Vascularizing the brain in vitro.
The brain is arguably the most fascinating and complex organ in the human body. Recreating the brain in vitro is an ambition restricted by our limited understanding of its structure and interacting elements. One of these interacting parts, the brain microvasculature, is distinguished by a highly selective barrier known as the blood-brain barrier (BBB), limiting the transport of substances between the blood and the nervous system. Numerous in vitro models have been used to mimic the BBB and constructed by implementing a variety of microfabrication and microfluidic techniques. However, currently available models still cannot accurately imitate the in vivo characteristics of BBB. In this article, we review recent BBB models by analyzing each parameter affecting the accuracy of these models. Furthermore, we propose an investigation of the synergy between BBB models and neuronal tissue biofabrication, which results in more advanced models, including neurovascular unit microfluidic models and vascularized brain organoid-based models.


Microbial population dynamics in response to increasing loadings of pre-hydrolyzed pig manure in an expanded granular sludge bed.
In recent years, pig manure (PM) has been regarded as a valuable substrate for energy and resource recovery via bioprocesses such as anaerobic digestion (AD), however, the efficiency of digesting raw PM is limited by the presence of refractory compounds. In this study, we applied a series of pretreatment on raw PM, consisting of subsequent thermochemical pretreatment, enzymatic hydrolysis, tyndallization and filtration. The liquid PM hydrolysates were fed to an expanded granular sludge bed (EGSB) for the production of biogas. The general performance and population dynamics of the EGSB reactor were assessed during an extended operational period of 339 days. An efficient and stable digestion process was achieved under high organic loading rates (OLRs) up to 21 kg-COD/(m(3)·d), agreeing with a sludge loading rate of 0.75 kg-COD/(kg-VSS·d), 1600 mg-NH4(+)-N/L and 17 mg/L of free ammonia nitrogen. The tyndallization decreased the total amount of active cells from 1 × 10(8) to 1 × 10(2) CFU/ml. Hence, bio-augmentation with pigs' intestinal microbiota was absent and the community dynamics were mainly credited to the composition of the substrate (i.e. PM hydrolysates) and the environmental conditions inside the reactor. The results showed the influence of both the seed community and the imposed loading rates on the evolutionary trajectory of the EGSB microbial community. Four bacterial genera (Clostridium, Cytophaga, Bacillus and Bacteroides) and two methanogenic genera (Methanosaeta and Methanobacterium) dominated the communities. An obvious shift from aceticlastic Methanosaeta to hydrogenotrophic Methanobacterium appeared when the OLR was increased to over 10 kg-COD/(m(3)·d).


Evaluation of Mitotic Figures and Cellular and Nuclear Morphometry of Various Histopathological Grades of Oral Squamous Cell Carcinoma: Comparative study using crystal violet and Feulgen stains.
The objectives of this study were to quantitatively estimate the number of mitotic figures (MFs) and evaluate the cellular and nuclear features of various histological grades of oral squamous cell carcinoma (OSCC) using Feulgen and 1% crystal violet stains. This case-control study took place at the Dr D. Y. Patil Dental College & Hospital in Mumbai, Maharashtra, India, between June and December 2016. A total of 51 samples were retrieved from the hospital archives. Of these, 15 well-differentiated, 15 moderately-differentiated and six poorly-differentiated OSCC samples formed the case group while 15 samples of normal gingival mucosa constituted the control group. Each sample was dyed using Feulgen and 1% crystal violet stains and the mitotic count, nuclear area (NA), cellular area (CA), nuclear perimeter (NP), cellular perimeter (CP) and nuclear-to-cytoplasmic (N/C) ratio was calculated using computer-aided morphometry techniques. The number of MFs visible per field was significantly higher in Feulgen-stained sections as compared to those stained with crystal violet (P = 0.050). In addition, the NA, NP, CA and CP values and N/C ratios of samples in the experimental group increased significantly in accordance with an increase in OSCC grade (P <0.001). The Feulgen stain is more reliable than 1% crystal violet in terms of the selective staining of MFs. Moreover, the findings of this study indicate that computer-based morphometric analysis is an effective tool for differentiating between various grades of OSCC.


Two novel calixarene functionalized iron oxide magnetite nanoparticles as a platform for magnetic separation in the liquid-liquid/solid-liquid extraction of oxyanions.
This article focuses on the syntheses of 25,27-bis[3-(N-ethylsulfonic acid)aminopropxy]-26,28-dihydroxy-5,11,17,23-tetra-tert-butyl-calix[4]arene (3) and 25,27-bis[3-(N-ethyl-dihydrogen phosphate)aminopropxy]-26,28-dihydroxy-5,11,17,23-tetra-tert-butyl-calix[4]arene (4) as well as their immobilization onto [3-(2,3-epoxypropoxy)-propyl]-trimethoxysilane-modified Fe3O4 magnetite nanoparticles, and the extraction abilities of four new extractants which were characterized by a combination of FTIR, (1)H NMR, elemental analyses, transmission electron microscopy (TEM) and thermogravimetric analyses (TGA) involving electrostatic and hydrogen bonding interactions between the calixarene and oxide anions such as arsenate and dichromate anions. The extraction results indicate that these new calixarene derivatives having high extraction capabilities would be used as effective extractants for the removal of the dichromate/arsenate ions from water.


Effects of diet on resource utilization by a model human gut microbiota containing Bacteroides cellulosilyticus WH2, a symbiont with an extensive glycobiome.
The human gut microbiota is an important metabolic organ, yet little is known about how its individual species interact, establish dominant positions, and respond to changes in environmental factors such as diet. In this study, gnotobiotic mice were colonized with an artificial microbiota comprising 12 sequenced human gut bacterial species and fed oscillating diets of disparate composition. Rapid, reproducible, and reversible changes in the structure of this assemblage were observed. Time-series microbial RNA-Seq analyses revealed staggered functional responses to diet shifts throughout the assemblage that were heavily focused on carbohydrate and amino acid metabolism. High-resolution shotgun metaproteomics confirmed many of these responses at a protein level. One member, Bacteroides cellulosilyticus WH2, proved exceptionally fit regardless of diet. Its genome encoded more carbohydrate active enzymes than any previously sequenced member of the Bacteroidetes. Transcriptional profiling indicated that B. cellulosilyticus WH2 is an adaptive forager that tailors its versatile carbohydrate utilization strategy to available dietary polysaccharides, with a strong emphasis on plant-derived xylans abundant in dietary staples like cereal grains. Two highly expressed, diet-specific polysaccharide utilization loci (PULs) in B. cellulosilyticus WH2 were identified, one with characteristics of xylan utilization systems. Introduction of a B. cellulosilyticus WH2 library comprising >90,000 isogenic transposon mutants into gnotobiotic mice, along with the other artificial community members, confirmed that these loci represent critical diet-specific fitness determinants. Carbohydrates that trigger dramatic increases in expression of these two loci and many of the organism's 111 other predicted PULs were identified by RNA-Seq during in vitro growth on 31 distinct carbohydrate substrates, allowing us to better interpret in vivo RNA-Seq and proteomics data. These results offer insight into how gut microbes adapt to dietary perturbations at both a community level and from the perspective of a well-adapted symbiont with exceptional saccharolytic capabilities, and illustrate the value of artificial communities.


Aging and Speech-in-Noise Perception.
The objective was investigating the effect of age on speech-in-noise perception (SINP) using word perception score in white noise (WPS in WN). This cross-sectional study was conducted on 76 participants, including 30 elderly (older than 61 years) and 46 young adults (between 14 and 35 years) with normal levels of stress, night sleep and mini-mental states. Audiological evaluations included acoustic immittance testing, pure tone audiometry, determination of speech reception threshold and WPS in WN. Data analysis were performed using Mann-Whitney and Tukey HSD tests. Based on the results of the tests, the participants were divided into three groups: (1) young adults with normal hearing (n = 30), (2) elderly adults with normal hearing (n = 16), (3) elderly adults with mild to moderate high frequency hearing loss (n = 14). In both groups of old adults, the means WPS in WN differences were significant only in the left ears (Pv = 0.008, 0.033, 0.025 for SNR = 0, +5, +10 dB). In the three groups and in the right ears, there were the significant differences between the means of WPS in WN (Pv = 0.002, 0.000, 0.001 for SNR = 0, +5, +10 dB), and also the left ears (Pv = 0.000, 0.002, 0.002 for SNR = 0,+5, +10 dB).There is a relationship between increasing age and decreasing WPS in WN. The deleterious effects of aging on SINP decline are greater than that of hearing loss.


High dose angiotensin-converting enzyme inhibition prevents fluid volume expansion in heart transplant recipients.
We sought to test the hypothesis that plasma volume (PV) expansion in heart transplant recipients (HTRs) is caused by failure to reflexively suppress the renin-angiotensin-aldosterone (RAA) axis. Extracellular fluid volume expansion occurs in clinically stable HTRs who become hypertensive. We have previously demonstrated that the RAA axis is not reflexively suppressed by a hypervolemic stimulus in HTRs. Plasma volume and fluid regulatory hormones were measured in eight HTRs (57+/-6 years old) both before and after treatment with captopril (225 mg/day). Antihypertensive and diuretic agents were discontinued 10 days before. The HTRs were admitted to the Clinical Research Center (CRC), and, after three days of a constant diet containing 87 mEq/day of Na+, PV was measured by using the modified Evans blue dye dilution technique. After approximately four months (16+/-5 weeks), the same HTRs again discontinued all antihypertensive and diuretic agents; they were progressed to a captopril dose of 75 mg three times per day over 14 days, and the CRC protocol was repeated. Captopril pharmacologically suppressed (p<0.05) supine rest levels of angiotensin II (-65%) and aldosterone (-75%). The reductions in vasopressin and atrial natriuretic peptide levels after captopril did not reach statistical significance. The PV, normalized for body weight (ml/kg), was significantly reduced by 12% when the HTRs received captopril. Extracellular fluid volume is expanded (12%) in clinically stable HTRs who become hypertensive. Pharmacologic suppression of the RAA axis with high-dose captopril (225 mg/day) returned HTRs to a normovolemic state. These findings indicate that fluid retention is partly engendered by a failure to reflexively suppress the RAA axis when HTRs become hypervolemic.


