. All treatments were applied topically on both cheek pouches for 20 weeks, and the animals were then sacrificed. Gross and microscopic evaluations revealed a statistically significant reduction in the number of invasive carcinomas, the total number of tumors, and the tumor mass for the DMBA + BBI treatment group compared to animals treated with DMBA alone, DMBA and autoclaved BBI (a preparation in which protease inhibitor activity is destroyed), or DMBA + SBTI. A protease activity (with the use of Boc-Val-Pro-Arg-MCA as substrate) was measured and found to be elevated about tenfold in tumorous and nontumorous tissue from DMBA-treated cheek pouches. This protease activity was found to be decreased in the DMBA and BBI treatment group but not in the DMBA + SBTI or DMBA and autoclaved BBI treatment groups, as compared to the protease activity in the DMBA treatment group. Partial characterization of the Boc-Val-Pro-Arg-MCA hydrolyzing activity with diisopropyl fluorophosphate suggests that the proteolytic activity is a serine protease. Iodoacetamide and diethyl pyrocarbonate also inhibit enzyme activity, suggesting that other residues may be necessary for catalysis, possibly including cysteine and histidine. Our results suggest that this protease activity may play a role in DMBA-induced cheek pouch carcinogenesis.


Rapid and efficient one-step purification of a serralysin family protease by using a p-aminobenzamidine-modified affinity medium.
The metalloproteinase MP belongs to the serralysin family, which is involved in important functions such as nutrient acquisition and infection pathogenesis. Serralysin proteases in highly purified form are commonly used at the industrial level with several purposes. In this study, we set up an efficient and rapid purification protocol for MP using a p-aminobenzamidine-modified affinity chromatography. The affinity medium was synthesized by using p-aminobenzamidine as affinity ligand immobilized via cyanuric chloride spacer to Sepharose 6B sorbent carrier. According to the adsorption analysis, the dissociation constant Kd and theoretical maximum adsorption Qmax of this medium were 24.2 μg/mL and 24.1 mg/g wet sorbent, respectively. The purity of MP was assessed by a high-performance liquid chromatography on a TSK3000SW column and sodium dodecyl sulfate polyacrylamide gel electrophoresis, revealing values of 98.7 and ∼98%, respectively. The specific activity of purified MP was 95.6 U/mg, which is similar to values obtained through traditional purification protocols. In conclusion, our protocol could be easily employed for the rapid isolation of MP with high purity, and could be implemented for other serralysin family proteases.


Podocytopathies related to either COVID-19 infection or its vaccination, our experience and literature review.
Coronavirus disease 2019 (COVID-19) affects several organs including the kidney resulting in acute kidney injury (AKI) and variants of podocytopathies. From the beginning to the middle period of the COVID-19 pandemic, we have collected eight renal biopsies with various renal diseases including 4 podocytopathies. In addition, from the middle period to the near end of the COVID-19 pandemic, we have seen two of the patients who developed nephrotic syndrome following COVID-19 vaccination. Three of 4 podocytopathies were collapsing glomerulopathy (also called collapsing focal segmental glomerulosclerosis) and the fourth was a minimal change disease (MCD). Two of three collapsing glomerulopathy were found in African American patients, one of who was tested positive for having the high-risk allele APOL-1 G1. In addition, the two renal biopsies showed either MCD or replaced MCD following COVID-19 vaccination. MCD can be a rare complication following COVID-19 infection and COVID-19 vaccination, raising the question if there are similar antigens induced by the infection or by the vaccination that trigger the MCD. This article reports our experience of diagnosing podocytopathies related to either COVID-19 infection or its vaccination and provides a literature review regarding the incidence and potential pathophysiology in the field.


Cancer cachexia.
Cancer cachexia is a severe debilitating disorder for which there are currently few therapeutic options. It is driven by the release of pro-inflammatory cytokines and cachectic factors by both host and tumour. Over the past few years, basic science advances have begun to reveal the breadth and complexity of the immunological mechanisms involved, and in the process have uncovered some novel potential therapeutic targets. The effectiveness of thalidomide and eicosapentaenoic acid at attenuating weight loss in clinical trials also provides a further rationale for modulating the immune response. We are now entering an exciting period in cachexia research, and it is likely that the next few years will see effective new biological therapies reach clinical practice.


[Nephronophthisis and medullary cystic kidney disease complex].
Nephronophthisis and medullary cystic kidney disease complex refers to the genetic heterogeneous group of inherited tubulointerstital nephritis. Nephronophthisis comprises at last 3 clinical manifestations, has the autosomal recessive pattern of inheritance, appears early in life and is the most frequent inherited kidney disease that causes terminal renal failure in childhood, while medullary cystic kidney disease has the autosomal dominant pattern of inheritance, is less frequent, and terminal renal failure appears later in life. These two forms have similar clinical and morphological findings but extrarenal manifestations, the median ages of occurence of terminal renal failure, and siblings presence help us distinguish these diseases. In this article we illustrated the case of a 20-years old patient with the suspicion of having complex nephornophthisis and medullary cystic kidney disease based upon mild renal failure, seen in routinely taken laboratory findings and bilateral cysts in corticomedullary region of the kidneys verified on abdominal ultrasound examination. This disease should rise suspicion in children or adolescents with progressive renal failure, a typical clinical manifestation, blood and urine samples results, bilateral cysts in the corticomedullary region of the kidneys seen during ultrasound examination of the kidneys and family inheritance.


Self-Powered Respiration Monitoring Enabled By a Triboelectric Nanogenerator.
In mammals, physiological respiration involves respiratory cycles of inhaled and exhaled breaths, which has traditionally been an underutilized resource potentially encompassing a wealth of physiologically relevant information as well as clues to potential diseases. Recently, triboelectric nanogenerators (TENGs) have been widely adopted for self-powered respiration monitoring owing to their compelling features, such as decent biocompatibility, wearing comfort, low-cost, and high sensitivity to respiration activities in the aspect of low frequency and slight amplitude body motions. Physiological respiration behaviors and exhaled chemical regents can be precisely and continuously monitored by TENG-based respiration sensors for personalized health care. This article presents an overview of TENG enabled self-powered respiration monitoring, with a focus on the working principle, sensing materials, functional structures, and related applications in both physical respiration motion detection and chemical breath analysis. Concepts and approaches for acquisition of physical information associated with respiratory rate and depth are covered in the first part. Then the sensing mechanism, theoretical modeling, and applications related to detection of chemicals released from breathing gases are systemically summarized. Finally, the opportunities and challenges of triboelectric effect enabled self-powered respiration monitoring are comprehensively discussed and criticized.


Three-dimensional digital imaging based on shifted point-array encoding.
An approach to three-dimensional (3D) imaging based on shifted point-array encoding is presented. A kind of point-array structure light is projected sequentially onto the reference plane and onto the object surface to be tested and thus forms a pair of point-array images. A mathematical model is established to formulize the imaging process with the pair of point arrays. This formulation allows for a description of the relationship between the range image of the object surface and the lateral displacement of each point in the point-array image. Based on this model, one can reconstruct each 3D range image point by computing the lateral displacement of the corresponding point on the two point-array images. The encoded point array can be shifted digitally along both the lateral and the longitudinal directions step by step to achieve high spatial resolution. Experimental results show good agreement with the theoretical predictions. This method is applicable for implementing 3D imaging of object surfaces with complex topology or large height discontinuities.


Serratia marcescens infected silk suture rejected by combined acupuncture, moxibustion and low-power laser therapy from the abdominal fascia.
Upper abdominal pains lasting 12 years after cholecystectomy, were improved in an 82-year-old woman following the rejection of indigestable silk surgical sutures induced by combined therapy of acupuncture, moxibustion and low-power laser beam irradiation directed to an old post-cholecystectomy scar. An inflammatory reaction followed by granulation tissue mass was developed. Embedded in the granulation tissue were the above mentioned silk sutures which finally were expelled through the skin at the operation scar. A surgical procedure suggested to the patient, in case of acupuncture therapy failure, was obviously avoided. Serratia-marcescens infection of the expelled material was bacteriologically defined.


Congenital chloridorrhoea. A question of reversed brush border transport processes and varying junctional tightness.
The surprising results of intestinal perfusion studies in an 8-month-old child with congenital chloridorrhoea offered a unique opportunity not only to elucidate the underlying defect, but also to test the adequacy of proposed models for normal intestinal transport. In ileum Na, K and Cl as well as water were secreted and HCO3 absorbed. Lumen was 91 mV negative to blood. Only Cl was transported against both electrical and chemical gradients, but discrepancies between observed and predicted Na flux ratios suggested the presence of a Na-absorbing mechanism as well. Mucosa was impermeable to Cl from the lumen side. 2.5 mM glycochenodeoxycholic acid (GCDC) mediated Na and water absorption and abolished any transport of Cl. PD was -95 mV. In colon a similar pattern was observed and mucosa to serosa fluxes of Cl were abnormally low. Rectal PD was -116 mV. GCDC made the epithelium more absorptive in function, but contrary to ileum the effect was due to an increase of Na and Cl fluxes from mucosa to serosa. The patient was at that time in severe electrolyte imbalance. He was reinvestigated three months later when he was in a good clinical condition with normal serum electrolytes. Net transfer of electrolytes and water and bidirectional fluxes of Cl and K were unchanged while bidirectional Na fluxes had increased considerably and PD decreased to -18 mV. Rectal PD was -45 mV. In jejunum water and electrolyte transport were normal and PD -3 mV. It is tentatively concluded that the abnormal transport in ileum is due to an inversion of the brush border transport processes, which also satisfies the paradoxical effects of GCDC. Furthermore, Na and Cl seem to migrate through separate pathways. A varying degree of junctional tightness, which is almost completely cationic, may be responsible for the functional differences observed in resonse to improvement of the general electrolyte status.


