Safety and utility of intravascular ultrasound-guided carotid artery stenting.
Intravascular ultrasound (IVUS) is useful in evaluating coronary stent deployment. The aim of this study was to assess the safety and utility of IVUS in carotid artery stenting (CAS). Ninety-eight consecutive high-risk patients (107 arteries) underwent CAS. IVUS was performed prior to predilatation in 87 of the 107 vessels and in all 107 following stent deployment when an optimal angiographic appearance was obtained. Quantitative carotid angiography (QCA) and IVUS analysis were performed offline. Procedural success was 97%. Combined stroke or death at 30 days was 5.6%. IVUS measurements of the minimum lumen diameter (MLD) of the distal internal carotid artery (ICA) reference segment were similar to QCA (4.60 +/- 0.74 vs. 4.74 +/- 0.71 mm; P = 0.21). The ICA stent MLD was significantly smaller by IVUS compared to QCA (3.65 +/- 0.68 vs. 4.31 +/- 0.76 mm; P < 0.001). IVUS detected stent malapposition in 11%. IVUS findings, after an optimal angiographic result, necessitated additional treatment in 9% of procedures. Calcium was detected in more arteries with IVUS than angiography (61% vs. 46%; P < 0.05). Arteries with superficial lesion calcification subtending three or four quadrants by IVUS had a 31% incidence of stroke compared with a 1% incidence in arteries without severe superficial calcium (P < 0.001). We found IVUS imaging in CAS to be safe even prior to plaque dilatation. IVUS provides a more accurate assessment of stent dimensions, expansion, and apposition than angiography. Severe calcification by IVUS was associated with a higher risk of stroke.


Experimental diabetes attenuates calcium mobilization and proliferative response in splenic lymphocytes from mice.
The present study was conducted to investigate the effects of the diabetic condition on cytosolic free Ca(2+) concentration, [Ca(2+)](i), and the proliferation of splenic lymphocytes from mice. Diabetes was induced in mice by intraperitoneal injection of alloxan. [Ca(2+)](i) and the proliferation ex vivo of splenic lymphocytes isolated from mice were examined using fura-2 and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide, respectively. Diabetes caused a significant increase in resting [Ca(2+)](i) and significantly reduced the ability of concanavalin A (Con A; a T-lymphocyte-selective mitogen) to increase [Ca(2+)](i), but not that of lipopolysaccharide (LPS; a B-lymphocyte-selective mitogen). In addition, diabetes significantly reduced Con A-stimulated but not LPS-stimulated lymphocyte proliferation. Verapamil (an L-type Ca(2+) channel blocker) inhibited Con A-induced increases in [Ca(2+)](i) and proliferation in lymphocytes from control and diabetic mice to a similar extent, respectively. These results suggest that diabetes attenuates Con A-stimulated T-lymphocyte proliferation by decreasing [Ca(2+)](i) via reduction of Ca(2+) entry through L-type Ca(2+) channels.


Surface-plasma-enhanced quantum efficiency of a Ag-Ti-n-GaAs grating photodiode.
An array of Ag-Ti-n-GaAs grating photodiodes was designed and fabricated, with each diode having an active area with a diameter of 400 microm. Both electrical and optical characterizations were performed. We have made two experimental observations concerning (1) the surface-plasma-enhanced detectivity as a function of wavelength for 30 degrees angle of incidence and (2) the offset in angle between the reflectivity minimum and the current maximum at the surface-plasma resonance.


The humorally mediated antihypertensive system of the rat kidney: a physiological depressor mechanism?
The humoral renomedullary antihypertensive system, described by Muirhead [1], is known to be strongly activated upon unclipping renal hypertensive rats. The present study was designed to determine whether this system is tonically active in normotensive rat kidneys at normotensive pressure levels. Anaesthetized normotensive donor rats (NDR) were used to perfuse an isolated age-matched normotensive recipient (NRR) kidney, via an extracorporal circuit, set at different perfusion pressures, while the NDR mean arterial pressure and heart rate were measured continuously. The results showed non-significant alterations in the NDR heart rate and mean arterial pressure at 80 mmHg NRR kidney perfusion pressure, while at 100 and 150 mmHg there were significant, dose-dependent and gradual reductions in both the heart rate and mean arterial pressure in NDR. We conclude that the renal humoral antihypertensive system is active in normotensive kidneys already in the normotensive pressure range, but becomes further engaged in a dose-dependent way when renal perfusion pressure is raised.


Evaluation of sorbent amendments for in situ remediation of metal-contaminated sediments.
The present study evaluated sorbent amendments for in situ remediation of sediments contaminated with two divalent metals. A literature review screening was performed to identify low-cost natural mineral-based metal sorbents and high-performance commercial sorbents that were carried forward into laboratory experiments. Aqueous phase metal sorptivity of the selected sorbents was evaluated because dissolved metals in sediment porewater constitute an important route of exposure to benthic organisms. Based on pH-edge sorption test results, natural sorbents were eliminated due to inferior performance. The potential as in situ sediment amendment was explored by comparing the sorption properties of the engineered amendments in freshwater and saltwater (10 PPT salinity estuarine water) matrices. Self-assembled monolayers on mesoporous supports with thiols (Thiol-SAMMS) and a titanosilicate mineral (ATS) demonstrated the highest sorption capacity for cadmium (Cd) and lead (Pb), respectively. Sequential extraction tests conducted after mixing engineered sorbents with contaminated sediment demonstrated transfer of metal contaminants from a weakly bound state to a more strongly bound state. Biouptake of Cd in a freshwater oligochaete was reduced by 98% after 5-d contact of sediment with 4% Thiol-SAMMS and sorbed Cd was not bioavailable. While treatment with ATS reduced the small easily extractable portion of Pb in the sediment, the change in biouptake of Pb was not significant because most of the native lead was strongly bound. The selected sorbents added to sediments at a dose of 5% were mostly nontoxic to a range of sensitive freshwater and estuarine benthic organisms. Metal sorbent amendments in conjunction with activated carbon have the potential to simultaneously reduce metal and hydrophobic contaminant bioavailability in sediments.


Substantial Intra-Individual Variability in Post-Prandial Time to Peak in Controlled and Free-Living Conditions in Children with Type 1 Diabetes.
The optimal time to bolus insulin for meals is challenging for children and adolescents with type 1 diabetes (T1D). Current guidelines to control glucose excursions do not account for individual differences in glycaemic responses to meals. This study aimed to examine the within- and between-person variability in time to peak (TTP) glycaemic responses after consuming meals under controlled and free-living conditions. Participants aged 8-15 years with T1D ≥ 1 year and using a continuous glucose monitor (CGM) were recruited. Participants consumed a standardised breakfast for six controlled days and maintained their usual daily routine for 14 free-living days. CGM traces were collected after eating. Linear mixed models were used to identify within- and between-person variability in the TTP after each of the controlled breakfasts, free-living breakfasts (FLB), and free-living dinners (FLD) conditions. Thirty participants completed the study (16 females; mean age and standard deviation (SD) 10.5 (1.9)). The TTP variability was greater within a person than the variability between people for all three meal types (between-person vs. within-person SD; controlled breakfast 18.5 vs. 38.9 min; FLB 14.1 vs. 49.6 min; FLD 5.7 vs. 64.5 min). For the first time, the study showed that within-person variability in TTP glycaemic responses is even greater than between-person variability.


Expression and characterization of soluble forms of the extracellular domains of the beta, gamma and epsilon subunits of the human muscle acetylcholine receptor.
The nicotinic acetylcholine receptor (AChR) is a ligand-gated ion channel found in muscles and neurons. Muscle AChR, formed by five homologous subunits (alpha2 beta gamma delta or alpha2 beta gamma epsilon), is the major antigen in the autoimmune disease, myasthenia gravis (MG), in which pathogenic autoantibodies bind to, and inactivate, the AChR. The extracellular domain (ECD) of the human muscle alpha subunit has been heterologously expressed and extensively studied. Our aim was to obtain satisfactory amounts of the ECDs of the non-alpha subunits of human muscle AChR for use as starting material for the determination of the 3D structure of the receptor ECDs and for the characterization of the specificities of antibodies in sera from patients with MG. We expressed the N-terminal ECDs of the beta (amino acids 1-221; beta1-221), gamma (amino acids 1-218; gamma1-218), and epsilon (amino acids 1-219; epsilon1-219) subunits of human muscle AChR in the yeast, Pichia pastoris. beta1-221 was expressed at approximately 2 mg.L(-1) culture, whereas gamma1-218 and epsilon1-219 were expressed at 0.3-0.8 mg.L(-1) culture. All three recombinant polypeptides were glycosylated and soluble; beta1-221 was mainly in an apparently dimeric form, whereas gamma1-218 and epsilon1-219 formed soluble oligomers. CD studies of beta1-221 suggested that it has considerable beta-sheet secondary structure with a proportion of alpha-helix. Conformation-dependent mAbs against the ECDs of the beta or gamma subunits specifically recognized beta1-221 or gamma1-218, respectively, and polyclonal rabbit antiserum raised against purified beta1-221 bound to (125)I-labeled alpha-bungarotoxin-labeled human AChR. Moreover, immobilization of each ECD on Sepharose beads and incubation of the ECD-Sepharose matrices with MG sera caused a significant reduction in the concentrations of autoantibodies in the sera, showing specific binding to the recombinant ECDs. These results suggest that the expressed proteins present some near-native conformational features and are thus suitable for our purposes.


The Potentials and Pitfalls of Microarrays in Neglected Tropical Diseases: A Focus on Human Filarial Infections.
Data obtained from expression microarrays enables deeper understanding of the molecular signatures of infectious diseases. It provides rapid and accurate information on how infections affect the clustering of gene expression profiles, pathways and networks that are transcriptionally active during various infection states compared to conventional diagnostic methods, which primarily focus on single genes or proteins. Thus, microarray technologies offer advantages in understanding host-parasite interactions associated with filarial infections. More importantly, the use of these technologies can aid diagnostics and helps translate current genomic research into effective treatment and interventions for filarial infections. Studying immune responses via microarray following infection can yield insight into genetic pathways and networks that can have a profound influence on the development of anti-parasitic vaccines.


