Nine new RNA viruses associated with the fire ant Solenopsis invicta from its native range

Virus Genes - The red imported fire ant (Solenopsis invicta) escaped its natural enemies when it was introduced into North America in the 1930s from South America. US efforts have focused on...     

Dissections of regional lymph nodes for treatment of skin cancer: predicting annual caseloads that will optimise outcomes

IntroductionDissection of regional lymph nodes (RLNs) can lead to significant morbidity and a high prevalence of complications. Published guidance states that these procedures should be carried out by surgeons who are members of a specialist skin multidisciplinary team who carry out a combined minimum of 15 axillary/groin dissections per year. However, there is little evidence to guide this minimum figure of procedures. We report on the burden of service provision and prevalence of complications across the South West of England and Wales.MethodsA 12-month review of dissections of RLNs for skin cancer was undertaken covering five Plastic Surgery Units with a collective catchment of 8.4 million people. Detailed data were collected on patient demographics, pathology, timing of surgery, and prevalence of complications.ResultsA total of 163 dissections were carried out. Forty-three per cent of patients experienced one or more complication. In that 12-month period, an average of 8 axillary/groin dissections was carried out per surgeon. A funnel plot demonstrated that the prevalence of complications for individual surgeons was within the limit of the plot but, in many cases, this was based only on a relatively small number of procedures per consultant. If surgeons carried out 10 procedures per year, the upper and lower limits on the plot were 73% and 11%, respectively.ConclusionsFunnel plots can provide a useful guide as to whether the prevalence of complications for procedures for individual surgeons lies within acceptable limits. Based on these results, 10 procedures per consultant per year should be sufficient to enable meaningful assessment of the prevalence of complications.     

Molecular basis of familial cleft lip and palate

Cleft lip and palate (CLP) is one of the commonest congenital malformations and although the aetiology is still very unclear, a familial genetic component is considered to be an important factor in certain individuals. Molecular biology techniques are being used to identify the genes involved and this paper reviews current knowledge and the advances that have already been made. Recent evidence suggests a potential major gene on 6p, and a modifying role for transforming growth factor alpha (TGFA). Moreover retinoic acid receptor alpha (RARA) (17q), MSXl (4p), 4q and BCL3 (19q) could all be implicated in certain CLP families. In addition, the potential modifying role of various genes with the environment are considered to be important areas of research in the future. The identification of a genetic locus associated with this disease would be an important advance in CLP genetic counselling and lead to a better understanding of the genetic basis of CLP.     

Aortic-carotid artery pressure differences and cephalic perfusion pressure during cardiopulmonary resuscitation in humans.

OBJECTIVE: Animal studies have shown an aortic-carotid artery pressure difference during cardiopulmonary resuscitation (CPR), which compromises cerebral perfusion. This pressure difference is most marked with prolonged CPR and can be abolished with administration of high doses of epinephrine. To better understand the mechanism of cerebral blood flow during CPR in humans, we determined the aortic-carotid artery pressure difference, the cephalic perfusion pressure (the carotid artery-jugular vein pressure difference), and thoracic inlet venous "valving" (the central venous-jugular vein pressure difference), while administering standard doses of epinephrine. DESIGN: Prospective study with randomization as to which side the carotid artery was catheterized. SETTING: The resuscitation room of a large urban hospital's emergency department. PATIENTS: Fifteen adults in normothermic, nontraumatic prehospital cardiac arrest treated according to Advanced Cardiac Life Support guidelines, including administration of 1 mg epinephrine iv every 5 mins. INTERVENTIONS: The descending aorta, cervical common carotid artery, internal jugular vein, and central venous system were catheterized. Pressures were recorded during standard CPR for 5 mins after administration of 1 mg epinephrine iv. MEASUREMENTS AND MAIN RESULTS: Most patients received CPR for greater than 20 mins before the first epinephrine dose and for greater than 45 mins before pressure recording as described above. There was no significant difference between aortic and carotid artery compression and relaxation phase pressures. The mean +/- SD compression central venous-jugular vein pressure difference was 22.1 +/- 15.0 mm Hg, and the mean cephalic perfusion pressure was 20.8 +/- 19.5 mm Hg. CONCLUSIONS: There is no clinically important aortic-carotid artery pressure difference during human CPR using the standard dose of epinephrine, even with prolonged CPR. Despite carotid artery patency and thoracic inlet venous valving, the cephalic perfusion pressure is low during CPR in humans.     