[The role of oxygen free radicals in the mechanisms of local and distant ischemic myocardial preconditioning].
The phenomenon of ischemic preconditioning consists in increase in myocardial tolerance to ischemia after short periods of ischemia and reperfusion of the myocardium (local preconditioning) or a distant organ (distant preconditioning). This study is dedicated to the role of oxygen free radicals (OFR) in the mechanisms of preconditioning; pharmacological inhibition of OFR with N-2-mercaptopropionylglycin, a synthetic anti-oxidant, was used. Mouse experiments demonstrated a reduction in the infarction-limiting effect of local preconditioning as a result of OFR inhibiting. This confirms the hypothesis according to which OFR play an important role in the mechanisms of launching and mediating the protective effect of local preconditioning. On the contrary, application of the same dose of N2-mercaptopropionylglycin does not lead to a significant weakening of the infarction-limiting effect of distant preconditioning caused by 20 min of ischemia and 15 min of reperfusion of the small intestine. Thus, it is unlikely that OFR participate in the realization of the effect of distant preconditioning caused by small intestinal ischemia. The authors discuss hypothetic molecular mechanisms of distant myocardial preconditioning.


The Potential Translational Applications of Nanoparticles in Endodontics.
Nanotechnology has substantially progressed in the past decades, giving rise to numerous possible applications in different biomedical fields. In particular, the use of nanoparticles in endodontics has generated significant interest due to their unique characteristics. As a result of their nanoscale dimensions, nanoparticles possess several properties that may enhance the treatment of endodontic infections, such as heightened antibacterial activity, increased reactivity and the capacity to be functionalized with other reactive compounds. Effective disinfection and sealing of the root canal system are the hallmarks for successful endodontic treatment. However, the presence of bacterial biofilms and resistance to endodontic disinfectants pose a significant challenge to this goal. This has encouraged the investigation of antibacterial nanoparticle-based irrigants and intracanal medicaments, which may improve the elimination of endodontic infections. In addition, photosynthesizer-functionalized nanoparticles could also serve as a worthy adjunct to root canal disinfection strategies. Furthermore, despite the myriad of commercially available options for endodontic obturation, the "ideal" material has yet to be conceived. This has led to the development of various experimental nanoparticle-incorporated obturation materials and sealers that exhibit a range of favourable physicochemical properties including enhanced antibacterial efficacy and bioactivity. Nanoparticle applications also show promise in the field of regenerative endodontics, such as supporting the release of bioactive molecules and enhancing the biophysical properties of scaffolds. Given the constantly growing body of research in this field, this article aims to present an overview of the current evidence pertaining to the potential translational applications of nanoparticles in endodontics.


Transmembrane domain sequence requirements for activation of the p185c-neu receptor tyrosine kinase.
The receptor tyrosine kinase p185c-neu can be constitutively activated by the transmembrane domain mutation Val664-->Glu, found in the oncogenic mutant p185neu. This mutation is predicted to allow intermolecular hydrogen bonding and receptor dimerization. Understanding the activation of p185c-neu has assumed greater relevance with the recent observation that achondroplasia, the most common genetic form of human dwarfism, is caused by a similar transmembrane domain mutation that activates fibroblast growth factor receptor (FGFR) 3. We have isolated novel transforming derivatives of p185c-neu using a large pool of degenerate oligonucleotides encoding variants of the transmembrane domain. Several of the transforming isolates identified were unusual in that they lacked a Glu at residue 664, and others were unique in that they contained multiple Glu residues within the transmembrane domain. The Glu residues in the transforming isolates often exhibited a spacing of seven residues or occurred in positions likely to represent the helical interface. However, the distinction between the sequences of the transforming clones and the nontransforming clones did not suggest clear rules for predicting which specific sequences would result in receptor activation and transformation. To investigate these requirements further, entirely novel transmembrane sequences were constructed based on tandem repeats of simple heptad sequences. Activation was achieved by transmembrane sequences such as [VVVEVVA]n or [VVVEVVV]n, whereas activation was not achieved by a transmembrane domain consisting only of Val residues. In the context of these transmembrane domains, Glu or Gln were equally activating, while Lys, Ser, and Asp were not. Using transmembrane domains with two Glu residues, the spacing between these was systematically varied from two to eight residues, with only the heptad spacing resulting in receptor activation. These results are discussed in the context of activating mutations in the transmembrane domain of FGFR3 that are responsible for the human developmental syndromes achondroplasia and acanthosis nigricans with Crouzon Syndrome.


Damage in InGaN/GaN bilayers upon Xe and Pb swift heavy ion irradiation.
350 nm and 550 nm thick InGaN/GaN bilayers were irradiated with different energies (from ∼82 to ∼38 MeV) of xenon (129Xe) ions and different fluences of 1.2 GeV lead (208Pb) ions, respectively. The radiation effects of the swift heavy ions' (SHIs) bombardment were investigated using Rutherford Backscattering Spectrometry in Channeling mode (RBS/C), X-Ray Diffraction (XRD), and micro-Raman spectroscopy. To assess damage profiles, the RBS/C analysis was followed by Monte Carlo simulations using the McChasy code, revealing that InGaN is more susceptible to irradiation damage than GaN. Moreover, the simulations suggest that both randomly displaced atoms (possibly due to partial amorphization) and dislocation loops are formed. The elastic response to radiation was estimated by measuring the expansion of the c-lattice parameter. XRD revealed the presence of strain even in low fluence samples where only a small fraction of the sample volume suffered direct SHI impacts. Micro-Raman suggests that for low defect concentrations, it is dominantly biaxial, while for high defect concentrations, the simultaneous increase of hydrostatic and biaxial occurs. As a driving force of the lattice expansion, we point out the Poisson effect resulting from the pressure exerted by the SHI tracks on the surrounding undamaged crystal structure.


Inhibition of late endosome-lysosome fusion: studies on the mechanism by which isotonic-K+ buffers alter intracellular ligand movement.
Incubation of alveolar macrophages or hepatocytes in media in which Na+ is replaced by K+ ("isotonic-K buffer") inhibited the movement of internalized ligand from late endosomes to lysosomes (Ward et al.: Journal of Cell Biology 110:1013-1022, 1990). In this study we investigate the mechanism responsible for the isotonic-K+ block in movement of ligand from late endosomes to lysosomes. We observed that iso-K+ inhibition of endosome-lysosome fusion is not unique to alveolar macrophages or hepatocytes but can be seen in a variety of cell types including J774 and Hela cells. The inhibition in intracellular ligand movement was time dependent with the maximum change occurring after 60 minutes. Once established the inhibition resulted in a prolonged and apparently permanent decrease in vesicle movement. Cells were able to recover from the effects of iso-K+ buffers over a time course of 5-10 minutes when placed back in Na(+)-containing media. The effect of iso-K+ buffers was independent of intracellular pH changes and appeared to involve cell swelling. When cells were incubated in iso-K+ buffers under conditions in which cell volume changes were reduced, intracellular ligand movement approached normal levels. Such conditions included replacing Cl- with the less permeant anion gluconate, and by addition of sucrose to isotonic-K+ buffers. Analysis of the mechanism by which changes in cell volume could alter intracellular movement ruled out changes in cyclic nucleotides, Ca2+, or microtubules. These results suggest that changes in cell shape or volume can alter intracellular transport systems by novel routes.


HPV vaccine catch up schedule - an opportunity for chlamydia screening.
The human papillomavirus (HPV) vaccine (Gardasil) catch up schedule in general practice is available until June 2009 to females not in school and under the age of 27 years. A course of three injections is given over 6 months. This provides a unique opportunity for sexual health screening in an age group where chlamydia screening is a priority.


Determination of natural radioactivity in drinking water in private dug wells in Akure, Southwestern Nigeria.
Gamma spectrometry of well water was done to measure the activity concentrations of gamma-emitters 226Ra and 228Ra from 238U and 232Th series, respectively, and 40K in their waters. Measurements were done using high-purity (HPGe) co-axial detectors (Canberra, GC 2018-7500 ) coupled to Canberra Multichannel Analyser system. Activity concentrations ranged from 0.57 to 26.86, 0.20 to 60.06 and 0.35 to 29.01 Bq l(-1) for 226Ra, 228Ra and 40K, respectively. Activity concentrations were compared with data from other parts of the world and used to estimate annual effective dose for three age groups. Total annual effective doses from the intake of these radionuclides in the waters ranged from 0.02 to 76.84, 0.02 to 38.80 and 0.05 to 481.60 mSv y(-1) for age group <1, 2-7 and > or =17 y, respectively. These values are considerably higher than both the World Health Organisation and the International Commission on Radiological Protection limits.