Variable toxicity of ionic liquid-forming chemicals to Lemna minor and the influence of dissolved organic matter.
Ionic liquids (ILs) are nonvolatile organic salts that remain liquid over a wide range of temperatures. Ionic liquids are promoted as environmentally friendly alternatives to the volatile organic solvents that are currently in widespread industrial usage. Although ILs are unlikely to contribute to air pollution, their potential effects on aquatic ecosystems are largely unknown. Furthermore, information is lacking on how ILs will interact with common features of aquatic environments, such as dissolved organic matter (DOM). We assessed the effect of five IL-forming chemicals on the growth of duckweed, Lemna minor, a common aquatic vascular plant. In general, 1-alkyl-3-methylimidazolium chemicals with longer alkyl chains were more toxic to L. minor than those with short alkyl chain lengths. The concentration that produced a 50% reduction (the EC50) in root growth was 8.56 ppm when a butyl chain was present but was 0.25 ppm (i.e., much more toxic) when an octyl chain was substituted. Butyl-substituted 3-methylpyridinium (root growth EC50 of 7.49 ppm) and 3-methylimidazolium cations had similar toxicity, whereas a tetrabutyl ammonium cation was considerably less toxic (root growth EC50 of 32.71 ppm). When we tested whether DOM reduced the toxicity of these cations, we saw no effect of a low-molecular-weight organic acid or commercial humic matter. In contrast, natural DOM reduced the toxicity of imidazolium, but only at low concentrations. Design and use of ILs and other new chemicals should incorporate not only standard toxicity tests but also information on how such chemicals will interact with other components of aquatic ecosystems.


[Effect of adrenomimetic and antiadrenergic agents on the gastric emptying function in peptic ulcer patients].
Stimulation with isadrin and blockade with inderal of beta-adrenergic processes exert no significant effect on the time of food evacuation from the stomach. The alpha-adrenergic action of mezaton and ephedrine manifests itself in delayed food evacuation from the stomach at its initial accelerated evacuatory function. Blockade of alpha-adrenoreceptors with pyrroxan reduces the time of the stomach evacuation at the initial delayed gastric evacuation.


Oral mucosal leishmaniasis presenting as a nonhealing chronic oral growth: A case report.
Oral mucosal leishmaniasis is a rare finding posing challenges in the diagnosis and treatment in a nonendemic setting. This disease is present in dental clinics as nonhealing chronic growth. Timely diagnosis and appropriate treatment are crucial to prevent further complications and death.


Combination of diabetes and cataract worsens the oxidative stress and micronutrient status in Indians.
We examined the synergism of cataract and diabetes in micronutrient and antioxidant statuses versus diabetes mellitus and cataract alone. Indian patients with type 2 diabetes mellitus (D; n = 76), those without diabetes and with cataract (NDC; n = 100), those with diabetes and cataract (DC; n = 53), and age- and sex-matched healthy controls (n = 90) 50-70 y were investigated. Plasma oxidative stress as thiobarbituric acid-reactive substances (TBARS) and the status of 11 micronutrients were studied as lens TBARS, opacity, and ratio of soluble to total proteins in patients with cataract with or without diabetes. Lipid profile, fasting glucose, and postprandial glucose were measured for all subjects. A subnormal status of ascorbic acid, beta-carotene, thiamine, and ceruloplasmin was elicited for all four study groups. Plasma TBARS and fasting glucose were significantly higher in the DC group than in the NDC (P < 0.05), D, and control groups. Lens TBARS were comparable between the NDC and DC groups (5.5 and 5.08 nm/g of lens). Chi-square values for lens turbidity within the DC and NDC groups and for the ratio of soluble to total proteins and opacity within the NDC group were significant (P < 0.01). The prevalence of poor riboflavin status was 30-36% in all patients and 15-22.5% in controls. Men in the DC group showed a higher value of glycosylated hemoglobin than did men from the D group. Multivariate analysis of variance indicated significant interactions (P < 0.02) between HS and socioeconomic grades for fasting glucose and high-density lipoprotein levels, riboflavin status, plasma vitamin C, TBARS, and selenium. The DC group was found to be significantly different from the other groups with respect to beta-coefficients of a logistic regression equation for plasma levels of selenium, zinc, iron, thiamine, triacylglycerols, total cholesterol, ceruloplasmin, vitamin A, and superoxide dismutase. The combination of diabetes and cataract coupled with gender bias and influence of socioeconomic factors seem to be associated with worsening of micronutrient status, oxidative stress, and lens opacity.


Dependence on cell-mediated mechanisms for the appearance of crisis forms during Plasmodium chabaudi AS infection in C57BL/6 mice.
The appearance of crisis forms or degenerate, intraerythrocytic parasites in the peripheral blood of C57BL/6 hosts during the course of Plasmodium chabaudi AS infection was analysed. Following intraperitoneal injection with 10(6) parasitized erythrocytes, C57BL/6 hosts, which are resistant to this species of rodent Plasmodium, eliminate the parasite from the peripheral blood by 4 weeks and recover from acute infection. Elimination of the parasite coincides with the appearance in the peripheral blood of almost all the parasites as crisis forms. A role for cell-mediated immunity in the induction of crisis forms of Plasmodium species has previously been suggested. To define the role of cell-mediated immunity in the appearance of intraerythrocytic crisis forms in the peripheral blood during acute malaria, the outcome of P. chabaudi AS infection, the course of parasitemia and the appearance of crisis forms in mice with either genetically determined or experimentally induced immunodeficiencies on the resistant C57BL-derived background were examined. The mice used were either B-cell deficient (mu-suppressed from birth). T-cell deficient (nu/nu mice), C5 deficient or splenectomized prior to infection. The appearance of intraerythrocytic crisis forms in the peripheral blood during the course of P. chabaudi AS infection is shown to be dependent on cell-mediated mechanisms which require the presence of T cells as well as an intact spleen for the most efficient elimination of this parasite.


PPM1D silencing by RNA interference inhibits proliferation and induces apoptosis in breast cancer cell lines with wild-type p53.
PPM1D is an oncogene that is amplified and overexpressed in many human tumors, including breast cancer. It functions as a negative regulator of the p38 MAP kinase-p53 signaling pathway and is also proposed to participate in other critical cell survival pathways. To define the functional significance of PPM1D specifically in breast cancer, we used RNA interference to inhibit PPM1D expression in BT-474, MCF7, and ZR-75-1 breast cancer cell lines harboring amplification and increased expression of PPM1D. Efficient downregulation of PPM1D resulted in significantly reduced cell proliferation in MCF7 and ZR-75-1 cells carrying wild-type p53 but not in BT-474 carrying mutant p53, which indicates that the antiproliferative effect of PPM1D silencing is dependent on the p53 status of the cells. This result is in excellent agreement with the notion that PPM1D activation is an alternative mechanism for p53 inactivation. Additionally, our data indicate that the reduced cell growth observed after PPM1D silencing is due at least in part to increased apoptotic cell death. Our findings demonstrate that PPM1D is involved in the regulation of cell proliferation in breast cancer in a p53-dependent manner and that overexpression of PPM1D contributes to malignant phenotype by promoting sustained cell growth and cell survival.


A comparative analysis of rapid methods for purification and refolding of recombinant bovine prion protein.
Bacterially-produced recombinant prion protein (rPrP) is a frequently used model system for the study of the properties of wild-type and mutant prion proteins by biochemical and biophysical approaches. A range of approaches have been developed for the purification and refolding of untagged rPrP expressed as inclusion bodies in Escherichia coli, including refolding by dialysis and simultaneous on-column purification and refolding. In order to perform a higher-throughput analysis of different rPrP proteins, an approach that produces highly pure rPrP with a minimum of purification steps and a high yield per liter of induced bacterial culture is desired. Here, we directly compare purification approaches for untagged bovine rPrP as adapted to rapid, small-scale formats useful for higher-throughput studies. An analysis of protein yield, purity, oxidation, and refolding revealed significant differences between preparative methods as adapted to the small-scale format, and based on these findings we provide recommendations for future purifications. We also describe the utility of a sensitive commercial kit for thiol analysis of these preparations, the pH dependence of dimer formation during refolding of bovine rPrP, and bovine rPrP binding to cobalt affinity resin.


Virus-induced eosinophil mediator release requires antigen-presenting and CD4+ T cells.
The most frequent trigger of asthma exacerbation is infection with common airway viruses; however, the precise mechanism regulating such severe reactions is not understood. The presence of airway eosinophil products is a unique feature detected in asthmatic airways. Using an animal model, we previously demonstrated that T cells play an important role in regulating an eosinophil-dependant pathway of virus-induced airway hyperreactivity. We hypothesize that human eosinophils respond to viruses, although only after interaction with T cells. We sought to determine whether eosinophils can respond to airway viruses in vitro and determine the mechanism of response. An in vitro coculture model of human eosinophils, antigen-presenting cells, and T cells was used with parainfluenza virus, respiratory syncytial virus, or rhinovirus. We measured release of eosinophil peroxidase (EPO) in concert with T-cell proliferation, cytokine release, and changes in T-cell phenotype. The viruses induced release of EPO when coincubated in the presence of antigen-presenting cells (dendritic cells or macrophages) and T cells. Virus-mediated release was associated with proliferation of CD3(+)CD4(+) T cells and release of cytokines. UV inactivation of the virus did not prevent virus-induced EPO release or T-cell proliferation. Proliferating CD4(+) T cells show increased expression of CD25 and CD45RO. CD8(+) T cells were not activated. Virus-induced EPO release can occur in the context of antigen presentation to CD4(+) T cells.


[Sterilization of women by laparoscopic electrocoagulation of the ovarian duct].
The authors present eleven women sterilized by the bicoagulation technique which has considerable advantages over formerly used electrocoagulation methods. The intervention is of short duration (10 to 15 minutes) and no complications were observed.


Overview of Immune Checkpoint Inhibitors in Gynecological Cancer Treatment.
In the last ten years, clinical oncology has been revolutionized by the introduction of oncological immunotherapy, mainly in the form of immune checkpoint inhibitors (ICIs) that transformed the standard of care of several advanced solid malignancies. Using ICIs for advanced gynecological cancers has yielded good results, especially for endometrial cancer. In ovarian or cervical cancer, combining ICIs with other established agents has shown some promise. Concurrently with the clinical development of ICIs, biomarkers that predict responses to such therapy have been discovered and used in clinical trials. The translation of these biomarkers to clinical practice was somewhat hampered by lacking assay standardization and non-comprehensive reporting of biomarker status in trials often performed on a small number of gynecological cancer patients. We can expect increased use of ICIs combined with other agents in gynecological cancer in the near future. This will create a need for reliable response prediction tools, which we believe will be based on biomarker, clinical, and tumor characteristics. In this article, we review the basic biology of ICIs and response prediction biomarkers, as well as the latest clinical trials that focus on subgroup effectiveness based on biomarker status in gynecological cancer patients.


