Phlebotomus papatasi exposure cross-protects mice against Leishmania major co-inoculated with Phlebotomus duboscqi salivary gland homogenate

Leishmania parasites are inoculated into host skin together with sand fly saliva and multiple exposures to uninfected sand fly bites protect mice against Leishmania infection. However, sand fly vectors differ in composition of the saliva and therefore the protection elicited by their salivary proteins was shown to be species-specific. On the other hand, the optimal vaccine based on sand fly salivary proteins should be based on conserved salivary proteins conferring cross-reactivity. In the present study we therefore focused on cross-protective properties of saliva from Phlebotomus papatasi and Phlebotomus duboscqi, the two natural vectors of Leishmania major. Two groups of mice exposed to bites of P. papatasi and two control, non-immunized groups were infected with L. major promastigotes along with either P. papatasi or P. duboscqi salivary gland homogenate. All mice were followed for the development of Leishmania lesions, parasite burdens, specific antibodies, and for production of NO, urea, or cytokines by peritoneal macrophages. Protection against Leishmania infection was observed not only in exposed mice challenged with homologous saliva but also in the group challenged with P. duboscqi saliva. Comparing both exposed groups, no significant differences were observed in parasite load, macrophage activity, or in the levels of anti-L. major and anti-P. papatasi/P. duboscqi antibodies. This is the first study showing cross-protection caused by salivary antigens of two Phlebotomus species. The cross-protective effect suggests that the anti-Leishmania vaccine based on P. papatasi salivary proteins might be applicable also in areas where L. major is transmitted by P. duboscqi.     

重组腺病毒介导HIP/PAP治疗小鼠实验性急性肝衰竭

目的 观察以重组腺病毒载体介导肝肿瘤-肠道-胰腺基因(HIP/PAP)腹腔注射对小鼠D-氨基半乳糖急性肝损害的保护作用,为急性肝衰竭的临床治疗探索新的方法.方法 Balb/C小鼠80只(雄性)随机分成四组,分别是正常组、Ad-HIP/PAP组、Ad-LacZ组及模型组;每组又分成a、b两组.分别予腹腔注射生理盐水、Ad-HIP/PAP、Ad-LacZ、生理盐水,2d后用D-氨基半乳糖(D-Gal)诱导急性肝衰竭模型(1.0 g/kg),后对a组小鼠进行肝功能指标、肝脏病理学、胃肠免疫组化的检测.b组观察14d,记录小鼠死亡时间及死亡数.结果 免疫组化证实Ad-HIP/PAP腹腔注射后,肠壁可测到HIP/PAP的表达,而正常组未检测到.Ad-HIP/PAP组血清丙氨酸氨基转移酶(ALT)、谷草转氨酶(AST)含量明显低于Ad-LacZ组、模型组(P＜0.05),差异有统计学意义.Ad-LacZ组及模型组肝组织坏死严重,Ad-HIP/PAP组肝组织病变稍轻.观察14 d后,Ad-LacZ组及模型组小鼠全部死亡,Ad-HIP/PAP组小鼠死亡较少.结论 重组腺病毒介导HIP/PAP腹腔表达具有能显著保护肝细胞,预防D-Gal所致小鼠急性肝衰竭作用.腺病毒介导HIP/PAP表达有可能成为急性肝衰竭的治疗手段之一.     

肺复张联合DuoPAP治疗早产儿呼吸窘迫综合征

目的：探讨肺复张联合Duo PAP治疗早产儿呼吸窘迫综合征的临床疗效。方法选取2013年6月1日-2014年6月30日收入我院NICU室的呼吸窘迫综合征早产儿患者68例,随机分为2组,实验组患儿入院后立即给予DuoPAP呼吸支持,呼吸支持24 h内给予肺复张（LRM）,间隔8 h给予1次RM,连续3 d。对照组给予管插管机械通气治疗。结果得出实验组肺复张联合DuoPAP治疗总有效率为91.1%高于对照组的70.5%,有统计学意义（P〈0.05）;治疗12h后对照组和观察组动脉血氧分压分别为的（149.2±19.7）mmHg和（162.3±18.1）mmHg;通气72 h后呼吸机参数对照组和观察组的潮气量分别为（427.2±78.5）mL和（503.6±93.2） mL;对照组和观察组的住院情况和治疗效果比较,主要包括住院天数分别为对照组的（32.2±6.8）d和肺复张联合DuoPAP治疗组的（25.9±5.1）d及死亡病例数分别为2例和0例。以上数据结果具有明显统计学意义（P〈0.05）。结论肺复张联合Duo PAP治疗早产儿呼吸窘迫综合征可有效改善患者的氧合功能,明显提高患者肺的顺应性,大幅降低呼吸机的使用条件,显著提高新生儿呼吸窘迫征的抢救成功率,降低插管率、撤机失败率、BPD、气漏及呼吸机相关性肺炎的发病率,缩短氧暴露时间,减少呼吸机应用时间和住院费用。是临床医师治疗早产儿NRDS首选的无创通气联合治疗方式,简便易行,耐受性好,具有临床推广应用的潜力。     

Pulmonary alveolar proteinosis

We report a 68-year-old female who presented with chronic cough and progressive dyspnoea. Computed tomography of the thorax and subsequent bronchoscopy confirmed the diagnosis of pulmonary alveolar proteinosis (PAP), which was treated with whole lung lavage. This case is reported in view of the low incidence of PAP.     