Anaerobic expression of the gadE-mdtEF multidrug efflux operon is primarily regulated by the two-component system ArcBA through antagonizing the H-NS mediated repression.
The gadE-mdtEF operon encodes a central acid resistance regulator GadE and two multidrug efflux proteins MdtEF. Although transcriptional regulation of gadE in the context of acid resistance under the aerobic growth environment of Escherichia coli has been extensively studied, regulation of the operon under the physiologically relevant environment of anaerobic growth and its effect on the expression of the multidrug efflux proteins MdtEF in the operon has not been disclosed. Our previous study revealed that anaerobic induction of the operon was dependent on ArcA, the response regulator of the ArcBA two-component system, in the M9 glucose minimal medium. However, the detailed regulatory mechanism remains unknown. In this study, we showed that anaerobic activation of mdtEF was driven by the 798 bp unusually long gadE promoter. Deletion of evgA, ydeO, rpoS, and gadX which has been shown to activate the gadE expression during acid stresses under aerobic condition did not have a significant effect on the anaerobic activation of the operon. Rather, anaerobic activation of the operon was largely dependent on the global regulator ArcA and a GTPase MnmE. Under aerobic condition, transcription of gadE was repressed by the global DNA silencer H-NS in M9 minimal medium. Interestingly, under anaerobic condition, while ΔarcA almost completely abolished transcription of gadE-mdtEF, further deletion of hns in ΔarcA mutant restored the transcription of the full-length PgadE-lacZ, and P1- and P3-lacZ fusions, suggesting an antagonistic effect of ArcA on the H-NS mediated repression. Taken together, we conclude that the anaerobic activation of the gadE-mdtEF was primarily mediated by the two-component system ArcBA through antagonizing the H-NS mediated repression.


The prevalence of mutations in the gene encoding filaggrin in the population of Polish patients with atopic dermatitis.
The genetic background of atopic dermatitis (AD) is complex, involves many genes and their participation varies in varied populations, and depends on the intensity and course of a disease. Changes in the nucleotide sequence of the FLG gene and a reduced number or a deficit of the functional product of processed profilaggrin can be one of risk factors for atopic dermatitis. To determine the prevalence of R501X and 2282del4 mutations of the FLG gene in patients with AD. The studied group included 60 patients with clinically diagnosed AD, and the control group included 61 healthy volunteers. The study protocol included collection of biological material for tests, DNA isolation and evaluation of its quality and quantity, and PCR amplification of the isolated genetic material. In the studied group, both changes in the nucleotide sequence of the FLG gene were detected and in the control group no tested mutations were detected. In 18 (30%) patients with AD, 22 mutations (4 heterozygous and 1 homozygous ones of R501X and 10 heterozygous and 7 homozygous ones of 2282del4) were detected. A high rate of mutations of the FLG gene in patients with clinically diagnosed AD and pathologically dry skin was observed in the studied population. The 2282del4 mutation occurred more often than R501X.


p73alpha isoforms drive opposite transcriptional and post-transcriptional regulation of MYCN expression in neuroblastoma cells.
MYCN activation, mainly by gene amplification, is one of the most frequent molecular events in neuroblastoma (NB) oncogenesis, and is associated with increased malignancy and decreased neuronal differentiation propensity. The frequency of concomitant loss of heterozygosity at the 1p36.3 locus, which harbours the p53 anti-oncogene homologue TP73, indicates that MYCN and p73 alterations may cooperate in the pathogenesis of NB. We have previously shown that p73 isoforms are deregulated in NB tumours and that TAp73 co-operates synergistically with p53 for apoptosis of NB cells, whereas DeltaNp73 activates the expression of neuronal differentiation genes such as BTG2. Herein, using both ectopic expression and RNA interference-mediated silencing of p73 in MYCN amplified NB cells, we show that p73alpha isoforms inhibit MYCN expression at both transcript and protein levels, in spite of transactivator effects on MYCN promoter. To explain this paradox, we found that TAp73alpha exerts negative post-transcriptional effects leading to reduced MYCN mRNA stability. RNA immunoprecipitation experiments suggest that this dominant inhibitory post-transcriptional effect could be due to an interaction between the p73 protein and MYCN mRNA, a hypothesis also raised for the regulation of certain genes by the p53 protein.


RRR-alpha-tocopherol regulation of gene transcription in response to the cell oxidant status.
RRR-alpha-Tocopherol, but not RRR-beta-tocopherol, negative regulates proliferation of vascular smooth muscle cells at physiological concentrations. At the same concentrations RRR-alpha-tocopherol inhibits protein kinase C activity, whereas RRR-beta-tocopherol is ineffective. Furthermore, RRR-beta-tocopherol prevents the inhibition of cell growth and of protein kinase C activity caused by RRR-alpha-tocopherol. The negative regulation by RRR-alpha-tocopherol of protein kinase C activity appears to be the cause of smooth muscle cell growth inhibition. RRR-alpha-Tocopherol does not act by binding to protein kinase C directly but presumably by preventing protein kinase C activation. A second RRR-alpha-tocopherol effect has been found at the level of AP 1, the latter becoming activated by RRR-alpha-tocopherol under condition of protein kinase C inhibition or down regulation. AP-1 inhibition by RRR-alpha-tocopherol is seen, however, under condition of protein kinase C stimulation. Compositional changes of AP-1 have been found to be at the basis of the RRR-alpha-tocopherol effects. RRR-beta-tocopherol, provided with similar antioxidant properties, not only it does not affect AP 1 but it prevents the effects of RRR-alpha-tocopherol. Moreover, it has been observed that RRR-alpha-tocopherol is able to affect TRE regulated gene transcription. It is concluded that RRR-alpha-tocopherol acts specifically in vascular smooth muscle cells, by controlling a signal transduction pathway leading to cell proliferation by a non-antioxidant mechanism.


Microbial counts in hands with and without nail varnish after surgical skin preparation: a randomized control trial.
Nail varnish is commonly removed from fingernails prior to surgical procedures. We report the results of a randomized controlled trial comparing the microbial counts in hands with and without nail varnish applied, following surgical skin preparation. Forty-three patients were randomized; three patients were lost to follow-up. Each patient had one hand painted with nail varnish and had both hands tested 1 week later. There was no significant difference in terms of positive microbial growth between the nail plates or hyponichia with or without nail varnish applied. Our results demonstrate that the presence of nail varnish does not have an effect on the microbial counts of hands following surgical skin preparation. I.


Enterocins L50A and L50B, two novel bacteriocins from Enterococcus faecium L50, are related to staphylococcal hemolysins.
Enterocin L50 (EntL50), initially referred to as pediocin L50 (L. M. Cintas, J. M. Rodríguez, M. F. Fernández, K. Sletten, I. F. Nes, P. E. Hernández, and H. Holo, Appl. Environ. Microbiol. 61:2643-2648, 1995), is a plasmid-encoded broad-spectrum bacteriocin produced by Enterococcus faecium L50. It has previously been purified from the culture supernatant and partly sequenced by Edman degradation. In the present work, the nucleotide sequence of the EntL50 locus was determined, and several putative open reading frames (ORFs) were identified. Unexpectedly, two ORFs were found to encode EntL50-like peptides. These peptides, termed enterocin L50A (EntL50A) and enterocin L50B (EntL50B), have 72% sequence identity and consist of 44 and 43 amino acids, respectively. Interestingly, a comparison of the deduced sequences of EntL50A and EntL50B with the corresponding sequences obtained by Edman degradation shows that these bacteriocins, in contrast to other peptide bacteriocins, are secreted without an N-terminal leader sequence or signal peptide. Expression in vivo and in vitro transcription/translation experiments demonstrated that entL50A and entL50B are the only genes required to obtain antimicrobial activity, strongly indicating that their bacteriocin products are not posttranslationally modified. Both bacteriocins possess antimicrobial activity on their own, with EntL50A being the most active. In addition, when the two bacteriocins were combined, a considerable synergism was observed, especially with some indicator strains. Even though the enterocins in some respects are similar to class II bacteriocins, several conserved features common to class II bacteriocins are absent from the EntL50 system. The enterocins have more in common with members of a small group of cytolytic peptides secreted by certain staphylococci. We therefore propose that the enterocins L50A and L50B and the staphylococcal cytolysins together constitute a new family of peptide toxins, unrelated to class II bacteriocins, which possess bactericidal and/or hemolytic activity.


Polymer entrapment in polymerized silicate for preparing highly stable capillary coatings for CE and CE-MS.
An easy-to-implement capillary coating strategy based on polymer entrapment in the network of polymerized silicate is described. In this manner, cationic polymers are tightly fixed onto the inner wall of the capillary for electroosmotic flow control without necessitating complex surface modification chemistries. The resulting coated capillary exhibited good stability over a wide range of pH, good reproducibility, strong endurance in more than 300 electrophoretic runs, and tolerance of commonly employed organic solvent additives in CE. Applications in CE-MS analysis of biologically important anions as well as sample enrichment are shown. Additionally, it was used as a durable base for attachment of multiple layers of charged polymers on the wall, via electrostatic interaction with the preceding layer. Thus, two novel types of highly stable coated capillaries, one with anodic EOF and the other cathodic, were developed.