Analysis of DAZL SNP260 and SNP386 in infertile Chinese males using multi-analyte suspension array.
The aim of the present study was to investigate the association between two single nucleotide polymorphisms (SNPs) and infertility in Chinese males using multi-analyte suspension array (MASA). A total of 196 male patients with azoospermia or severe oligospermia (sperm density <5x106/ml, non‑obstructed) who had a normal karyotype and no azoospermia factor microdeletions were recruited, along with 40 healthy, fertile males as controls. Two SNPs of the deleted in azoospermia-like (DAZL) gene, SNP260 and SNP386, were genotyped by allele‑specific primer extension (ASPE) combined with MASA technology. The SNP260A>G and SNP386A>G mutations were found in the males with infertility. The SNP260, but not the SNP386, mutation was detectable in the control group. The mutation rates in the controls and patients were 2.5 and 3.06% for SNP260, and 0 and 2.04% for SNP386, respectively. A χ2 analysis did not identify any significant differences in the frequency of either mutation between the fertile and infertile males. In conclusion, the combination of ASPE and MASA methods for SNP genotyping was high‑throughput, accurate and cost‑efficient. The method was applied to detect SNP polymorphisms in the DAZL gene; and neither the A260G nor the A386G polymorphism of DAZL appeared to be involved in male infertility in the Chinese population.


Beyond genome-wide association studies: genetic heterogeneity and individual predisposition to cancer.
Genome-wide association studies (GWAS) using population-based designs have identified many genetic loci associated with risk of a range of complex diseases including cancer; however, each locus exerts a very small effect and most heritability remains unexplained. Family-based pedigree studies have also suggested tentative loci linked to increased cancer risk, often characterized by pedigree-specificity. However, comparison between the results of population- and family-based studies shows little concordance. Explanations for this unidentified genetic 'dark matter' of cancer include phenotype ascertainment issues, limited power, gene-gene and gene-environment interactions, population heterogeneity, parent-of-origin-specific effects, and rare and unexplored variants. Many of these reasons converge towards the concept of genetic heterogeneity that might implicate hundreds of genetic variants in regulating cancer risk. Dissecting the dark matter is a challenging task. Further insights can be gained from both population association and pedigree studies.


Effects of exogenous AHLs on the spoilage characteristics of Pseudomonas koreensis PS1.
Some specific spoilage organisms (SSO) respond to the presence of exogenous N-acyl-homoserine lactones (AHLs) through the quorum sensing (QS) system to modulate their spoilage characteristics. To explore the effect of exogenous AHLs on the spoilage characteristics of Pseudomonas koreensis PS1 from spoiled chilled pork, four kinds of AHLs were added to the liquid medium to analyze their effect on the cell growth and spoilage characteristics of P. koreensis PS1, and N-hexanoyl-l-homoserine lactone (C6-HSL) was added to evaluate its effect on spoilage characteristics of P. koreensis PS1 inoculated in fresh chilled pork. The results showed that the addition of low concentrations of C6-HSL (10 µmol/L) to the liquid medium could remarkably promote the protease activity, lipase activity, and biofilm formation of P. koreensis PS1 (p < 0.05), and more than 30 µmol/L C6-HSL could significantly increase the cell density (p < 0.05). Furthermore, the addition of 10 µmol/L C6-HSL into fresh chilled pork could increase the lipase and protease activities of P. koreensis PS1. The enzyme activity accelerated the decomposition of total protein, total fat, and total sugar, and led to an increase in putrescine, tyramine, cadaverine, and total volatile basic nitrogen (TVB-N) content in chilled pork during the storage at 4°C. PRACTICAL APPLICATION: The infestation of chilled pork with SSO may be a challenge for the meat industry. In this study, exogenous AHLs were found to have a positive effect on the spoilage of chilled pork. The elimination of the QS phenomenon of bacteria should be considered when looking for ways to prolong the preservation of chilled pork.


Nerve entrapment syndromes of the elbow, forearm, and wrist.
Nerve entrapment syndromes usually have typical clinical presentations and findings on physical examination. Imaging can be used to evaluate a structural cause of the entrapment, such as a mass or enlarged muscle or to show secondary findings that confirm the diagnosis, such as nerve swelling or muscle edema or atrophy. This article will review entrapment syndromes of the elbow, forearm, and wrist. To make an accurate assessment of the images, the radiologist must know the normal anatomy of the nerve, the places where the nerve can be compressed, and the muscles that are innervated by a particular nerve.


[The temporomandibular joint meniscus in MRI].
The continuing improvement of the MRI's equipment and software led us to a continuous adaptation of the exam technique. We use today a bilateral coil technique, 3 inches in diameter. Four slices are performed for each articulation (4 mm thick) in the true sagittal plane. A fast spin echo, balanced in proton density, for one minute, allows the study of 15 steps inside a full open/close cycle. Oblique coronal cuts are also performed parallel to the long axis of the condyle in a T1-weighted spin echo sequence in close and half-open positions. The analysis of 350 subjects allows to detail more precisely the meniscal displacement. Beside the classic anterior luxation, the meniscus slips medially, laterally and may rotate. These different situations may be isolated or combined. The dynamic study is specifically useful in the displacement with reduction exams. It enables permits to point out the timing of the disk disturbance: this information may be of great help in therapeutic decisions.


IRANIAN SCIENCE: Earthquake Researchers Prepare for the Next Big One.
When a devastating earthquake rocked the Manjil region in Iran on 20 June 1990, the tremors also shook seismology research in that country. That night, Mohsen Ghafory-Ashtiany rolled out of his bed in Tehran and headed to the danger zone in northwestern Iran, where 13,000 persons perished and 60,000 were injured. He and his then-tiny staff surveyed the damage and mapped out a plan for bolstering earthquake research and preparedness.


Correcting the Experimental Enthalpies of Formation of Some Members of the Biologically Significant Sulfenic Acids Family.
Sulfenic acids are important intermediates in the oxidation of cysteine thiol groups in proteins by reactive oxygen species. The mechanism is influenced heavily by the presence of polar groups, other thiol groups, and solvent, all of which determines the need to compute precisely the energies involved in the process. Surprisingly, very scarce experimental information exists about a very basic property of sulfenic acids, the enthalpies of formation. In this Article, we use high level quantum chemical methods to derive the enthalpy of formation at 298.15 K of methane-, ethene-, ethyne-, and benzenesulfenic acids, the only ones for which some experimental information exists. The methods employed were tested against well-known experimental data of related species and extensive CCSD(T) calculations. Our best results consistently point out to a much lower enthalpy of formation of methanesulfenic acid, CH3SOH (ΔfH0(298.15K) = -35.1 ± 0.4 kcal mol-1), than the one reported in the NIST thermochemical data tables. The enthalpies of formation derived for ethynesulfenic acid, HC≡CSOH, +32.9 ± 1.0 kcal/mol, and benzenesulfenic acid, C6H5SOH, -2.6 ± 0.6 kcal mol-1, also differ markedly from the experimental values, while the enthalpy of formation of ethenesulfenic acid CH2CHSOH, not available experimentally, was calculated as -11.2 ± 0.7 kcal mol-1.


Phase II clinical study of alternate-day oral therapy with S-1 as first-line chemotherapy for locally advanced and metastatic pancreatic cancer.
Based on the results of first-line chemotherapy for advanced pancreatic cancer, S-1 was confirmed to be non-inferior to gemcitabine. However, the recommended regimen of 4 weeks of administration followed by 2 weeks of drug withdrawal frequently causes adverse effects. On the other hand, we experienced in clinical practice that alternate-day administration of S-1 reduced adverse effects and were tolerable for advanced pancreatic cancer patients unwilling to continue the standard daily administration. We therefore conducted a multicenter cooperative prospective study to compare daily with alternate-day administration of S-1 for advanced pancreatic cancer. Patients with advanced pancreatic cancer were eligible for enrollment in this trial. S-1 was administered at a dose of 40-60 mg twice daily, calculated according to body surface area, on Monday, Wednesday, Friday, and Sunday. Each treatment cycle was 42 days. The primary end point was overall survival (OS). Secondary end points were safety, response rate (RR), progression-free survival (PFS), and time to treatment failure (TTF). Forty-eight patients were evaluable for response. OS as the primary end point was 8.4 months (95 % CI 5.4-10.8), and the 1-year survival rate was 29.2 %. PFS was 5.5 months, and TTF was 3.9 months. RR was 10.4 %, and the disease control rate was 79.2 %. Grade 3/4 hematological and non-hematological toxicities were minor. All of these adverse reactions were tolerable and reversible. The current data demonstrate the mitigation of adverse effects with alternate-day administration of S-1, and this appears to be a more sustainable option for advanced pancreatic cancer.


Cromolyn sodium for the prevention of chronic lung disease in preterm infants.
Chronic lung disease (CLD) frequently occurs in preterm infants (< 37 weeks gestational age) and has a multifactorial etiology including inflammation. Cromolyn sodium is a mast cell stabiliser that inhibits neutrophil activation and neutrophil chemotaxis. Therefore it is possible that cromolyn sodium might have a role in the prevention of CLD. in preterm infants, does the prophylactic administration of cromolyn sodium reduce the incidence of CLD, mortality or the combined outcome of mortality or CLD at 28 days of life without undue side effects? The search strategy used to identify studies was according to the guidelines of the Cochrane Neonatal Review Group. Searches were made of MEDLINE, EMBASE, CINAHL up to and including December 2000, the Cochrane Library 2000 Issue 4, personal files and reference lists of identified trials. The following terms were used: chronic lung disease, cromolyn sodium or cromoglycate. newborn, infant; human, clinical trial or controlled clinical trial or meta analysis or randomised controlled trial. No language restrictions were applied. Randomised or quasi-randomised controlled clinical trials involving preterm infants. Initiation of cromolyn sodium administration during the first two weeks of life. The intervention had to include administration of cromolyn sodium by nebulizer or metered dose inhaler with or without spacer device, versus placebo or no intervention. Eligible studies had to include at least one of the following outcomes: overall mortality, CLD at 28 days, CLD at 36 weeks corrected gestational age, or the combined outcome mortality or CLD at 28 days. Secondary outcomes included number of days on oxygen, number of days on mechanical ventilation, patent ductus arteriosus (PDA), air leaks [pulmonary interstitial emphysema (PIE), pneumothorax], any grade of intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC), sepsis and adverse effects due to cromolyn sodium. We used the standard method for the Cochrane Collaboration as described in the Cochrane Collaboration handbook. Both investigators extracted and assessed all data for each study. Any disagreement was resolved by discussion. Relative risk (RR) and risk difference (RD) with 95% confidence intervals (CI) are reported for dichotomous outcomes and weighted mean difference (WMD) for continuous data. Number needed to treat was not calculated as no outcome showed a statistically significant RD. A fixed effect model was used for meta-analysis. Two eligible studies were identified with small numbers of infants enrolled. Prophylaxis with cromolyn sodium did not result in a statistically significant effect on the combined outcome, death or CLD at 28 days [RR 1.05 (95% CI 0.73, 1.52); RD 0.03 (95% CI -0.20, 0.27)], CLD at 28 days [RR 0.93 (95% CI 0.53, 1.64; RD -0.03 (95% CI -0.27, 0.20)], CLD at 36 weeks corrected gestational age [RR 1.25 (95% CI 0.43, 3.63); RD 0.08 (95% CI -0.29, 0.44)], CLD in survivors at 28 days [RR 0.97 (95% CI 0.58, 1.63); RD -0.02 (95% CI -0.29, 0.26)] or CLD in survivors at 36 weeks corrected gestational age [RR 1.04 (95% CI 0.38, 2.87); RD 0.02 (95% CI -0.40, 0.43)]. Prophylaxis with cromolyn sodium did not show a statistically significant difference in overall mortality [RR 1.31 (95% CI 0.52, 3.29); RD 0.06 (95% CI -0.13, 0.26)]. There were no statistically significant differences in the incidence of air leaks, NEC, IVH, sepsis, days on mechanical ventilation or PDA. No side effects were noted. There is currently no evidence from randomized trials that cromolyn sodium has a role in the prevention of CLD. Cromolyn sodium cannot be recommended for the prevention of CLD in preterm infants. Additional clinical trials do not appear to be justified using the protocols for drug administration used to date unless a more efficient type of delivery device than the jet nebulizer is employed.