The LINC00501-HSP90B1-STAT3 positive feedback loop promotes malignant behavior in gastric cancer cells.
Long non-coding RNAs (lncRNAs) have been implicated in gastric cancer (GC) carcinogenesis and progression. However, the role of LINC00501 in GC growth and metastasis remains unclear. In this study, we found that LINC00501 was frequently upregulated in GC cells and tissues and was closely related to adverse GC clinicopathological features. Aberrant overexpression of LINC00501 promoted GC cell proliferation, invasion, and metastasis both in vitro and in vivo. Mechanistically, LINC00501 stabilized client protein STAT3 from deubiquitylation by directly interacting with cancer chaperone protein HSP90B1. Furthermore, the LINC00501-STAT3 axis modulated GC cell proliferation and metastasis. In turn, STAT3 bound directly to the LINC00501 promoter and positively activated LINC00501 expression, thus forming a positive feedback loop, thereby accelerating tumor growth, invasiveness, and metastasis. In addition, LINC00501 expression was positively correlated with STAT3 and p-STAT3 protein expression levels in gastric clinical samples. Our results reveal that LINC00501 acts as an oncogenic lncRNA and that the LINC00501-HSP90B1-STAT3 positive feedback loop contributes to GC development and progression, suggesting that LINC00501 may be a novel potential biomarker and treatment target for GC.


Analysis of Retrospective Laboratory Data on the Burden of Bacterial Pathogens Isolated at the National Veterinary Research Institute Nigeria, 2018-2021.
Farm animals harbour bacterial pathogens, which are often viewed as important indicators of animal health and determinants of food safety. To better understand the prevalence and inform treatment, we audited laboratory data at the Bacteriology Laboratory of the NVRI from 2018-2021. Antibiotics were classified into seven basic classes: quinolones, tetracyclines, beta-lactams, aminoglycosides, macrolides, nitrofuran, and cephalosporins. Trends were analysed using a generalised linear model with a log link function for the Poisson distribution, comparing proportions between years with an offset to account for the variability in the total number of organisms per year. Avian (73.18%) samples were higher than any other sample. The major isolates identified were Escherichia. coli, Salmonella spp., Klebsiella spp., Staphylococcus spp., Proteus spp., and Pseudomonas spp. We found that antimicrobial resistance to baseline antibiotics increased over the years. Of particular concern was the increasing resistance of Klebsiella spp. to cephalosporins, an important second-generation antibiotic. This finding underscores the importance of farm animals as reservoirs of pathogens harbouring antimicrobial resistance. Effective biosecurity, surveillance, and frugal use of antibiotics in farms are needed because the health of humans and animals is intricately connected.


Galectin-related protein: An integral member of the network of chicken galectins: 2. From expression profiling to its immunocyto- and histochemical localization and application as tool for ligand detection.
Galectin-related protein (GRP), present in vertebrates, is special within this family of adhesion/growth-regulatory proteins due to its strong positive selection and loss of canonical lectin activity. RT-PCR and Western blotting together with flow cytofluorimetry and immunocyto- and histochemistry monitor expression and localization of chicken GRP. The promoter sequence of the GRP gene is processed computationally to detect putative sites for binding transcription factors. The labeled protein is applied as probe to detect binding sites on cells and in sections, along with glycocompounds to test inhibition of the association. Expression of GRP in chicken is limited to bursa of Fabricius, immunohistochemically found in B cells, also in bursal epithelium and vessels. Presence in B cells is shared with only one canonical galectin, i.e. CG-8. Binding to a chicken lymphoma line was specific and saturable, not affected by lactose but completely blocked by heparin, as also seen in sections. Expression monitoring initiated for GRP reveals a distinct site of localization in chicken, much more restricted than for any of its canonical galectins.


Steps Ahead: Optimising physical activity in adults with cystic fibrosis: A pilot randomised trial using wearable technology, goal setting and text message feedback.
Regular participation in physical activity (PA) is encouraged for people with Cystic Fibrosis (CF). This study aimed to assess the effectiveness of an intervention using wearable technology, goal setting and text message feedback on PA and health outcomes in people with CF. This was a pilot randomised trial conducted at University Hospital Limerick. Participants were randomly assigned to the intervention (INT) or active comparator (AC). The 12-week intervention consisted of wearable technology (Fitbit Charge 2) which was remotely monitored, and participants set step count goals. Participants were sent a one-way text message once a week over 12 weeks to positively reinforce and encourage PA participation. The AC group received the wearable technology alone. Follow up was assessed at 24 weeks. Outcomes assessed were PA, aerobic capacity, lung function, sleep, quality of life and wellbeing. Step count increased significantly for the INT group over 12 weeks when compared to the AC group (p=0.019). The INT group had a 28% week-to-week percentage change (Weeks 1-12), while the AC group reduced by 1%, p=0.023. Within group changes demonstrated that VO2 peak (ml/kg/min) significantly increased for the INT group at 12 weeks (24.4 ±7.65 to 26.13 ±7.79, p=0.003) but not at 24 weeks (24.45 ±7.05, p=0.776). There were no significant differences observed for VO2 peak (ml/kg/min) for the AC group. There was no significant effect on lung function, sleep, well-being, or quality of life for either group. A personalised PA intervention using wearable technology, goal setting and text message feedback increased PA and aerobic capacity in people with CF. Integration of this intervention into usual care may encourage regular PA participation for people with CF.


The sweet and sour of cancer: glycans as novel therapeutic targets.
A growing body of evidence supports crucial roles for glycans at various pathophysiological steps of tumour progression. Glycans regulate tumour proliferation, invasion, haematogenous metastasis and angiogenesis, and increased understanding of these roles sets the stage for developing pharmaceutical agents that target these molecules. Such novel agents might be used alone or in combination with operative and/or chemoradiation strategies for treating cancer.


An improved real-time navigator gating algorithm for reducing motion effects in coronary magnetic resonance angiography.
The phase ordering with automatic window selection (PAWS) algorithm for respiratory gating in magnetic resonance imaging is improved by further smoothing motion distribution in k-space. This is achieved by requiring that the displacement discontinuities in k-space and the range of displacement during the acquisition of the center 30% region of k-space are limited to a fraction (1/3 in this study) of the gating window. Simulation results and in vivo imaging experiments suggest that these modifications reduce the amount of artifacts at a reasonable cost of additional scan time as compared to the original PAWS algorithm.


A neural degeneration mutation that spares primary neurons in the zebrafish.
We describe an embryonic lethal mutation in the zebrafish Brachydanio rerio that specifically affects the viability of most cells in the embryonic central nervous system (CNS). The mutation ned-1 (b39rl) was induced with gamma-irradiation and segregates as a single recessive allele closely linked to its centromere. It produces massive cell death in the CNS but a small set of specific neurons, including Rohon-Beard sensory neurons, large hindbrain interneurons, and primary motoneurons, survive embryogenesis and are functional. Synaptic connections between embryonic motoneurons and muscle cells appear physiologically normal, and the normally observed spontaneous flexions are present. Correlated with the presence of sensory neurons and interneurons, mutant embryos display reflexive movements in response to mechanical stimulation. Together, the surviving neurons, called primary neurons, form a class of cells that are prominent in size and arise early during development. Thus, this mutation may define a function that is differentially required by developmentally distinguishable sets of cells in the embryonic CNS.


Involucrin expression in keratinization disorders of the skin--a preliminary study.
We have studied the expression of involucrin in a variety of keratinization disorders, mostly of genetic origin using an avidin-biotin-peroxidase technique. In normal human epidermis 25% of the living epidermis was labelled. The diseases studied fell into two groups. Diseases with greatly increased involucrin staining including collodion baby (38%), Darier's disease (49%), Flegel's disease (56%), erythrokeratoderma variabilis (60%), epidermal naevus with epidermolytic hyperkeratosis (45%) and congenital bullous (58%) and non-bullous (44%) ichythyosiform erythroderma; and diseases with normal or slightly increased staining, including ichthyosis vulgaris (27%), X-linked ichthyosis (25%), confluent and reticulate papillomatosis (27%) and simple epidermal naevus (28%). These results demonstrate that involucrin expression is altered in some keratinization disorders and suggest that in such conditions cellular functions other than keratin metabolism are also affected.


[Continued driving habits of patients diagnosed with excessive daytime sleepiness].
Description of driving behaviour of patients with excessive daytime sleepiness (EDS) and the influence on their driving of diagnosis, therapy, legal guidelines and advices. Inventory based on questionnaires. Centre for Sleep and Wake Disorders, The Hague, the Netherlands. All patients with EDS who were in a stable condition for at least 6 months after therapy were sent a questionnaire (n = 138). The questions concerned actual driving behaviour, EDS and the effects of diagnosis, therapy and advice given by the Centre. The response was 67% (n = 92). Eighteen patients had never driven a car. Eighteen of the other 74 patients quit driving or drove less. Fifty-six patients did not change their behaviour or drove even more. There was little effect on driving behaviour of diagnosis, therapy and advice to stop driving. Patients with EDS often participate as drivers in modern traffic. Legal guidelines and advice given by physicians have only little influence on this behaviour. As general measures seem to be ineffective, approaches tailored to the individual patient may lead to more acceptable results.


Expressing treatment-associated changes.
The Osteoarthritis Research Society International is attempting to establish a consensus on outcome measures, so as to facilitate comparability between different clinical studies in this area of research. There are no general recommendations on how changes in outcome measure (effect size) should be expressed. We therefore used data from a recently published study to express change as: a) the mean of the change from baseline divided by the individual baseline, b) the median of the change from baseline divided by the individual baseline, c) the mean of the change from baseline divided by the SD of baseline and d) the median of change from baseline divided by the SD of baseline. The results show that the correlations between different ways of expressing effect sizes were poor and the perceived relative magnitudes of various effects depended on how they were expressed. Organisations aiming at consensus ought to recommend the way in which change ought to be expressed. Until they do, authors should justify their choice of expression, particularly if it critically influences their conclusion, and/or present their data as fully as possible on a website.


Regulation of GH and TSH release from hyperplastic and ectopic pituitaries: effects of dopamine in vitro.
This study was undertaken to examine the consequences of prolonged removal of the pituitary from hypothalamic control and of estrogen-induced pituitary tumors on the susceptibility of GH and TSH release to regulatory influences of dopamine (DA). Adult male Fischer 344 rats were treated with transplants of female anterior pituitaries under the renal capsule or with Silastic capsules containing diethylstilbestrol (DES). Capsules with DES remained in place until the animals were killed (DES-IN) or were removed 7 weeks prior to sacrificing the rats (DES-OUT). Both pituitary grafts and DES caused the expected elevation in plasma prolactin and suppression of plasma GH and TSH levels. Basal GH release in vitro was not affected by exposure to DES in vivo but was reduced by transplantation of the pituitary to an ectopic site. Treatment with DA in vitro suppressed GH release from the in situ pituitaries of control, DES treated and grafted rats but increased GH release from the ectopic pituitaries. Basal release of TSH in vitro was reduced in the pituitaries of DES-IN and DES-OUT animals but was not affected by the presence of pituitary transplants. No detectable TSH was released from the ectopic pituitaries in the absence of DA. DA decreased TSH release from the pituitaries of control, DES-OUT and DES-IN rats but not from the in situ pituitaries of grafted rats. In contrast, DA produced an increase in TSH release from ectopic pituitaries. These results demonstrate that somatotrophs and thyrotrophs removed from the hypothalamic influences on subjected to direct and indirect effects of DES exhibit abnormal responses to DA. We suspect that prolonged absence of normal pituitary control leads to the development of regulatory mechanism of pituitary hormone release which are different from those operating under physiological conditions.