Long-term dietary nitrite and nitrate deficiency causes the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice.
Nitric oxide (NO) is synthesised not only from L-arginine by NO synthases (NOSs), but also from its inert metabolites, nitrite and nitrate. Green leafy vegetables are abundant in nitrate, but whether or not a deficiency in dietary nitrite/nitrate spontaneously causes disease remains to be clarified. In this study, we tested our hypothesis that long-term dietary nitrite/nitrate deficiency would induce the metabolic syndrome in mice. To this end, we prepared a low-nitrite/nitrate diet (LND) consisting of an amino acid-based low-nitrite/nitrate chow, in which the contents of L-arginine, fat, carbohydrates, protein and energy were identical with a regular chow, and potable ultrapure water. Nitrite and nitrate were undetectable in both the chow and the water. Three months of the LND did not affect food or water intake in wild-type C57BL/6J mice compared with a regular diet (RD). However, in comparison with the RD, 3 months of the LND significantly elicited visceral adiposity, dyslipidaemia and glucose intolerance. Eighteen months of the LND significantly provoked increased body weight, hypertension, insulin resistance and impaired endothelium-dependent relaxations to acetylcholine, while 22 months of the LND significantly led to death mainly due to cardiovascular disease, including acute myocardial infarction. These abnormalities were reversed by simultaneous treatment with sodium nitrate, and were significantly associated with endothelial NOS downregulation, adiponectin insufficiency and dysbiosis of the gut microbiota. These results provide the first evidence that long-term dietary nitrite/nitrate deficiency gives rise to the metabolic syndrome, endothelial dysfunction and cardiovascular death in mice, indicating a novel pathogenetic role of the exogenous NO production system in the metabolic syndrome and its vascular complications.


Association between malnutrition risk and hemorrhagic transformation in patients with acute ischemic stroke.
Malnutrition is a prevalent problem occurring in different diseases. Hemorrhagic transformation (HT) is a severe complication of acute ischemic stroke (AIS). Few studies have evaluated the association between malnutrition risk and hemorrhagic transformation in patients with acute stroke. We aim to investigate the influence of malnutrition risk on the risk of hemorrhagic transformation in patients with AIS. A total of 182 consecutive adults with HT and 182 age- and sex-matched patients with stroke were enrolled in this study. The controlling nutritional status (CONUT) score was calculated to evaluate the malnutrition risk. HT was detected by follow-up imaging assessment and was radiologically classified as hemorrhagic infarction type 1 or 2 or parenchymal hematoma type 1 or 2. Logistic regression models were conducted when participants were divided into different malnutrition risk groups according to the objective nutritional score to assess the risk for HT. The prevalence of moderate to severe malnutrition risk in patients with AIS was 12.5%, according to the CONUT score. Univariate analysis showed that the CONUT score is significantly higher in patients with HT than those without HT. After adjusting for potential covariables, the patients with mild risk and moderate to severe malnutrition risk were associated with a higher risk of HT compared to the patients in the normal nutritional status group [odds ratio, 3.180 (95% CI, 1.139-8.874), P = 0.027; odds ratio, 3.960 (95% CI, 1.015-15.453), P = 0.048, respectively]. Malnutrition risk, measured by CONUT score, was significantly associated with an increased risk of hemorrhagic transformation in patients with AIS.


Reference range of thyroid hormones in very low birth weight infants at the time of discharge.
There is little information regarding the reference range for thyroid hormones in preterm babies, especially those with very low birth weight (VLBW) of less than 1500 g. The objective of our study was to evaluate the relationship between thyroid hormone levels and postmenstrual age in a cohort of stable VLBW infants. An observational cohort study of VLBW infants preparing for discharge from a high-dependency nursery in Singapore. The infants' free thyroxine (fT4) and thyrotropin (TSH) levels were assayed just before discharge and correlated with postmenstrual age, calculated as the sum of the duration of gestation at birth and chronological age in weeks. fT4 and TSH levels were sampled in 129 ex-VLBW babies at a mean postmenstrual age of 38.5 (±4.6) weeks. The babies were born at a mean±SD gestation of 28.9±2.4 weeks (median 29.0 weeks, range 24.0-34.5 weeks) with mean±SD birth weight of 1081±268 g (median 1090 g, range 490-1490 g). Linear regression analysis revealed negative and fair correlation between fT4 and postmenstrual age (r=-0.302). The mean±SD fT4 level was 16.8±3.2 pmol/L (median 16.8 pmol/L, range 8.5-28.9 pmol/L). However, there was only a very weak negative correlation between TSH levels and postmenstrual age, both with (r=-0.116) or without logarithmic transformation. The mean±SD TSH was 4.56±2.50 mIU/L (median 4.42 mIU/L, range 1.0-13.5 mIU/L). Our study shows a fair and inverse correlation of fT4 with postmenstrual age in a large cohort of growing ex-VLBW infants, in keeping with maturation of the hypothalamic-pituitary-thyroid axis. It suggests that fT4 levels in growing infants are best compared to postmenstrual age-specific norms instead of a single reference interval.


Antigenic phenotype of chronic granulocytic leukaemia progenitor cells in chronic phase and in blastic transformation characterized by means of monoclonal antibodies.
We studied the surface antigens of "early" and "late" granulocyte-macrophage progenitor cells (CFU-GM) from bone marrow and peripheral blood of 18 patients with chronic granulocytic leukaemia in chronic phase (CGL-CP) using 14 selected murine monoclonal antibodies (McAbs) in complement dependent cytotoxicity assay followed by culture in methyl cellulose. The same panel of McAbs was used to determine the antigens on leukaemic blast cells from peripheral blood of 15 patients with CGL in blastic transformation (BT) by complement mediated lysis and in vitro culture technique for clonogenic blasts (CFU-L) and immunofluorescence assay for total blast population. McAb for HLA-DR antigens (L243) and McAbs MY9, S3-13, S17-25 and 53/6 reacted with CFV-GM and CFU-L. In contrast, McAbs PM81 and AML-2-23 recognizing antigens on more mature myeloid cells did not react with these progenitor cells. McAb S4-7 reacted with the majority of CFU-L and a small proportion of "early" and "late" CFU-GM. This McAb may be useful for the prediction of blastic transformation in CGL patients. Generally, the reactivity of most McAbs was more heterogeneous with CFU-L than with CFU-GM in individual patients. The majority of McAbs included in our study reacted with a higher percentage of CFU-L and CFU-GM than predominant blast cell population in individual patients perhaps because the detected antigens are expressed more strongly on dividing progenitors than on relatively nonproliferative progeny. Thus we interpret the results of these studies showing that the antigenic phenotypes of the blast colony progenitor cells in CGL-BT are very similar to but not identical with those of CFU-GM from CGL-CP patients.


MicroRNA-34c is regulated by p53 and is involved in sevoflurane-induced apoptosis in the developing rat brain potentially via the mitochondrial pathway.
The commonly used inhalation anesthetic, sevoflurane, has been previously demonstrated to induce apoptosis in the developing brain; however, the underlying molecular mechanisms remain largely unknown. MicroRNAs (miRNAs) serve important roles in multiple physiological/pathological processes, such as cell death and survival. In the present study, the miRNA sequence that was most closely associated with sevoflurane‑induced apoptosis in the hippocampus of neonatal rat brains was identified. Seven‑day‑old Sprague Dawley rats were first exposed to 2.3% sevoflurane for 6 h. Hippocampal brain tissues were harvested at 6 h following sevoflurane exposure. Cleaved caspase‑3 levels were examined using an immunofluorescence assay. Alterations in miRNA expression were assessed by microarray analysis and reverse transcription-quantitative polymerase chain reaction. The protein levels of p53, phosphorylated (p)‑p53, B-cell lymphoma-2 (Bcl-2) and Bax were assessed by western blot analysis. Sevoflurane exposure significantly increased the levels of cleaved caspase‑3 in the hippocampus. In addition, among the 688 miRNAs that were observed to be expressed in the hippocampus, sevoflurane exposure altered the expression levels of 266 miRNAs. Among these differentially expressed miRNAs, eight were significantly upregulated and one (miRNA‑34c) was significantly downregulated following sevoflurane exposure. Bioinformatics analyses indicated the miRNA‑34c was a direct downstream target of p53. Sevoflurane exposure induced significant alterations in the level of p‑p53, Bcl‑2 and Bax in the hippocampus of neonatal rats. In conclusion, the results of the present study suggest that miRNA‑34c may be regulated by p53 and is involved in sevoflurane‑induced neural apoptosis in the hippocampus of developing rat brains, potentially via the mitochondrial pathway.


Small-bowel atresias: a case series with review of the disease and imaging findings.
Small-bowel atresias are among the most common causes of intestinal obstruction in newborns, and they often require urgent surgical treatment. Imaging techniques play a very important role in their diagnosis, which is often suspected on prenatal obstetric ultrasound and confirmed on postnatal plain-film X-rays. Abdominal ultrasound's lack of ionizing radiation, wide availability, low cost, and high resolution is making this technique increasingly important in confirming atresias and in detecting possible complications in newborns. This review analyzes a series of cases seen at our center. It summarizes the different types of small-bowel atresias, focusing on the clinical presentation, imaging findings on different modalities, presence of associated disease, management, clinical course, and outcomes.