The Pressor Response to the Drinking of Cold Water and Cold Carbonated Water in Healthy Younger and Older Adults.
Purpose: Water drinking has been proposed for the treatment of orthostatic hypotension because it can increase blood pressure in patients. This study aimed to investigate whether drinking water with a cold or carbonation stimulus would cause a more effective pressor response, and whether it would be greater in older than in younger adults. Methods: We assessed blood pressure and heart rate from non-invasive arterial pressure (a volume-clamp method) and type II electrocardiography in 13 healthy young adults (6 females, 7 males; mean age, 19.9 ± 1.1 years) and nine healthy older adults (all females; mean age, 71.4 ± 4.2 years) who drank 200 mL of cold, cold carbonated, and room temperature water. Results: The pressor response to the drinking of cold and cold carbonated water was greater than that to room temperature water in both younger and older participants (p < 0.05; changes in systolic blood pressure of room temperature water, cold water and cold carbonated water in young: 15.31 ± 9.66, 22.56 ± 11.51 and 32.6 ± 17.98 mmHg, respectively; changes in systolic blood pressure of room temperature water, cold water and cold carbonated water in elderly: 21.84 ± 14.31, 41.53 ± 19.82 and 48.16 ± 16.77 mmHg, respectively). In addition, the pressor response to cold and cold carbonated water was persistent during the recovery period by about 5-10 mmHg (p < 0.05). Furthermore, the pressor response during the drinking and recovery periods was greater in the older than in the younger participants (p < 0.05). Conclusion: Our data suggest that even smaller amounts of water are able to elicit a sustained pressor response, in particular if the water is cold and carbonated. We speculate that the pressor effect may render cold and carbonated water an appropriate first aid method against certain forms of acute hypotension.


Molecular analysis of pyrethroid resistance in Cimex hemipterus (Hemiptera: Cimicidae) collected from different parts of Iran.
The present study was aimed to assess the bedbugs susceptibility to pyrethroid insecticides using molecular analysis. With the aid of pest control companies, adult bedbugs were collected from various places such as hotels, residential houses, and industrial buildings in seven cities highly crowded with domestic and foreign tourists in Iran from May 2016 to August 2017. Bedbugs were colonized in the laboratory to evaluate their resistance to pyrethroid using insecticide resistance bioassay. Genomic DNA was extracted from susceptible and resistant bedbugs. At first, specie specific primers targeting cytochrome oxidase subunit I (COI) gene was performed to confirm Cimex hemipterus species. Then, kdr-like gene was examined for point mutation using PCR and nucleotide sequencing. Bioassay showed that 11 out of 35 examined bedbugs were resistant to pyrethroids (31.43%; 95.00% confidence interval: 29.48-33.08%). The DNA sequencing showed that all examined bedbugs collected from Tehran province had homozygous V419L kdr-like gene mutations. The level of pyrethroid resistance found in the collected bugs from Tehran province indicated that this phenomenon has already been prevailed in the site and prompts the need to reevaluate the large use of pyrethroids to control the bedbugs.


Infliximab restores the balance between pro- and anti-apoptotic proteins in regressing psoriatic lesions.
Psoriasis and psoriatic arthritis are treated very efficaciously with infliximab, a chimaeric human-murine antitumour necrosis factor (TNF)-α antibody. As we reported earlier, infliximab, besides its anti-inflammatory properties, induces a caspase-independent programmed cell death of psoriatic keratinocytes. To elucidate this finding further, we investigated the epidermal expression of proteins involved in the mitochondria-dependent (intrinsic) pathway of cell death. Quantification of proteins with pro- (p53, AIF, Bax) and anti-apoptotic functions (Bcl-2, Bcl-XL) and of NF-κB was performed by means of immunohistochemistry and digital image analysis of the staining of nonlesional skin and lesional psoriatic skin from patients treated with infliximab at weeks 0, 2 and 6. Serial biopsies from psoriatic plaques of samples taken at days 0, 5, 14 and 21 of therapy demonstrated a significant downregulation of anti-apoptotic proteins Bcl-2, Bcl-XL and NF-κB during treatment and, in parallel, a significant upregulation of pro-apoptotic proteins p53, Bax and AIF. These differences in expression correlated with decreases in epidermal thickness and clinical outcome (Psoriasis Area and Severity Index). At day 21, expression levels of apoptosis-related proteins in lesional skin approximated those found in nonlesional skin. Our data therefore suggest that TNF-targeting agents may induce the regression of psoriasis at least in part by normalizing the expression of apoptosis-related proteins in lesional keratinocytes.


Diet self-selection and food hoarding after food deprivation by Siberian hamsters.
Siberian hamsters (Phodopus sungorus) increase food hoarding, but not food intake, after a fast. Because the physiological mechanisms underlying these changes in food hoarding are virtually unknown, we sought insight into these mechanisms by allowing hamsters to self-select their diet from food sources varying in macronutrient composition and caloric density ("dietary wisdom"). Therefore, the effects of food deprivation length on diet self-selection were tested in adult female hamsters after adaptation to three composite diets: sunflower seeds (SS), pellet chow (PC), and rabbit chow (RC). One group initially was fasted for 32 h, the other for 56 h, and then each was refed. The remaining nonexperienced fast was instated after prefast body mass, food intake, and hoarding were recovered. Food hoarding, but not food intake, was increased regardless of fast length or sequence; moreover, the largest increase in food hoarding was on the first day of refeeding and was primarily reflected as increased SS hoarding. When the longer fast occurred first body mass loss was greater and the increased food hoard size was maintained for more days than when the longer fast came second. The order of food intake and hoarding preferences was not changed after a fast (SS > PC > RC), but the degree of food hoarding preference for SS was exaggerated. Collectively, these results support the notion that food hoarding increases with decreases in lipid stores, and show that when internal lipid stores are decreased, external lipid stores are preferentially increased.


Bone substitute materials supplemented with prolyl hydroxylase inhibitors decrease osteoclastogenesis in vitro.
Inhibition of prolyl hydroxylases stimulates bone regeneration. Consequently, bone substitute materials were developed that release prolyl hydroxylase inhibitors. However, the impact of prolyl hydroxylase inhibitors released from these carriers on osteoclastogenesis is not clear. We therefore assessed the effect of bone substitute materials that release prolyl hydroxylase inhibitors on osteoclastogenesis. Dimethyloxalylglycine, desferrioxamine, and l-mimosine were lyophilized onto bovine bone mineral and hydroxyapatite, and supernatants were generated. Osteoclastogenesis was induced in murine bone marrow cultures in the presence of the supernatants from bone substitute materials. The formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and TRAP activity were determined. To test for possible effects on osteoclast progenitor cells, we measured the effect of the supernatants on proliferation and viability. In addition, experiments were performed where prolyl hydroxylase inhibitors were directly added to the bone marrow cultures. We found that prolyl hydroxylase inhibitors released within the first hours from bone substitute materials reduce the number and activity of TRAP-positive multinucleated cells. In line with this, addition of prolyl hydroxylase inhibitors directly to the bone marrow cultures dose-dependently reduced the number of TRAP-positive multinucleated cells and the overall resorption activity. Moreover, the released prolyl hydroxylase inhibitors decreased proliferation but not viability of osteoclast progenitor cells. Our results show that prolyl hydroxylase inhibitors released from bone substitute materials decrease osteoclastogenesis in murine bone marrow cultures.


Benchmarking: a method for continuous quality improvement in health.
Benchmarking, a management approach for implementing best practices at best cost, is a recent concept in the healthcare system. The objectives of this paper are to better understand the concept and its evolution in the healthcare sector, to propose an operational definition, and to describe some French and international experiences of benchmarking in the healthcare sector. To this end, we reviewed the literature on this approach's emergence in the industrial sector, its evolution, its fields of application and examples of how it has been used in the healthcare sector. Benchmarking is often thought to consist simply of comparing indicators and is not perceived in its entirety, that is, as a tool based on voluntary and active collaboration among several organizations to create a spirit of competition and to apply best practices. The key feature of benchmarking is its integration within a comprehensive and participatory policy of continuous quality improvement (CQI). Conditions for successful benchmarking focus essentially on careful preparation of the process, monitoring of the relevant indicators, staff involvement and inter-organizational visits. Compared to methods previously implemented in France (CQI and collaborative projects), benchmarking has specific features that set it apart as a healthcare innovation. This is especially true for healthcare or medical-social organizations, as the principle of inter-organizational visiting is not part of their culture. Thus, this approach will need to be assessed for feasibility and acceptability before it is more widely promoted.


Foreskin management: Survey of Canadian pediatric urologists.
To study the approaches to foreskin management of pediatric urologists in Canada. An online questionnaire comprising several survey questions and clinical vignettes. Canada. All members of the Pediatric Urologists of Canada. Diagnoses and management strategies for common foreskin conditions seen in consultation, including how many pediatric urologists perform neonatal circumcisions, patient costs, and the reasons for performing the surgery. Of the 32 members surveyed, 24 (75%) responded. By far most respondents do not perform neonatal circumcisions; however, many perform circumcisions under general anesthesia for religious and cultural purposes. Typically, patient costs for circumcision range from $500 to $1000. Management of asymptomatic physiologic phimosis is very conservative, with surgeons unlikely to intervene. Neither the presence of ballooning of the foreskin during voiding nor the child's age affects physicians' tendency toward conservative management. Balanitis xerotica obliterans was the only scenario in which most respondents believed there was a need to intervene with either topical steroids or circumcision. Our data support the hypothesis that pediatric urologists across Canada are very similar in their conservative approach to the management of common foreskin issues. Our goal is to improve the knowledge base among primary care providers and subsequently decrease patient and family anxieties.


