Management of neglected lateral condyle fractures of humerus in children: A retrospective study.
Late presentation of humeral lateral condylar fracture in children is a surgical dilemma. Osteosynthesis of the fracture fragment or correction of elbow deformity with osteotomies and ulnar nerve transposition or sometimes both procedures combined is a controversial topic. We retrospectively evaluated open reduction and fixation cases in late presentation of lateral humeral condyle fracture in pediatric cases with regards to union and functional results. Twenty two pediatric (≤12 years) patients with fractures of lateral condyle presenting 4 weeks or more post injury between the study period of 2006 and 2010 were included. Multiple K-wires / with or without screws along with bone grafting were used. At final evaluation, union (radiologically) and elbow function (Liverpool Elbow Score, LES) was assessed. There were 19 boys and 3 girls. Followup averaged 33 months. Pain (n=9), swelling (n=6), restriction of elbow motion (n=6), prominence of lateral condylar region (n=4), valgus deformity (n=4) were the main presenting symptoms. Ulnar nerve function was normal in all patients. There were nine Milch type I and 13 type II fractures. Union occurred in 20 cases. One case had malunion and in another case there was resorption of condyle following postoperative infection and avascular necrosis. Prominent lateral condyles (4/12), fish tail appearance (n=7), premature epiphyseal closure (n=2) were other observations. LES averaged 8.12 (range, 6.66-9.54) at final followup. There is high rate of union and satisfactory elbow function in late presenting lateral condyle fractures in children following osteosynthesis attempt. Our study showed poor correlation between patient's age, duration of late presentation or Milch type I or II and final elbow function as determined by LES.


'We are not going anywhere': a qualitative study of Kenyan healthcare worker perspectives on adolescent HIV care engagement during the COVID-19 pandemic.
Adolescents living with HIV (ALHIV) may be vulnerable to widescale impacts of the COVID-19 pandemic and to health system responses which impact HIV care. We assessed healthcare worker (HCW) perspectives on impacts of the COVID-19 pandemic on adolescent HIV care delivery and engagement in western Kenya. We performed in-depth qualitative interviews with HCW at 10 clinical sites in the Academic Model Providing Access to Healthcare in Kenya, from January to March, 2021. Semistructured interviews ascertained pandemic-related impacts on adolescent HIV care delivery and retention. Interviews were conducted with 22 HCWs from 10 clinics. HCWs observed adolescent financial hardships, unmet basic needs and school dropouts during the pandemic, with some adolescents relocating to rural homes, to partners or to the street. Marked increases in adolescent pregnancies and pregnancy complications were described, as well as barriers to family planning and antenatal care. Transportation challenges and restrictions limited access to care and prompted provision of multi-month refills, refills at local dispensaries or transfer to local facilities. Adolescent-friendly services were compromised, resulting in care challenges and disengagement from care. Clinic capacities to respond to adolescent needs were limited by funding cuts to multidisciplinary staff and resources. HCW and youth peer mentors (YPMs) demonstrated resilience, by adapting services, taking on expanded roles and leveraging available resources to support adolescent retention and access to care. ALHIV are uniquely vulnerable, and adolescent-friendly services are essential to their treatment. The combined effects of the pandemic, health system changes and funding cuts compromised adolescent-friendly care and limited capacity to respond to adolescent needs. There is a need to reinforce adolescent-friendly services within programmes and funding structures. Support for expanded YPM roles may facilitate dedicated, scalable and effective adolescent-friendly services, which are resilient and sustainable in times of crisis.


Reviewing Muscle Cocontraction.
From a purely mechanical standpoint, muscle cocontraction is an inefficient utilization of muscle forces. Muscles resist each other producing little, if any, net movement. In mature gait and posture, as well as in many skilled motor activities, reciprocal activation or inhibition commonly occurs. Muscle cocontraction is frequently seen in infants and toddlers, in persons with central nervous system (CNS) damage, and interestingly, it is also seen in normal adults when they are attempting a novel complex motor skill. How might these three situations be related? This article summarizes the developmental trend of decreasing cocontraction with age. The relationship of cocontraction to motor skill development is described. Finally, the role of co contraction in movement disorders of persons with CNS deficits is explored, and an attempt is made to synthesize the presented material.


[Quantitative ultrasonic naked gene delivery and the effect control].
To study ultrasonic naked gene delivery and its effect control, and to investigate the new methods, which are easy-to-use, reliable and non-cytotoxic for application in gene therapy so as to build an optimal parameter set. Suspensions of different kinds of cells were exposed to calibrated ultrasound field (35.1 kHz) with different parameters for gene delivery. Morphology, membrane permeability, naked gene expression efficiency, threshold of cell damage and cell viability were examined by laser scanning confocal microscopy, fluorescent microscopy, flow cytometry and spectrophotometer. The plasmid of green fluorescent protein (GFP) was delivered into S180 cells under optimal parameters without cell damage. The transfection rate was about 35.83% +/- 2.53% (n=6) in viable cells. The GFP expression intensity in ultrasound exposure group had a higher fluorescent peak than AVV-GFP group and control group (P<0.001). Ultrasound can effectively deliver naked gene into cells using optimal parameters without cell damage. The gene uptake depends on energy accumulation at 90% of cell viability, and the tendency of apoptosis is found in S180 tumor cells.


Effects of triptolide on pharmacokinetics of amlodipine in rats by using LC-MS/MS.
Triptolide and amlodipine are often simultaneously used for reducing urine protein excretion after renal transplantation in China clinics. This study investigated the effects of triptolide on the pharmacokinetics of amlodipine in male Sprague-Dawley rats. The pharmacokinetics of amlodipine (1 mg/kg) with or without triptolide pre-treatment (2 mg/kg/day for seven days) were investigated using a sensitive and reliable LC-MS/MS method. Additionally, the inhibitory effects of triptolide on the metabolic stability of amlodipine were investigated using rat liver microsome incubation systems. The results indicated that when the rats were pre-treated with triptolide, the Cmax of amlodipine increased from 13.78 ± 3.57 to 19.96 ± 4.56 ng/mL (p < 0.05), the Tmax increased from 4.04 ± 1.15 to 5.89 ± 1.64 h (p < 0.05), and the AUC0-t increased by approximately 104% (p < 0.05), which suggested that the pharmacokinetic behaviour of amlodipine was affected after oral co-administration of triptolide. Additionally, the metabolic half-life was prolonged from 22.5 ± 4.26 to 36.8 ± 6.37 min (p < 0.05) with the pre-treatment of triptolide. In conclusion, these results indicated that triptolide could affect the pharmacokinetics of amlodipine, possibly by inhibiting the metabolism of amlodipine in rat liver when they are co-administered.


Biomineralization of gold by Mucor plumbeus: The progress in understanding the mechanism of nanoparticles' formation.
This contribution describes the deposition of gold nanoparticles by microbial reduction of Au(III) ions using the mycelium of Mucor plumbeus. Biosorption as the major mechanism of Au(III) ions binding by the fungal cells and the reduction of them to the form of Au(0) on/in the cell wall, followed by the transportation of the synthesized gold nanoparticles to the cytoplasm, is postulated. The probable mechanism behind the reduction of Au(III) ions is discussed, leading to the conclusion that this process is nonenzymatic one. Chitosan of the fungal cell wall is most likely to be the major molecule involved in biomineralization of gold by the mycelium of M. plumbeus. Separation of gold nanoparticles from the cells has been carried out by the ultrasonic disintegration and the obtained nanostructures were characterized by UV-vis spectroscopy and transmission electron micrograph analysis. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1381-1392, 2017.


A Multimedia Hydrological Fate Modeling Framework To Assess Water Consumption Impacts in Life Cycle Assessment.
Many new methods have recently been developed to address environmental consequences of water consumption in life cycle assessment (LCA). However, such methods can only partially be compared and combined, because their modeling structure and metrics are inconsistent. Moreover, they focus on specific water sources (e.g., river) and miss description of transport flows between water compartments (e.g., from river to atmosphere via evaporation) and regions (e.g., atmospheric advection). Consequently, they provide a partial regard of the local and global hydrological cycle and derived impacts on the environment. This paper proposes consensus-based guidelines for a harmonized development of the next generation of water consumption LCA indicators, with a focus on consequences of water consumption on ecosystem quality. To include the consideration of the multimedia water fate between compartments of the water cycle, we provide spatial regionalization and temporal specification guidance. The principles and recommendations of the paper are applied to an illustrative case study. The guidelines set the basis of a more accurate, novel way of modeling water consumption impacts in LCA. The environmental relevance of this LCA impact category will improve, yet much research is needed to make the guidelines operational.


New Insights into the Role of E2s in the Pathogenesis of Diseases: Lessons Learned from UBE2O.
Intracellular communication via ubiquitin (Ub) signaling impacts all aspects of cell biology and regulates pathways critical to human development and viability; therefore aberrations or defects in Ub signaling can contribute to the pathogenesis of human diseases. Ubiquitination consists of the addition of Ub to a substrate protein via coordinated action of E1-activating, E2-conjugating and E3-ligating enzymes. Approximately 40 E2s have been identified in humans, and most are thought to be involved in Ub transfer; although little information is available regarding the majority of them, emerging evidence has highlighted their importance to human health and disease. In this review, we focus on recent insights into the pathogenetic roles of E2s (particularly the ubiquitin-conjugating enzyme E2O [UBE2O]) in debilitating diseases and cancer, and discuss the tantalizing prospect that E2s may someday serve as potential therapeutic targets for human diseases.


Extended Pancreatectomy: Does It Have a Role in the Contemporary Management of Pancreatic Adenocarcinoma?
Pancreatic cancer is a low-incident but highly mortal disease. Surgery is still the preferred treatment option for resectable pancreatic cancer as it offers the only realistic chance for cure. As many patients present with locally advanced disease, which is generally considered as not amenable to surgical treatment, it is important to know the limits of surgical therapy in this disease. In this review, the indication and outcomes of extended pancreatectomies as well as the alternative treatment options for locally advanced pancreatic cancer are described. Furthermore, controversies as well as ongoing and future directions for the treatment options of locally advanced pancreatic cancer are discussed. Extended pancreatectomy can be performed with higher morbidity and mortality rates in patients with locally advanced pancreatic cancer compared to patients undergoing formal pancreatic resections. These procedures offer significant advantages with respect to both perioperative results and to long-term outcome when compared to chemotherapy. Due to the higher morbidity and mortality rates, these operations should be limited to specialist units with great experience in pancreatic surgery as well as experience in peri- and post-operative management of patients with pancreatic diseases.