Simple Perylene Diimide Cyclohexane Derivative With Combined CPL and TPA Properties.
In this work we describe the linear and non-linear (chiro)optical properties of an enantiopure bis-perylenediimide (PDI) cyclohexane derivative. This compound exhibits upconversion based on a two-photon absorption (TPA) process with a cross-section value of 70 GM together with emission of circularly polarized luminescence (CPL), showing a glum in the range of 10-3. This simple structure represents one of the scarce examples of purely organic compounds combining both TPA and CPL responses, together with large values of molar absorptivity and fluorescence quantum yield with emission in the 500-600 nm. Self-assembly induced by introduction of a poor solvent allows for a spectacular shift of the emission into the near-infrared (NIR, 650-750 nm) by formation of well-defined rotationally displaced dimers. Therefore, we are here presenting a versatile platform whose optical properties can be simply tuned by self-assembly or by functionalization of the electron-deficient aromatic core of PDIs.


ICOS signaling promotes a secondary humoral response after re-challenge with Plasmodium chabaudi chabaudi AS.
The co-stimulatory molecule ICOS is associated with the induction and regulation of T helper cell responses, including the differentiation of follicular helper T (Tfh) cells and the formation and maintenance of memory T cells. However, the role of ICOS signaling in secondary immune responses is largely unexplored. Here we show that memory T cell formation and maintenance are influenced by persistent infection with P. chabaudi chabaudi AS infection, as memory T cell numbers decline in wild-type and Icos-/- mice after drug-clearance. Following drug-clearance Icos-/- mice display a relapsing parasitemia that occurs more frequently and with higher peaks compared to wild-type mice after re-challenge. The secondary immune response in Icos-/- mice is characterized by significant impairment in the expansion of effector cells with a Tfh-like phenotype, which is associated with a diminished and delayed parasite-specific Ab response and the absence of germinal centers. Similarly, the administration of an anti-ICOSL antagonizing antibody to wild-type mice before and after reinfection with P. c. chabaudi AS leads to an early defect in Tfh cell expansion and parasite-specific antibody production, confirming a need for ICOS-ICOSL interactions to promote memory B cell responses. Furthermore, adoptive transfer of central memory T (TCM) cells from wild-type and Icos-/- mice into tcrb-/- mice to directly evaluate the ability of TCM cells to give rise to Tfh cells revealed that TCM cells from wild-type mice acquire a mixed Th1- and Tfh-like phenotype after P. c. chabaudi AS infection. While TCM cells from Icos-/- mice expand and display markers of activation to a similar degree as their WT counterparts, they displayed a reduced capacity to upregulate markers indicative of a Tfh cell phenotype, resulting in a diminished humoral response. Together these findings verify that ICOS signaling in memory T cells plays an integral role in promoting T cell effector responses during secondary infection with P. c. chabaudi AS.


[Preliminary study of tumor perfusion assessment with multidetector CT in carcinoma of esophagus and cardia].
To investigate the clinical application of first-pass perfusion MDCT in the assessment of tumor angiogenesis in carcinoma of esophagus and cardia. CT perfusion was performed with multi-detector row CT (MDCT) in 44 patients with carcinoma of esophagus and esophagogastric junction, who was diagnosed with pathological results and did not received any anti-tumor therapy. Twenty-one patients with peripheral lung cancer but normal esophagus were served as controls. Perfusion parameters were compared between normal and malignant esophagus, between adenocarcinoma and squamous cell carcinoma, as well as between tumors with metastases and those without metastases. Carcinoma of esophagus and esophagogastric junction showed higher blood flow, peak enhancement index, blood volume, and shorter time to peak compared with normal esophagus (P < 0.05). There were no statistically significant differences in perfusion parameters between adenocarcinoma and squamous cell carcinoma (P > 0.05), whereas tumors with metastases showed higher blood flow and shorter time to peak compared with those without metastases (P < 0.05). MDCT perfusion could assess tumor vascularity in carcinoma of esophagus and esophagogastric junction, and tumor vascularity or angiogenesis was not influenced by its histological type. However, high blood flow and short time-to-peak may be helpful to predict tumor metastases.


Site specific integration of FLP recombinase in BHK-21 cell line.
A binary system for gene activation and site specific integration based on conditional recombination of transfected sequences mediated by FLP recombinase from yeast was implemented in mammalian cells. In several cell lines, FLP rapidly and precisely recombined copies of its specific target sequences to activate an otherwise silent beta-galactosidase reporter gene. Clones of marked cells were generated by excisional recombination within a chromosomally integrated copy of the silent reporters. These clones exhibited intense blue colour with X-Gal staining solution.


Effectiveness of a preventive program based on caries risk assessment and recall intervals on the incidence and regression of initial caries lesions in children.
Evidence on caries risk assessment (CRA) and recall intervals are limited in terms of caries prevention. To assess the effectiveness of a program on the incidence and regression of initial caries lesions. A total of 296 children aged 1-12 years old were assessed by calibrated examiners for Gingival Bleeding Index, Dental Plaque Index, dmf-t/DMF-T Index, initial caries lesions, and caries lesion activity. Children were classified as low, moderate, and high caries risk with different recall interval visits. Statistical analysis included Cox regression and Kaplan-Meier curves. The mean (SD) time of total follow-up for the sample was 11.5(5.5). Higher dmft index at baseline showed a higher risk of new initial lesions (HR = 1.93; P < 0.0001). Higher number of active initial lesions, at baseline and during follow-up visits, is a higher risk predictor for new initial lesions (HR = 9.49; P < 0.0001), as well as for no arrestment of active lesions during follow-up (HR = 1.32; P < 0.0001). Each follow-up visit attended presented a 77% lower risk of initial lesions. The majority (94.8%) of patients did not show new initial lesions. The Program is effective on reducing the incidence and promoting regression of initial caries lesions in children.


Evaluation of Parkinson's disease by neuromelanin-sensitive magnetic resonance imaging and 123I-FP-CIT SPECT.
Background Both neuromelanin-sensitive magnetic resonance imaging (NmMRI) and 123I-FP-CIT single photon emission computed tomography (SPECT) (DaTSCAN) assist the diagnosis of Parkinson's disease (PD). However, there have been few studies investigating a correlation between them. Purpose To correlate the utility of NmMRI and DaTSCAN and to evaluate the relationship between both imaging findings and the Unified PD rating scale part III (UPDRS III) score for the diagnosis and management of PD. Material and Methods Seventeen patients with PD who underwent both NmMRI and DaTSCAN were included. We measured the volume of the neuromelanin-positive substantia nigra pars compacta (SNc volume) on NmMRI and measured the specific binding ratio (SBR) on DaTSCAN. The asymmetry index (AI) of the SNc volume and SBR were also calculated. We evaluated the relationship between the UPDRS III score and the SNc volume and SBR, respectively. Results The SNc volume showed a significant correlation with the SBR. The AIs of them also showed a significant correlation. Both the mean of the bilateral SBR and the mean of the bilateral SNc volume showed significant negative correlations with the UPDRS III score. However, the correlation between the SBR and the UPDRS III score was stronger than that between the SNc volume and the UPDRS III score. Conclusion Both NmMRI and DaTSCAN are helpful for PD diagnosis. However, we conclude that DaTSCAN is more suitable for the evaluation of the clinical motor severity and would be more useful for the management of PD patients than NmMRI.


Regression of a plasmablastic lymphoma in a patient with HIV on highly active antiretroviral therapy.
We describe an HIV-infected 44-year-old man who presented 1 month after discontinuation of HAART therapy with a large mass extending from the mediastinum, enclosing the heart and extending through the diaphragm to the epigastric region. Biopsies subsequently revealed a highly aggressive non-Hodgkin's lymphoma (NHL) producing sheets of cells with an organoid distribution. The cells had abundant basophilic cytoplasm and a plasmacytic appearance. Although immunohistochemistry failed to show either B- or T-cell markers, antigens consistent with plasma cells were found. An immunoglobulin heavy chain clonal rearrangement was identified by PCR analysis. These studies were supportive of a diagnosis of a plasmablastic lymphoma. While awaiting the results of these tests, the patient was reinitiated on his HAART regimen. He was found on follow-up a month later to have complete resolution of his bulky mediastinal mass. He remained free of disease for 3 months with subsequent rectal and abdominal recurrence. Treatment with CHOP chemotherapy with filgrastim support was begun which resulted in another remission. Plasmablastic lymphoma is now reported in some studies to account for 2.6% of all HIV-related NHL. Originally described in 1997 in a series of 16 patients, this entity is highly associated with HIV infection in its later stages. Often, patients present with oral or jaw lesions with a rapidly progressive course. The tumors have the morphologic appearance of a plasmacytoid tumor with high proliferative index. Markers are positive mainly for LCA, CD79a, VS38C, and CD138. Co-infection with HHV-8 and EBV has not been consistently reported. Therapy with standard regimens has variable response. One case has been reported with a 3.5 year disease free survival. The regression of disease after resumption of HAART therapy alone in this patient suggests that HAART has an important role in the treatment of lymphoma in the HIV infected patient.


A pilot study of nonverbal cues in videotelecommunication.
With the increasing popularity of low-cost videocommunications systems and their attendant low bandwidth-resolution problems, receivers are likely to experience difficulties in recognising the sender's intended expression and feeling. As an extension of previous work in the area, this pilot study investigated the effects of three forms of degraded imaging (and their combined effects) on the nonverbal aspects of communication for one person. Degraded video messages significantly impaired the meaning of the sender.