Treating navicular syndrome in equine patients.
Navicular syndrome is a chronic, progressive condition affecting the navicular bone and bursa, deep digital flexor tendon (DDFT), and associated soft tissue structures composing the navicular apparatus. The treatment options for navicular syndrome are as varied as the proposed causes of the condition. The severity of clinical signs, intended use and workload of the horse, and owner compliance with therapy are important considerations in developing a treatment plan. Nonsurgical treatment of navicular syndrome consists of rest, hoof balance and corrective trimming/shoeing, and medical therapy, including administration of systemic antiinflammatories, hemorheologic medications, and intraarticular medications. While surgical therapy can include desmotomy of the collateral (suspensory) ligaments of the navicular bone, palmar digital neurectomy is more commonly performed when medical therapy is ineffective. Recently, adjunct therapies, such as acupuncture and extracorporeal shock wave therapy, have also been used to treat horses with navicular syndrome. Because of the wide range of pathologic changes and the lack of a definitive cure associated with navicular syndrome, treatment is directed toward the individual horse, focusing on the management of clinical signs to alleviate stress and retard degenerative changes of the navicular bursal and navicular regions.


Quantum heat engine power can be increased by noise-induced coherence.
Laser and photocell quantum heat engines (QHEs) are powered by thermal light and governed by the laws of quantum thermodynamics. To appreciate the deep connection between quantum mechanics and thermodynamics we need only recall that in 1901 Planck introduced the quantum of action to calculate the entropy of thermal light, and in 1905 Einstein's studies of the entropy of thermal light led him to introduce the photon. Then in 1917, he discovered stimulated emission by using detailed balance arguments. Half a century later, Scovil and Schulz-DuBois applied detailed balance ideas to show that maser photons were produced with Carnot quantum efficiency (see Fig. 1A). Furthermore, Shockley and Quiesser invoked detailed balance to obtain the efficiency of a photocell illuminated by "hot" thermal light (see Fig. 2A). To understand this detailed balance limit, we note that in the QHE, the incident light excites electrons, which can then deliver useful work to a load. However, the efficiency is limited by radiative recombination in which the excited electrons are returned to the ground state. But it has been proven that radiatively induced quantum coherence can break detailed balance and yield lasing without inversion. Here we show that noise-induced coherence enables us to break detailed balance and get more power out of a laser or photocell QHE. Surprisingly, this coherence can be induced by the same noisy (thermal) emission and absorption processes that drive the QHE (see Fig. 3A). Furthermore, this noise-induced coherence can be robust against environmental decoherence.Fig. 1.(A) Schematic of a laser pumped by hot photons at temperature T(h) (energy source, blue) and by cold photons at temperature T(c) (entropy sink, red). The laser emits photons (green) such that at threshold the laser photon energy and pump photon energy is related by Carnot efficiency (4). (B) Schematic of atoms inside the cavity. Lower level b is coupled to the excited states a and β. The laser power is governed by the average number of hot and cold thermal photons, and . (C) Same as B but lower b level is replaced by two states b(1) and b(2), which can double the power when there is coherence between the levels.Fig. 2.(A) Schematic of a photocell consisting of quantum dots sandwiched between p and n doped semiconductors. Open circuit voltage and solar photon energy ℏν(h) are related by the Carnot efficiency factor where T(c) is the ambient and T(h) is the solar temperature. (B) Schematic of a quantum dot solar cell in which state b is coupled to a via, e.g., solar radiation and coupled to the valence band reservoir state β via optical phonons. The electrons in conduction band reservoir state α pass to state β via an external circuit, which contains the load. (C) Same as B but lower level b is replaced by two states b(1) and b(2), and when coherently prepared can double the output power.Fig. 3.(A) Photocell current j = Γρ(αα) (laser photon flux P(l)/ℏ(ν(l))) (in arbitrary units) generated by the photovoltaic cell QHE (laser QHE) of Fig. 1C (Fig. 2C) as a function of maximum work (in electron volts) done by electron (laser photon) E(α) - E(β) + kT(c) log(ρ(αα)/ρ(ββ)) with full (red line), partial (brown line), and no quantum interference (blue line). (B) Power of a photocell of Fig. 2C as a function of voltage for different decoherence rates , 100γ(1c). Upper curve indicates power acquired from the sun.


How to protect yourself after body fluid exposure.
An accidental exposure to blood or other potentially infectious material (OPIM) such as cerebrospinal or pleural fluid can be a life changing experience. Among the bloodborne and OPIM pathogens are HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV). Postexposure prophylaxis (PEP) exists for HBV and HIV, but not for HCV, which is the most common chronic bloodborne infection in the United States; approximately 3.2 million persons are chronically infected. Fortunately, however, exposure to blood or OPIM usually doesn't translate into disease transmission. In this article, we'll discuss how you can minimize the risk of disease transmission if you or a coworker is accidentally exposed to blood or another potentially infectious body fluid. But first, let's review some key definitions.


Photodynamic therapy: the imminent milieu for treating oral lesions.
Photodynamic therapy (PDT) is used in curative and palliative treatment of head and neck squamous cell carcinoma (HNSCC) and other oral lesions. Oral infections (such as mucosal and endodontic infections, periodontal diseases, caries, and peri-implantitis) are among the specific targets where PDT can be applied Photodynamic therapy (PDT) efficacy depends on the local dose deposited in the lesion as well as oxygen availability in the lesion. Further long-term clinical studies are necessary in establishing a more specific place of the technique in the field of dentistry.


The Intracellular Localisation and Phosphorylation Profile of the Human 5-Lipoxygenase Δ13 Isoform Differs from That of Its Full Length Counterpart.
5-Lipoxygenase (5-LO) catalyzes leukotriene (LT) biosynthesis by a mechanism that involves interactions with 5-lipoxygenase activating protein (FLAP) and coactosin-like protein (CLP). 5-LO splice variants were recently identified in human myeloid and lymphoid cells, including the catalytically inactive ∆13 isoform (5-LO∆13) whose transcript lacks exon 13. 5-LO∆13 inhibits 5-LO product biosynthesis when co-expressed with active full length 5-LO (5-LO1). The objective of this study was to investigate potential mechanisms by which 5-LO∆13 interferes with 5-LO product biosynthesis in transfected HEK293 cells. When co-expressed with 5-LO1, 5-LO∆13 inhibited LT but not 5-hydroxyeicosatetraenoic acid (5-HETE) biosynthesis. This inhibition was independent of 5-LO∆13-FLAP interactions since it occurred in cells expressing FLAP or not. In cell-free assays CLP enhances 5-LO activity through interactions with tryptophan-102 of 5-LO. In the current study, the requirement for W102 was extended to whole cells, as cells expressing the 5-LO1-W102A mutant produced little 5-LO products. W102A mutants of 5-LO∆13 inhibited 5-LO product biosynthesis as effectively as 5-LO∆13 suggesting that inhibition is independent of interactions with CLP. Confocal microscopy showed that 5-LO1 was primarily in the nucleoplasm whereas W102A mutants showed a diffuse cellular expression. Despite the retention of known nuclear localisation sequences, 5-LO∆13 was cytosolic and concentrated in ER-rich perinuclear regions where its effect on LT biosynthesis may occur. W102A mutants of 5-LO∆13 showed the same pattern. Consistent with subcellular distribution patterns, 5-LO∆13 was hyper-phosphorylated on S523 and S273 compared to 5-LO1. Together, these results reveal a role for W102 in nuclear targeting of 5-LO1 suggesting that interactions with CLP are required for nuclear localization of 5-LO1, and are an initial characterisation of the 5-LO∆13 isoform whose inhibition of LT biosynthesis appears independent of interactions with CLP and FLAP. Better knowledge of the regulation and properties of alternative 5-LO isoforms will contribute to understanding the complex regulation of LT biosynthesis.


Passive random walkers and riverlike networks on growing surfaces.
Passive random walker dynamics is introduced on a growing surface. The walker is designed to drift upward or downward and then follow specific topological features, such as hill tops or valley bottoms, of the fluctuating surface. The passive random walker can thus be used to directly explore scaling properties of otherwise somewhat hidden topological features. For example, the walker allows us to directly measure the dynamical exponent of the underlying growth dynamics. We use the Kardar-Parisi-Zhang (KPZ) -type surface growth as an example. The world lines of a set of merging passive walkers show nontrivial coalescence behaviors and display the riverlike network structures of surface ridges in space-time. In other dynamics, such as Edwards-Wilkinson growth, this does not happen. The passive random walkers in KPZ-type surface growth are closely related to the shock waves in the noiseless Burgers equation. We also briefly discuss their relations to the passive scalar dynamics in turbulence.


Minor salivary gland tumors of the palate: clinical and pathologic correlates of outcome.
Minor salivary gland tumors of the palate are rare and may pose a diagnostic and therapeutic dilemma for the head and neck surgeon. The authors reviewed their 46 years of experience with minor salivary gland tumors of the palate to determine the factors that influence outcome and their implications for treatment. Malignant tumors were seen in 116 patients (78%) and benign tumors were found in 33 patients (22%). Adenoid cystic carcinoma was the most common malignant tumor, occurring in 43 patients, and pleomorphic adenoma was the most common benign tumor, occurring in 30 patients. Univariate analysis on the malignant lesions showed that grade 3 tumor histology (P < .001), tumor size greater than 3 cm (P < .001), perineural invasion (P = .031), bone invasion (P = .012), positive surgical margins (P < .001), and positive initial but negative final margins (P = .004) were all associated with decreased survival. With multivariate analysis, tumor size, margin status, and grade were shown to be independently associated with decreased survival (P < .05). The recurrence rate at the primary site was significantly higher for adenoid cystic carcinoma than for other histologies (P = .0059). The 2-, 5-, and 10-year disease-specific survival rates for patients with malignant disease were 96%, 87%, and 80%, respectively. Wide surgical excision with adequate margins is essential for a favorable outcome in patients with malignant minor salivary gland tumors. Postoperative radiotherapy is reserved for patients with grade 3 tumor histology, large primary lesions, perineural invasion, bone invasion, cervical lymph node metastasis, and positive margins, although a clear-cut survival advantage has not been proven. Recurrence, especially regional and distant metastasis, portends an extremely poor prognosis.