The promise and performance of progestogens as contraceptives.
Progestogens were first suggested as possible contraceptives in the 1920s, but it was not until the early 1960s that effective progestogen-only contraceptive methods were developed. Since then it has become possible to deliver a range of different progestogens at varying doses, by a variety of routes, over greatly differing durations of time. Some of these systems have demonstrated extraordinarily high contraceptive efficacy with relatively few side-effects apart from unpredictable, but almost universal, disturbances of the menstrual pattern. It is now recognized that some systems may exhibit substantial non-contraceptive health benefits, which should become an important part of the overall performance profile of each method. The high technology and differing attributes associated with some of the systems raise important considerations in relation to user's perceptions and programmatic requirements. Overall, progestogens are able to offer women a varied range of valuable choices for contraception. The differing performance characteristics of these methods now provide women with a major portion of their current contraceptive choices.


[Characteristics of sexual violence against adolescent and adult women reported by the public health services in Santa Catarina State, Brazil].
Sexual violence against women is a form of gender violence and both a severe human rights violation and public health problem. This ecological, descriptive, and temporal series study aims to analyze sexual violence against pre-adolescent, adolescent, and adult females in Santa Catarina State, Brazil, based on data from the Information System for Notifiable Diseases, in order to describe the characteristics of cases of sexual violence perpetrated against women, reported by health professionals from 2008 a 2013. A total of 15,508 cases of violence were reported, including 2,010 cases of sexual violence (12.9%). Cases of violence totaled 950 reports in the 10 to 14 year bracket (47.3%), 450 in the 15 to 19 year bracket (22.4%), and 610 (30.3%) in women 20 years or older (adults). Adolescent females suffered violence by a single aggressor, at home, at night, with vaginal penetration, and with greater tendency to repeated assault and pregnancy as a result. For females 10 to 14 and 15 to 19 years of age, the aggressors were unknown in 32.9% and 33.1% of the reports, respectively. Adult women were sexually assaulted either at home or on public byways, at night or in the early morning hours, by a single aggressor, with vaginal penetration in more than half of the cases, with more physical injuries, and with more subsequent suicide attempts. The information should contribute to awareness-raising of policymakers, health professionals, researchers, and health field professors concerning the importance of reporting violence in order to help develop interventions to prevent such violence against women.


Fracture load of complete-arch implant-supported prostheses reinforced with nylon-silica mesh: An in vitro study.
Complete-arch implant-supported prostheses without a framework have a high risk of failure: a straightforward and inexpensive reinforcement material, such as nylon mesh, could improve their longevity. The purpose of this in vitro study was to evaluate a nylon-silica mesh compound on the fracture strength of acrylic resin and the fracture load of complete-arch implant-supported prostheses. Twenty-four complete mandibular arch implant-supported prostheses were divided into 2 groups according to cantilever length (molar and premolar) and subdivided into another 2 subgroups according to the presence or absence of reinforcing mesh. The specimens were submitted to a maximum load-to-fracture test in a universal testing machine, with a 100-N load cell, a 2 mm/min crosshead speed, and a spherical metal tip diameter of 4 mm at different points (molar and premolar). These were submitted to 1-way analysis of variance for repeated measurement and the post hoc Tukey multiple comparison test (α=.05). The mean maximum load ±standard deviation for the molar group was 393.4 ±95.0 N with reinforcement and 305.4 ±76.3 N without reinforcement (P=.02); and for the premolar group was 1083.3 ±283.7 N with reinforcement and 605.3 ±90.5 N without reinforcement (P=.001). Reinforcement with nylon mesh increased the mean maximum load of implant-supported complete-arch prostheses at both cantilever lengths. The cantilever to the premolar (5 mm) presented the highest maximum load values to fracture.


A Time-motion Comparison of Itemized Treatment Costs in First and Second In Vitro Fertilization Attempts: A United Kingdom Fertility Centre Experience.
Objective: To assess the difference in cost between initial and second in vitro fertilization (IVF) cycles in the United Kingdom. Methods: This prospective time-motion analysis captured data on average time spent on 31 representative components of the IVF sequence as provided by clinical team members in seven categories. Audits of consumables and observations on personnel costs were made from total of 120 fertility patients undergoing initial or second IVF cycles (n=736) between 1 January 2002 and 31 December 2002 at a UK assisted fertility unit. Results: Patients spent an average of 16.71±4.3 hrs with staff during an initial IVF cycle, resulting in direct personnel costs of £577.05±151.01. When consumables were included, each initial cycle cost the clinic approximately £2246.57±151.01. For second IVF cycles, patients spent significantly less time with staff compared to their first IVF cycle (6.94±2.44 hrs; p<0.05), corresponding to £257.53±90.77 in personnel cost. Conclusions: This is the first economic appraisal of the IVF treatment sequence in the UK using a timemotion analysis model. Our study found that when combined with consumables, total institutional costs for second IVF cycles were significantly reduced when compared to initial cycles (£1813.12±90.77; p<0.05). Aggregating data from all IVF cycles performed within the fertility centre during the study interval, initial cycles were found to be front-loaded, resulting in £252,420 more in institutional costs as compared with subsequent IVF cycles. While these observations were registered in 2003, an inflation adjustment using recent European Commission Eurostat data for healthcare finds the difference between initial and subsequent fresh IVF cycles in present currency to be approximately £579.14 per cycle. Time-motion analysis can identify episodes of care that can be streamlined to improve outcomes and reduce cost.


Sink or surf: atmospheric implications for succinic acid at aqueous surfaces.
Small organic compounds are increasingly being invoked as important players in atmospheric processes that occur on aerosol surfaces. The diacid succinic acid is one such constituent that is prevalent in the troposphere, surface active, and also water-soluble. This article presents a thorough examination of the surface characteristics of succinic acid at the vapor/water interface using a combination of theoretical simulation and experiments using vibrational sum frequency spectroscopy and surface tension. The adsorption and orientation of succinic acid at the water surface is characterized for a series of aqueous solution compositions relevant to atmospheric conditions. Fully protonated succinic acid is found to be particularly surface active. A new computational technique is introduced that provides a detailed picture of the different surface species that are contributing to the experimentally derived spectroscopic measurements. Additional results are presented for how SO2, a copollutant of succinic acid in the atmosphere, behaves at a water surface in the presence of surface adsorbed succinic acid.


Infection of porcine circovirus 2 (PCV2) in intestinal porcine epithelial cell line (IPEC-J2) and interaction between PCV2 and IPEC-J2 microfilaments.
Porcine circovirus-associated disease (PCVAD) is caused by a small pathogenic DNA virus, Porcine circovirus type 2 (PCV2), and is responsible for severe economic losses. PCV2-associated enteritis appears to be a distinct clinical manifestation of PCV2. Most studies of swine enteritis have been performed in animal infection models, but none have been conducted in vitro using cell lines of porcine intestinal origin. An in vitro system would be particularly useful for investigating microfilaments, which are likely to be involved in every stage of the viral lifecycle. We confirmed that PCV2 infects the intestinal porcine epithelial cell line IPEC-J2 by means of indirect immunofluorescence, transmission electron microscopy, flow cytometry and qRT-PCR. PCV2 influence on microfilaments in IPEC-J2 cells was detected by fluorescence microscopy and flow cytometry. We used Cytochalasin D or Cucurbitacin E to reorganize microfilaments, and observed changes in PCV2 invasion, replication and release in IPEC-J2 cells by qRT-PCR. PCV2 infection changes the ultrastructure of IPEC-J2 cells. PCV2 copy number in IPEC-J2 cells shows a rising trend as infection proceeds. Microfilaments are polymerized at 1 h p.i., but densely packed actin stress fibres are disrupted and total F-actin increases at 24, 48 and 72 h p.i. After Cytochalasin D treatment, invasion of PCV2 is suppressed, while invasion is facilitated by Cucurbitacin E. The microfilament drugs have opposite effects on viral release. PCV2 infects and proliferates in IPEC-J2 cells, demonstrating that IPEC-J2 cells can serve as a cell intestinal infection model for PCV2 pathogenesis. Furthermore, PCV2 rearranges IPEC-J2 microfilaments and increases the quantity of F-actin. Actin polymerization may facilitate the invasion of PCV2 in IPEC-J2 cells and the dissolution of cortical actin may promote PCV2 egress.


Transfer of C alpha-hydrogen of glutamate to coenzyme of aspartate aminotransferase during transamination reaction.
During the transamination reaction of mitochondrial aspartate aminotransferase, transfer of tritium from the alpha-position of glutamate to the pro-S position of C4' of pyridoxamine 5'-phosphate was detected. A fast mixing and quenching device had to be used in order to reduce the number of transamination cycles undergone by the enzyme and thus to minimize the accompanying exchange of label with water. The extent of transfer of label (mean value 1.5%; range 0.8-4%) indicates that the 1,3-prototropic shift follows a stepwise rather than a concerted mechanism and that a single acid/base group is responsible for the proton transfer. The actual extent of proton transfer has to be much higher because the rate of alpha-tritium exchange with solvent was only approximately 10% of that of the turnover of unlabeled substrate, reflecting either an isotope effect or a retention of the tritium label in the reaction center during tautomerization. Under the assumption of an isotope effect, the actual transfer may be estimated to be 13%. This value is consistent with the notion of Lys-258 acting as the proton transferring group in which case the maximal value of transfer in an active site not accessible to solvent during the 1,3-prototropic shift would be 33%. However, alternative mechanisms involving Tyr-70 or a water molecule enclosed in the active site serving as acid/base group cannot be excluded on the basis of the present results. Furthermore, in these investigations aspartate aminotransferase was found to catalyze also the exchange of tritium from the beta-position of glutamate, though at a rate 350 times slower than that of the alpha-exchange.