Enzyme immunoassay of cyclazocine using peroxidase as label.
A sensitive enzyme immunoassay for the determination of serum or urinary cyclazocine was developed. Horseradish peroxidase was used as the labelling enzyme; it was conjugated with cyclazocine derivatives by the mixed anhydride method. After the immune reaction, bound and free fractions were separated by a double-antibody solid-phase method, using Sepharose 4B gel coupled with purified IgG from goat anti-rabbit IgG serum. The enzyme activity was measured fluorophotometrically, with p-hydroxyphenyl propionic acid and hydrogen peroxide as substrates. The correlation coefficients verified that there was excellent agreement between the results obtained by the new enzyme immunoassay and those of radioimmunoassay (r=0.92) and gas chromatography-mas spectrometry (r=0.94).


Development of TNFSF as molecular adjuvants for ALVAC HIV-1 vaccines.
A phase III clinical trial finished in Thailand recently showed that an ALVAC HIV-1 vaccine prime-gp120 protein boost vaccination regimen could modestly protect persons from HIV-1 infection, demonstrating that development of an effective and safe HIV-1 preventive vaccine is possible. ALVAC HIV-1 vaccines are candidate HIV-1 vaccines based on canarypox vectors. Previous clinical trials proved that ALVAC HIV-1 vaccines were safe but weak in immunogenicity when used in human subjects. We have been exploring to use tumor necrosis factor superfamily (TNFSF) members as adjuvants to enhance the immunogenicity of ALVAC HIV-1 vaccines. In this commentary, we will summarize our findings in using two TNFSF molecules, CD40L and OX40L, as adjuvants for an ALVAC HIV-1 vaccine in mouse model. We will also briefly discuss the challenges and prospects of using TNFSF molecules as adjuvants for HIV-1 vaccines in humans.


Evaluation of the efficacy & biochemical mechanism of cell death induction by Piper longum extract selectively in in-vitro and in-vivo models of human cancer cells.
Currently chemotherapy is limited mostly to genotoxic drugs that are associated with severe side effects due to non-selective targeting of normal tissue. Natural products play a significant role in the development of most chemotherapeutic agents, with 74.8% of all available chemotherapy being derived from natural products. To scientifically assess and validate the anticancer potential of an ethanolic extract of the fruit of the Long pepper (PLX), a plant of the piperaceae family that has been used in traditional medicine, especially Ayurveda and investigate the anticancer mechanism of action of PLX against cancer cells. Following treatment with ethanolic long pepper extract, cell viability was assessed using a water-soluble tetrazolium salt; apoptosis induction was observed following nuclear staining by Hoechst, binding of annexin V to the externalized phosphatidyl serine and phase contrast microscopy. Image-based cytometry was used to detect the effect of long pepper extract on the production of reactive oxygen species and the dissipation of the mitochondrial membrane potential following Tetramethylrhodamine or 5,5,6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine chloride staining (JC-1). Assessment of PLX in-vivo was carried out using Balb/C mice (toxicity) and CD-1 nu/nu immunocompromised mice (efficacy). HPLC analysis enabled detection of some primary compounds present within our long pepper extract. Our results indicated that an ethanolic long pepper extract selectively induces caspase-independent apoptosis in cancer cells, without affecting non-cancerous cells, by targeting the mitochondria, leading to dissipation of the mitochondrial membrane potential and increase in ROS production. Release of the AIF and endonuclease G from isolated mitochondria confirms the mitochondria as a potential target of long pepper. The efficacy of PLX in in-vivo studies indicates that oral administration is able to halt the growth of colon cancer tumors in immunocompromised mice, with no associated toxicity. These results demonstrate the potentially safe and non-toxic alternative that is long pepper extract for cancer therapy.


Colocalization of NADPH-diaphorase and estrogen receptor immunoreactivity in the rat ventromedial hypothalamic nucleus: stimulatory effect of estrogen on NADPH-diaphorase activity.
NADPH-diaphorase (NADPH-d) histochemistry was combined with estrogen receptor (ER) immunohistochemistry in order to study effect of estrogen on NADPH-d activity and establish an anatomical relationship between NADPH-d and ER-immunoreactivity (ir) containing neurons in the ventromedial hypothalamic nucleus (VMN). Gonadectomized female and male rats received either oil (control group) or 10 micrograms of estradiol benzoate (EB) for two successive days and were sacrificed on day 4. While NADPH-d histochemistry stained a specific subpopulation of neurons in the ventrolateral portion of the VMN of all groups, there was a marked sex difference in the effect of EB treatment. EB elevated the number of NADPH-d positive neurons in females but had no significant effect in males. Double-labeling histochemistry revealed that more than 70% of the NADPH-d positive neurons contained ER-ir in the VMN of all groups, with EB-treated females having a significantly higher frequency than all other groups. Since neuronal NADPH-d is nitric oxide synthase (NOS), these results provide anatomical evidence for an association of estrogen with NOS in the rat VMN and suggest that NOS activity can be modulated by estradiol in estrogen sensitive neurons.


Characterization of the Rifamycin-Degrading Monooxygenase From Rifamycin Producers Implicating Its Involvement in Saliniketal Biosynthesis.
Rifamycin derivatives, such as rifampicin, have potent antibiotic activity and have long been used in the clinic as mainstay components for the treatment of tuberculosis, leprosy, and AIDS-associated mycobacterial infections. However, the extensive usage of these antibiotics has resulted in the rapid development of bacterial resistance. The resistance mechanisms mainly include mutations of the rifamycin target RNA polymerase of bacteria and enzymatic modifications of rifamycin antibiotics. One modification is the recently characterized rifamycin degradation catalyzed by Rox enzymes, which belong to the widely occurring flavin monooxygenases. Intriguingly, our recent sequence analysis revealed the rifamycin producers also encode Rox homologs that are not yet characterized. In this work, we expanded the study of the Rox-catalyzed rifamycin degradation. We first showed that the Rox proteins from rifamycin producers have the enzymatic rifamycin SV-degrading activity. Then we used the structurally diverse rifamycin compounds rifampicin and 16-demethylrifamycin W to probe the substrate scope and found that they each have a slightly different substrate scope. Finally, we demonstrated that Rox proteins can also catalyze the transformation of 16-demethylsalinisporamycin to 16-demethylsaliniketal A. Since 16-demethylsalinisporamycin and 16-demethylsaliniketal A are the counterpart analogs of salinisporamycin and saliniketal A, our biochemical findings not only uncover a previously uncharacterized self-resistance mechanism in the rifamycin producers, but also bridge the gap between the biosynthesis of the potential antitumor compound saliniketal A.


Rituximab in lymphocyte-predominant Hodgkin disease.
Lymphocyte-predominant Hodgkin disease (LPHD) differs in biology and clinical behaviour from classic Hodgkin disease. Almost 100% of LPHD neoplastic cells express CD20 and thus rituximab could be effective; yet limited data are available. We performed a retrospective analysis on patients with LPHD who were treated with rituximab at our institution to determine the magnitude of benefit offered by this drug. Seven patients were identified; 4 received the drug as single agent while the rest received it in combination with chemotherapy. All except 2 received the drug in the salvage setting. Response rate was 100% with 6 of 7 patients achieving complete remission. At a median follow-up of 2 years, 4 patients are still disease free while the rest relapsed at a median time of 27 months. Rituximab is effective in LPHD and should be considered; however, the optimal schedule remains to be determined.


Young Children's Understanding of Teaching and Learning and Their Theory of Mind Development: A Causal Analysis from a Cross-Cultural Perspective.
Children's understanding of the concepts of teaching and learning is closely associated with their theory of mind (ToM) ability and vital for school readiness. This study aimed to develop and validate a Preschool Teaching and Learning Comprehension Index (PTLCI) across cultures and examine the causal relationship between children's comprehension of teaching and learning and their mental state understanding. Two hundred and twelve children from 3 to 6 years of age from Hong Kong and the United States participated in study. The results suggested strong construct validity of the PTLCI, and its measurement and structural equivalence within and across cultures. ToM and PTLCI were significantly correlated with a medium effect size, even after controlling for age, and language ability. Hong Kong children outperformed their American counterparts in both ToM and PTLCI. Competing structural equation models suggested that children's performance on the PTLCI causally predicted their ToM across countries.


Psychological effect of the Nagasaki atomic bombing on survivors after half a century.
In 1997 a mental health survey using a 30-item General Health Questionnaire (GHQ-30) and an interview survey of an atomic bombing experience were conducted in survivors of the Nagasaki atomic bombing. Overall psychological distress measured on the basis of the GHQ-30 was greater in the atomic bombing survivors than in the controls. As for the contents of psychological distress, those concerning emotion such as anxiety and depression were milder in survivors than in the controls, but those related to social activities such as apathy, disturbance of human relations, loss of enjoyment of living were more severe. Furthermore, recurring and distressing recollection of the experience of the atomic bombing, suspicion over the relationship between the atomic bombing and an unhealthy physical condition, and the experience of witnessing death or severe injury of close relatives due to the atomic bombing were significantly related to the degree of psychological distress of the survivors.