脑出血大鼠脑组织膜型基质金属蛋白酶、基质金属蛋白酶2和基质金属蛋白酶9表达及益气活血中药的干预效应

目的:观察益气活血中药对脑出血大鼠脑组织中膜型基质金属蛋白酶、基质金属蛋白酶2和基质金属蛋白酶9表达量的影响,从脑出血损伤区微血管系统重建的角度,探讨益气活血中药治疗脑出血的作用机制。方法:实验于2006-03/10在中南大学湘雅医院中西医结合研究所实验室完成。实验材料:补阳还五汤全方(黄芪,当归,赤芍,红花,川芎,地龙,桃仁按20∶3∶3∶3∶2∶3∶3的比例);补阳还五汤益气成分(黄芪按上述比例);补阳还五汤活血成分(当归,赤芍,地龙,川芎,桃仁,红花按3∶3∶3∶2∶3∶3的比例)。用蒸馏水两次水煎,分别浓缩为1.54,0.81和0.73g/mL。实验分组:155只SD大鼠随机分为正常对照组、假手术组、模型组、益气活血组、益气组、活血组。正常对照组5只大鼠,其余每组30只,再随机分为术后灌胃2,4,7,14,21,28d6个观察时间点,各个时间点5只大鼠。实验干预:造模:采用立体定位技术将胶原酶Ⅶ注入大鼠大脑右苍白球制成脑出血大鼠模型。假手术组大鼠仅注入2μL生理盐水,其余手术过程相同。给药:正常对照组:普通饲养,自由饮水;假手术组和模型组术后予蒸馏水灌胃2次/d,2mL/次;益气活血组、益气组、活血组分别给予补阳还五汤全方、补阳还五汤益气成分、补阳还五汤活血成分30.80,16.20,14.60g/(kg·d)(按体表面积计算为临床70kg成人剂量的3倍)灌胃,2次/d,2mL/次。各组大鼠分别于灌胃2,4,7,14,21,28d麻醉下取脑,制备切片;正常组动物于28d处死。实验评估:免疫组织化学染色方法检测各组灌胃不同时间脑组织基质金属蛋白酶2、基质金属蛋白酶9和膜型基质金属蛋白酶的阳性微血管数。结果:155只大鼠均进入结果分析。①正常组、假手术组皮质偶见膜型基质金属蛋白酶、基质金属蛋白酶2和基质金属蛋白酶9表达。②模型组膜型基质金属蛋白酶、基质金属蛋白酶2呈双峰表达,4d为最高峰,至14～21d再有小高峰出现。③益气活血组给药4d时,膜型基质金属蛋白酶、基质金属蛋白酶2为表达低谷,低于模型组(P<0.01)、益气组和活血组(P<0.05);在中后期,益气活血组膜型基质金属蛋白酶表达高峰为7～14d,较模型组提前出现,21d后与模型组比,各治疗组膜型基质金属蛋白酶已表达极少(P<0.01);益气活血组基质金属蛋白酶2在7d后一直呈高水平维持,高于其他各组(P<0.05),28d后开始逐渐下降。④模型组基质金属蛋白酶9在造模后4d达最高峰(P<0.01),两周后几乎无表达。益气活血组基质金属蛋白酶9高峰推迟至7d出现(P<0.05),之后逐渐下降。结论:益气活血中药可通过调节脑出血后膜型基质金属蛋白酶、基质金属蛋白酶2和基质金属蛋白酶9表达,改善出血后脑组织的微环境,有利于微血管系统重建,促进组织修复。     