Molecularly engineered poly(ortho ester) microspheres for enhanced delivery of DNA vaccines.
Genetic vaccination using plasmid DNA presents a unique opportunity for achieving potent immune responses without the potential limitations of many conventional vaccines. Here we report the design of synthetic biodegradable polymers specifically for enhancing DNA vaccine efficacy in vivo. We molecularly engineered poly(ortho ester) microspheres that are non-toxic to cells, protect DNA from degradation, enable uptake by antigen-presenting cells, and release DNA rapidly in response to phagosomal pH. One type of microsphere of poly(ortho esters) that releases DNA vaccines in synchrony with the natural development of adaptive immunity, elicited distinct primary and secondary humoral and cellular immune responses in mice, and suppressed the growth of tumour cells bearing a model antigen. This polymer microparticulate system could, with further study, have implications for advancing the clinical utility of DNA vaccines as well as other nucleic-acid-based therapeutics against viral infections and cancer.


Relationship between photoperiod and hospital admissions for mania in New South Wales, Australia.
Causes for a seasonal impact on admissions for mania remain to be clarified. We examined the impact of photoperiod, rate of change of photoperiod and hours of sunshine on admissions over an extended period. Monthly admission data to NSW psychiatric hospitals for more than twenty thousand patients admitted for mania over a fifteen-year period were correlated with photoperiod and sunshine changes. While the peak in admissions occurred in spring, the shift in admissions being under-represented to being precipitously over-represented corresponded with the photoperiod commencing to increase in winter (i.e. July). Analyses identified rate of change in photoperiod as somewhat more influential than change in photoperiod and with hours of sunshine not making a distinctive contribution. Immediate and delayed impacts of rate of change as well as change in photoperiod across the whole year accounted for a distinctive 20% of the variance in hospital admissions. Validity of mania diagnoses cannot be established from the data set, admission data were obtained from across the state while meteorological data were obtained from the capital city, lag periods between onset of a mania and hospitalization (while identified) would impact on associations, social factors were not included and study associations do not imply causality. The lack of a strong year-long correlation may reflect photoperiod changes being only a weak causal factor or that its influence may be through a strong impact phase after the winter solstice and with the spring peaking of admissions reflecting secondary photoperiod or other influences.


Enzymatic synthesis of geranyl acetate in packed bed reactor in supercritical carbon dioxide under various pressure-temperature conditions and reactor configurations.
Data in this paper describes the catalytic performances, expressed in terms of conversion %, of geraniol and acetic acid to geranyl acetate, using the immobilized lipase B from Candida antarctica in packed bed reactors (PBR) using supercritical CO2 as a solvent. Readers will find data related to different Figures or equations of the article as well as supplementary data that will help to make the difference between flowrates of CO2 in a liquid state and corresponding flowrates of supercritical CO2 for various CO2 pressure and temperature combinations.


Selenium-based nanozyme as a fluorescence-enhanced probe and imaging for chlortetracycline in living cells and foods.
Developing rapid monitoring methods to detect antibiotic residues in food plays an important role in safeguarding human health. This study presents the development of a novel fluorescence-enhanced detection method for chlortetracycline (CTC) using a GSH-Se nanozyme. A GSH-Se nanozyme prepared using a one-pot hydrothermal method not only possesses excellent fluorescent properties but also exhibits good glutathione peroxidase-like activity. The results show that the addition of CTC leads to a significant enhancement in the fluorescence intensity of GSH-Se, and this increase exhibits a good linear relationship with the concentration of CTC. The linear range of this method is 0.02-1 µM, and the limit of detection (LOD) for CTC was 0.02 µM. Moreover, the cell toxicity of GSH-Se is low and can be used for monitoring and imaging of CTC in cells, and satisfactory results have been obtained in the analysis of actual food samples.


Laparoscopic inguinal herniotomy in bladder exstrophy: a new solution to an old problem?
Laparoscopy is now the established management for infants with inguinal hernia at our institution. Open inguinal herniotomy in children with bladder exstrophy can be a difficult operation and is associated with a high rate of recurrence (15%). Here, we report our initial experience with laparoscopic repair of inguinal hernia in three children with bladder exstrophy. Three boys with repaired bladder exstrophy presented with inguinal hernia during follow up. The clinical presentation was bilateral in one and findings at surgery were bilateral open internal rings in two. Under general anaesthesia, pneumoperitoneum of 10 mmHg was raised with a Hasson port at the umbilicus. Two further instruments were inserted in the right and left flanks without ports. Two 4/0 Prolenetrade mark purse string sutures were placed to securely close the internal ring. The umbilicus was closed with an absorbable suture, and the skin incisions were closed with Indermil Gluetrade mark. All infants made an uneventful recovery, being discharged within 24h. There were no complications. There has been no sign of recurrence during a mean follow up of 16 months. Laparoscopic inguinal herniotomy is a technically straightforward and effective way to treat inguinal hernias in children with bladder exstrophy.


Sedentary time is associated with the metabolic syndrome in older adults with mobility limitations--The LIFE Study.
Epidemiological and objective studies report an association between sedentary time and lower risk of the metabolic syndrome (MetS) and its risk factors in young and middle-age adults. To date, there is a lack of objective data on the association between sedentary time and MetS among older adults. The association between objectively measured sedentary time (accelerometry) with MetS and MetS components was examined in a large sample of older adults with mobility limitations (N=1198; mean age=78.7 ± 5.3 years) enrolled in the Lifestyle Interventions and Independence for Elders (LIFE) study. Participants were divided into tertiles according to percentage of daily sedentary time, and the relation between sedentary time with MetS and MetS components was examined after adjusting for age, sex, ethnicity, and BMI. Participants in the highest sedentary time tertile had significantly higher odds of MetS (OR=1.54) (95% CI 1.13 to 2.11) in comparison with participants in the lowest tertile (p=0.03). Participants in the highest sedentary time tertile had larger waist circumference (p=0.0001) and lower HDL-C (p=0.0003) than participants in the lowest sedentary time tertile. Sedentary time was strongly related to higher odds of MetS. These results, based on objectively measured sedentary time, suggest that sedentary time may represent an important risk factor for the development of MetS in older adults with high likelihood for disability.


The impact of ICAM1 and VCAM1 gene polymorphisms on chronic allograft nephropathy and transplanted kidney function.
ICAM-1 and VCAM-1 adhesion molecules play important roles in the immune response and emergence of chronic allograft nephropathy (CAN). The several polymorphisms of ICAM1 and VCAM1 genes are associated with changes in molecular expression therefore affecting allograft function and immune responses after kidney transplantation. The aim of this study was to examine the impact of polymorphisms in ICAM1 and VCAM1 genes on biopsy-proven CAN and renal allograft function. The 270 Caucasian renal transplant recipients (166 men and 104 women) were genotyped for the rs5498 ICAM1 and rs1041163 and rs3170794 VCAM1 gene polymorphisms using real-time polymerase chain reaction. There was no correlation between polymorphisms and CAN. Creatinine concentrations in the first month after transplantation differed between the rs5498 ICAM1 genotypes (P = .095), being higher for GG carriers (AA + AG vs GG, P =.07) albeit not with statistical significance. Creatinine concentrations at 12, 24, and 36 months after transplantation differed significantly among rs5498 ICAM1 genotypes (P = .0046, P =.016, and P = .02) and were higher among GG carriers (AA + AG vs GG, P = .001, P = .004, and P = .006). Rs5498 ICAM1 GG genotype and receipient male gender were independent factors associated with higher creatinine concentrations. These results suggest that the rs5498 ICAM1 GG genotype may be associated with long-term allograft function.


An alternative and new approach to free flap in treatment of calcaneal region and lower third of the lower extremity reconstruction: reverse flow posterior tibial fasciocutaneous skin island flaps.
Fasciocutaneous flaps, whether of the upper or lower extremity, have certain distinct advantages. These flaps are very simple to raise, quick to execute, and have a high reliability. On the basis of experimental studies, it is reasonable to accept that a fasciocutaneous flap has a 15% to 20% increased survival over comparable cutaneous flaps. The distal-based posterior tibial fasciocutaneous flap was designed and successfully transferred clinically to cover lower leg and foot defects in four patients. No complications, including distal ischemia, infection, and failure, in flaps were seen. Although donor site of fasciocutaneous flaps is significant and can often be justified, it is not as significant as the donor area of the free flaps. The versatility, advantages, and disadvantages of this new flap in the reconstruction of defects of the lower leg and foot are discussed.


Are urologists in trouble with SARS-CoV-2? Reflections and recommendations for specific interventions.
To assess the risk of viral infection during urological surgeries due to the possible hazards in tissue, blood, urine and aerosolised particles generated during surgery, and thus to understand the risks and make recommendations for clinical practice. We reviewed the available literature on urological and other surgical procedures in patients with virus infections, such as human papillomavirus, human immunodeficiency virus and hepatitis B, and current publications on coronavirus disease 2019 (COVID-19). Several possible pathways for viral transmission appear in the literature. Recently, groups have detected severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in the urine and faeces, even after negative pharyngeal swabs. In addition, viral RNA can be detected in the blood and several tissues. During surgery, viral particles are released, aerosol-borne and present a certain risk of transmission and infection. However, there is currently no evidence on the exact risk of infection from the agents mentioned above. It remains unclear whether or not viral particles in the urine, blood or faeces are infectious. Whether SARS-CoV-2 can be transmitted by aerosols remains controversial. Irrespective of this, standard surgical masks offer inadequate protection from SARS-CoV-2. Full personal protective equipment, including at least filtering facepiece-2 masks and safety goggles should be used. Aerosolised particles might remain for a long time in the operating theatre and contaminate other surfaces, e.g. floors or computer input devices. Therefore, scrupulous hygiene and disinfection of surfaces must be carried out. To prevent aerosolisation during laparoscopic interventions, the pneumoperitoneum should be evacuated with suction devices. The use of virus-proof high-efficiency particulate air filters is recommended. Local separation of anaesthesia/intubation and the operating theatre can reduce the danger of viral transmission. Lumbar anaesthesia should be considered especially in endourology. Based on current knowledge, COVID-19 is not a contraindication for acute urological surgery. However, if possible, as European guideline committees recommend, non-emergency urological interventions should be postponed until negative SARS-CoV-2 tests become available.