Thermal Simulations of Cancerous Breast Tumors and Cysts on a Realistic Female Torso.
Medical thermography has been around for several decades however due to its low specificity it has not become a popular medical diagnostic technique. The development of computational models of heat transfer in biological tissue can provide a deeper knowledge of healthy and nonhealthy thermal patterns which could increase the specificity of this technique increasing its usefulness in clinical diagnosis. In this work, the thermal pattern of cancerous tumors and cysts are calculated through finite element computer simulations using a real human female torso. The simulation results show a thermal pattern that agrees with infrared thermal images taken from female subjects, the simulated thermal patterns show real thermal features that do not appear in simulations performed using other approximate geometries of the breast. Results show that the temperature on the region of the skin closest to the tumor decreases for cysts while it increases for malignant tumors. The temperature patterns show a 20% deviation from thermal simulations using a hemispherical model of the breast, these results reinforce the notion that the geometry used for thermal simulation plays an important role in the accuracy of the simulations. These results are a first step in understanding benign and malignant thermal processes of the breast which might help increase the usefulness of infrared imaging in breast clinical diagnosis.


The direct posterior esthetic restoration using state-of-the-art composite resin technology.
As a result of the evolution of both materials and techniques, the direct posterior composite restoration has become a common procedure in today's dental practice. Advances in the adhesive protocol have allowed for the conservative preparation of the dentition by using the micromechanical potential of the sound tooth structure. Improvements of composite resin materials have further enabled the practitioner to re-create the natural esthetic beauty of the dentition while at the same time restoring the functional morphology. This article describes the technical protocol and materials necessary to perform the direct posterior composite restoration in the posterior dentition.


Augmentative and Alternative Communication and Speech Production for Individuals with ASD: A Systematic Review.
This review evaluated the effects of augmentative and alternative communication (AAC) on speech development in children with autism spectrum disorders (ASD); replicated, updated, and extended the systematic review by Schlosser and Wendt (American Journal of Speech-Language Pathology 17:212-230, 2008). Twenty-five single case design articles and three group design articles published between 1975 and May 2020 met inclusion criteria related to participant characteristics, intervention type, design, and visual analysis of dependent variable outcomes. Overall, AAC resulted in improved speech production; however, speech gains that did occur did not surpass AAC use.


Comparative Evolutionary Patterns of Burkholderia cenocepacia and B. multivorans During Chronic Co-infection of a Cystic Fibrosis Patient Lung.
During chronic respiratory infections of cystic fibrosis (CF) patients, bacteria adaptively evolve in response to the nutritional and immune environment as well as influence other infecting microbes. The present study was designed to gain insights into the genetic mechanisms underlying adaptation and diversification by the two most prevalent pathogenic species of the Burkholderia cepacia complex (Bcc), B. cenocepacia and B. multivorans. Herein, we study the evolution of both of these species during coinfection of a CF patient for 4.4 years using genome sequences of 9 B. multivorans and 11 B. cenocepacia. This co-infection spanned at least 3 years following initial infection by B. multivorans and ultimately ended in the patient's death by cepacia syndrome. Both species acquired several mutations with accumulation rates of 2.08 (B. cenocepacia) and 2.27 (B. multivorans) SNPs/year. Many of the mutated genes are associated with oxidative stress response, transition metal metabolism, defense mechanisms against antibiotics, and other metabolic alterations consistent with the idea that positive selection might be driven by the action of the host immune system, antibiotic therapy and low oxygen and iron concentrations. Two orthologous genes shared by B. cenocepacia and B. multivorans were found to be under strong selection and accumulated mutations associated with lineage diversification. One gene encodes a nucleotide sugar dehydratase involved in lipopolysaccharide O-antigen (OAg) biosynthesis (wbiI). The other gene encodes a putative two-component regulatory sensor kinase protein required to sense and adapt to oxidative- and heavy metal- inducing stresses. This study contributes to understanding of shared and species-specific evolutionary patterns of B. cenocepacia and B. multivorans evolving in the same CF lung environment.


Clinical significance of the dispersion of the activation--recovery interval and recovery time as markers for ventricular fibrillation susceptibility in patients with Brugada syndrome.
Brugada syndrome (BS) is associated with sudden cardiac death and the markers for ventricular fibrillation (VF) remain unclear, so the activation-recovery interval (ARI) dispersion and recovery time (RT) dispersion were investigated as possible markers in 20 subjects with BS (BS group) and 22 healthy individuals (H group). The 20 BS subjects were divided into 8 cases with documented VF (BS-VF group), 3 of which had recurrences, and 12 without (BS-N group). The corrected dispersion measurements from the standard 12-lead ECG of the QT interval (QTcd), ARI (ARIcd) and RT (RTcd) were compared among the groups. There were significant differences noted between the BS-VF and BS-N groups for the ARIcd and the RTcd, but not for the QTcd. Further, there were critical differences, 150 ms(1/2), observed for the ARIcd and RTcd, and these were associated with a prolongation of the maximum ARI or RT, shortening of the minimum ARI or RT, and prolongation only of the maximum QT for the QTcd. Susceptibility to VF may be predicted by the ARIcd or RTcd in BS.


A few autoreactive cells in an autoimmune infiltrate control a vast population of nonspecific cells: a tale of smart bombs and the infantry.
Inflammatory infiltrates in tissue-specific autoimmune disease comprise a collection of T cells with specificity for an antigen in the target organ. These specific cells recruit a population of nonspecific T cells and macrophages. The rare tissue-specific T cells in the infiltrate have the capacity to regulate both the influx and the efflux of cells from the tissue. Administration of an altered peptide ligand for the specific T cell which triggers autoimmunity can lead to the regression of the entire inflammatory ensemble in a few hours. Interleukin 4 is a critical cytokine involved in the regression of the inflammatory infiltrate.


Pleiotropic Effect of IL-6 Produced by B-Lymphocytes During Early Phases of Adaptive Immune Responses Against TB Infection.
The role of B cells migrating to the lung and forming follicles during tuberculosis (TB) inflammation is still the subject of debate. In addition to their antibody production and antigen-presenting functions, B cells secrete different cytokines and chemokines, thus participating in complex networks of innate and adaptive immunity. Importantly, lung B-cells produce high amounts of the pleiotropic gp130 cytokine IL-6. Its role during TB infection remains controversial, partly due to the fact that IL-6 is produced by different cell types. To investigate the impact of IL-6 produced by B cells on TB susceptibility and immune responses, we established a mouse strain with specific IL-6 deficiency in B cells (CD19cre-IL-6fl/fl, B-IL-6KO) on the B6 genetic background. Selective abrogation of IL-6 in B cells resulted in shortening the lifespan of TB-infected B-IL-6KO mice compare to the wild-type controls. We provide evidence that at the initial TB stages B cells serve as a critical source of IL-6. In the lung, the effect of IL-6 deficiency in B cells is associated rather with B and T cell functioning, than with macrophage polarization. TB-infected B-IL-6KO mice displayed diminished sizes of B cells themselves, CD4+IFN-γ+, Th17+, and CD4+CXCR5+ follicular T cell populations. The pleiotropic effect of B-cell-derived IL-6 on T-cells demonstrated in our study bridges two major lymphocyte populations and sheds some light on B- and T-cells interactions during the stage of anti-TB response when the host switches on a plethora of acquired immune reactions.


[Application of Cheng's needling method like a dragonfly skimming the surface of the water in treatment of pain syndrome].
Cheng's needling method like a dragonfly skimming the surface of the water is a needling method handed down in the family of chief TCM physician Cheng Zi-jun and it has been applied clinically for over one hundred years. It is a unique reinforcing-reducing method of acupuncture with simple and convenient manipulation and excellent therapeutic effect, which is created and gradually completed by Cheng's grandfather Mr. Cheng Jin-he on the basis of studying ancient various reinforcing-reducing methods. In the method, stimulating amount of acupuncture is introduced into reinforcing-reducing. Clinically, this method is used to treat various chronic pain syndromes with rapid effect.


Biochemical and morphological responses in Chironomus riparius (Diptera, Chironomidae) larvae exposed to lead-spiked sediment.
The aim of the present study was to assess the potential use of biochemical markers and mentum deformities as indicators of long-term exposure to lead (Pb) in Chironomus riparius larvae. To do this, the authors measured 3 biochemical markers (i.e., malondialdehyde level, metallothionein concentration, and energy reserve content) as well as larval growth and mentum deformities after 16-d exposure to sediment containing Pb. The concentrations studied ranged from 3.5 mg/kg to 505.5 mg/kg dry weight. Despite the bioaccumulation of Pb in C. riparius bodies, frequencies of both mentum deformities and the dry weight were not significantly different between the control and stressed groups. On the contrary, Pb exposure caused a significant increase of both malondialdehyde level and metallothionein concentration. The increase of body Pb concentrations did not significantly modify body copper and zinc concentrations. Moreover, we observed a decrease of total lipid content and an increase of glycogen content as a function of a dose-response relationship, while no variation in protein concentrations was observed. Despite the adverse effects observed at the biochemical level, larval development was not affected. These results suggested that measurements of malondialdehyde level, metallothionein concentration, and energy reserve content can be used as relevant biomarkers of long-term sublethal exposure to Pb in C. riparius larvae.


Bone regeneration by stem cell and tissue engineering in oral and maxillofacial region.
Clinical imperatives for the reconstruction of jaw bone defects or resorbed alveolar ridge require new therapies or procedures instead of autologous/allogeneic bone grafts. Regenerative medicine, based on stem cell science and tissue engineering technology, is considered as an ideal alternative strategy for bone regeneration. In this paper, we review the current choices of cell source and strategies on directing the osteogenic differentiation of stem cells. The preclinical animal models for bone regeneration and the key translational points to clinical success in oral and maxillofacial region are also discussed. We propose comprehensive strategies based on stem cell and tissue engineering researches, allowing for clinical application in oral and maxillofacial region.


Levels of circulating fibronectin receptor in adult and pediatric patients with human immunodeficiency virus type 1 infection.
We found a significant increase in fibronectin receptor (FNR) levels in the sera of adult human immunodeficiency virus type 1 (HIV-1)-infected patients, especially in those with AIDS (1,026.9 +/- 583.9 ng/ml; P < 0.0001). In contrast, AIDS patients with neurologic disorders and HIV-1-seropositive patients showed normal levels of FNR in serum. In addition, HIV-1-infected children showed increased levels of FNR in serum (824.4 +/- 333.5 ng/ml; P = 0.03). We suggest that an increase of FNR levels in AIDS patients is related to enhanced expression of FNR on HIV-1-infected cells.