H-2-restricted cytotoxic effectors generated in vitro by the addition of trinitrophenyl-conjugated soluble proteins

Murine spleen cells from normal donors were cultured in vitro with trinitrobenzene sulfonate (TNBS)-conjugated soluble proteins, i.e., bovine gamma globulin (TNP-BGG) or bovine serum albumin (TNP-BSA). Addition of 100 μg of any of these TNP-proteins to the spleen cell cultures led to the generation of cytotoxic T-cell effectors which were H-2-restricted and TNP- specific. The lytic potential of such effectors was comparable to that generated by sensitization with TNBS-modified syngeneic cells, and was restricted to haplotypes shared at the K or K plus I-A, or the D regions of the H-2 complex. Greater effecter cell activity was generated by addition of TNP-BGG against TNBS-modified targets which shared K plus I-A than against modified targets which shared the D region with the responding cells, which suggests that the same immune response genes are involved when the response is generated by the addition of TNP-conjugated soluble proteins or of TNBS- modified cells. H-2-restricted, TNP-specific effecter cells were generated by culturing mouse spleen cells with syngeneic cells which had been preincubated with TNP- BGG or TNP-BSA for 1.5 h. The addition of unconjugated soluble proteins to the cultures did not result in cytotoxic effectors detectable on H-2-matched targets, whether the targets were prepared by modification with TNBS, or by incubation with either the unconjugated or TNP-conjugated proteins. Depletion of phagocytic cells in the tumor preparation by Sephadex G-10 column fractionation before incubation with TNP-BSA had no effect on their lysis by the relevant effector cells. Immunofluorescent staining of tumor target cells with anti-TNP antibodies indicated that TNP could be detected on the tumor cells within 10 rain of incubation with TNP-BSA. The cytotoxic response generated by addition of the TNP-proteins to spleen cell cultures was found to be T-cell dependent at the effector phase, as shown by the sensitivity of the lytic phase to absorbed RAMB and complement. Furthermore, the response did not appear to be attributable to antibody-dependent cellular cytotoxicity. Three mechanisms were considered which could account for the generation of H-2-restricted, TNP-specific, cytotoxic T-cell effectors by the addition of soluble TNP-proteins. These include covalent linkage of activated TNP groups from the soluble proteins to cell surface components, macrophage processing of the soluble conjugates and presentation to the responding lymphocytes in association with H-2-coded self structures, or hydrophobic interaction of the TNP-proteins to cell surfaces. Results obtained from sodium dodecyl sulfate gel patterns indicating that cell-bound TNP was still linked to BSA, and the observation that phagocytic-depleted cells could interact with the soluble TNP-proteins and function as H-2-restricted targets, appear not to favor the first two proposed mechanisms.     

ACCM/PALS haemodynamic support guidelines for paediatric septic shock: an outcomes comparison with and without monitoring central venous oxygen saturation