Clinicopathological Characteristics and Prognosis of Diffuse Large B-Cell Lymphoma in Relation to CA-125 and CA 19-9 Expression.
Background: Some epithelial tumors express the carbohydrate antigen 125 (Cancer antigen-125, CA-125) and CA 19-9, especially ovarian and pancreatic tumors. Patients with non-Hodgkin lymphoma (NHL) were reported to have a close association between serum CA-125 levels and adverse prognostic factors with worse survival. We aimed to investigate CA-125 and 19-9 expression in nodal diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS) tissues using immunohistochemistry (IHC) and their relations to clinicopathological manifestations and patients' survival. Methods: 65 cases of DLBCL NOS were examined. A modified mechanical pencil tip was used to construct Manual Tissue Micro-array (TMA) blocks. Immunohistochemical staining for CA-125 and CA 19-9 was performed and scored semi-quantitatively. All relations were analyzed using established statistical methodologies. Results: Aberrant expression of CA 19-9 was detected in 12% of cases without any expression of CA-125. Moreover, 75% of the CA 19-9 positive cases were statistically significantly associated with anemia and performance status 1. Also, 75% of the CA 19-9 positive cases were females. Conclusions: CA 19-9 was aberrantly expressed in 12% of nodal DLBCL NOS cases and significantly related to anaemia and performance status but not to survival. In cases of DLBCL NOS, CA 19-9 expression cannot be considered an independent prognostic factor. CA-125 was not expressed in nodal DLBCL NOS tissues, necessitating re-evaluation studies. Therefore, it is advised to conduct more research to clarify the potential correlation between serum and tissue CA 19-9 levels and other clinic-pathological characteristics of nodal and extranodal DLBCL NOS patients.


Intraspecific competition and density dependence of food consumption and growth in Arctic charr.
1. Intraspecific competition for restricted food resources is considered to play a fundamental part in density dependence of somatic growth and other population characteristics, but studies simultaneously addressing the interrelationships between population density, food acquisition and somatic growth have been missing. 2. We explored the food consumption and individual growth rates of Arctic charr Salvelinus alpinus in a long-term survey following a large-scale density manipulation experiment in a subarctic lake. 3. Prior to the initiation of the experiment, the population density was high and the somatic growth rates low, revealing a severely overcrowded and stunted fish population. 4. During the 6-year period of stock depletion the population density of Arctic charr was reduced with about 75%, resulting in an almost twofold increase in food consumption rates and enhanced individual growth rates of the fish. 5. Over the decade following the density manipulation experiment, the population density gradually rose to intermediate levels, accompanied by corresponding reductions in food consumption and somatic growth rates. 6. The study revealed negative relationships with population density for both food consumption and individual growth rates, reflecting a strong positive correlation between quantitative food intake and somatic growth rates. 7. Both the growth and consumption rate relationships with population density were well described by negative power curves, suggesting that large density perturbations are necessary to induce improved feeding conditions and growth rates in stunted fish populations. 8. The findings demonstrate that quantitative food consumption represents the connective link between population density and individual growth rates, apparently being highly influenced by intraspecific competition for limited resources.


ROR alpha gene expression in the perinatal rat cerebellum: ontogeny and thyroid hormone regulation.
Deficiency of thyroid hormone (TH) during the perinatal period results in severe neurological abnormalities in rodent cerebellar development. However, the molecular mechanisms of TH action in the developing cerebellum are not fully understood. Of note, a mutant mouse, staggerer, in which the orphan nuclear hormone receptor ROR alpha gene is disrupted, exhibits cerebellar abnormalities similar to those seen in the hypothyroid animals, despite normal thyroid function. We, therefore, speculated that TH (tetraiodo-L-thyronine; T4) may regulate ROR alpha gene expression, which then may regulate genes essential for normal brain development. To test this hypothesis, we studied the changes in ROR alpha gene expression in perinatal hypothyroid rat cerebellum and the effect of TH replacement using Northern blot analysis, ribonuclease protection assay and in situ hybridization histochemistry. During cerebellar development, an approximately 3-fold increase in the cerebellar content of ROR alpha messenger RNA (mRNA) was seen in both propylthiouracil-treated, and propylthiouracil-treated and T4-replaced animals. However, the increase was accelerated when T4 was injected, although the ROR alpha mRNA content was identical, with or without T4, by 30 days after birth (P30). In contrast, T4 treatment suppressed the TH receptor alpha1 and c-erbA alpha2 mRNA content by P30; retinoic acid X receptor-beta mRNA content was not influenced by thyroid status. A significant hybridization signal for ROR alpha mRNA was seen only over Purkinje cells in the cerebellar cortex by in situ hybridization histochemistry. These results indicate that TH alters the timing of expression of the ROR alpha gene in the Purkinje cells of the cerebellar cortex, which may, in turn, influence Purkinje cell differentiation.


The interaction of electrodermal activity and expressed emotion in predicting symptoms in recent-onset schizophrenia.
In the present study, expressed emotion (EE) was assessed among immediate family members of 94 recent-onset schizophrenia patients at initial study entry point, and patients' electrodermal activity (EDA) was measured without the presence of family members at a baseline outpatient stabilization assessment. Psychiatric symptoms were also rated, both at the baseline outpatient test and at 1-year follow-up. Electrodermal activity × expressed emotion interactions were observed at both test points. In each case, the highest levels of negative symptoms were observed among those who exhibited greater EDA and lived in a high-EE environment. These results support the view that the combination of high family EE and sympathetic nervous system arousal confer especially high risk for poor negative symptom outcomes.


Giant Orbital Melanoma in a Heroin Abuser.
The aim of this report was to report a heroin abuser with nondiagnosed giant uveal melanoma infiltrating the orbit and prolapsing through the face. We conducted a case report of the patient with giant melanoma. In March 2013, a 39-year-old male with bleeding from the right side of his face was taken to the Emergency Center of the University Hospital Bratislava by ambulance. The heroin abusing, homeless male who had never been treated before reported a 2-year history of a prolapsed, dark colored mass from his eye. Acute computed tomography confirmed a solid mass 20 × 20 cm prolapsing from the orbit. The patient rejected primary care, accepted only 1 transfusion and left the hospital. Two months later, he was admitted to the hospital due to anemia after many collapses. Liver metastasis was present. Surgical palliative therapy was not possible due to his general status. The patient started fractionated external radiotherapy with 8.0 Gy Co60. Histopathological examination of the biopsy specimen showed malignant melanoma of the epitheloid type G2-3. The patient died in December 2013. Extraorbital formation of a melanoma mass may progress to a giant volume, and without treatment, led to metastases in the liver and to death after 9 months in our patient with anemia.


[Antigenic structure of hemagglutinins of influenza H1N1 (Hsw1N1) virus isolated from humans and ducks].
The method of specific adsorption followed by the use of antisera in HI test and competitive enzyme immunoassay was used to study the antigenic composition of hemagglutinins (HA) Hsw1 in influenza viruses isolated in 1982 from humans in Bulgaria and in 1976 in Canada from ducks as well as their antigenic relationships with HA of Hsw1 variant isolated from swine and man. Hemagglutinins of Hsw1 strains isolated from man in Bulgaria and Alma-Ata were found to be similar to HA of A/New Jersey/8/76 virus in two determinants and with hemagglutinin of the classic virus of swine in three determinants. The HA of A/duck/Alberta/35/76 virus was similar in three determinants to HA of A/New Jersey/8/76 virus and in two determinants with other Hsw1 variants. The similarities and differences in antigenic determinants of HA in Hsw1 viruses isolated from man and animals attest to their common origin and different modes of variability.


A preoperative score to predict early death after pancreatic cancer resection.
This study aimed to develop and validate a preoperative prognostic model for death within one year post-surgery in patients with resectable pancreatic ductal adenocarcinoma (PDAC). A derivation cohort study of 296 patients who underwent surgical resection of PDAC was prospectively enrolled in an observational study. Preoperative predictors of one year mortality were used to develop a risk score which was then validated in an external cohort of 182 patients with resectable PDAC. Seventy-eight out of 296 patients (26%) died within the first year. Preoperative independent predictors of one year mortality were: nutritional status (Geriatric Nutritional Risk Index, OR 2.23, 1.14-4.38; p=0.02), American Society of Anaesthesiologists' score (OR 2.56, 1.1-5.98; p=0.03), abdominal or back pain at presentation (OR 2.51, 1.05-5.9; p=0.038) and non metastatic liver disease as comorbidity (OR 4.5, 1.05-19.3; p=0.043). A score ranging from 0 to 7 points was developed. In the validation cohort, the model was able to predict early mortality (OR 7.1, 3.9-12.7; p<0.0001), with a predictive ability of 53.5% (Nagelkerke R2), an area under the receiver operating characteristic curve of 88.7% and an acceptable calibration (goodness-of-fit test, p=0.403). Our new simple risk score proved reliable in forecasting one year mortality in patients with resectable PDAC.


Intermittent outpatient based ECUM. A case report.
Extracorporeal Ultrafiltration Method (ECUM) could be used in patients with refractory congestive heart failure (CHF). We have encountered a 56-year-old woman with refractory congestive heart failure (CHF) (NYHA II-III) due to coronary artery disease, complicated by moderately advanced diabetic nephropathy (Cr = 2.4 mg/dl). Due to the non-responsiveness to medical treatments, she has begun receiving the intermittent ECUM once or twice a week on an outpatient basis. ECUM effectively reduced cardiac preload and temporarily relieved her intractable respiratory distress. Based on our present clinical experience, we propose that one could consider an outpatient based intermittent ECUM as one of the useful therapeutic modalities to ameliorate refractory CHF.