Long-day photoperiods affect expression of OPN5 and the TSH-DIO2/DIO3 pathway in Magang goose ganders.
This study sought to understand the regulation mechanism of OPN5 through the TSH-DIO2/DIO3 pathway mediated photoperiod on the breeding activity of short-day breeding birds. In this study, the reproductive activity of Magang goose was regulated by artificial light, and the reproductive activity of the ganders were determined according to the daily laying rate of female geese. The testicular development and the serum reproductive hormone concentrations of ganders were measured during the reproductive period (d 0), the reproductive degeneration period (d 13 and 27) and the resting period (d 45). The mRNA and protein expression patterns of OPN5, the HPG axis reproductive genes, and TSH-DIO2/DIO3 pathway related genes were examined. Results showed that the laying rate of geese and the gonadal indices (GSI) decreased gradually after the photoperiod increased. Histological observation found that the spermatogenic function of the testis was normal on d 0 and 13, while degeneration occurred by d 27 and 45. Serum testosterone, FSH, and LH concentration showed a slight increase on d 13, followed by a sharp decrease on d 27 and 45 (P < 0.01), while PRL concentrations were low on d 0 and 13, and increased rapidly on d 27 and 45 (P < 0.01).The expression pattern of GnRH, FSH, LH, and THRβ mRNA were similar, with high levels on d 0 and 13 and a decreasing trend on d 27 and 45 (P < 0.05 or P < 0.01); and GnRHR mRNA levels were higher on d 13 (P < 0.05), but then had decreased by d 27 and 45 (P < 0.01). The expression pattern of GnIH and GnIHR was similar, which was opposite to that of GnRHR. VIP, PRL, and PRLR increased gradually and peaked on d 45 (P < 0.01). The expression trend of TRH, TSHβ, and DIO2 was similar to that of GnRHR, and the expression abundance increased on d 13, and then decreased on d 27 and 45. GnRH protein expression was significantly higher than during the other 3 periods (P < 0.01) while the GnIH protein levels were extremely low on d 0, had gradually increased by d 13, and significantly increased by d 27 and 45 (P < 0.01). The protein expression trends of THR and DIO2 were similar to that of GNIH. DIO3 protein expression was low on d 0 and 13, and increased by d 27 and 45. These results suggest that when the photoperiod increased, the hypothalamus OPN5 gene and protein were upregulated and the pituitary TSHβ, TSHR, and hypothalamus THRβ, TRH, and DIO2 were downregulated, and thus the reproductive activity of geese was inhibited.


Effect of UV irradiation on functional activity of donor blood neutrophils.
Activation of NADPH-oxidase enzymatic complex was observed after UV irradiation of the blood and neutrophil suspension in a dose of 151 J/m(2). UV irradiation in doses of 75.5 and 151.0 J/m(2) corrected myeloperoxidase activity and intensity of LPO processes in donor blood.


Differential epigenetic changes in the hippocampus and prefrontal cortex of female mice that had free access to cocaine.
Alterations in gene expression within the neural networks of prefrontal cortex (PFC) and hippocampus (HPC) are known to contribute to behavioural phenotypes associated with drug intake. However, the functional consequences of regulated expression patterns of Fosb and Crem (cAMP response element modulator) in both brain regions in response to volitional intake of cocaine in social environment is yet to be explored. Here, we first exposed young adult mice to cocaine (300 mg/L) and water concurrently for 30 days in the IntelliCage to investigate consumption preference, and subsequently for 28 days during which persistent motivated drug seeking behaviours were examined. Thereafter, locomotor activity and memory performance of the mice were assessed. DNA methylation status in the promoters of Fosb and Crem genes were also evaluated. We show that mice that had extended access to cocaine exhibited motivational deficit and demonstrated decreased locomotor activity and intact recognition memory. These changes were accompanied by hypomethylation or hypermethylation in the promoters of Fosb and Crem genes in the PFC and HPC of the cocaine-experienced mice, respectively. Together, these findings correlate the molecular changes to behavioural effects of the treatment and further suggests a possible activation of prefrontal cortical networks by social interaction episodes in the IntelliCage which possibly enhanced behavioural control that dampens mice sensitivity to cocaine rewards. Furthermore, our data delineate the molecular response of Crem and Fosb to oral cocaine in group-housed mice and demonstrates differential regulation of activities within the substrate brain regions studied.


Microbially mediated metal corrosion.
A wide diversity of microorganisms, typically growing as biofilms, has been implicated in corrosion, a multi-trillion dollar a year problem. Aerobic microorganisms establish conditions that promote metal corrosion, but most corrosion has been attributed to anaerobes. Microbially produced organic acids, sulfide and extracellular hydrogenases can accelerate metallic iron (Fe0) oxidation coupled to hydrogen (H2) production, as can respiratory anaerobes consuming H2 as an electron donor. Some bacteria and archaea directly accept electrons from Fe0 to support anaerobic respiration, often with c-type cytochromes as the apparent outer-surface electrical contact with the metal. Functional genetic studies are beginning to define corrosion mechanisms more rigorously. Omics studies are revealing which microorganisms are associated with corrosion, but new strategies for recovering corrosive microorganisms in culture are required to evaluate corrosive capabilities and mechanisms. Interdisciplinary studies of the interactions among microorganisms and between microorganisms and metals in corrosive biofilms show promise for developing new technologies to detect and prevent corrosion. In this Review, we explore the role of microorganisms in metal corrosion and discuss potential ways to mitigate it.


The racemization rate of selenomethionine and methionine in yeast at 100 degrees C and neutral pH.
The rate of racemization of selenomethionine in yeast at 100 degrees C and pH 7.4 was determined using gas chromatography to separate the trifluoroacetyl-L-prolyl-D,L-selenomethionine methyl esters. The racemization half-life (i.e., the time required to attain a D/L ratio of 0.33) of selenomethionine was found to be similar to that of methionine and have a value of 19-20 days.


Enhancement of electricity production in a mediatorless air-cathode microbial fuel cell using Klebsiella sp. IR21.
A novel dissimilatory iron-reducing bacteria, Klebsiella sp. IR21, was isolated from the anode biofilm of an MFC reactor. Klebsiella sp. IR21 reduced 27.8 % of ferric iron to ferrous iron demonstrating that Klebsiella sp. IR21 has electron transfer ability. Additionally, Klebsiella sp. IR21 generated electricity forming a biofilm on the anode surface. When a pure culture of Klebsiella sp. IR21 was supplied into a single chamber, air-cathode MFC fed with a mixture of glucose and acetate (500 mg L(-1) COD), 40-60 mV of voltage (17-26 mA m(-2) of current density) was produced. Klebsiella sp. IR21 was also utilized as a biocatalyst to improve the electrical performance of a conventional MFC reactor. A single chamber, air-cathode MFC was fed with reject wastewater (10,000 mg L(-1) COD) from a H2 fermentation reactor. The average voltage, current density, and power density were 142.9 ± 25.74 mV, 60.5 ± 11.61 mA m(-2), and 8.9 ± 3.65 mW m(-2), respectively, in the MFC without inoculation of Klebsiella sp. IR21. However, these electrical performances of the MFC were significantly increased to 204.7 ± 40.24 mV, 87.5 ± 17.20 mA m(-2), and 18.6 ± 7.23 mW m(-2), respectively, with inoculation of Klebsiella sp. IR21. The results indicate that Klebsiella sp. IR21 can be utilized as a biocatalyst for enhancement of electrical performance in MFC systems.


Chemical modulation of metallothionein I and III mRNA in mouse brain.
Metallothioneins (MTs) are sulfhydryl-rich proteins. MT-I and MT-II are found in all tissues of the body, while MT-III exists only in brain. Regulation of MT-I and MT-III mRNA was studied in brain and liver of control C57BL/6J mice and mice given chemicals known to increase MT-I, namely, lipopolysaccharide (LPS), zinc chloride (Zn), cadmium chloride (Cd), dexamethasone (Dex), ethanol, and kainic acid (KA). Northern blot analysis revealed that MT-I mRNA levels in liver were induced dramatically (12-27-fold over basal levels) by all of the chemicals, while in brain only LPS produced an increase in MT-I mRNA (2-fold). Interestingly, the MT-I inducers, Cd, Dex, ethanol, and KA, down-regulated brain MT-III mRNA levels by approx. 30%. Because brain is such a heterogenous tissue, in situ hybridization was used to localize MT-I and MT-III mRNA in control and treated mice. MT-I mRNA signal, which was most abundant in the glial cells of the Purkinje cell layer of the cerebellum in control mice, appeared to be enhanced in mice given the MT-I inducers (LPS, Zn, Cd, Dex, ethanol, and KA). MT-I mRNA hybridization signal was also enhanced in the olfactory bulbs from LPS- and Cd-treated mice, while this signal was present but weak in control brains. MT-III mRNA hybridization signals were localized in hippocampus and co-localized with MT-I message in the glial cells of the Purkinje cell layer of the cerebellum. In addition, diffuse MT-III mRNA signals were visible in areas of the cerebral cortex, and in the molecular layer of the cerebellum. Signals for MT-III in hippocampus appeared to be reduced by KA, Dex and LPS treatment, while in the cortical region, MT-III mRNA signals appeared to be enhanced by KA, Cd, and ethanol treatment. In conclusion, both MT-I and MT-III expression in brain appears to be modulated by exogenous treatment, however, the changes are small in relation to those observed in liver. Chemical-induced alterations of MT mRNA are non-uniform throughout the brain, and thus best studied in a region-specific manner.


TRAF1/C5, eNOS, C1q, but not STAT4 and PTPN22 gene polymorphisms are associated with genetic susceptibility to systemic lupus erythematosus in Turkey.
A significant source of variability in the literature on systemic lupus erythematosus (SLE) susceptibility genes has been the inability to replicate genetic findings across different racial or ethnic groups. We investigated whether a single nucleotide polymorphism (SNP) of the STAT4 (rs7574865), PTPN22 (rs2476601), TRAF1/C5 (rs10818488), and C1q (rs292001) genes as well as the 27-bp VNTR polymorphism on intron 4 of eNOS, previously associated with SLE in other populations, are also associated with SLE risk in Turkey. A group of 158 SLE patients and 155 healthy controls were included in this study. A genetic association of the TRAF1/C5, C1q, and eNOS gene polymorphism, but not of STAT4 and PTPN22, was found to confer a degree of risk for SLE. These data highlight the importance of comparative studies in different populations to confirm the previously detected genetic associations.