INTRODUCTION: The ACCM/PALS guidelines address early correction of paediatric septic shock using conventional measures. In the evolution of these recommendations, indirect measures of the balance between systemic oxygen delivery and demands using central venous or superior vena cava oxygen saturation (ScvO(2) > or = 70%) in a goal-directed approach have been added. However, while these additional goal-directed endpoints are based on evidence-based adult studies, the extrapolation to the paediatric patient remains unvalidated. OBJECTIVE: The purpose of this study was to compare treatment according to ACCM/PALS guidelines, performed with and without ScvO(2) goal-directed therapy, on the morbidity and mortality rate of children with severe sepsis and septic shock. DESIGN, PARTICIPANTS AND INTERVENTIONS: Children and adolescents with severe sepsis or fluid-refractory septic shock were randomly assigned to ACCM/PALS with or without ScvO(2) goal-directed resuscitation. MEASUREMENTS: Twenty-eight-day mortality was the primary endpoint. RESULTS: Of the 102 enrolled patients, 51 received ACCM/PALS with ScvO(2) goal-directed therapy and 51 received ACCM/PALS without ScvO(2) goal-directed therapy. ScvO(2) goal-directed therapy resulted in less mortality (28-day mortality 11.8% vs. 39.2%, p=0.002), and fewer new organ dysfunctions (p=0.03). ScvO(2) goal-directed therapy resulted in more crystalloid (28 (20-40) vs. 5 (0-20 ml/kg, p<0.0001), blood transfusion (45.1% vs. 15.7%, p=0.002) and inotropic (29.4% vs. 7.8%, p=0.01) support in the first 6 h. CONCLUSIONS: This study supports the current ACCM/PALS guidelines. Goal-directed therapy using the endpoint of a ScvO(2)> or =70% has a significant and additive impact on the outcome of children and adolescents with septic shock.     

Potassium efflux fires the canon: Potassium efflux as a common trigger for canonical and noncanonical NLRP3 pathways

Murine caspase‐11 and its human orthologues, caspase‐4 and caspase‐5, activate an inflammatory response following cytoplasmic recognition of cell wall constituents from Gram‐negative bacteria, such as LPS. This inflammatory response involves pyroptotic cell death and the concomitant release of IL‐1α, as well as the production of IL‐1β and IL‐18 through the noncanonical NLR family, pyrin domain containing 3 (NLRP3) pathway. This commentary discusses three papers in this issue of the European Journal of Immunology that advance our understanding of the roles of caspase‐11, ‐4, and ‐5 in the noncanonical pathway. By utilizing the new gene editing technique, clustered regularly interspaced short palindromic repeats (CRISPR), as well as sensitive cell imaging techniques, these papers establish that cytoplasmic LPS‐dependent IL‐1β production requires the NLRP3 inflammasome and that its activation is dependent on K⁺ efflux, whereas IL‐1α release and pyroptotic cell death pathways are NLRP3‐independent. These findings expand on previous research implicating K⁺ efflux as the principal trigger for NLRP3 activation and suggest that canonical and noncanonical NLRP3 pathways are not as dissimilar as first thought.     

Transferrin receptor-2 (TFR2) mutation Y250X in Alabama Caucasian and African American subjects with and without primary iron overload

Most cases of hemochromatosis are associated with mutations of the HFE gene on Ch6p. In southern Italy and central Alabama, the percentages of patients with hemochromatosis who have "atypical" HFE genotypes (defined as lack of C282Y homozygosity, C282Y/H63D compound heterozygosity, or H63D homozygosity) are relatively great. A mutation of the transferrin receptor-2 gene (TFR2; exon 6, nt 750 C --> G, replaces TAC with stop signal TAG; Y250X) on Ch7q22 was recently identified in two Sicilian families with HFE mutation-negative hemochromatosis. We wanted to estimate the frequency of this mutation in persons from central Alabama. We evaluated Caucasian hemochromatosis probands with atypical HFE genotypes and African Americans with primary iron overload. We also studied control Caucasians, including persons of southern Italian/Sicilian heritage, and control African Americans. Analysis of genomic DNA was performed using a PCR-sequence-specific priming assay and positive control specimens from Sicilian hemochromatosis subjects heterozygous and homozygous for Y250X. Among Alabama subjects, this allele was not detected in 113 Caucasians, including 21 hemochromatosis probands with atypical HFE genotypes and 92 normal control subjects (including 27 of southern Italian/Sicilian descent). In African Americans, Y250X was not detected in 20 index cases with primary iron overload or in 274 unrelated control subjects. We conclude that Y250X is uncommon in Caucasians with hemochromatosis associated with atypical HFE genotypes, in African Americans with primary iron overload, and in the general Caucasian and African American population subgroups in central Alabama.