Adjuvant-carrying synthetic vaccine particles augment the immune response to encapsulated antigen and exhibit strong local immune activation without inducing systemic cytokine release

Augmentation of immunogenicity can be achieved by particulate delivery of an antigen and by its co-administration with an adjuvant. However, many adjuvants initiate strong systemic inflammatory reactions in vivo, leading to potential adverse events and safety concerns. We have developed a synthetic vaccine particle (SVP) technology that enables co-encapsulation of antigen with potent adjuvants. We demonstrate that co-delivery of an antigen with a TLR7/8 or TLR9 agonist in synthetic polymer nanoparticles results in a strong augmentation of humoral and cellular immune responses with minimal systemic production of inflammatory cytokines. In contrast, antigen encapsulated into nanoparticles and admixed with free TLR7/8 agonist leads to lower immunogenicity and rapid induction of high levels of inflammatory cytokines in the serum (e.g., TNF-a and IL-6 levels are 50- to 200-fold higher upon injection of free resiquimod (R848) than of nanoparticle-encapsulated R848). Conversely, local immune stimulation as evidenced by cellular infiltration of draining lymph nodes and by intranodal cytokine production was more pronounced and persisted longer when SVP-encapsulated TLR agonists were used. The strong local immune activation achieved using a modular self-assembling nanoparticle platform markedly enhanced immunogenicity and was equally effective whether antigen and adjuvant were co-encapsulated in a single nanoparticle formulation or co-delivered in two separate nanoparticles. Moreover, particle encapsulation enabled the utilization of CpG oligonucleotides with the natural phosphodiester backbone, which are otherwise rapidly hydrolyzed by nucleases in vivo. The use of SVP may enable clinical use of potent TLR agonists as vaccine adjuvants for indications where cellular immunity or robust humoral responses are required.     

Long-term follow-up of a fenestrated Amplatzer atrial septal occluder in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive disease, with right-heart failure being the main cause of death. In patients refractory to conventional drug therapy, atrial septostomy can serve as palliative treatment or as a bridge to transplantation. A 41-year-old woman with a 15-year history of PAH associated with a corrected atrial septal defect presented with severe deterioration of symptoms. Echocardiography confirmed reocclusion of an atrial septal stoma that had been created several months before. After performing a repeat atrial septostomy, we implanted a custom-made atrial septostomy device, an Amplatzer septal occluder that had been fenestrated to serve as a custom-made atrial septostomy device. This resulted in an improvement in cardiac output and a marked symptomatic relief. During the 6-year follow-up, the patient was clinically stable with limited but constant exercise tolerance, under specific medical therapy. Repeated echocardiography confirmed long-term patency of the device.     

Comparison of high-frequency oscillatory ventilation and high-frequency jet ventilation in cats with normal lungs

Four adult cats received alternating high-frequency oscillatory ventilation (HFOV) and high-frequency jet ventilation (HFJV) at equivalent proximal airway pressures. Physiologic measurements were made before and after each ventilator change. Proximal airway pressures were then adjusted as necessary to reestablish normal pH and PaCO2 values. Aortic, pulmonary artery, and central venous pressures were monitored. Cardiac outputs were measured. Pulmonary and systemic vascular resistance, intrapulmonary shunt, and alveolar-arterial oxygen gradient were determined. Following the change from HFOV to HFJV at similar proximal airway pressures, HFJV always produced higher pH values (P less than 0.0001), higher PaO2 values (P less than 0.05), lower PaCO2 values (P less than 0.0001), as well as higher cardiac outputs (P less than 0.01), lower pulmonary artery pressures (P less than 0.001), and lower pulmonary vascular resistances (P less than 0.001). Following the reciprocal crossover, from HFJV to HFOV, HFJV pH values were again higher (P less than 0.001), and PaCO2 values were again lower (P less than 0.001). A comparison of HFOV and HFJV at similar pH and PaCO2 values showed that HFOV consistently required higher peak inspiratory pressures (P less than 0.001), higher mean airway pressure (P less than 0.001), and higher pressure wave amplitudes (P less than 0.001). Under the circumstances of this study, HFJV produced better gas exchange at lower proximal airway pressures.     

PAP、PSA与前列腺癌的诊断

本院从1992年7月至1996年9月收治经病理检查证实的前列腺癌52例,均行直肠指检(DRE)、B超、血清前列腺酸性磷酸酶(PAP)和前列腺特异抗原(PSA)检查,其诊断前列腺癌阳性率分别为78.8%、50.0%、61.5%、84.6%,PSA阳性率明显高于其它检查(P<0.005),若结合DRE、TRUS(直肠B超),则诊断前列腺癌的敏感性达到96.2%;经直肠前列腺穿刺活检31例,其穿刺阳性率为87.1%。PAP、PSA升高患者的比例与前列腺癌的分期、肿瘤细胞分化程度具相关性。因此,PAP、PSA对前列腺癌的诊断、临床分期、判断预后有较大价值。     

Service users' perspectives of social treatment in social service departments in Israel: Differences between standard and poverty-aware treatments

This article uses mixed methods to examine service user satisfaction with social work treatment in social services departments (SSDs) in Israel—its level, the factors that influence it and its experiential dimensions. A total of 235 service users (SUs) from 11 SSDs were interviewed for this study. They were divided into three groups: (a) SUs receiving standard treatment; (b) SUs participating in poverty-aware programs and (c) SUs receiving a poverty-aware standard treatment. The quantitative findings indicated a significant higher level of satisfaction among the SUs who had been included on poverty-aware programs or received a poverty-aware standard care compared to SUs who had received standard treatment. Additionally, high reported levels of satisfaction were influenced by the frequency of meetings between the service user and the social worker, while the history of care in the SSD had no apparent impact on satisfaction levels. The qualitative analysis indicated that high levels of satisfaction were linked to the service user perceiving the social worker as active, supportive and respectful, and as responsive to the user's emotional and material needs. These findings are discussed in the context of the Poverty-Aware Paradigm and relationship-based social work.