Central and peripheral contributions of deafferentation-induced norepinephrine increase in the habenula.
This work examined the contributions of sympathetic and central noradrenergic (NA) innervation to habenular norepinephrine (NE) increase after partial deafferentation. Adult rats received bilateral stria medullaris lesions and after 4 weeks a second lesion was produced which removed bilaterally the dorsal NA bundle or the superior cervical ganglia. The rats were sacrificed 7 days after the second lesion. The data show that strial lesions induced a non-uniform NE increase in discrete habenular regions, which was contributed to by sympathetic innervation in the medial habenula and by central NA projections in both medial and lateral habenular nuclei. It is suggested that NE increase in response to strial lesions is attributed to differential sprouting of peripheral and central NA innervation in the habenula.


Switching patients with glaucoma or ocular hypertension from dual therapy to monotherapy: evaluation of brimonidine as a model.
A multicenter open-label study investigated the clinical effectiveness and economic feasibility of switching 142 patients from dual therapy to twice-daily monotherapy with brimonidine for glaucoma or ocular hypertension. Evaluations were performed at baseline and 2 (visit 2) and 8 (visit 3) weeks after the switch. Patients completed a questionnaire that rated medication-related visual function and satisfaction (comfort, convenience, vision, ease of remembering to use drops) at each visit. At visit 3, investigators, taking into account IOP measurements, safety, and responses on the questionnaire, recommended whether the patient should remain on brimonidine. A pharmacoeconomic analysis, including the number of visits, cost of medication, and success rates, compared the cost of dual therapy with that of switching to brimonidine monotherapy. Of the 131 patients who completed the study, 77 (59%) had no change or a decrease in IOP from baseline, and 53 (41%) had an increase. Investigators recommended that 77% of the study completers continue to take brimonidine monotherapy. Extending treatment with brimonidine for 12 months would achieve a significant cost savings of 16%. Brimonidine monotherapy is an efficacious and cost-effective alternative to dual therapy for glaucoma and ocular hypertension. Appropriate monotherapy may be as effective as dual therapy for many patients, and a clinically relevant trial such as this may be economically advantageous for testing a switch.


The effectiveness of calcitonin on chronic back pain and daily activities in postmenopausal women with osteoporosis.
The aim of this study was to investigate the effect of nasal calcitonin on chronic back pain and disability attributed to osteoporosis. The study design involved three groups of osteoporotic postmenopausal women suffering from chronic back pain. Group I consisted of 40 women with vertebral fractures, group II of 30 women with degenerative disorders and group III of 40 patients with non specific chronic back pain and without abnormality on plain X-rays. Pain intensity was measured using a numerical rating scale (NRS) and disability due to back pain was measured using the Oswestry disability questionnaire. The patients were randomly assigned to receive, for three months, either 200 IU intranasal salmon calcitonin and 1,000 mg of oral calcium daily (groups IA, IIA, IIIA) or 1,000 mg of oral calcium daily (groups IB, IIB, IIIB). Repeated measures ANOVA showed that there were no significant time, group or interaction effects for pain intensity and disability in any of the groups studied. Mean Oswestry and NRS scores were reduced during the follow-up period in the groups IA, IIIA, but the differences between the two time points were not statistically significant. Intranasal calcitonin has no effect on chronic back pain intensity and functional capacity of osteoporotic women regardless of the presence of fractures, degenerative disorders or chronic back pain of non-specific etiology.


MICE: a new active combination for non-small cell lung cancer.
We have treated 38 patients with stage III/IV non-small cell lung cancer with the following regimen: mitomycin-C = 6 mg/m2, ifosfamide = 3 g/m2, cisplatin = 75 mg/m2, vindesine = 3 mg/m2 (MICE), intravenously (i.v.) on day 1, every 3 weeks. Among 26 patients with stage IV disease, 15 obtained a partial remission (PR) (response rate = 57%, 95% confidence interval = 38-76), with a median time to disease progression and a median survival of 4.9 and 7.1 months, respectively. 6 out 7 patients with stage IIIA disease were documented as PR and 5 of them underwent radical surgery with two pathologically confirmed complete remissions. Overall toxicity was substantial but manageable: 3 patients had grade III/IV leucopenia (although 5 patients had neutropenic fever) whereas 13 patients experienced grade II/II anaemia. In conclusion we believe that MICE regimen is an interesting combination and warrants further evaluations both for palliation and in a neoadjuvant setting.


Giant duodenal ulcers.
Twenty-six giant duodenal ulcers, all correctly diagnosed prior to endoscopy, are presented. The concept of the ulcer/bulb ratio (ratio of longest diameter of the ulcer to that of the total bulb including the ulcer) is introduced. In all cases this ratio was 0.8 or greater; in 18 cases (69%) the ulcer completely replaced the duodenal bulb. An 'ulcer within an ulcer' appearance, representing a small area of deeper ulceration within the giant ulcer, was noted in 8 (31%). Half of the patients have remained symptom-free on medical therapy alone. Only two patients in our series (8%) died of complications of giant duodenal ulcer.


Improvement of photoreceptor integrity and associated visual outcome in neovascular age-related macular degeneration.
To evaluate the association between improvement of photoreceptor integrity and visual acuity (VA) after anti-vascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (AMD). Retrospective, cross-sectional study. Eighty-seven eyes of 84 patients who were newly diagnosed with neovascular AMD and treated with anti-VEGF injections were reviewed retrospectively. Using spectral-domain optical coherence tomography, the status of the inner segment/outer segment photoreceptor junction (IS/OS) was graded and classified into 3 groups at baseline and 1 and 2 months after 3 monthly injections. The proportion of the improved IS/OS line after treatment was analyzed and correlated with VA. The number of eyes in the IS/OS+ group, representing disrupted IS/OS line less than 200 μm, was increased from 9 (10%) at baseline to 33 (38%) at 1 month. There was a significant difference in the ratio of IS/OS+ group between baseline and 1 month (P < .001). Those in the IS/OS± group, showing focal disrupted IS/OS line between 200 and 800 μm, decreased from 29 (33%) to 22 eyes (25%). Improvement of the IS/OS line at 1 month compared to baseline was noted in 43 eyes (49%) and correlated with better VA (P < .016). No increase of VA was observed in 44 eyes without definite improvement. There was no significant correlation between improvement of the IS/OS line and VA from 1 to 2 months. Assessing the change of the photoreceptor integrity before and after treatment would be a useful indicator to predict initial response to treatment and visual prognosis in patients with neovascular AMD.


Liquid nitrogen spray cryotherapy in Barrett's esophagus with high-grade dysplasia: long-term results.
Liquid nitrogen endoscopic spray cryotherapy can safely and effectively eradicate high-grade dysplasia in Barrett's esophagus (BE-HGD). Long-term data on treatment success and safety are lacking. To assess the long-term safety and efficacy of spray cryotherapy in patients with BE-HGD. Single-center, retrospective study. Tertiary-care referral center. A total of 32 patients with BE-HGD of any length. Patients were treated with liquid nitrogen spray cryotherapy every 8 weeks until complete eradication of HGD (CE-HGD) and intestinal metaplasia (CE-IM) was found by endoscopic biopsy. Surveillance endoscopy with biopsies was performed for at least 2 years. CE-HGD, CE-IM, durability of response, disease progression, and adverse events. CE-HGD was 100% (32/32), and CE-IM was 84% (27/32) at 2-year follow-up. At last follow-up (range 24-57 months), CE-HGD was 31/32 (97%), and CE-IM was 26/32 (81%). Recurrent HGD was found in 6 (18%), with CE-HGD in 5 after repeat treatment. One patient progressed to adenocarcinoma, downgraded to HGD after repeat cryotherapy. BE segment length ≥3 cm was associated with a higher recurrence of IM (P = .004; odds ratio 22.6) but not HGD. No serious adverse events occurred. Stricture was seen in 3 patients (9%), all successfully dilated. Retrospective study design, small sample size. In patients with BE-HGD, liquid nitrogen spray cryotherapy has an acceptable safety profile and success rate for eliminating HGD and IM and is associated with a low rate of recurrence or progression to cancer with long-term follow-up.


Development of sensitive and stable electrochemical impedimetric biosensor based on T1R1 receptor and its application to detection of umami substances.
Umami substances can provide a palatable flavour for food. In this study, an electrochemical impedimetric biosensor was developed for detecting umami substances. This biosensor was fabricated by immobilising T1R1 onto AuNPs/reduced graphene oxide/chitosan which was in advance electro-deposited onto a glassy carbon electrode. The evaluation by the electrochemical impedance spectrum method showed that the T1R1 biosensor performed well with low detection limits and wide linear ranges. Under the optimised incubation time (60 s), the electrochemical response was linearly related to the concentrations of the detected targets monosodium glutamate and inosine-5'-monophosphate within their respective linear range of 10-14 to 10-9 M and 10-16 to 10-13 M. The low detection limit of monosodium glutamate and inosine-5'-monophosphate was 10-15 M and 10-16 M, respectively. Moreover, the T1R1 biosensor exhibited high specificity to umami substances even in the real food sample. The developed biosensor still retained 89.24% signal intensity after 6-day storage, exhibiting a desirable storability.


Risk and resilience correlates of reading among adolescents with language-based learning disabilities during COVID-19.
Students with language-based learning disabilities (LBLD) can face elevated socio-emotional well-being challenges in addition to literacy challenges. We examined the prevalence of risk and resilience factors among adolescents with LBLD (N = 93), ages 16-18, and the association with reading performance during the COVID-19 pandemic. Data were collected at the start and end of the first fully remote academic year of COVID-19 (2020-2021). Participants completed standardized word and text reading measures, as well as self-report surveys of executive functions (EF), and socio-emotional skills associated with resilience (grit, growth mindset, self-management, self-efficacy, and social awareness) or risk (anxiety, depression, COVID-19 related PTSD, and perceived COVID-19 impact). Survey data at the start of the school year (Time 1) captured three underlying factors associated with socioemotional risk, socioemotional resilience, and regulation (i.e., EF). Path analyses revealed that students' Time 2 oral reading scores were significantly and uniquely predicted by socioemotional resilience, even when controlling for word-level reading at Time 1. Socioemotional risk, EF, and perceived COVID-19 impact were not directly related to Time 2 oral reading scores; however, students' resilience mediated the associations between risk and reading outcomes. These results demonstrate that adolescents' mental health concerns, self-regulatory ability, and socioemotional resilience were all associated with their experiences of the COVID-19-related stress. However, despite the high-risk context of the pandemic, and socio-emotional challenges faced by students with LBLD, our findings indicate that resilience directly predicts end-of-year reading outcomes and mediates the impact of socioemotional risk on achievement. The online version contains supplementary material available at 10.1007/s11145-022-10361-8.