Double-Shelled CdS- and CdSe-Cosensitized ZnO Porous Nanotube Arrays for Superior Photoelectrocatalytic Applications.
The effective separation and transport of photoinduced electron-hole pairs in photoanodes is of great significance to photoelectrochemical and catalytic performance. Here, a facile and effective two-step strategy is developed to fabricate double-shelled ZnO/CdS/CdSe porous nanotube photoanodes from ZnO nanorod arrays (NRAs). Surprisingly, after the process of the deposition of CdS and CdSe, the ZnO nanorod arrays are partially dissolved, resulting in the formation of ZnO/CdS/CdSe porous nanotube arrays (NTAs). By virtue of their unique porous nanotube structure and cosensitization effect, the ZnO/CdS/CdSe porous NTAs show superior photoelectrochemical water-splitting performance and organic-pollutant-degradation ability under visible light irradiation, as well as excellent long-term photostability.


PRUNE2 inhibits progression of colorectal cancer in vitro and in vivo.
Prune homolog 2 with BCH domain (PRUNE2) is associated with prostate cancer, neuroblastoma, glioblastoma and melanoma; however, the function of PRUNE2 in colorectal cancer (CRC) remains unknown. The present study aimed to evaluate the effects of PRUNE2 on the development of CRC. The biological function of PRUNE2 in CRC cell lines was investigated by using Cell Counting Kit-8, colony formation, flow cytometry and Transwell assay. Additionally, a mouse model was established to investigate the effect of PRUNE2 on metastasis of CRC cells. The expression levels of PRUNE2 were lower in CRC compared with adjacent normal tissue and this expression pattern was associated with poor relapse-free survival probability. PRUNE2 overexpression significantly decreased cell proliferation and invasion, increased cell apoptosis and arrested the cell cycle. Consistently, it increased the protein expression levels of pro-apoptosis genes and decreased the expression of antiapoptotic proteins. PRUNE2 knockdown had the opposite effects. Furthermore, PRUNE2 overexpression decreased the tumorigenicity of CRC cells. In conclusion, PRUNE2 decreased cell survival, proliferation, invasion and tumorigenicity and promoted apoptosis, suggesting that PRUNE2 may function as a tumor-suppressive gene in CRC.


Dietary non-heme iron bioavailability among children (ages 5-8) in a rural, high-anemia-prevalent area in North India: comparison of algorithms.
Non-heme iron bioavailability of diet consumed by children (ages 5 to 8) in rural area of India was estimated by comparison of algorithms. A cross-sectional observational study was conducted among 232 children and consisted of a 24-hour recall on 2 nonconsecutive days. Four algorithms were chosen to estimate the non-heme iron bioavailability. Daily average non-heme iron bioavailability as calculated by different algorithms was low (between 3.2% and 4.6%). Correlations of bioavailable non-heme iron among different algorithms were strong, ranging from rs = 0.67 to rs = 0.85 (p ≤ .01).


Corticosteroid-use in primary and secondary brain tumour patients: a review.
Corticosteroids have been effective in the management of cerebral oedema, in the context of brain tumours, for many decades. Though their effectiveness is well-established, this needs to be balanced against their potential to cause significant side effects. There is currently little consensus in the literature about how this should be done. This article reviews the literature, specifically in relation to the role of corticosteroids in primary and secondary brain tumour patients. Areas reviewed include corticosteroid pharmacology, indications, mechanism of action, toxicity profile, prescribing practices, and corticosteroid-sparing agents.


Confabulation and the control of recollection.
It is argued that current models of memory do not adequately account for the confabulations that are found in the recall of certain neurological patients. A model of the relation between control processes and memory involved in recalling autobiographical episodes is put forward. It is based on detailed analysis of the protocols of healthy volunteers' autobiographical recollections of recent everyday events. It is held that damage to different components of the model fits with the different patterns of performance found in confabulators, and examples of the errors that confabulators make are discussed in terms of those made by normal subjects.


Discovery of Novel Alphacoronaviruses in European Rodents and Shrews.
Eight hundred and thirteen European rodents and shrews encompassing seven different species were screened for alphacoronaviruses using PCR detection. Novel alphacoronaviruses were detected in the species Rattus norvegicus, Microtus agrestis, Sorex araneus and Myodes glareolus. These, together with the recently described Lucheng virus found in China, form a distinct rodent/shrew-specific clade within the coronavirus phylogeny. Across a highly conserved region of the viral polymerase gene, the new members of this clade were up to 22% dissimilar at the nucleotide level to the previously described Lucheng virus. As such they might represent distinct species of alphacoronaviruses. These data greatly extend our knowledge of wildlife reservoirs of alphacoronaviruses.


Angiotensin II induces nuclear factor (NF)-kappaB1 isoforms to bind the angiotensinogen gene acute-phase response element: a stimulus-specific pathway for NF-kappaB activation.
The vasopressor angiotensin II (AII) activates transcriptional expression of its precursor, angiotensinogen. This biological "positive feedback loop" occurs through an angiotensin receptor-coupled pathway that activates a multihormone-responsive enhancer of the angiotensinogen promoter, termed the acute-phase response element (APRE). Previously, we showed that the APRE is a cytokine [tumor necrosis factor-alpha (TNFalpha)]- inducible enhancer by binding the heterodimeric nuclear factor-kappaB (NF-kappaB) complex Rel A x NF-kappaB1. Here, we compare the mechanism for NF-kappaB activation by the AII agonist, Sar1 AII, with TNFalpha in HepG2 hepatocytes. Although Sar1 AII and TNFalpha both rapidly activate APRE-driven transcription within 3 h of treatment, the pattern of inducible NF-kappaB binding activity in electrophoretic mobility shift assay is distinct. In contrast to the TNFalpha mechanism, which strongly induces Rel A x NF-kappaB1 binding, Sar1 AII selectively activates a heterogenous pattern of NF-kappaB1 binding. Using a two-step microaffinity DNA binding assay, we observe that Sar1 AII recruits 50-, 56-, and 96-kDa NF-kappaB1 isoforms to bind the APRE. Binding of all three NF-kappaB1 isoforms occurs independently of changes in their nuclear abundance or proteolysis of cytoplasmic IkappaB inhibitors. Phorbol ester-sensitive protein kinase C (PKC) isoforms are required because PKC down-regulation completely blocks AII-inducible transcription and inducible NF-kappaB1 binding. We conclude that AII stimulates the NF-kappaB transcription factor pathway by activating latent DNA-binding activity of NF-kappaB subunits through a phorbol ester-sensitive (PKC-dependent) mechanism.


Karyotype Analysis of the New Talpa Species Talpa aquitania (Talpidae; Insectivora) from Northern Spain.
Karyotypes of 3 male Talpa specimens from northern Spain were analyzed. The mesostyles of upper molars and cytochrome b sequence analysis identified these specimens as belonging to Talpa aquitania, a new Talpa species recently described from northern Spain and southern France. We describe here for the first time the karyotype of Talpa aquitania. Its diploid number is 2n = 34 and NFa = 64, and all chromosomes including the sex chromosomes are biarmed, either metacentric or submetacentric. G-banding demonstrated that the karyotypes of T. aquitania and T. occidentalis (the most closely related species) are almost identical. However, the karyotype of T. aquitania differs from the karyotypes of both T. europaea and T. occidentalis in that it has a medium-sized biarmed Y chromosome rather than a dot-like chromosome and that chromosome 16 is submetacentric in T. aquitania but has a small p-arm in both T. europaea and T. occidentalis. Pericentromeric C-bands were scarce and only clearly visible in a few chromosomal pairs. In addition, C-banding demonstrated that half of the 14p, the 16p, and the Y chromosome are all heterochromatic. rDNA genes were located at the secondary constriction in autosomal pair 3, a common feature in the karyotypes of all Talpa species. Hybridization signals for telomeric repeats were found on the telomeres and the pericentric regions of some chromosomes and co-localized in the secondary constriction of pair 3 with the rDNA genes. In conclusion, the karyotype of T. aquitania from northern Spain is very similar to the karyotype of other species belonging to the genus Talpa.


Synchronous gene expressions during embryogenesis of Oncorhynchus masou (Yamame).
In order to detect periods of synchronous gene expressions during embryogenesis of Oncorhynchus masou (Yamame), we analyzed the peptide constituents of the embryos by means of two-dimensional electrophoresis. New kinds of peptides were mainly detected in three periods, i.e. between the 12th and 13th day, between the 20th and 21st day, and between the 30th and 31st day after fertilization. Hatching occurred between the 34th and 37th day. These indicate that these three periods, which corespond to (1) the shifting stage from maternal to nuclear events in gene expression, (2) the development of external organs such as fins, and (3) the preparative stage for hatching, respectively, may be critical stages in gene expression.


Localization of endothelin-1 (ET-1), ET-2, and ET-3, mouse VIC, and sarafotoxin S6b binding sites in mammalian heart and kidney.
Quantitative in vitro receptor autoradiography was used to identify and compare binding sites for endothelin-1 (ET-1), ET-2, and ET-3, mouse vasoactive intestinal contractor (VIC), and sarafotoxin S6b in human, porcine, and rat cardiac and renal tissues. In the rat kidney, the highest densities of binding sites for all five labeled peptides were present in the glomeruli, with lower levels in the papilla, cortex, and inner band of the medulla. A similar pattern was found in porcine and human kidney except that no discrete glomerular binding could be detected. In the heart, higher densities were detected in the atria compared to the ventricle. Although the pattern of binding in cardiac and renal tissue was similar for all four labeled ET isoforms, nonspecific binding was consistently higher with ET-3, resulting in lower levels of specific binding. These results suggest that these peptides could be acting via the same population of binding sites, but multiple receptor subtypes may exist that differ in their rank order of affinity for the ET isoforms and sarafotoxin S6b, as proposed in other tissues.


Characterization of mouse spermatogonia by transmission electron microscopy.
Characteristics of the various type A, intermediate (In) and B spermatogonia were determined in C57BL/6J mice using transmission electron microscopy. Spermatogonia were photographed at all stages of the cycle of the seminiferous epithelium. Over 450 images were taken. Spermatogonia could be classified into As, Apr, Aal, A1 cells, A2 cells, A3 cells, A4 cells, intermediate type and type B cells primarily on the basis of nuclear and nucleolar characteristics. The most primitive spermatogonia (As, Apr, Aal) had mottled chromatin; A1 cells contained homogeneously finely granular chromatin throughout the nucleus; A2, A3, A4 and intermediate type spermatogonia had progressively increasing amounts of chromatin encrusting the nuclear envelope; type B spermatogonia had less heterochromatin along the nuclear envelope, although the particles were more dense and rounded than in intermediate type spermatogonia. Mitochondrial size and position of Golgi complexes varied in different types of spermatogonia. These data show that types of spermatogonia can be differentiated such that these characteristics can be used in functional studies.