Colistin plus Sulbactam or Fosfomycin against Carbapenem-Resistant Acinetobacter baumannii: Improved Efficacy or Decreased Risk of Nephrotoxicity?
Acinetobacter baumannii has been recognized as a cause of nosocomial infection. To date, polymyxins, the last-resort therapeutic agents for carbapenem-resistant A. baumannii (CRAB). Thus, the small number of effective antibiotic options against CRAB represents a challenge to human health. This study examined the appropriate dosage regimens of colistin alone or in combination with sulbactam or fosfomycin using Monte Carlo simulation with the aims of improving efficacy and reducing the risk of nephrotoxicity. Clinical CRAB isolates were obtained from patients admitted to Phramongkutklao Hospital in 2014 and 2015. The minimum inhibitory concentration (MIC) of colistin for each CRAB isolate was determined using the broth dilution method, whereas those of sulbactam and fosfomycin were determined using the agar dilution method. Each drug regimen was simulated using the Monte Carlo technique to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR). Nephrotoxicity based on RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria was indicated by colistin trough concentration exceeding ≥3.3 μg/mL. A total of 50 CRAB isolates were included. The MIC50 and MIC90 were 64 and 128 μg/mL, respectively, for sulbactam, 256 and 2,048 μg/mL, respectively, for fosfomycin, and 1 and 4 μg/mL, respectively, for colistin. In patients with creatinine clearance of 91 - 130 m/min, the dosing regimens of 180 mg every 12 h and 150 mg every 8 h achieved ≥ 90% of target of the area under the free drug plasma concentration-time curve from 0 to 24 hr (fAUC24)/MIC ≥25 against isolates MICs of ≤0.25 and ≤0.5 μg/mL, respectively, and their rates of colistin trough concentration more than ≥3.3 μg/mL were 35 and 54%, respectively. Colistin combined with sulbactam or fosfomycin decreased the colistin MIC of CRAB isolates from 1 - 16 μg/mL to 0.0625 - 1 and 0.0625 - 2 μg/mL, respectively. Based on CFR ≥ 90%, no colistin monotherapy regimens in patients with creatinine clearance of 91 - 130 mL/min were effective against all of the studied CRAB isolates. For improving efficacy and reducing the risk of nephrotoxicity, colistin 150 mg given every 12 h together with sulbactam (≥6 g/day) or fosfomycin (≥18 g/day) was effective in patients with creatinine clearance of 91 - 130 mL/min. Additionally, both colistin combination regimens were effective against five colistin-resistant A. baumannii isolates. Colistin monotherapy at the maximum recommended dose might not cover some CRAB isolates. Colistin combination therapy appears appropriate for achieving the pharmacokinetic/pharmacodynamic targets of CRAB treatment.


In silico Identification of Peptide as Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Lung Cancer Treatment.
Epidermal growth factor receptor (EGFR) is the biomarker for lung cancer in which the protein has the most active mutated genes in lung cancer patients. Peptides have pharmacological potential as drugs because of their bioactivity and accessibility. The research objective was to obtain peptide compounds drug candidates with good interaction and pharmacological properties that can act as an inhibitor for EGFR for lung cancer treatment by using in silico method. EGFR protein structure was obtained from Protein Data Bank and the peptide compounds were retrieved from PubChem. Optimization and energy minimization process were done to prepare the peptides for the simulation. Protein-Ligand Interaction Fingerprint (PLIF) was used to determine the pharmacophore features in the EGFR binding site. Both proteins and ligands underwent a virtual screening through rigid and flexible molecular docking simulation and the best ligands were subjected to a computational ADME-Tox properties prediction. After screening through molecular docking simulation, nine best compounds were identified to have a good interaction with EGFR protein according to its binding energy and RMSD value. The compounds were identified to form hydrogen bond interactions with the macromolecule. Two peptide compounds (PubChem ID: 20832941 and 9805315) have been predicted as the best ligands with desired pharmacological properties for the inhibition of EGFR tyrosine kinase.


[Differential echographic diagnosis of salivary gland tumors].
76 patients with tumorous swellings of the salivary glands were examined by means of standardized A-scan and B-scan sonography. B-scan echography allowed a differentiation between benign and malignant tumours in all cases. Analysis of the various A-scan criteria (internal structure, reflectivity, borders, consistency and sound attenuation) provided a pathognomonic combination of these criteria for each lesion, enabling further histological diagnosis.


Glibenclamide reveals role for endothelin in hypoxia-induced vasoconstriction in rat intrapulmonary arteries.
The present study investigated whether activation of vasodilatory mechanisms masks the involvement of endothelin in hypoxic pulmonary vasoconstriction. Rat intrapulmonary arteries were mounted in microvascular myographs. In arteries with endothelium and contracted with phenylephrine, hypoxia, evoked by exchanging 5% CO2 in air for CO2 in N2, caused a transient contraction followed by a sustained contraction. Hypoxia evoked relaxation in preparations without endothelium. An inhibitor of ATP-sensitive K+ channels (KATP), glibenclamide (10 microM), blunted hypoxic relaxation in arteries without endothelium and enhanced the sustained hypoxic vasoconstriction in arteries with endothelium. Hypoxic contraction was more pronounced in endothelin compared with phenylephrine-contracted preparations in the absence, but not in the presence of glibenclamide. Antagonism of the endothelin ETA and ETB receptors with SB217242 or the combination of BQ123 and BQ788 inhibited endothelin and hypoxic contraction, but the latter only in the presence of glibenclamide. An inhibitor of nitric oxide (NO) synthase, N-nitro-L-arginine (100 microM), evoked contractions, which were left unaltered by SB217242 in hypoxic conditions. In conclusion, hypoxic contraction is mediated in part by an unknown endothelium-derived contractile factor and incubation with glibenclamide shows endothelin enhances hypoxic contraction in part through inhibition of KATP channels. Moreover, inhibition of NO formation in pulmonary arteries does not change endothelin receptor activation in severe hypoxia.


Expression of Novel CD44st and MMP2 in NSCLC Tissues and Their Clinical Significance.
Abnormal expression of some CD44 molecules in tumor tissues can induce the degradation of the extracellular matrix, and is closely associated with axillary lymph node metastasis, angiogenesis, cancer progression, and drug resistance. We measured and confirmed the expression of CD44st and MMP2 mRNAs and proteins in the cancer tissues and adjacent normal tissues of postoperative non-small cell lung cancer (NSCLC) patients with either adenocarcinoma (n = 72) or squamous cell carcinoma (n = 53) using quantitative reverse transcription polymerase chain reaction, gene sequencing, and immunohistochemical analysis. CD44st and MMP2 expression were closely associated with the histopathological classification, lymph node metastasis, and TNM stage of the tumors, and the difference was statistically significant (p < 0.05). The median overall survival (OS) for the high CD44st expression group was 30.52 months (95% confidence interval (CI) 24.02-36.15); for the low expression group it was 43.23 months (95% CI 31.81-52.02) (p = 0.020). The median OS for the high MMP-2 expression group was 30.53 months (95% CI 26.69-33.31); for the low expression group it was 40.06 months (95% CI 33.55-46.45) (p = 0.022). The rates of CD44st and MMP2 expression were higher in squamous cell carcinomas than in adenocarcinomas, were closely associated with lymph node metastasis and TNM stage, and affected patients' prognoses.


[Correlation of the CTD structural domain of hepatitis B virus core protein with the encapsulation effect of indocyanine green].
Hepatitis B virus core protein (HBc) has become a hot spot in drug carrier protein research due to its natural particle self-assembly ability and ease of modification. The truncation of the C-terminal polyarginine domain (CTD, aa 151-183) of HBc does not affect the self-assembly of the particles. However, it does affect the internal and external charges of the particles, which may subsequently affect drug encapsulation. Thus, the truncated C-terminal polyarginine domain (CTD) of HBc and the inserted RGD peptide were selected to construct and express three HBc variants (RH) encapsulated with ICG (RH/ICG) with different C-terminal lengths to compare the stability and drug activity of their nanoformulations. RH160/ICG was found to have a great advantages in encapsulation efficiency and biological imaging. Compared with other HBc variants, RH160/ICG significantly improved encapsulation efficiency, up to 32.77%±1.23%. Cytotoxicity and hemolysis assays further demonstrated the good biocompatibility of RH160/ICG. Cell uptake and in vivo imaging experiments in mice showed that RH160/ICG could efficiently deliver ICG in tumor cells and tumor sites with good imaging effect. This research provides a new direction for further expanding the diagnosis and treatment application of ICG and development of HBc-based nanoparticle drug carrier platform.


Mutagenesis of vitamin K-dependent carboxylase demonstrates a carboxyl terminus-mediated interaction with vitamin K hydroquinone.
The gamma-glutamyl carboxylase and vitamin K epoxidase activities of a series of mutants of bovine vitamin K-dependent carboxylase with progressively larger COOH-terminal deletions have been analyzed. The recombinant wild-type (residues 1-758) and mutant protein carboxylases, Cbx 711, Cbx 676, and Cbx 572, representing residues 1-711, 1-676, and 1-572, respectively, were expressed in baculovirus-infected Sf9 cells. Wild-type carboxylase had a Km for the substrate Phe-Leu-Glu-Glu-Leu (FLEEL) of 0.87 mM; the carboxylation of FLEEL was stimulated 2.5-fold by proPT18, the propeptide of prothrombin. Its Km for vitamin K hydroquinone was 23 microM and the specific epoxidase activity of the carboxylase was 938 pmol vitamin KO/30 min/pmol of carboxylase. Cbx 711, which was also stimulated by proPT18, had a Km for FLEEL, a Km for vitamin K hydroquinone, and a specific epoxidase activity that was comparable to the wild-type carboxylase. In contrast Cbx 572 lacked both carboxylase and epoxidase activities. Although Cbx 676 had a normal carboxylase active site in terms of the Km for FLEEL and its stimulation by proPT18, the Km for vitamin K hydroquinone was 540 microM, and the specific epoxidase activity was 97 pmol KO/30 min/pmol of Cbx 676. The catalytic efficiencies of Cbx 676 for glutamate carboxylation and vitamin K epoxidation were decreased 15- and 400-fold, respectively, from wild-type enzyme reflecting the requirement for formation of an activated vitamin K species for carboxylation to occur. These data indicate that the truncation of COOH-terminal segments of the carboxylase had no effect on FLEEL or propeptide recognition, but in the case of Cbx 676, selectively affected the interaction with vitamin K hydroquinone and the generation of epoxidase activity. These data suggest that a vitamin K epoxidase activity domain may reside near the COOH terminus while the carboxylase active site domain resides toward the NH2 terminus.


Setting standards in the presence of developing scientific understanding.
The setting of standards for potential hazards as result of the application of a new technology depends on both the philosophy with respect to risk and the state of knowledge about the circumstances under which the technology can cause damage. Typically, biological damage is first observed for high levels of exposure and short times. As our understanding of the technology and its effects on the biology improve, biological effects are observed at lower levels and longer exposure times. For extended low-level exposures it also becomes more difficult to demonstrate a hazard that is independent of other influences. This has been true for electric and magnetic fields both at low and radio frequencies. In this article it is recognized that a set number is needed for both manufactures and system operators to meet if the technology is to serve the public. It is also recommended that the public be presented with tables of relative risks that include levels of exposure and other risks for comparison. Three tables of relative risks are included as a possible starting point.