Increased proliferation of endothelial cells with overexpression of soluble TNF-alpha receptor I gene.
Vascular endothelial growth factor (VEGF) can overcome a potential anti-angiogenic effect of TNF-alpha by inhibiting endothelial apoptosis induced by this cytokine. Soluble TNF-alpha receptor I (sTNFRI) is an extracellular domain of TNFRI and antagonizes the activity of TNF-alpha. Here we report that sTNFRI is able to stimulate the growth of endothelial cells not by antagonizing TNF-alpha. Exogenously added recombinant human sTNFRI stimulated significantly more cell growth of human umbilical venous endothelial cells (HUVEC) with a low dose (50-200 pg/ml) compared with smooth muscle cells. In contrast, monoclonal antibody against TNF-alpha did not stimulate growth of human HUVEC. The sTNFRI expression plasmid (pcDNA3.1 plasmid) was introduced into the cell culture using OPTI-MEM, lipofectin and transferrin. Growth of HUVEC transfected with sTNFRI vector also increased significantly compared with those transfected with control vector. HUVEC transfected with sTNFRI vector increased the extracellular domain of TNFRI mRNA levels, but did not affect the intracellular domain of TNFRI mRNA levels. Accumulation of sTNFRI significantly increased in conditioned medium from HUVEC transfected with sTNFRI vector compared with those transfected with control vector. HUVEC transfected with sTNFRI vector not only increased sTNFRI but also prevented shedding of sTNFRI from TNFRI. The TNF-alpha -induced internucleosomic fragmentation was also significantly prevented in HUVEC transfected with sTNFRI vector compared with those transfected with control vector. These results suggest that instead of growth factors such as VEGF, local transfection of the sTNFRI gene may have potential therapeutic value in vascular diseases in which TNF-alpha is also usually highly expressed.


Effects of paeoniflorin on tumor necrosis factor-α-induced insulin resistance and changes of adipokines in 3T3-L1 adipocytes.
TNFα plays an important role in the adipocyte dysfunction, including lipolysis acceleration, insulin resistance and changes of adipokines. Recently, we showed that paeoniflorin attenuates adipocyte lipolysis and inhibits the phosphorylation of ERK, JNK, IKK stimulated by TNFα. However, the effects of paeoniflorin on adipocytes insulin resistance and changes of adipokines remain unknown. The aim of the current study was to investigate the role of paeoniflorin in preventing insulin resistance or inflammation in 3T3-L1 adipocytes treated with TNFα. Our results showed that paeoniflorin restored insulin-stimulated [(3)H]2-DOG uptake, which was reduced by TNFα, with concomitant restoration in serine phosphorylation of IRS-1 and insulin-stimulated phosphorylation of AKT in adipocytes. Paeoniflorin attenuated TNFα-mediated suppression of the expressions of PPARγ and PPARγ target genes, and the improvement of paeoniflorin on TNFα-induced insulin resistance was attenuated by GW9662, an antagonist of PPARγ activity. Moreover, paeoniflorin could inhibit the expressions and secretions of IL-6 and MCP-1 from adipocytes induced by TNFα. These results, together with our previous data, indicate that paeoniflorin exerts a beneficial effect on adipocytes to prevent TNFα-induced insulin resistance and inflammatory adipokine release. Our studies provide important evidence for an ability of paeoniflorin in amelioration of TNFα-induced adipocyte dysfunction, which would be helpful to clarify its potential role in the treatment of obesity.


Ochronosis of prostate presenting as advanced carcinoma.
Ochronosis is the clinical manifestation of alkaptonuria, a rare inborn error of metabolism. It is characterized by widespread pigmentation of the fibroconnective tissues, arthritis, and passage of dark urine. Prostatic involvement is usually limited to the incidental finding of calculi within the gland. Herein, we report a case of diffuse ochronotic involvement of the prostate clinically presenting as a neoplasm.


Functional and structural changes in the visual pathway in multiple sclerosis.
Multiple sclerosis (MS) is a heterogeneous disease with an unpredictable course. Visual pathway is a target of the disease and may reflect mechanisms that lead to disability. Structural and functional changes in the visual pathway may be studied by noninvasive techniques such as optical coherence tomography (OCT), visual evoked potentials (VEP), or B-mode transorbital sonography (TOS). The aim is to assess changes in the visual pathway in eyes of MS patients with and without a history of optic neuritis over a 3-year period and to explore their relationship with disability. In total, 112 eyes from 56 patients with relapsing MS were recruited: 29 with, and 83 without a history of ON (hON and nhON, respectively). Several parameters were measured by OCT, VEP, and TOS. Baseline measurements were also compared to 29 healthy controls. At 36 months, measurements were repeated in all eyes. At baseline, all tests showed significant differences in optic nerve structure and function in both patient cohorts in all the parameters studied, suggestive of more impairment of the visual pathway among the hON cohort. OCT showed significant differences between healthy controls and the nhON cohort. At 36 months, the nhON cohort showed significant changes by OCT, VEP, and TOS suggestive of further visual pathway impairment. OCT measurements also correlated with baseline EDSS among the nhON cohort. OCT is the most suitable technique and outperforms VEP and TOS to detect subclinical damage in the visual pathway. It discriminated MS patients from healthy controls and showed a progressive decline in optic nerve thickness over time among these patients.


Management of soft-tissue infections of the upper extremity in parenteral drug abusers.
Management of extensive soft-tissue infections of the upper extremity in 23 parenteral drug abusers was reviewed. Bacterial cultures most often revealed oral flora, including streptococcal species in 77 percent of patients and anaerobes in 59 percent. Staph. aureus was present in only one patient. Ninety percent of the organisms were sensitive to penicillin and 98 percent to first-generation cephalosporins. Blood culture specimens, obtained at admission, were negative in 15 patients. All patients responded well to operative debridement, excision of involved veins, and local wound care. Surgical debridement is the mainstay of therapy. We believe that intravenous antibiotic therapy with a first-generation cephalosporin should be used in the acute phase for control of surrounding cellulitis and prevention of bacteremia.


The evaluation, classification, and management of septic arthritis of the shoulder: the comprehensive shoulder sepsis system.
Septic arthritis of the shoulder is distinctly challenging to diagnose and treat. Guidelines for appropriate workup and management are limited and do not account for the variations in clinical presentation. The purpose of this study was to present a comprehensive and anatomically based classification system and treatment algorithm for septic arthritis of the native shoulder joint. A multicenter, retrospective analysis of all patients treated surgically for septic arthritis of the native shoulder joint was performed at 2 tertiary care academic institutions. Preoperative magnetic resonance imaging and operative reports were used to classify patients as having 1 of 3 infection subtypes: type I, confined to the glenohumeral joint; type II, extra-articular extension; or type III, concomitant osteomyelitis. On the basis of these clinical groupings of patients, the comorbidities, types of surgical management, and outcomes were analyzed. Sixty-five shoulders in 64 patients met the inclusion criteria for the study. Of these infected shoulders, 9.2% had type I infections, 47.7% had type II, and 43.1% had type III. Age and the time between symptom onset and diagnosis were the only significant risk factors for the development of a more severe infection. Fifty-seven percent of shoulder aspirates revealed cell counts below the standard surgical cutoff of 50,000 cells/mL. On average, each patient required 2.2 surgical débridements to eradicate the infection. Infections recurred in 8 shoulders (12.3%). Body mass index was the only risk factor for recurrence of infection. Of the 64 patients, 1 (1.6%) died acutely of sepsis and multiorgan system failure. We propose a comprehensive system for the classification and management of spontaneous shoulder sepsis based on stage and anatomy. Preoperative magnetic resonance imaging can help determine the severity of disease and aid in surgical decision making. A systematic approach to septic arthritis of the shoulder as a unique entity from septic arthritis of other large peripheral joints may lead to more timely diagnosis and treatment and improve the overall prognosis.


Non-specific vaginitis: diagnostic features and response to imidazole therapy (metronidazole, ornidazole).
Detailed quantitative aerobic, anaerobic, fungal and mycoplasma flora was obtained for 43 women presenting with complaints of vaginal discharge and malodour. Clinical response was associated with eradication of the abnormal anaerobic flora, despite persistence of G vaginalis in nine (26%). Topical imidazole therapy appeared to have some advantage over oral therapy. Gram stains of vaginal swabs were found to be the most useful laboratory investigation.


Probing the active site of aromatase with 2-methyl-substituted androstenedione analogs.
To gain insight into the spatial nature of the androstenedione (AD) binding (active) site of aromatase in relation to the catalytic function of the enzyme, we synthesized 2,2-dimethylAD (4), 2beta- and 2alpha-methylADs (5 and 6), 19-oxygenated derivatives of compounds 4 and 6, and 2-methyleneAD (17), and we then tested their inhibitory activity as well as their aromatase reaction (aromatization for 2-methyl and 2-methylene analogs or 19-oxygenation for 2,2-dimethyl steroids) with human placental aromatase. 2-Methyl and 2-methylene steroids 5, 6, and 17 were good competitive inhibitors of aromatase (K(i)=22-68nM), but less effective compared to the 2,2-dimethyl analog 4 (K(i)=8.8nM), indicating that a combination of 2beta- and 2alpha-methyl moieties is essential for the formation of a thermodynamically stable inhibitor-aromatase complex. A series of 2alpha-methyl steroids were good substrates for aromatase, whereas 2beta-methyl steroid 5 was an extremely poor substrate, and a series of 2,2-dimethyl steroids did not serve as substrate, suggesting that a 2beta-methyl moiety of the 2,2-dimethyl and 2beta-methyl steroids would prevent the aromatase reaction probably due to steric hindrance in each case. The 2-methylene compound 17 was also aromatized to produce 2-methylestrogen with a low conversion rate where the 1,4-diene structure may have been created before the C(10)-C(19) bond cleavage. Kinetic analysis of the aromatization of androgens revealed that a good substrate was not essentially a good inhibitor for aromatase.