Toxoplasmosis among cancer patients undergoing chemotherapy: a population study based on the serological, molecular and epidemiological aspects.
Toxoplasmosis is highly prevalent in northern Iran and immunocompromised individuals are more susceptible to this infection. The present study aimed to determine the seroprevalence, parasitism and genetic diversity of Toxoplasma gondii among patients with cancer undergoing chemotherapy in northern Iran. A total of 350 serum samples obtained from cancer patients were collected from laboratory centers in northern Iran. Immunodiagnosis and DNA detection were accomplished by ELISA and PCR. Thereafter, multiplex-nested PCR-restriction fragment length polymorphism was used for the genotyping of T. gondii. In general, out of 350 patients, 264 (75.4%) and 9 (2.57%) cases were positive for anti-T. gondii IgG and IgM, respectively. Moreover, 19 (5.43%) samples contained T. gondii DNA. From 19 positive samples, 10 high-quality samples with sharp and non-smear bands were selected to determine the genotypes of T. gondii. Accordingly, the samples were classified as genotype #1 (type II clonal; n=4, 40%), genotype #2 (type III clonal; n=3, 30%), genotype #10 (type I clonal; n=2, 20%) and genotype #27 (type I variant; n=1, 10%). As evidenced by the results, due to the high prevalence of T. gondii, cancer patients in northern Iran are at serious risk of severe toxoplasmosis and its complications. Therefore, oncologists need to regard this critical health problem as a matter requiring urgent attention.


Diversity of the genus Sugiyamaella and description of two new species from rotting wood in China.
Species of the genus Sugiyamaella (Trichomonascaceae, Saccharomycetales), found in rotting wood in China, were investigated using morphology and the molecular phylogeny of a combined ITS and nrLSU dataset. Nine taxa were collected in China: two were new species (viz. Sugiyamaella chuxiong sp. nov. and S. yunanensis sp. nov.) and seven were known species, S. americana, S. ayubii, S. novakii, S. paludigena, S. valenteae, S. valdiviana and S. xiaguanensis. The two new species are illustrated and their morphology and phylogenetic relationships with other Sugiyamaella species are discussed. Our results indicate a potentially great diversity of Sugiyamaella spp. inhabiting rotting wood in China just waiting to be discovered.


Women's walking program for African American women: expectations and recommendations from participants as experts.
Effective interventions that increase adherence to physical activity are important for African American women because generally they are less active and more obese compared to white American women. The purpose of the authors in this study was to elicit from women who began a 12-month physical activity program between 2002 and 2005: (1) their recollections of outcome expectations and barriers, (2) feedback on program components, and (3) suggestions for program change. In 2007, the authors conducted qualitative post-intervention focus group interviews with women who had participated in the enhanced treatment group. Thirty-three African American women aged 44-69 years at the time of the study participated in one of four focus groups held at their community intervention site. Focus groups were formed on the basis of low (walked<50% of expected walks) versus high (walked≥50% of expected walks) adherence and low (0-2) versus high (3-4) attendance at the four workshops held during the 6-month adoption phase. Audio-taped sessions were transcribed, coded independently, and then uploaded into NVivo7 for final coding and data analysis. Suggestions for future program components include a lifestyle physical activity prescription, pedometers for self-monitoring, ongoing group support, and automated telephone support. Focus group participants can serve as experts to assist in content development for improving program effectiveness.


Coma after spinal anaesthesia in a patient with an unknown intracerebral tumour.
Spinal anaesthesia is contraindicated in patients with elevated intracranial pressure or space-occupying intracranial lesions. Drainage of the lumbar cerebrospinal fluid (CSF) can increase the pressure gradient between the spinal, supratentorial and infratentorial compartments. This can result in rapid herniation of the brain stem or occluding hydrocephalus. We present a case of a female patient with an occult brain tumour who received a spinal anaesthesia for an orthopaedic procedure. The primary course of anaesthesia was uneventful. Several hours after surgery, the patient became increasingly disoriented and agitated. The next day, she was found comatose. A computed tomogram of the head revealed herniation of the brain stem, resulting in an occluding hydrocephalus due to a prior not known infratentorial mass. By acute relieving of the intracranial pressure by external CSF drainage, the mass was removed 2 days later. The further post-operative course was uneventful and the patient was discharged from the hospital without neurological deficit 3 weeks after the primary surgery.


Retrieval of the Günther Tulip and OptEase filters using the recovery cone removal system.
The Recovery Cone Removal System was evaluated in vitro to determine its feasibility as an alterative retrieval device for the Günther tulip and OptEase inferior vena cava filters. The cone removal system was then used electively in eight patients to determine feasibility and safety in vivo and subsequently in a single patient when wire-snare removal failed. The Recovery Cone Removal System allowed in vitro and in vivo retrieval in all cases without difficulty or complication. The Recovery Cone Removal System offers an alternative to the wire-snare-based retrieval systems for removal of the Günther tulip and OptEase filters.


Does a non-invasive hemoglobin monitor correlate with a venous blood sample in the acutely ill?
Non-invasive hemoglobin measuring technology has potential for rapid, portable, and accurate way of providing identification of blood loss or anemia. Our objective is to determine if this technology is reliable in critically ill patients presenting to the Emergency Department. Prospective cross-sectional observational study was done at an urban level-one trauma center, 135 subjects were conveniently sampled, suspected of having active bleeding, sepsis, or other critically ill condition. Non-invasive measurements with Masimo (Irvine, CA, USA) Radical-7 and Rad-57 hemoglobin monitors were compared with the Beckman-Coulter LH-550 (Brea, CA, USA) clinical laboratory blood cell analyzer. The primary outcome was the relationship of the non-invasive device to the clinical laboratory results. Secondary evaluations included the effect of pulse rate, systolic BP, respiratory rate, temperature, capillary refill, skin color, nail condition, extremity movement. The Radical-7 was able to capture reading in 78% (88/113) of subjects, and the Rad-57 in 65% (71/110) of subjects. The correlation (R(2)) of the device Hb was 0.69 and 0.67 (p < 00.01) for the Radical-7 and Rad-57, respectively. The coefficient of variation for the Radical-7 was 18%, and for the Rad57 it was 13%. Univariate analysis shows none of the observed factors is associated with the difference values between the device Hb and laboratory Hb. Our results show that Radical-7 and Rad-57 devices do not report readings in 29% of patients and accuracy is significantly lower than reported by the manufacturer with over 50% of readings falling outside of ± 1 g/dL. We determined that none of the several potential factors examined are associated with the degree of device accuracy.


[How to detect and what to do with child abuse?].
Child abuse is a major public health problem. The consequences including death, but also physical injuries and psychological troubles. To know and recognize the possibility of child abuse is essential for all doctors. This diagnostic hypothesis must be considered alongside all pathologies in varied clinical presentations. The practitioner must keep in mind that an unusual location, incoherent mechanism, a health seeking delay, no painful expression are warning signs and particularly a traumatic injury unexplained in an infant who does not move. To overcome the denial that surrounds these situations, the health professional should emphasize teamwork and not hesitate in doubt to be hospitalized children or at least contact a specialized team.


Zero-valent iron sand filtration reduces concentrations of virus-like particles and modifies virome community composition in reclaimed water used for agricultural irrigation.
Zero-valent iron sand filtration can remove multiple contaminants, including some types of pathogenic bacteria, from contaminated water. However, its efficacy at removing complex viral populations, such as those found in reclaimed water used for agricultural irrigation, has not been fully evaluated. Therefore, this study utilized metagenomic sequencing and epifluorescent microscopy to enumerate and characterize viral populations found in reclaimed water and zero-valent iron-sand filtered reclaimed water sampled three times during a larger greenhouse study. Zero-valent iron-sand filtered reclaimed water samples had significantly less virus-like particles than reclaimed water samples at all collection dates, with the reclaimed water averaging between 108 and 109 and the zero-valent iron-sand filtered reclaimed water averaging between 106 and 107 virus-like particles per mL. In addition, for both sample types, viral metagenomes (viromes) were dominated by bacteriophages of the order Caudovirales, largely Siphoviridae, and genes related to DNA metabolism. However, the proportion of sequences homologous to bacteria, as well as the abundance of genes possibly originating from a bacterial host, was higher in the viromes of zero-valent iron-sand filtered reclaimed water samples. Overall, zero-valent iron-sand filtered reclaimed water had a lower total concentration of virus-like particles and a different virome community composition compared to unfiltered reclaimed water.


Highly photoactive, low bandgap TiO2 nanoparticles wrapped by graphene.
Highly photoactive, graphene-wrapped anatase TiO(2) nanoparticles are synthesized through one-step hydrothermal reduction of graphene oxide (GO) and TiO(2) crystallization from GO-wrapped amorphous TiO(2) NPs. Graphene-TiO(2) nanoparticles exhibit a red-shift of the band-edge and a significant reduction of the bandgap (2.80 eV). Graphene-TiO(2) nanoparticles possess excellent photocatalytic properties under visible light for the degradation of methylene blue.


Binomial Sequential Sampling Plans for Macadamia Felted Coccid (Hemiptera: Eriococcidae) Infesting Hawaii Macadamia Orchards.
The macadamia felted coccid, Eriococcus ironsidei (Williams) is an invasive pest of macadamia orchards that causes severe damage to the trees and reduces nut yield in Hawaii. Their feeding results in distortion and stunting of new growth, and with high population densities, dieback of entire branches may result. Ten macadamia orchards were sampled on the Hawaii island over a period of 18 mo to characterize the dispersion of the pest in the field, and to use those data as the basis for the development of a binomial sampling plan. Analyses based on Taylor's Power Law and Iwao's mean crowding index indicated an aggregated pattern of dispersion of the pest in the field. Curvilinear relationships between mean crawler density and the proportion of infested trees based on four tally thresholds (crawlers per unit area, T > 0, 5, 10, 20) were plotted. Results showed that a tally threshold T > 10 was the best predictor to model mean crawler density. Binomial sequential sampling plans based on three critical proportions of trees infested (0.40, 0.60, and 0.80) were developed. The adoption of a binomial sequential sampling plan for use in decision making can contribute to improve the management of E. ironsidei and optimize the number of samples needed to make decisions to control this pest.


Characterization of a member of the immunoglobulin gene superfamily that possibly represents an additional class of growth factor receptor.
We have screened cDNA libraries prepared from embryonic chicken tissues to isolate additional genes encoding growth factor receptors. Nucleotide sequencing of a cDNA encoding a gene, which we have termed klg, revealed it to represent an additional member of the immunoglobulin gene superfamily, which also possesses extensive sequence similarity to the protein-tyrosine kinase growth factor receptor genes. The klg gene was shown to encode a 140-kDa glycoprotein. However, the sequence of the tyrosine kinase domain is unusual in that the aspartate residue located within the highly conserved Asp-Phe-Gly triplet is replaced by an alanine residue. The presence of this aspartate has previously been found to be essential for tyrosine kinase activity. Consistent with the replacement of this aspartate, we were unable to detect any evidence of an associated kinase activity with the klg-encoded protein. These observations raise the possibility that the klg gene product represents a newly discovered class of receptor that plays a role in signal attenuation rather than signal propagation.


Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt.
Cell survival has been closely linked to both trophic growth factor signaling and cellular metabolism. Such couplings have obvious physiologic and pathophysiologic implications, but their underlying molecular bases remain incompletely defined. As a common mediator of both the metabolic and anti-apoptotic effects of growth factors, the serine/threonine kinase Akt - also known as protein kinase B or PKB - is capable of regulating and coordinating these inter-related processes. The glucose dependence of the antiapoptotic effects of growth factors and Akt plus a strong correlation between Akt-regulated mitochondrial hexokinase association and apoptotic susceptibility suggest a major role for hexokinases in these effects. Mitochondrial hexokinases catalyse the first obligatory step of glucose metabolism and directly couple extramitochondrial glycolysis to intramitochondrial oxidative phosphorylation, and are thus well suited to play this role. The ability of Akt to regulate energy metabolism appears to have evolutionarily preceded the capacity to control cell survival. This suggests that Akt-dependent metabolic regulatory functions may have given rise to glucose-dependent antiapoptotic effects that evolved as an adaptive sensing system involving hexokinases and serve to ensure mitochondrial homeostasis, thereby coupling metabolism to cell survival. We hypothesize that the enlistment of Akt and hexokinase in the control of mammalian cell apoptosis evolved as a response to the recruitment of mitochondria to the apoptotic cascade. The central importance of mitochondrial hexokinases in cell survival also suggests that they may represent viable therapeutic targets in cancer.


Paraproteins and plasma cell dyscrasias.
Serum protein electrophoresis done on 1100 patients with various diseases in one year demonstrated M-band in 31 patients. Most (87%) had the classical features of plasma cell dyscrasia (PCD), however a few had unusual presentations which are highlighted. A 22-year-old male operated for a massive tumour of the scapula clinically diagnosed as chondrosarcoma revealed plasmacytoma with amyloid on histology. Another case of kala-azar presented with features akin to that of PCD and one case had dual malignancies. Such a high incidence of PCDs with varied picture in a short time is not usually seen in other parts of this country; a fact which may be due to lack of awareness.


Enzymatic and histologic investigations into the course of pancreatic alterations induced by anti-acinar-cell-antiserum.
A model of acute pancreatitis (AP) was developed by application of anti-acinar-cell-antiserum in rats. Within 24 h postoperatively the binding of antibodies to the pancreas, histological findings, and the activities of lipase and a-amylase in serum and pancreas were analyzed. While after intraaortic administration morphological alterations could not be observed, after single dose intraductal injection, typical macroscopical and histological signs of AP were found. This pancreatic injury was characterized by a mild and protracted course favoring investigations of the early phase of pathogenesis. As soon as 2 h after intraductal application of antiserum, serum amylase and lipase were already increased and microscopic examination of the pancreatic tissue revealed pancreatic edema, inflammatory infiltration and parenchymal necrosis. Intra- and extrapancreatic fat necrosis occurred at 16 h post injectionem. The results suggest that parenchymal damage plays an essential role in the manifestation of this experimental AP and that fat necrosis seems to be a secondary event.


Endogenous Sulfur Dioxide Improves the Survival Rate of Sepsis by Improving the Oxidative Stress Response during Lung Injury.
To explore the regulation of endogenous sulfur dioxide on oxidative stress in lung injury induced by sepsis. Forty male Sprague Dawley rats were divided into control, sepsis, sepsis + SO2, and SO2 group randomly used to observe survival rate. The other group of twenty-eight rats were randomly divided as the same manner for mechanism research. The number of WBCS and the percentage of PMN cells were calculated. The microphotographs of morphological changes and the index of quantitative assessment (IQA) of lung tissues were calculated. The ratio of wet/dry (W/D) of lung tissues was calculated. Levels of H2O2, MDA, NO, MPO, SOD, GSH-px, and TNF-α in plasma and lung tissues were measured. The number of WBCS and the percentage of PMN cells decreased in sepsis (p all < 0.05), and rebound in sepsis+SO2 (p all < 0.05). The IQA and W/D of lung tissues increased in sepsis (p for W/D < 0.05), and decreased in sepsis+SO2 (p all < 0.05). H2O2 and MDA of plasma and lung tissues increased in sepsis (p all < 0.05) and rebound in sepsis+SO2 (p for H2O2 of plasma and lung tissues <0.05). NO and MPO of plasma and lung tissues increased in sepsis (p for NO and MPO of lung tissues <0.05) and rebound in sepsis+SO2 (p all < 0.05). SOD of plasma and lung tissues in sepsis group decreased (p all <0.05) and increased in sepsis+SO2 (p all < 0.05). GSH-px of plasma and lung tissues decreased in sepsis (p for plasma <0.05) and increased in sepsis+SO2 (p for GSH-px of lung tissues <0.05). TNF-α of plasma and lung tissues increased in sepsis (p all<0.05) and decreased in sepsis+SO2 (p for lung tissue <0.05). Endogenous sulfur dioxide improves the survival rate of sepsis by improving the oxidative stress response during lung injury.


Screening for tinea unguium by thermography in older adults with subungual hyperkeratosis.
The purpose of the present study was to assess the difference in foot temperature between tinea unguium-positive older adults with subungual hyperkeratosis and tinea unguium-negative older adults with subungual hyperkeratosis to develop a temperature-based screening method for tinea unguium. The present cross-sectional, observational study investigated 51 residents with subungual hyperkeratosis in two facilities covered by long-term care insurance between October 2011 and December 2011. One dermatologist recorded the clinical signs of abnormal toenails. Nail specimens were collected from all abnormal nails, and the presence of tinea unguium was confirmed when fungus was detected by direct microscopy. Foot temperature was measured by infrared thermography. A receiver operating characteristic curve was used to assess the ability to determine whether residents with subungual hyperkeratosis have tinea unguium and to determine the cut-off point. Among the people with subungual hyperkeratosis, the mean toe temperature in the tinea unguium-positive group (30.2 ± 2.6°C) was significantly lower than that in the tinea unguium-negative group (32.8 ± 3.2°C, P = 0.001). The area under the receiver operating characteristic curve was 0.74 (95% confidence interval 0.621-0.876), and the threshold temperature was set at 33.0°C, resulting in a sensitivity of 81.8% and specificity of 65.7%. Our study suggests that foot temperature can be used to screen for tinea unguium in people with subungual hyperkeratosis. This non-invasive and simple screening method would help clinicians to set priorities in terms of carrying out direct microscopy to diagnose tinea unguium in elderly residents in care facilities.


Potential toxicity and safety evaluation of nanomaterials for the respiratory system and lung cancer.
Engineered nanomaterials (ENMs) are a diverse group of materials finding increasing use in manufacturing, computing, food, pharmaceuticals, and biomedicine due to their very small size and exceptional properties. Health and safety concerns for ENMs have forced regulatory agencies to consider preventive measures and regulations for workers' health and safety protection. Respiratory system toxicity from inhalable ENMs is the most important concern to health specialists. In this review, we focus on similarities and differences between conventional microparticles (diameters in mm and μm), which have been previously studied, and nanoparticles (sizes between 1 and 100 nm) in terms of size, composition, and mechanisms of action in biological systems. In past decades, respirable particulate matter (PM), asbestos fibers, crystalline silicate, and various amorphous dusts have been studied, and epidemiological evidence has shown how dangerous they are to human health, especially from exposure in working environments. Scientific evidence has shown that there is a close connection between respirable PM and pulmonary oxidative stress through the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). There is a close connection between oxidative stress in the cell and the elicitation of an inflammatory response via pro-inflammatory gene transcription. Inflammatory processes increase the risk for lung cancer. Studies in vitro and in vivo in the last decade have shown that engineered nanoparticles (ENPs) at various doses can cause ROS generation, oxidative stress, and pro-inflammatory gene expression in the cell. It is assumed that ENPs have the potential to cause acute respiratory diseases and probably lung cancer in humans. The situation regarding chronic exposure at low doses is more complicated. The long-term accumulation of ENPs in the respiratory system cannot be excluded. However, at present, exposure data for the general public regarding ENPs are not available.


CLINICAL PHASES OF CHRONIC HEPATITIS B AMONG GEORGIAN PATIENTS.
Hepatitis B virus infection remains one of the major healthcare problems in Georgia with an exposure prevalence of 25.9% (Positive Anti-HBc) and chronic HBV infection (Positive HBsAg) 2.9%. Determination of clinical phase of chronic HBV infection is crucial for evaluation prognosis and accordingly, initiation of antiviral treatment, which might be lifelong. The specific aim of our study was to collect data on clinical characteristics of HBV-infected patients and determine the clinical phases of chronic HBV infection in the Georgian population. We randomly selected 111 chronic HBV-infected patients from the database of the medical center Mrcheveli. Liver fibrosis was assessed by Fibroscan, and viral load data were computed by the Real Time polymerase chain reaction (PCR) methodology. Liver fibrosis results were available for 74 of the patients (67%), and a majority of patients (72 of the 74, 97%) had no signs of advanced liver fibrosis. Viral load data were available for 94 patients, of whom 70 (74.5%) had an HBV-DNA level less than 2000 IU/ml, while 18 (19.1%) had an HBV-DNA level between 2000 and 20000 IU/ml and 6 (6.4%) were higher than 20000 IU/ml. Data for the assessment of the clinical phase of chronic HBV infection were available for 54% of patients (60 of the 111). Only 3.3% (2/60) of patients had undetectable HBV-DNA and 75% (45/60) had a viral load <2000 IU/ml. Two patients were HBeAg-positive, one of them with hepatitis and another with normal ALT. A few patients classified as HBeAg-negative with chronic hepatitis given normal ALT criteria: 3/60 (5%) by EASL and 6/50 (10%) patients by AASLD. In summary, 11/60 (18.5%) and 8/60 (13.5%) patients had HBV-DNA >2000 IU/ml but a normal ALT. Given the small number of patients, we cautiously conclude that most patients (75%) had HBeAg-positive or -negative chronic HBV infection without hepatitis. However, up to 19% of patients were not possible to classify in any of the internationally recognized phases of HBV infection. Patients within this indeterminate grey area, should be evaluated cautiously and management needs to be individualized. It will be interesting to evaluate the reason high viral load in HBeAg negative patients with normal ALT and long-term outcome among these patients (liver fibroses and/or HCC development).