Costs and Survival of Patients having Experienced a Hospitalized Fall-Related Injury in France: A Population-Based Study.
To assess the annual costs 2 years before and 2 years after a hospitalized fall-related injury (HFRI) and the 2-year survival among the population 75+ years old. We performed a population-based, retrospective cohort study using the French national health insurance claims database. Patients 75+ years old who had experienced a fall followed by hospitalization, identified using an algorithm based on International Classification of Diseases codes. Data related to a non-HFRI population matched on the basis of age, sex, and geographical area were also extracted. Cost analyses were performed from a health insurance perspective and included direct costs. Survival analyses were conducted using Kaplan-Meier curves and Cox regression. Descriptive analyses of costs and regression modeling were carried out. Both regression models for costs and on survival were adjusted for age, sex, and comorbidities. A total of 1495 patients with HFRI and 4484 non-HFRI patients were identified. Patients with HFRI were more comorbid than the non-HFRI patients over the entire periods, particularly in the year before and the year after the HFRI. Patients with HFRI have significantly worse survival probabilities, with an adjusted 2.14-times greater risk of death over 2-year follow-up and heterogeneous effects determined by sex. The annual incremental costs between patients with HFRI and non-HFRI individuals were €1294 and €2378, respectively, 2 and 1 year before the HFRI, and €11,796 and €1659, respectively, 1 and 2 years after the HFRI. The main cost components differ according to the periods and are mainly accounted for by paramedical acts, hospitalizations, and drug costs. When fully adjusted, the year before the HFRI and the year after the HFRI are associated with increase in costs. We have provided real-world estimates of the cost and the survival associated with patients with HFRI. Our results highlight the urgent need to manage patients with HFRI at an early stage to reduce the significant mortality as well as substantial additional cost management. Special attention must be paid to the fall-related increasing drugs and to optimizing management of comorbidities.


Murine macrophages kill the vegetative form of Bacillus anthracis.
Anti-protective antigen antibody was reported to enhance macrophage killing of ingested Bacillus anthracis spores, but it was unclear whether the antibody-mediated macrophage killing mechanism was directed against the spore itself or the vegetative form emerging from the ingested and germinating spore. To address this question, we compared the killing of germination-proficient (gp) and germination-deficient (DeltagerH) Sterne 34F2 strain spores by murine peritoneal macrophages. While macrophages similarly ingested both spores, only gp Sterne was killed at 5 h (0.37 log kill). Pretreatment of macrophages with gamma interferon (IFN-gamma) or opsonization with immunoglobulin G (IgG) isolated from a subject immunized with an anthrax vaccine enhanced the killing of Sterne to 0.49 and 0.73 log, respectively, but the combination of IFN-gamma and IgG was no better than either treatment alone. Under no condition was there killing of DeltagerH spores. To examine the ability of the exosporium to protect spores from macrophages, we compared the macrophage-mediated killing of nonsonicated (exosporium+) and sonicated (exosporium-) Sterne 34F2 spores. More sonicated spores than nonsonicated spores were killed at 5 h (0.98 versus 0.37 log kill, respectively). Pretreatment with IFN-gamma increased the sonicated spore killing to 1.39 log. However, the opsonization with IgG was no better than no treatment or pretreatment with IFN-gamma. We conclude that macrophages appear unable to kill the spore form of B. anthracis and that the exosporium may play a role in the protection of spores from macrophages.


Lung growth and pulmonary function after prematurity and bronchopulmonary dysplasia.
Bronchopulmonary dysplasia (BPD) still carries a heavy burden of morbidity and mortality in survivors of extreme prematurity. The disease is characterized by simplification of the alveolar structure, involving a smaller number of enlarged alveoli due to decreased septation and a dysmorphic pulmonary microvessel growth. These changes lead to persistent abnormalities mainly affecting the smaller airways, lung parenchyma, and pulmonary vasculature, which can be assessed with lung function tests and imaging techniques. Several longitudinal lung function studies have demonstrated that most preterm-born subjects with BPD embark on a low lung function trajectory, never achieving their full airway growth potential. They are consequently at higher risk of developing a chronic obstructive pulmonary disease-like phenotype later in life. Studies based on computer tomography and magnetic resonance imaging, have also shown that in these patients there is a persistence of lung abnormalities like emphysematous areas, bronchial wall thickening, interstitial opacities, and mosaic lung attenuation also in adult age. This review aims to outline the current knowledge of pulmonary and vascular growth in survivors of BPD and the evidence of their lung function and imaging up to adulthood.


Arthroscopic remplissage: Is it still an option?
Posterolateral humeral head defects can be large and engage on the anterior glenoid, and they usually contribute to anterior shoulder instability in 40% to 90% of cases.The purpose of this study is to evaluate the results of the largest series of patients who underwent arthroscopic remplissage with Bankart repair for recurrent anterior shoulder instability due to associated Bankart lesions, with large and engaging (> 25% involvement) humeral Hill-Sachs defects (HSDs).A total of 51 patients underwent arthroscopic Bankart repair with remplissage technique for the treatment of recurrent anterior glenohumeral instability with large and medial HSDs. Pre-operative imaging in all patients identified a Bankart lesion with an associated HSD that involved > 25% of the humeral head. The Rowe score was used to assess the patients clinically.A total of 46 patients were male. The mean age of the patients was 28.7 years (18 to 43). The mean follow-up period was 31 months (20 to 39). At the final follow-up, three patients reported recurrence of instability (two dislocations and one subluxation). The mean Rowe score improved to 95.4 points (function, 45.5 of 50; stability, 26.4 of 30; motion, 8 of 10; pain, 8 of 10).The arthroscopic remplissage technique with Bankart repair gave satisfactory results and is still considered to be an effective, safe and reliable procedure for treatment of glenohumeral instability in cases with large and medial HSDs. Cite this article: EFORT Open Rev 2017;2:478-483. DOI: 10.1302/2058-5241.2.160070.


[Meralgia paresthetica after spinal anesthesia].
A 27-year-old man underwent appendectomy under spinal anesthesia with 0.3% dibucaine 2.7 ml. The perioperative course was uneventful. The surgical procedure, however, lasted for 1.5 hours in the supine position. On the second postoperative day, a postspinal headache occurred and lasted for 18 days. On the seventh postoperative day the patient complained of numbness along the anterolateral aspect of the left thigh innervated by the lateral cutaneous nerve. There was no reflex or motor deficit indicative of the involvement of other nerves. The disorder was diagnosed as meralgia paresthetica caused by the surgical procedures. The numbness disappeared after the oral administration of mecobalamin in several days. In the treatment of a case like this, it is important to exclude neurological complications caused by spinal anesthesia.


[Study of insulin resistance in cirrhosis by the hyperinsulin euglycemia clamp].
To explore the insulin resistance state in liver cirrhosis and to assess the respective role of insulin sensitivity and cellular metabolism alterations, an euglycemic glucose clamp was performed in 12 cirrhotic patients and 6 healthy volunteers with 3 successive hyperinsulinemic periods of 90 mn (infusions of 7, 20 and Iu/h). An artificial beta-cell model allowed to quantify the amount of glucose needed to keep glycemia at 4.70 mmol/l. In 7 cirrhotic patients, insulin secretion was tested by an intravenous glucose tolerance test. The dose-response curves showed a significant (p less than 0.01) decrease of the theoretical maximal metabolic clearance rate of glucose (capacity). The insulin concentration corresponding to the half-maximal response (ED50) did not differ between cirrhotic and control subjects because of a very important dispersion of individual values in cirrhotics. The ED50 value was lower than the values of control subjects in five cirrhotic patients and normal or enhanced in seven other patients; the former showed the most reduced values for capacity, and the latter a more marked hyperinsulinemia during the intravenous glucose tolerance test. The two subgroups of patients did not differ for clinical or biological parameters of cirrhosis, or for glucose tolerance. These results 1) show a constant and marked impairment of glucose metabolism capacity in liver cirrhosis, 2) and suggest that the insulin resistance inconstantly observed in this state is a consequence of chronic hyperinsulinemia.


Health risk appraisal: some methodologic considerations.
This is an outline of the structure and limitations of existing health risk appraisal tools (HRA). A general model is discussed, where average populations risk data are modified in a risk computation algorithm. This process requires information on risk relevant characteristics of the individual and rules or assumptions where sufficient data do not exist. The basis for risk estimation algorithms, the derivation of risk factors, and their combination into composites are described. HRA feedback to the individual user is discussed, including summarization of risk results in terms of risk age and life expectancy.


Decreased c-Myc expression and its involvement in X-ray-induced apoptotic cell death of human T-cell leukaemia cell line MOLT-4.
To investigate the possible involvement of c-Myc and ceramide-c-Jun N-terminal kinase (JNK) pathway in X-ray-induced apoptotic cell death of MOLT-4 cells. The expressions of c-Myc protein and c-myc mRNA after X-irradiation were analysed by Western blotting and RT-PCR between radiosensitive MOLT-4 and radioresistant variant Rh-1a cells with less JNK activation than the parental cells. Apoptotic cell death was determined by a dye exclusion test, the appearance of chromatin condensation and DNA fragmentation. The effect of a JNK activator anisomycin or c-Myc inhibitor peptides (Int-H1-S6A, F8A) on the amount of c-Myc protein and on the induction of apoptosis was investigated, respectively. In X-irradiated MOLT-4 cells, amounts of both c-myc mRNA and c-Myc protein rapidly decreased, which was followed by apoptotic cell death, while little change or limited reduction of c-Myc protein was observed in X-irradiated Rh-1a cells with accompanying higher cell viability. Exposure of MOLT-4 and Rh-1a cells to c-Myc inhibitor peptides similarly induced apoptotic cell death with decreases of c-Myc protein. Anisomycin rapidly induced JNK activation and a subsequent decrease of c-Myc protein, causing cell death in MOLT-4 cells. On the other hand, Rh-1a cells were more resistant to anisomycin than parental MOLT-4 cells, showing less JNK activation and a delayed decrease of c-Myc protein. A decrease of c-Myc protein was considered important in X-ray-induced apoptotic cell death of MOLT-4 cells; activation of the JNK pathway caused reduction in the amounts of c-myc mRNA and c-Myc protein, and finally induced apoptotic cell death.