Reserpine increases chromaffin cell enkephalin stores without a concomitant decrease in other proenkephalin-derived peptides.
Reserpine increases the levels of enkephalins in adrenal medullary chromaffin cells; however, the origin of the newly apparent pentapeptides has been the subject of debate, because no increase in the levels of proenkephalin mRNA has been observed. The present study was performed for determining if the reserpine-induced increase in context of enkephalins was derived from processing of preexisting fragments of proenkephalin. Bovine chromaffin cell enkephalins and larger enkephalin-containing peptides were separated by reversed-phase HPLC and identified by approximate molecular weight, elution with peptide standards, and enkephalin sequences contained. Treatment of the cells with reserpine increased the levels of enkephalins and of enkephalin-containing peptides of up to approximately 3 kilo-daltons without reducing the levels of larger enkephalin-containing peptides. Similar results were obtained with another catecholamine-depleting drug, tetrabenazine. In contrast, treatment of chromaffin cells with theophylline or forskolin increased the levels of both enkephalins and enkephalin-containing peptides of all sizes. The results suggest that new synthesis of proenkephalin is required for the effects of reserpine, although proenkephalin processing is also altered by this drug.


A 6-month follow-up of successful refits from daily disposable soft contact lenses to continuous wear of high-Dk silicone-hydrogel lenses.
To compare, in routine optometric practice, the outcome of keeping successful soft contact lens (SCL) wearers in their lenses to re-fitting them with continuous wear of silicone hydrogel (SiH) lenses. Forty-nine successful daily disposable lens wearers were recruited; 19 continued to wear daily SCLs and 30 were refitted with high-Dk SiH lenses on a 30-day/night schedule. Patients were assessed at baseline, 3 and 6 months by slit lamp examination along with the Efron grading scales, and central corneal thickness (CCT) and the corneal endothelium were assessed by non-contact specular microscopy. No substantial changes in subjective vision, refraction, visual acuity or overall lens comfort occurred for those completing the study, although five SiH lens wearers did discontinue due to reduced comfort, eyelid problems or seasonal allergy. Contact lens induced peripheral ulcers (CLPU) were observed in three patients in the first 3 months in the SiH lens group and these were also discontinued. Over the 6 month period, a complete set of records was obtained for 16 in each group. For those completing the study, lens dryness scores were variable, but there was a slight improvement in favour of SiH lenses. Small, but statistically significant, reductions in corneal staining, bulbar hyperaemia, and limbal neovascularisation in favour of the SiH lenses were also evident but mainly because of further increases in the daily lens wearers. Contact lens induced papillary conjunctivitis (CLPC) and corneal endothelial polymegethism were mild to moderate and showed slight increases in the daily lens wearers at 6 months. The present studies confirm that the continuous wear of SiH lenses for up to 30 days can be considered as an alternative to daily disposable soft lens wear, but is not suitable for everyone.


HIV glycoprotein as a superantigen. A mechanism of autoimmunity and implications for a vaccination strategy.
The pathogenic effects of HIV may reflect mimicry of several key immunological molecules. The surface glycoprotein of HIV has superantigenic properties responsible for the sequential deletion of T-cell clones. In addition, the glycoprotein has several regions sharing homology with class II MHC products. It can elicit cross-reactive antibodies which block replenishment of these T-cells in the thymus. The usefulness of conventional vaccination strategies in the fight against AIDS has been subject to debate. Based on these considerations, we argue that effective vaccines should avoid viral sequences homologous to class II MHC proteins which might exacerbate this process.


Defensins Potentiate a Neutralizing Antibody Response to Enteric Viral Infection.
α-defensins are abundant antimicrobial peptides with broad, potent antibacterial, antifungal, and antiviral activities in vitro. Although their contribution to host defense against bacteria in vivo has been demonstrated, comparable studies of their antiviral activity in vivo are lacking. Using a mouse model deficient in activated α-defensins in the small intestine, we show that Paneth cell α-defensins protect mice from oral infection by a pathogenic virus, mouse adenovirus 1 (MAdV-1). Survival differences between mouse genotypes are lost upon parenteral MAdV-1 infection, strongly implicating a role for intestinal defenses in attenuating pathogenesis. Although differences in α-defensin expression impact the composition of the ileal commensal bacterial population, depletion studies using broad-spectrum antibiotics revealed no effect of the microbiota on α-defensin-dependent viral pathogenesis. Moreover, despite the sensitivity of MAdV-1 infection to α-defensin neutralization in cell culture, we observed no barrier effect due to Paneth cell α-defensin activation on the kinetics and magnitude of MAdV-1 dissemination to the brain. Rather, a protective neutralizing antibody response was delayed in the absence of α-defensins. This effect was specific to oral viral infection, because antibody responses to parenteral or mucosal ovalbumin exposure were not affected by α-defensin deficiency. Thus, α-defensins play an important role as adjuvants in antiviral immunity in vivo that is distinct from their direct antiviral activity observed in cell culture.


Upper urinary tract transitional cell carcinoma. A 10-year experience.
To present our 10-year experience with patients surgically treated for upper urinary tract transitional cell carcinoma. We reviewed the medical records of 264 patients (218 males and 46 females), aged 37-93 years (mean, 69.5), treated surgically for upper tract transitional cell carcinoma during the period January 1996 to December 2005. During the mean follow-up of 58 months (range, 12-120), local relapse was diagnosed in 14% of the patients. The mean time to recurrence was 13 months (range, 1-102). The overall mortality was 14%, and the mean survival was 109 months. Survival was significantly influenced by the following parameters: male gender (P = 0.0151), age over 80 years (P = 0.0012), location in both the pelviocaliceal system and the ureter (P = 0.051), a two incision operation (P = 0.0075), grade III (P = 0.0314), stage T3 and T4 (P < 0.0001). Tumor stage was identified as the most important determinant in predicting recurrence and survival. Other predictors of survival included male gender, age over 80 years, location in the pelviocaliceal system and the ureter, a two incision operation, and high grade.


The role of colour doppler ultrasonography of facial and occipital arteries in patients with giant cell arteritis: A prospective study.
Colour Doppler Sonography (CDS) in giant cell arteritis (GCA) allows the study of involvement of cranial arteries other than the temporal arteries, which are inconvenient to biopsy, such as the facial (FaA), and occipital (OcA) arteries. We aimed to estimate the frequency of the FaA, and OcA involvement in GCA; and to explore the clinical characteristics of these subgroups of patients. From 1 January 2014 to 31 December 2016 we prospectively performed a CDS of the FaA, and OcA in addition to the temporal (TA), and the extracranial supra-aortic arteries in all newly diagnosed patients suspected of having GCA. All the arteries were evaluated in two planes for the highly specific halo sign. During the 36-month observation period we performed a CDS of the cranial and extra-cranial arteries in 93 GCA patients. We observed the halo sign on the FaA, and OcA in 38 (40.9%), and 29 (31.2%) cases, respectively. The FaA, or OcA were affected in 4/22 (18.2%) patients with a negative TA CDS. FaA involvement significantly correlated with jaw claudication and with severe visual manifestations, including permanent visual loss. A fifth of patients with a negative CDS of the TAs had signs of vasculitis on the CDS of the FaA, or OcA. The addition of FaA and OcA CDS to the routine CDS of the TAs could identify 4.3% more patients and thus further improve the sensitivity of the CDS in the suspected GCA.


Medical costs for Korean patients with rheumatoid arthritis based on the national claims database.
The purposes of this study are to investigate medical resource utilization and medical costs of Korean rheumatoid arthritis (RA) patients and to analyze predictors in relation to medical costs. National claims data on medical treatment were analyzed for the 151,472 RA patients in 2009. For outpatients, the mean annual number of visits was 32.5, and the mean annual total outpatient care costs were 2.0 million KRW (US$1,594) per patient. On the other hand, the mean annual length of stay of inpatients was 22.2 days, and the mean annual total inpatient care costs were 3.8 million KRW (US$3,013). Average annual total medical costs per patient for all of the RA patients were 2.9 million KRW (US$2,310). Total medical costs consisted of 26.1% outpatients' costs, 25.4% inpatient, and 48.6% medication costs, making medication costs a predominant cost driver. In the multiple regression analysis, biologic use was an important cost factor in relation to the annual total medical costs. This study provides information on the cost of illness of RA with the population-based representative RA patients in Korea, which had not been reported until now.


Toxicological study on intravenous thiopental anesthesia--interrelation between rate of injection and distribution of thiopental.
A simple, rapid and accurate method to extract and clean thiopental in biological materials rich in fat was developed by using a separation column packed with Extrelut and Florisil. A Quantitative determination of thiopental by means of a gas chromatograph equipped with a flame photometric sulfur detector was attempted. The calibration curve was linear over the range of 5-200 micrograms/ml. Extraction of replicate tissues involving 3 micrograms of thiopental resulted in a recovery of the 99.7-101.8% range and a coefficient of deviation of the 0.3-1.9% range. Replicate extraction of five tissues from rats treated with thiopental resulted in a coefficient of deviation of below 6%. In rats given 40 mg/kg of thiopental and sacrificed after 5 min, the thiopental levels in fat were found to be higher after a slow intravenous injection than after a quick injection. The same tendency, however, was not observed in other tissues. It seems that the rate of intravenous thiopental injections might be estimated by comparison with thiopental levels in fat tissues.


Exosomal lncRNA DOCK9-AS2 derived from cancer stem cell-like cells activated Wnt/β-catenin pathway to aggravate stemness, proliferation, migration, and invasion in papillary thyroid carcinoma.
Exosomal long non-coding RNAs (lncRNAs) are crucial factors that mediate the extracellular communication in tumor microenvironment. DOCK9 antisense RNA2 (DOCK9-AS2) is an exosomal lncRNA which has not been investigated in papillary thyroid carcinoma (PTC). Based on the result of differentially expressed lncRNAs in PTC via bioinformatics databases, we discovered that DOCK9-AS2 was upregulated in PTC, and presented elevation in plasma exosomes of PTC patients. Functionally, DOCK9-AS2 knockdown reduced proliferation, migration, invasion, epithelial-to-mesenchymal (EMT) and stemness in PTC cells. PTC-CSCs transmitted exosomal DOCK9-AS2 to improve stemness of PTC cells. Mechanistically, DOCK9-AS2 interacted with SP1 to induce catenin beta 1 (CTNNB1) transcription and sponged microRNA-1972 (miR-1972) to upregulate CTNNB1, thereby activating Wnt/β-catenin pathway in PTC cells. In conclusion, PTC-CSCs-derived exosomal lncRNA DOCK9-AS2 activated Wnt/β-catenin pathway to aggravate PTC progression, indicating that DOCK9-AS2 was a potential target for therapies in PTC.


Life threatening complication of high-frequency jet ventilation.
High-frequency jet ventilation is being increasingly used as an alternative to conventional methods of ventilation in both anaesthesia and intensive care. We report a case of severe respiratory obstruction as a complication of high-frequency jet ventilation. Patients with bleeding diathesis, including patients on haemodialysis, may particularly be at risk.