Tuning Chromophore-Based LMOF Dimensionality to Enhance Detection Sensitivity for Fe3+ Ions.
Herein, we report the synthesis of two new manganese-based luminescent metal-organic frameworks (LMOFs) [Mn0.5(tipe)(1,4-ndc)] n (1) and [Mn(tipe)(1,4-ndc) (H2O)·(DMF)2·(H2O)3] n (2) [tipe = 1,1,2,2-tetrakis(4-(1H-imidazol-1-yl)phenyl)ethene (tipe) and 1,4-ndc = 1,4-naphthalenedicarboxylic acid] constructed from an aggregation-induced emission (AIE) chromophore ligand. Compound 1 can undergo a facile single-crystal-to-single-crystal transformation to form compound 2, which results in an increase in dimensionality from a two-dimensional (2D) network to a three-dimensional (3D) network. Both compounds demonstrate excellent performance for the solution-phase detection of Fe3+ ions through a significant and rapid quench in luminescence emission. Fluorescence titration experiments reveal that compound 2 is more selective toward Fe3+ compared to compound 1 because of its 3D stacking mode. The K sv value for compound 2 (32 378 M-1) is twice as large as that for compound 1 (15 854 M-1) for the detection of Fe3+ ions. We attribute this significant increase in performance to the increase in dimensionality. In addition, compound 2 demonstrates high selectivity and sensitivity for the detection of Cr3+ cations and Cr2O7 2- anions.


Emergent endovascular treatment with direct carotid puncture for exsanguinating Carotid Blowout Syndrome.
Carotid Blowout Syndrome (CBS) carries an exceedingly high mortality rate. Various established endovascular techniques are successful in treating less acute CBS, but exsanguinating patients with hemodynamic compromise continue to pose a significant clinical challenge. We report a 53-year-old male with squamous cell carcinoma of the anterior tongue presented with a sentinel hemoptysis followed by a massive oral hemorrhage. The patient suffered a cardiac arrest secondary to acute blood loss, from which he was successfully resuscitated. An occlusion technique is presented involving direct carotid puncture for successful treatment of hemodynamically unstable, exsanguinating patients. This technique accomplishes rapid arrest of exsanguination, minimal hemorrhage site manipulation, and successful carotid occlusion.


d-enantiomers of CATH-2 enhance the response of macrophages against Streptococcus suis serotype 2.
Due to the increase of antibiotic resistant bacterial strains, there is an urgent need for development of alternatives to antibiotics. Cathelicidins can be such an alternative to antibiotics having both a direct antimicrobial capacity as well as an immunomodulatory function. Previously, the full d-enantiomer of chicken cathelicidin-2 (d-CATH-2) has shown to prophylactically protect chickens against infection 7 days post hatch when administered in ovo three days before hatch. To further evaluate d-CATH-2 in mammals as a candidate for an alternative to antibiotics.In this study, the prophylactic capacity of d-CATH-2 and two truncated derivatives, d-C(1-21) and d-C(4-21), was determined in mammalian cells. Antibacterial assays; immune cell differentiation and modulation; cytotoxicity, isothermal titration calorimetry; in vivo prophylactic capacity of peptides in an S. suis infection model. d-CATH-2 and its derivatives were shown to have a strong direct antibacterial capacity against four different S. suis serotype 2 strains (P1/7, S735, D282, and OV625) in bacterial medium and even stronger in cell culture medium. In addition, d-CATH-2 and its derivatives ameliorated the efficiency of mouse bone marrow-derived macrophages (BMDM) and skewed mouse bone marrow-derived dendritic cells (BMDC) towards cells with a more macrophage-like phenotype. The peptides directly bind lipoteichoic acid (LTA) and inhibit LTA-induced activation of macrophages. In addition, S. suis killed by the peptide was unable to further activate mouse macrophages, which indicates that S. suis was eliminated by the previously reported silent killing mechanism. Administration of d-C(1-21) at 24 h or 7 days before infection resulted in a small prophylactic protection with reduced disease severity and reduced mortality of the treated mice. d-enantiomers of CATH-2 show promise as anti-infectives against pathogenic S. suis for application in mammals.


Immunomodulatory Potential of Human Adipose Mesenchymal Stem Cells Derived Exosomes on in vitro Stimulated T Cells.
In the recent years, it has been demonstrated that the biological activity of mesenchymal stem cells (MSCs) is mediated through the release of paracrine factors. Many of these factors are released into exosomes, which are small membranous vesicles that participate in cell-cell communication. Exosomes from MSCs are thought to have similar functions to MSCs such as repairing and regeneration of damaged tissue, but little is known about the immunomodulatory effect of these vesicles. Based on an extensive bibliography where the immunomodulatory capacity of MSCs has been demonstrated, here we hypothesized that released exosomes from MSCs may have an immunomodulatory role on the differentiation, activation and function of different lymphocyte subsets. According to this hypothesis, in vitro experiments were performed to characterize the immunomodulatory effect of human adipose MSCs derived exosomes (exo-hASCs) on in vitro stimulated T cells. The phenotypic characterization of cytotoxic and helper T cells (activation and differentiation markers) together with functional assays (proliferation and IFN-γ production) demonstrated that exo-hASCs exerted an inhibitory effect in the differentiation and activation of T cells as well as a reduced T cell proliferation and IFN-γ release on in vitro stimulated cells. In summary, here we demonstrate that MSCs-derived exosomes are a cell-derived product that could be considered as a therapeutic agent for the treatment of inflammation-related diseases.


Superior ophthalmic vein thrombosis in a patient with dacryocystitis-induced orbital cellulitis.
A 71-year-old-man presented with chronic left-sided epiphora and a 5-day history of progressive left orbital swelling that had started with a "bump" on the left side of his nose. Orbital CT revealed left-sided preseptal and postseptal inflammation, along with marked thickening of the left superior ophthalmic vein. Orbital MRI with gadolinium enhancement and fat suppression revealed a low-intensity signal in the left superior ophthalmic vein, consistent with a superior ophthalmic vein thrombosis. There was no cavernous sinus involvement. A diagnosis was made of left-sided dacryocystitis-induced orbital cellulitis and superior ophthalmic vein thrombosis. Treatment consisted of intravenous vancomycin, followed by early dacryocystorhinostomy and postoperative intravenous dexamethasone. Anticoagulation was not used. Within 1 week after surgery, the orbital congestion had dramatically improved. Though rare, isolated superior ophthalmic vein thrombosis can be a harbinger of cavernous sinus thrombosis; therefore, early detection is the key to avoiding cavernous sinus thrombosis.


Underestimation of uncertainty in statistical regression of environmental models: influence of model structure uncertainty.
As the quality of sensors increases, systematic discrepancies between measurements and model outputs become more apparent Applying regression type analysis in these cases leads to autocorrelated residuals, biased parameter estimates, and underestimation of uncertainty. This paper examines how parameter estimates are affected by model structure uncertainty for an application from wastewater treatment. A Monod model is fitted to synthetic data generated by a reference system exhibiting predefined Tessier kinetics and a known error process. A range of methods are suggested to test if the resulting residuals fulfill the IID (independent and identically distributed)-requirement visual examination of time series, autocorrelation, and partial autocorrelation functions, the Jarque-Bera normality test, the Runs test for independence, and the BDS test for IID. The tests are shown to perform well at low measurement noise but not at higher levels of noise where transferring the parameter estimates gained from a batch system leads to erroneous estimation of steady state concentrations in a completely stirred tank reactor. Additional diagnostics are suggested which include second order autocorrelation functions of the residuals in the case of a single experiment and examination of moving averages of residuals in the case of multiple experiments.


Determining cancer stage at diagnosis in population-based cancer registries: A rapid scoping review.
Population-based cancer registries are the main source of data for population-level analysis of cancer stage at diagnosis. This data enables analysis of cancer burden by stage, evaluation of screening programs and provides insight into differences in cancer outcomes. The lack of standardised collection of cancer staging in Australia is well recognised and is not routinely collected within the Western Australia Cancer Registry. This review aimed to explore how cancer stage at diagnosis is determined in population-based cancer registries. This review was guided by the Joanna-Briggs Institute methodology. A systematic search of peer-reviewed research studies and grey literature from 2000 to 2021 was conducted in December 2021. Literature was included if peer-reviewed articles or grey literature sources used population-based cancer stage at diagnosis, and were published in English between 2000 and 2021. Literature was excluded if they were reviews or only the abstract was available. Database results were screened by title and abstract using Research Screener. Full-texts were screened using Rayyan. Included literature were analysed using thematic analysis and managed through NVivo. The findings of the 23 included articles published between 2002 and 2021 consisted of two themes. (1) "Data sources and collection processes" outlines the data sources used, as well as the processes and timing of data collection utilised by population-based cancer registries. (2) "Staging classification systems" reveals the staging classification systems employed or developed for population-based cancer staging, including the American Joint Committee on Cancer's Tumour Node Metastasis and related systems; simplified systems classified into localised, regional, and distant categories; and miscellaneous systems. Differences in approaches used to determine population-based cancer stage at diagnosis challenge attempts to make interjurisdictional and international comparisons. Barriers to collecting population-based stage at diagnosis include resource availability, infrastructure differences, methodological complexity, interest variations, and differences in population-based roles and emphases. Even within countries, disparate funding sources and funder interests can challenge the uniformity of population-based cancer registry staging practices. International guidelines to guide cancer registries in collecting population-based cancer stage is needed. A tiered framework of standardising collection is recommended. The results will inform integrating population-based cancer staging into the Western Australian Cancer Registry.