Evolution of paired domains: isolation and sequencing of jellyfish and hydra Pax genes related to Pax-5 and Pax-6.
Pax proteins are a family of transcription factors with a highly conserved paired domain; many members also contain a paired-type homeodomain and/or an octapeptide. Nine mammalian Pax genes are known and classified into four subgroups: Pax-1/9, Pax-2/5/8, Pax-3/7, and Pax-4/6. Most of these genes are involved in nervous system development. In particular, Pax-6 is a key regulator that controls eye development in vertebrates and Drosophila. Although the Pax-4/6 subgroup seems to be more closely related to Pax-2/5/8 than to Pax-3/7 or Pax-1/9, its evolutionary origin is unknown. We therefore searched for a Pax-6 homolog and related genes in Cnidaria, which is the lowest phylum of animals that possess a nervous system and eyes. A sea nettle (a jellyfish) genomic library was constructed and two pax genes (Pax-A and -B) were isolated and partially sequenced. Surprisingly, unlike most known Pax genes, the paired box in these two genes contains no intron. In addition, the complete cDNA sequences of hydra Pax-A and -B were obtained. Hydra Pax-B contains both the homeodomain and the octapeptide, whereas hydra Pax-A contains neither. DNA binding assays showed that sea nettle Pax-A and -B and hydra Pax-A paired domains bound to a Pax-5/6 site and a Pax-5 site, although hydra Pax-B paired domain bound neither. An alignment of all available paired domain sequences revealed two highly conserved regions, which cover the DNA binding contact positions. Phylogenetic analysis showed that Pax-A and especially Pax-B were more closely related to Pax-2/5/8 and Pax-4/6 than to Pax-1/9 or Pax-3/7 and that the Pax genes can be classified into two supergroups: Pax-A/Pax-B/Pax-2/5/8/4/6 and Pax-1/9/3/7. From this analysis and the gene structure, we propose that modern Pax-4/6 and Pax-2/5/8 genes evolved from an ancestral gene similar to cnidarian Pax-B, having both the homeodomain and the octapeptide.


[Neuropediatric approach to autism].
Autism is defined by 3 main criteria: disturbance of reciprocal social interaction, disturbance of communication (including language comprehension and spoken language) and disturbance of normal variation in behaviour and imaginative activities; an onset before age 36 months is also required. The neuropediatric contribution to autism is dominated by the search for an underlying organic etiology, especially if there are arguments for an associated encephalopathy: ante- or perinatal medical history, dysmorphic signs, skin spots, neurological abnormalities, somatic abnormalities compatible with a neurometabolic disorder. The main associated conditions with autism are: chromosome anomalies, monogenic syndrome (including fragile X syndrome), neurocutaneous syndromes, epileptic encephalopathies, neurometabolic diseases, and dystrophinopathies. The identification of an associated medical condition to autism is primordial in prospect of genetic counselling, and by the change induced in familial perception of autism.


Towards a cardiac allocation score: a retrospective calculation for 73 patients from a German transplant center.
Due to a growing discrepancy between the transplant waiting list and decreasing numbers of available donor hearts, cardiac transplantation rates in Germany have been declining in the past years. Currently, patients on the waiting list are prioritized by medical urgency and waiting time and therefore a majority of all cardiac transplants is performed in very ill patients. Recently, a different allocation algorithm was proposed that included predicted post-transplant survival as a parameter for organ allocation. So far, little data exists on how such a "Cardiac Allocation Score" (CAS) relates to our current transplant patient population and on how such a change in organ allocation could change clinical practice. We calculated a theoretical retrospective Cardiac Allocation Score for 73 patients recruited and transplanted at our medium-volume center in Germany based on a hypothetical scoring algorithm recently published by Eurotransplant. Overall, 37 patients (50.7%) were transplanted on high urgency status (HU), 27 (37%) were being supported by a VAD at time of transplant. 57 (78.1%) were male. We found a relatively normal distribution of the hypothetical CAS with a median of 32.91 and a mean of 31.95 +/-10.02. Overall, CAS-Scores were lower than previously described for a Eurotransplant patient cohort of high urgency patients, but there was a significant overlap in score values between patients on HU and T status. CAS-values of VAD-supported patients were lower than in patients without mechanical support. The IMPACT-score as part of the CAS was used for prediction of post-transplant survival and seems suitable to predict outcome in our patient population. In a retrospective analysis, the recently proposed Cardiac Allocation Score seems to show a normal distribution of priority values in our patient cohort. The IMPACT-score predicted outcome after transplantation and could serve as part of the CAS-algorithm to predict post-transplant survival in this single center real-world scenario. Implementation of the CAS could significantly change organ allocation practice, including a potential prioritization of current T-status patients over HU-status patients.


[Automatic calculation of left ventricular volume and ejection fraction from gated myocardial perfusion SPECT--basic evaluation using phantom].
We evaluated accuracy of Quantitative Gated SPECT Program that enabled calculation of the left ventricular (LV) volume and ejection fraction by automatically tracing the contour of the cardiac surface. Cardiac phantoms filled with 99mTc-solution were used. Data acquisition was made by 180-degree projection in L type and 360-degree projection in opposed type. Automatic calculation could be done in all processes, which required 3-4 minutes. Reproducibility was sufficient. The adequate cut off value of a prefilter was 0.45. At this value LV volume was 93% of the actual volume in L type acquisition and 95.9% in opposed type acquisition. The LV volume obtained in L type was smaller than that obtained in opposed type (p < 0.05). The tracing of the defects was fair, on the cardiac phantoms with all of 90-degree defects and 180-degree defects of the septal and lateral wall. The LV volume was estimated to be larger on the phantom with 180-degree defect of the anterior wall, and to be smaller on the phantom of 180-degree defect of the inferoposterior wall. Because tracing was deviated anteriorly at the defects. In the patients with similar conditions to 180-degree defect of the anterior wall or inferoposterior wall, the LV volume should be carefully evaluated.


MOPA: An integrative multi-omics pathway analysis method for measuring omics activity.
Pathways are composed of proteins forming a network to represent specific biological mechanisms and are often used to measure enrichment scores based on a list of genes in means to measure their biological activity. The pathway analysis is a de facto standard downstream analysis procedure in most genomic and transcriptomic studies. Here, we present MOPA (Multi-Omics Pathway Analysis), which is a multi-omics integrative method that scores individual pathways in a sample wise manner in terms of enriched multi-omics regulatory activity, which we refer to mES (multi-omics Enrichment Score). The mES score reflects the strength of regulatory relations between multi-omics in units of pathways. In addition, MOPA is able to measure how much each omics contribute to mES that may be used to observe what kind of omics are active in a pathway within a sample group (e.g., subtype, gender), which we refer to OCR (Omics Contribution Rate). Using nine different cancer types, 93 clinical features and three types of omics (i.e., gene expression, miRNA and methylation), MOPA was used to search for clinical features that were explainable in context of multi-omics. By evaluating the performance of MOPA, we showed that it yielded higher or at least equal performance compared to previous single and multi-omics pathway analysis tools. We find that the advantage of MOPA is the ability to explain pathways in terms of omics relation using mES and OCR. As one of the results, the TGF-beta signaling pathway was captured as an important pathway that showed distinct mES and OCR values specific to the CMS4 subtype in colon adenocarcinoma. The mES and OCR metrics suggested that the mRNA and miRNA expressions were significantly different from the other subtypes, which was concordant with previous studies. The MOPA software is available at https://github.com/jaeminjj/MOPA.


Hybrid 20/23-G pars plana vitrectomy in endophthalmitis and trauma: a strategic approach.
To assess the safety and efficacy of hybrid vitreous surgery combining active 23-G ports with a sutured 20-G 6-mm infusion cannula for performing vitrectomy in endophthalmitis and trauma. This is a retrospective analysis of 10 eyes with endophthalmitis and 10 eyes with trauma requiring vitreous surgery, having corneal clarity suitable for vitrectomy and best-corrected visual acuity (BCVA) greater than or equal to light perception. All patients underwent hybrid 20/23-G vitrectomy. Intraoperative notes were analyzed for peroperative complications. The BCVA and retinal status at 3 months were analyzed. In the endophthalmitis group, patients ranged from 5 to 85 years of age and showed varied etiologies. Retinal detachment was present in 5 eyes, which received silicone oil tamponade. Mean preoperative logMAR visual acuity (VA) was 2.29 ± 0.45, which improved to 1.10 ± 0.72 at 3 months postoperatively (p<0.001). Trauma cases ranged from 21 to 75 years of age. Retinal detachment was present in 9 out of 10 eyes, all of which received silicone oil tamponade. Preoperative logMAR VA was 2.26 ± 0.71, which improved to 1.33 ± 0.50 postoperatively (p<0.001). At 3 months postsurgery, the retina was attached in all eyes in both groups. The longer sutured 20-G cannula was easier to visualize through fibrin, exudates, and hemorrhage and did not slip out or enter the suprachoroidal space in any of our cases. The 23-G active ports and vitrectomy cutter enhanced safety and efficacy. Hybrid vitrectomy enabled safe surgery in these difficult cases.


Looking for immunological risk genotypes.
Several functional markers of the immune system may be used either as markers of successful aging or conversely as markers of unsuccessful aging. Particularly, a combination of high CD8 and low CD4 and poor T cell proliferation has been associated with a higher two-year mortality in very old subjects. Therefore, genetic determinants of longevity should reside in those polymorphisms for the immune system genes that regulate immune responses. Concerning these changes in T cell subpopulations, how much they depend on the immunogenetic background and how much they depend on individual antigenic load, such as chronic infections, should be assessed. As previously demonstrated in our population, the interleukin (IL)-2 high-producer genotype is less frequent in old men than in young people; conversely, the IL-10 high-producer genotype is increased in old men. In this study, we tried to assess the role of low- and high-producer genotypes for IL-10 and IL-2 in the CD4 and CD8 absolute values, taking into account gender and age. The results suggest that old men carrying an anti-inflammatory IL-10 high-producer genotype or a proinflammatory IL-2 low-producer genotype show the lowest values of CD8 cells. Although in our study we were not able to show any correlation with CD4 values and no functional assessment of T cell was performed, these results suggest that cytokine genotypes may be involved in the subpopulation dynamics in old age.


Bandpass sampling based digital coherent receiver with free-running local oscillator laser for phase-modulated radio-over-fiber links.
A bandpass sampling based digital coherent receiver is presented for phase modulated radio-over-fiber links with coherent detection. In the scheme, the bandpass sampling technique is introduced in RoF systems to overcome the high sampling rate requirement and front-end hardware dependency of conventional digtal coherent receivers. In particular, the selection rule of bandpass sampling rate was defined by taking into account the frequency offset induced by free-running optical local oscillator. Analytical assessment and simulations are used to determine the ultimate performance in terms of tolerances to ADC bit resolution and laser linewidth. Thereafter, a 40Mbps QPSK modulated data signal at 2.4GHz RF carrier frequency is experimentally demonstrated over the proposed 50.6-km radio-over-fiber link employing bandpass sampling.


Introduction: leading lesbians fight disease and disability.
This thematic issue of the Journal of Lesbian Studies focuses on the ways in which lesbian leaders have dealt with disease and disability. In the articles that follow, eight prominent lesbians describe what it means to cope with serious illness and medical treatment in the context of lesbian identity and community. This introduction provides an overview of some of the themes that arose in the various articles, focusing on lesbian support systems as well as best medical practices.


Did exposure to a severe outbreak of pandemic influenza in 1918 impact on long-term survival?
There is some suggestion that infection with pandemic influenza may increase long-term mortality risks. Therefore we aimed to determine if exposure to a severe outbreak of pandemic influenza on a troopship in 1918 impacted on lifespan in the survivors. The troopship with the outbreak cohort had 1107 personnel and the comparison cohort was from two contemporaneous troopships (1108 randomly selected personnel). Data were collected from online individual military files. The main finding was that there was no statistically significant difference in the lifespan of the outbreak cohort and the comparison cohort (means of 71·5 and 71·0 years, respectively). Indeed, the outbreak cohort was actually more likely to survive into the period from 1950 onwards (P = 0·036) and to participate in the Second World War (P = 0·043). There were no significant differences between the cohorts in terms of occupational class, but the comparison cohort had a higher proportion of rural occupations (33·3% vs. 27·0%, P < 0·001) and was very slightly older in mid-1918 (27·8 vs. 27·2 years, P = 0·028). In conclusion, this study found no support for the hypothesis that exposure to the 1918 influenza pandemic adversely impacted on the lifespan in the survivors, at least in this male and military-age population.


Preparation and Properties of Low-Carbon Foamed Lightweight Soil with High Resistance to Sulphate Erosion Environments.
Foamed lightweight soil (FLS) is a lightweight cementitious material containing a large number of tiny closed pores and has been widely used as a filler in places such as railways, roads and airports. However, there has been little research into the resistance of FLS to sulphate attack in practical engineering applications. The performance of FLS against different sulphate erosion concentrations was studied to elucidate the engineering characteristics of using large volumes of FLS as fill material for the road base in the construction of intelligent networked vehicle test sites. The results showed that the compressive strength of FLS prepared using 30% Portland cement (C), 30% granulated blast furnace slag (GBFS), 40% fly ash (FA) and a small amount of a concrete antiseptic agent (CA) as cementitious materials reached 0.8 and 1.9 MPa at 7 and 28 d, respectively, when the wet density was about 600 kg/m3, which met the design requirements. The FLS prepared via the above-mentioned cementitious system had a low carbon emission, with a CO2 emission reduction rate of up to 70%. It also had excellent sulphate attack resistance: the corrosion resistance coefficient of the cementitious material system reached 0.97, which was considerably better than that of C (0.83). For an erosion medium environment with SO42- concentrations of less than 1000 mg/L (moderate), 40% GBFS or FA can be used to prepare FLS. When the concentration of SO42- is less than 4000 mg/L (severe), 30% C, 30% GBFS and 40% FA can be used as cementitious materials, preferably in combination with an appropriate amount of CA, to prepare FLS.


[Injuries of the first web. Surgical indications].
Treatment of the first web injuries are based on the concept of one stage repair of the complex injuries of the hand with early motion. Radical debridement is specially important in case of muscular attrition. Fasciotomie of the first web is systematic in case of crush injuries for avoiding compartimental syndrome. For prevention of first web retraction, one or two Kirchner wires are placed in emergency between first and second metacarpal, and later a spilt in maximal anti-position of the first ray. In case of communited fractures, skeletal stabilisation use inlay internal devices, such the blocked intramedullary nail. First web reconstruction must take into consideration the cutaneous functionnal units of the hand, described by Michon. Thin and split-thickness grafts are rarely used for covering skin defects of the first web space, because their ability of retraction. Exposition of bone or tendons leads to the realisation of a flap. Soft tissue coverage must be achieved in emergency or after a second look within the first 48 hours. The kite flap is the most useful local flap for the first web space. The interosseous flap is the best choice among the regional pedicled flap. The use of the Chinese flap must be very careful, because the possibility of contusion of the radial pedicle in these types of injuries. It is only in case of contra-indication of the interosseous flap that free flaps can be realised, as the lateral arm flap or the parascapular flap. The groin flap keeps few indications for aesthetic reasons, or when regional flaps and microsurgery are contra-indicated.


Component-Customizable Porous Rare-Earth-Based Colloidal Spheres towards Highly Effective Catalysts and Bioimaging Applications.
Multicomponent porous colloidal spheres are of interest because they not only show a combination of the properties associated with all different components, but also usually present synergy effects. However, a combination of different components in a single porous sphere is still greatly challenged due to the different precipitation behaviors of each component. In this work, we have developed a general synthetic route to prepare several categories of porous monodisperse rare-earth (RE)-based colloidal spheres with customizable elemental compositions and a uniform element distribution. The two-step synthetic strategy is based on the integration of coordination chemistry precipitation of RE ions and a subsequent ion-exchange process, which steers clear of obstacles, such as differences in solubility product constant, that are to be found in traditional co-precipitation methods. Our approach provides a new mixing mechanism to realize homogeneous distribution of each element within the porous spheres. An array of binary, ternary, and even senary RE colloidal porous spheres with diameters of 500 nm to 700 nm has been successfully synthesized. Taking advantage of their good dispersibility, porosity, and customizable components, these porous RE oxide spheres show excellent catalytic activity for the reduction of 4-nitrophenol, and promising application in single-phase multifunctional bioprobes.


Novel quinazoline and acetamide derivatives as safe anti-ulcerogenic agent and anti-ulcerative colitis activity.
Two novel quinazoline derivatives named as; 3-[(4-hydroxy-3-methoxy-benzylidene)-amino]-2-p-tolyl-3H-quinazolin-4-one (5) and 2-p-Tolyl-3-[3,4,5-trimethoxy-benzylidene-amino]-3H-quinazolin-4-one (6) in addition to one acetamide derivative named as 2-(2-Hydroxycarbonylphenylamino)-N-(4-aminosulphonylphenyl) 11 were synthesized, and evaluated for their anti-ulcerogenic & Anti-Ulcerative colitis activities. All of the three compounds showed curative activity against acetic acid induced ulcer model at a dose of 50 mg/kg, they produced 65%, 85% & 57.74% curative ratio for compounds 5, 6 & 11 respectively. The effect of the tested compounds 5, 6 & 11 at dose 50 mg/kg were significantly (P < 0.01) more effective than dexamesathone (0.1 mg/kg) in reducing all parameters. Compounds showed curative activity of for peptic ulcer (induced by absolute alcohol (at a dose of 50 mg/kg, it produced Curative of control ulcer 56.00%, 61.70% & 87.1% for compounds 5, 6 & 11 respectively at dose 50 mg/kg, while the standard drug (Omeprazole 20 mg/kg) produced 33.3%. In both tests, the activity of our target compounds were higher than the standard drugs used for treatment of peptic ulcer and ulcerative colitis. No side effects were reported on liver and kidney functions upon prolonged oral administration of this compounds.


The spectrum of lesions and clinical results of arthroscopic stabilization of acute anterior shoulder instability.
The purpose of this study is to investigate and analyze accompanying lesions including injury types of anteroinferior labrum lesion in young and active patients who suffered traumatic anterior shoulder dislocation for the first time. The study used magnetic resonance angiography (MRA) to 40 patients with acute anterior shoulder dislocation from April 2004 to April 2008, and of those, 36 with abnormal MRA finding were treated with arthroscopy. There was a total of 25 cases of anteroinferior glenoid labrum lesions. A superior labrum anterior-posterior lesion (SLAP) lesion was observed in 8 cases. For bony lesions, 22 cases of Hill-sachs lesions, 4 cases of lesions in greater tuberosity fracture of humerus, and 4 cases of loose body were found. For lesions involving rotator cuff, partial articular side rupture was found in 2 cases and 2 cases were found to have a complete rupture. Under MRA and arthroscopy performed on patients with acute anterior shoulder dislocation, it was observed to have varying types of anteroinferior labrum lesions such as Perthes, Bankart, ALPSA, and bony Bankart lesion. that MRA is a remarkably useful tool to classify various lesions in acute anterior dislocation of the shoulder and to make a diagnosis, making it a useful tool to decide a treatment method while consulting patients and their families.


Filamin A (FLNA) is required for cell-cell contact in vascular development and cardiac morphogenesis.
Mutations in the human Filamin A (FLNA) gene disrupt neuronal migration to the cerebral cortex and cause cardiovascular defects. Complete loss of Flna in mice results in embryonic lethality with severe cardiac structural defects involving ventricles, atria, and outflow tracts, as well as widespread aberrant vascular patterning. Despite these widespread developmental defects, migration and motility of many cell types does not appear to be affected. Instead, Flna-null embryos display abnormal epithelial and endothelial organization and aberrant adherens junctions in developing blood vessels, heart, brain, and other tissues. Essential roles for FLNA in intercellular junctions provide a mechanism for the diverse developmental defects seen in patients with FLNA mutations.


A regional survey of dentists' preferences for hiring a dental associate.
For many new dental school graduates, working as an associate may be an attractive option. To provide practical information for new job-seeking dentists, the authors conducted a survey to assess dentists' preferences with regard to hiring an associate. The authors mailed surveys to a random sample of 3,875 general dentists in four states that asked questions about the characteristics they preferred when hiring an associate. Five hundred seventy-four dentists (14.8 percent) responded to the survey. The results of this survey showed a wide variation in the characteristics dentists prefer when hiring an associate, but interpersonal skills appear to be at least as important as technical skills for new dentists' success. Opportunities for associate positions appear to be available to new dentists who have a range of skills, experience and training. Practical Implications. These results provide new dentists with information regarding the variety of career opportunities available for associates.


The efficacy of the diode laser at 800-980 nm as an aid to non-surgical therapy in periodontitis treatment: a review of literature.
The aim of this literature review is to assess the effectiveness of diode laser at a wavelength of 800-980 nm in addition to non-surgical periodontal therapy in periodontitis treatment. The authors performed an electronic research on Pubmed inserting as keywords: (laser OR laser therapy OR diode laser) and (periodontitis OR periodontal disease). The field has been narrowed to select only Randomized controlled clinical trials (RCT) performed from 2010 to 2020. The result of this research was 84 articles, of which eight were included in the review because they respect the inclusion criteria. The clinical, immunological, and microbiological parameters studied in the various clinical random trials were analysed. It has been shown that four out of eight studies have achieved greater benefits, in terms of clinical parameters, with the use of diode laser compared to Scaling and Root Planing. However, the greater increase in clinical parameters in diode laser-treated patients compared to the control group was mainly detected in the short term rather than in the long term. In terms of microbiological parameters, no improvement was detected after six months. Only one study reported six-month improvements in immunological parameters in patients treated with DL compared to the Scaling and Root Planing only group. In conclusion, considering the limitations of this review of literature, there is no evidence that the diode laser at 800-980 nm in addition to non-surgical periodontal therapy is more effective than SRP alone in the long term.


Domino Reaction Sequence for the Synthesis of [2.2.2]Diazabicycloalkenes and Base-Promoted Cycloreversion to 2-Pyridone Alkaloids.
A new domino reaction sequence for the construction of 2-pyridone structures is reported. The reaction sequence begins with diacetyldiketopiperazine and proceeds via aldol condensation, alkene isomerization, and intramolecular Diels-Alder cycloaddition. The intermediate [2.2.2]diazabicycloalkene cycloadducts can be isolated or can engage in a base-accelerated extrusion of one lactam bridge to provide the 2-pyridone cycloreversion products. The operation leading to pyridone products can occur in one reaction vessel and proceeds at convenient temperatures.


Large-scale cryovolcanic resurfacing on Pluto.
The New Horizons spacecraft returned images and compositional data showing that terrains on Pluto span a variety of ages, ranging from relatively ancient, heavily cratered areas to very young surfaces with few-to-no impact craters. One of the regions with very few impact craters is dominated by enormous rises with hummocky flanks. Similar features do not exist anywhere else in the imaged solar system. Here we analyze the geomorphology and composition of the features and conclude this region was resurfaced by cryovolcanic processes, of a type and scale so far unique to Pluto. Creation of this terrain requires multiple eruption sites and a large volume of material (>104 km3) to form what we propose are multiple, several-km-high domes, some of which merge to form more complex planforms. The existence of these massive features suggests Pluto's interior structure and evolution allows for either enhanced retention of heat or more heat overall than was anticipated before New Horizons, which permitted mobilization of water-ice-rich materials late in Pluto's history.


Virulence and genomic features of a bla CTX-M-3 and bla CTX-M-14 coharboring hypermucoviscous Klebsiella pneumoniae of serotype K2 and ST65.
Capsular serotype K2 Klebsiella pneumoniae of sequence type (ST) 65 has been recognized as a hypervirulent clone. Simultaneous presence of different bla CTX-M genes has never been reported in this clone. In the present study, the genetic characteristics and virulence phenotype of a CTX-M-3 and CTX-M-14 coproducing ST65 K. pneumoniae human isolate, KP_06, that caused an intracranial infection, are evaluated. The potential virulence of KP_06 was assayed by in vitro and in vivo methods. The molecular biology and whole-genome sequencing technology were used to analyze the genomic features associated with the virulence of this strain. The KP_06 exhibited typical features of hypervirulent K. pneumoniae (hvKP), showing hypermucoviscosity phenotype and belonging to K2 and ST65. Apart from virulence genes linked to hvKP, including rmpA, rmpA2, and clb cluster and genes encoding siderophores, it was found to harbor a ~170 kb pLVPK-like virulence plasmid. In contrast to most hvKP, KP_06 was resistant to cephalosporins and the coexistence of bla CTX-M-3 and bla CTX-M-14 was detected. Further experiments demonstrated that this strain was classified as a nonbiofilm producer and serum sensitivity (grade 1) and killed only 30% of Galleria mellonella inoculated with 1×106 colony-forming unit of the specimen within 48 hours, suggesting relatively low virulence. Comparative genomic analysis of KP_06 with five K2 hypermucoviscous K. pneumoniae (HMKP) revealed seven unique orthologies with varied function in this strain. Intriguingly, the virulence genes identified in KP-06 were unexpectedly more diverse than those observed in five other K2 HMKP strains. Our data support the notion that neither virulence-associated genes (clusters) nor the pLVPK-like virulence plasmid is sufficient for the hypervirulence of K. pneumoniae. Future studies aiming to explore the virulence of K. pneumoniae should take genome-based profile together with experimental work. The detailed mechanism involving in the impaired virulence of KP_06 remains to be further explored.


Age- and Gender-Normalized Coronary Incidence and Mortality Risks in Primary and Secondary Prevention.
Epidemiologic differences in ischemic heart disease incidence between women and men remain largely unexplained. The reasons of women's "protection" against coronary artery disease (CAD) are not still clear. However, there are subsets more likely to die of a first myocardial infarction. The purpose of this review is to underline different treatment strategies between genders and describe the role of classical and novel factors defined to evaluate CAD risk and mortality, aimed at assessing applicability and relevance for primary and secondary prevention. Women and men present different age-related risk patterns: it should be important to understand whether standard factors may index CAD risk, including mortality, in different ways and/or whether specific factors might be targeted gender-wise. Take home messages include: HDL-cholesterol levels, higher in pre-menopausal women than in men, are more strictly related to CAD. The same is true for high triglycerides and Lp(a). HDL-cholesterol levels are inversely related to incidence and mortality. In primary prevention the role of statins is not completely ascertained in women although in secondary prevention these agents are equally effective in both genders. Weight and glycemic control are effective to reduce cardiovascular disease (CVD) mortality in women from middle to older age. Blood pressure is strongly and directly related to CVD mortality, from middle to older age, particularly in diabetic and over weighted women. Kidney dysfunction, defined using UAE and eGFR predicts primary CVD incidence and risk in both genders. In secondary prediction, kidney dysfunction predicts sudden death in women in conjunction with left ventricular ejection fraction evaluation. Serum uric acid does not differentiate gender-related CVD incidences, although it increases with age. Age-related differences between genders have been related to loss of ovarian function traditionally and to lower iron stores more recently. QT interval, physiologically longer in women than men, may be an index of arrhythmic risk in patients with mitral valve prolapse and increased circulating levels of catecholamines. However, there are no large population-based studies to assess this. In conjunction with novel parameters, such as inflammatory markers and reproductive hormones, classical risk score in women may be implemented in the future.


Evaluation of a pediatric multiple vitamin preparation for total parenteral nutrition in infants and children. I. Blood levels of water-soluble vitamins.
This study represents the first attempt to evaluate the response to the only intravenous vitamin preparation (MVI Pediatric) for infants and children receiving total parenteral nutrition. Eighteen preterm infants (group 1), 26 term infants and children receiving total parenteral nutrition for 2 to 4 weeks (group 2A), and eight infants and children receiving total parenteral nutrition for 3 to 6 months (group 2B) were studied. Term gestation infants and children up to 11 years of age received daily vitamin doses that approximated the 1974 Recommended Dietary Allowances and coincided with the 1975 American Medical Association Nutrition Advisory Group total parenteral nutrition dosage guidelines for children weighing more than 10 kg. Preterm infants received 65% of these dosages. RBC transketolase (vitamin B1), glutathione reductase (B2), and glutamic oxaloacetic transaminase (B6) activities were maintained at normal levels, and niacin levels were maintained within the reference range (7.1 +/- 0.32 micrograms/mL) in all study patients. Pantothenate, biotin, and ascorbate were maintained at reference levels in groups 2A and 2B. In group 1, ascorbic acid was increased significantly during treatment from 1.53 +/- 0.16 to 3.60 by seven days and to 2.54 +/- 0.62 by day 28 of treatment (reference normals = 0.99 +/- 0.1 mg/dL). RBC folate was maintained within the reference range of 411 +/- 76 pg/mL; however, pantothenate and biotin levels increased significantly to more than 2 SD above reference values during treatment, and vitamin B12 levels, which were above the reference range initially, were maintained at more than 2 SD above the reference range throughout treatment. The elevation in vitamin B12 was seen in both group 1 and 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)


[Mild head trauma: complications and acousticovestibular sequelae].
Head injury with fracture of the petrous bone is frequent and directly related to the development of human activity. Head trauma is associated with nearly 75% of traffic accidents; 5% of them with petrous bone fracture. Based on a clinical case, the acute injuries and secondary acoustic or vestibular sequelae after low-energy cranio-cerebral trauma are discussed here. The subject was a victim of a low-energy head trauma with brief loss of consciousness and translabyrinthine fracture of the petrous bone. This fracture caused invalidating equilibrium disorders related to a perilymphatic fistula. These disorders persisted for 3.5 years and required several hospitalizations and three surgical procedures. The acoustic problems progressed towards cophosis and persistent and invalidating tintinus. We discuss the pathogenesis and treatment of these different sequelae of the middle ear as well as the external lesions. Among labyrinthine involvement, especially unilateral destruction, fistulization, concussion, and post concussion syndrome are especially descripted. Bony dislocations dominate middle ear sequelae. We also discuss the medicolegal problems associated with this type of pathology.


Correlations and cumulative frequency distributions of maternal and newborn hematologic data.
Nonparametric correlation coefficients and cumulative frequency distributions of hematologic data and birth weight obtained from 151 mothers and most of their newborns have been analyzed. Taken overall, the data reaffirm considerable fetal autonomy in maintaining hematologic homeostasis; a dissociation was found between maternal and newborn hemoglobin (Hb) levels, there was no evidence for an effect of maternal iron deficiency on the fetus, nor was birth weight correlated with maternal Hb levels. However, the lack of significance of the latter two correlations was apparent only when three maternal-newborn pairs with alpha-thalassemia were excluded from analysis. An inverse relation was found between birth weight and Hb level in the newborn, and this was present over the entire birth weight range, rather than being restricted to small-for-gestational-age newborns.


A POSTINSEMINATION BARRIER TO FERTILIZATION ISOLATES TWO CLOSELY RELATED GROUND CRICKETS.
Postinsemination barriers to fertilization generally have been ignored by biologists interested in the origin and nature of reproductive isolation among closely related terrestrial animals. Yet evidence presented in this paper indicates that such a barrier bears primary responsibility for the reproductive isolation between the ground crickets Allonemobius fasciatus and Allonemobius socius. Postinsemination barriers to fertilization may isolate many other terrestrial animals as well, but the design of most laboratory hybridization experiments precludes the detection of these barriers.


Acute Renal and Hepatic Failure in an Adolescent: An Unusual Presentation of Multiple Aortic Aneurysms.
Aortic dissection secondary to thoracoabdominal aortic aneurysms is very uncommon in children, and this life-threatening diagnosis requires a high clinical index of suspicion. Unlike adults, in whom atherosclerosis, inflammation, and advanced age are typically contributing factors, aortic dissection in children is usually due to nonatherosclerotic causes.Aortic aneurysms can be asymptomatic when small but, when significantly enlarged, can compromise organ function and dissect, resulting in high mortality rates. It is therefore critical that children with this uncommon condition be identified early when medical or surgical management can potentially improve outcome. We describe a 15-year-old patient with multiple aortic aneurysms with dissection whose presentation includes chronic anemia, acute-on-chronic renal failure with hyperkalemia, and liver injury.


Removal of natural steroid hormones from wastewater using membrane contactor processes.
Growing demands for potable water have strained water resources and increased interest in wastewater reclamation for potable reuse. This interest has brought increased attention to endocrine-disrupting chemicals (EDCs) as emerging water contaminants. The effect of EDCs, and in particular natural steroid hormones, on humans is of heightened interest in the study of wastewater reuse in advanced life support systems (e.g., space missions) because they are excreted in urine and have high endocrine-disrupting potencies. Direct contact membrane distillation (DCMD) and forward osmosis (FO) are being investigated for wastewater treatment in space. Retention of two natural steroid hormones, estrone and 17beta-estradiol, by these two processes was evaluated in the current investigation. DCMD provided greater than 99.5% hormone rejection; DCMD also provided constant flux, greater than 99.9% urea and ammonia rejection, and high water recovery. FO provided from 77 to 99% hormone rejection depending on experiment duration and feed solution chemistry.


Curability of multiple myeloma.
Among 792 patients with multiple myeloma treated from 1987 to 2010 and assessed after 18 months, there were 167 patients with complete remission. For those 60 patients treated between 1987-1998 and with long followup, the latest relapse occurred after 11.8 years, so that 13 patients have remained in sustained complete remission for longer than 12 years (range 12-22 years). These results suggest that 3% of all patients treated during that period may be cured of multiple myeloma. In addition to immunofixation, more sensitive techniques for the detection of residual disease should be applied more consistently in patients with apparent complete remission in order to identify those with potential cure.


Life-threatening bleomycin pulmonary toxicity with ultimate reversibility.
A 60-year-old man with advanced seminoma was treated with four cycles of a cisplatin, etoposide and bleomycin. He then developed severe pulmonary toxicity with diffuse infiltrates as evidenced on a chest x-ray film. The room air PaO2 value was 32 mm Hg. The patient was treated with steroids and oxygen supplementation, including a high FIo2 for several days, and survived and eventually experienced marked improvement in his pulmonary status. Aggressive management of severe bleomycin-induced pneumonitis appears justified.


A case of multiple sebaceous epithelioma: analysis of microsatellite instability.
Sebaceous gland tumor is a rare disease that is a sign of Muir-Torre syndrome, an autosomal, dominantly inherited genodermatosis characterized by the presence of at least one sebaceous gland tumor and a minimum of one internal malignancy. Recent studies have indicated that defective DNA mismatch repair occurs in Muir-Torre syndrome. Cutaneous lesions may occur before diagnosis of the internal cancer. We describe a 64-year-old male patient with multiple sebaceous epitheliomas with no evident internal malignancy. Microsatellite instability, determined by examining dinucleotide CA repeats at the microsatellite loci, was observed in DNA from one sebaceous epithelioma but not from the other two sebaceous epitheliomas or from one basal cell epithelioma with sebaceous differentiation, suggesting that this condition is unlikely to be due to germ-line mutation of mismatch repair genes.


Potential antiinflammatory role of insulin via the preferential polarization of effector T cells toward a T helper 2 phenotype.
Hyperglycemia in critical illness is a common complication and a strong independent risk factor for morbidity and death. Intensive insulin therapy decreases this risk by up to 50%. It is unclear to what extent this benefit is due to reversal of glucotoxicity or to a direct effect of insulin, because antiinflammatory effects of insulin have already been described, but the underlying mechanisms are still poorly understood. The insulin receptor is expressed on resting neutrophils, monocytes, and B cells, but is not detectable on T cells. However, significant up-regulation of insulin receptor expression is observed on activated T cells, which suggests an important role during T cell activation. Exogenous insulin in vitro induced a shift in T cell differentiation toward a T helper type 2 (Th2)-type response, decreasing the T helper type 1 to Th2 ratio by 36%. This result correlated with a corresponding change in cytokine secretion, with the interferon-gamma to IL-4 ratio being decreased by 33%. These changes were associated with increased Th2-promoting ERK phosphorylation in the presence of insulin. Thus, we demonstrate for the first time that insulin treatment influences T cell differentiation promoting a shift toward a Th2-type response. This effect of insulin in changing T cell polarization may contribute to its antiinflammatory role not only in sepsis, but also in chronic inflammation associated with obesity and type 2 diabetes.


Evaluation of the effect of recombinant thrombomodulin on a lipopolysaccharide-induced murine sepsis model.
To evaluate the effect of recombinant human thrombomodulin (rTM) on sepsis, the levels of nucleosome as well as high-mobility group box 1 (HMGB1) and cytokines in sera and peritoneal fluids were measured in a mouse model of lipopolysaccharide (LPS)-induced sepsis after administration of rTM. C57BL/6 mice were intraperitoneally injected with LPS (15 mg/kg; Escherichia coli O111:B4) with or without the intravenous administration of rTM (3 mg/kg; 30 min prior to or 2 h after LPS injection). The survival rates were evaluated and levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, HMGB1 and nucleosome in sera and peritoneal fluids were analyzed by ELISA. Administration of rTM prior to or after LPS improved the survival rate of septic mice. In addition, rTM administered prior to or after LPS suppressed the level of pro-inflammatory cytokine TNF-α in sera at 1-3 h after LPS injection, whereas only the administration of rTM after LPS suppressed the levels of HMGB1 and nucleosome (late-phase mediators of sepsis) (9-12 h) in sera after the LPS injection. Furthermore, administration of rTM prior to or after LPS suppressed the level of TNF-α in the peritoneal fluids at 1-3 h after LPS injection, whereas only the administration of rTM after LPS suppressed the levels of IL-6 and MCP-1 in the peritoneal fluids at 6-9 h after LPS injection. These observations indicated that administration of rTM significantly improves the survival rate and suppresses the increased levels of TNF-α, IL-6, MCP-1, HMGB1 and nucleosome in the LPS-induced septic shock model. Thus, rTM may exert a protective action on sepsis and reduce mortality, possibly by reducing not only the levels of cytokines and chemokine but also the levels of late-phase mediators of sepsis.


Screening of Phospholipids in Plasma of Large-Artery Atherosclerotic and Cardioembolic Stroke Patients With Hydrophilic Interaction Chromatography-Mass Spectrometry.
Ischemic stroke (IS) is a deadly and debilitating disease with a high incidence and recurrence rate in elderly people worldwide. Large-artery atherosclerotic (LAA) and cardioembolic (CE) stroke are two leading subtypes and require different management. As a complementary biochemistry method for current diagnostic techniques, a sensitive and accurate phospholipid (PL) targeted lipidomic method was developed in this study. Plasma PLs were selectively extracted with titanium dioxide/fibrous silica nanosphere material, then characterized and quantified with hydrophilic interaction chromatography-mass spectrometry. A total of 31 molecular species of PLs were determined and ten biomarkers including seven molecular species of sphingomyelins (SM d18:1/18:1, d18:1/18:0, d18:1/24:1, d18:1/16:1, d18:1/22:1, d18:1/24:2, and d18:1/16:0) and three molecular species of phosphatidylcholines (16:0/18:1, 16:0/18:2 and 16:0/22:6) showed significant differences in LAA, CE, and healthy control (HC) groups. The independent diagnostic capabilities of these PL biomarkers were successfully evaluated and validated with receiver operating characteristic curves. Additionally, the oleic acid-enriched SMs, which can result in atherogenic lipoprotein aggregation, were proved to be positively related to IS and may perform as the potential risk factors in the future. Meanwhile, valuable suggestions for dietary interventions as an essential source of endogenous PLs could be obtained from this study.


[Inflammatory bowel diseases: in search of novel cytokines and genes].
Inflammatory bowel diseases are chronic idiopathic intestinal disorders that have diverse manifestations such as diarrhea, rectal bleeding, abdominal pain, weight loss, fever and extraintestinal manifestations. The current concept regarding their immunopathogenesis is that, in a genetically susceptible host, an aberrant response of the mucosa associated lymphoid tissue (MALT) towards a non-pathogenic microorganism, elicits the cascade that culminates in intestinal inflammation. In this issue of HAREFUAH, Waterman M & al have screened IBD vs. control population in search of a genetic association between IBD and the interleukin 13 polymorphism 2044+G/A, on chromosome 5. Although they have found no such association, the editorial addresses the importance of cytokines and novel genes for the understanding of the immunopathogenesis of inflammatory bowel diseases, and its treatment.


Co-stimulatory pathways in lymphocyte regulation: the immunoglobulin superfamily.
The controlled orchestration of immune responses is a vital feature of cellular immunity in a system that must be able to reliably distinguish self from non-self. Contrary to early beliefs, peptide recognition by T cells exhibits a relatively high level of promiscuity. The requirement for a second signalling event to be present in addition to that provided by T cell receptor ligation for T cell activation to proceed helps to prevent inappropriately directed responses. An expanding array of co-stimulatory or inhibitory signalling receptors and ligands are now recognised to be involved in the control of the crucial decisions made determining the activation, expansion, and effector functions of responding cells, and ultimately the final targeting and execution of these functions. Tight regulation of the temporal and spatial organisation of receptor/ligand expression, combined with both forward and reverse signalling, endows an extraordinary elegance to these co-stimulatory pathways. The immunoglobulin superfamily occupies a central importance in this coordination of immune responses. The understanding of its relevance in a variety of physio-pathological circumstances is now yielding a number of potential targets for therapeutic manipulation, and such immunological molecular adjuvants are beginning to enter clinical trials.