A fatal case of necrotizing Aeromonas schubertii fasciitis after penetrating injury

Necrotizing fasciitis is an uncommon but life-threatening condition with a high associated mortality and morbidity. Most infections are polymicrobial, another distinct form of necrotizing fasciitis that occurred by penetrating freshwater trauma, such as fishing or wading in wet fields. Aeromonas species are responsible. The rapidity of the infectious process is similar to that of clostridial infection, but gas production is not a consistent feature. We report a patient who presented with fever, chills, and bullae on left forearm, despite antibiotics and wound debridement; the infection extend to mid humerus with a rapid onset of skin necrosis and progressive sepsis. Aeromonas schubertii fasciitis is particularly virulent. An apparent superficial cellulitis that fails to respond to standard therapy must raise suspicion of a more extensive underlying subcutaneous infection. Aggressive surgical debridement and antibiotic coverage for gram-negative rods are the essential features of treatment. Delay caused by a mistaken diagnosis of cellulitis and subsequent inadequate debridement would likely prove fatal.     

Reduced-intensity conditioning stem cell transplantation: comparison of double umbilical cord blood and unrelated donor grafts

There are little data comparing umbilical cord blood (UBC) and conventional stem cell sources for reduced-intensity conditioning (RIC) hematopoietic stem cell transplantation (HSCT). We performed a retrospective analysis of RIC HCST using double UCB (dUCB) grafts and RIC HSCT using unrelated donor (URD) grafts. The study included 64 dUCB transplantations and 221 URD transplantations performed at Dana-Farber Cancer Institute and Massachusetts General Hospital between 2004 and 2008. The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 14.1% for dUCB and 20.3% for URD (P = .32). The 2-year cumulative incidence of chronic GVHD was significantly lower in dUCB compared with URD (21.9% versus 53.9%; P < .0001). The 2-year cumulative incidence of nonrelapse mortality was significantly higher in dUCB (26.9% versus 10.4%; P = .0009). In our analysis, dUCB HSCT and URD HSCT had comparable 3-year overall survival (46% in dUCB and 50% in URD; P = .49) and progression-free survival (30% in dUCB and 40% in URD; P = .47). dUCBT was associated with greater nonrelapse mortality despite less chronic GVHD. Our findings suggest that the use of 2 partially matched UCB units appears to be a suitable alternative for patients undergoing RIC HSCT without an HLA-matched donor.     

Impact of Residual Stretch and Remodeling on Collagen Engagement in Healthy and Pulmonary Hypertensive Calf Pulmonary Arteries at Physiological Pressures

Understanding the mechanical behavior of proximal pulmonary arteries (PAs) is crucial to evaluating pulmonary vascular function and right ventricular afterload. Early and current efforts focus on these arteries' histological changes, in vivo pressure-diameter behavior and mechanical properties under in vitro mechanical testing. However, the in vivo stretch and stress states remain poorly characterized. To further understand the mechanical behavior of the proximal PAs under physiological conditions, this study computed the residual stretch and the in vivo circumferential stretch state in the main pulmonary arteries in both control and hypertensive calves by using in vitro and in vivo artery geometry data, and modeled the impact of residual stretch and arterial remodeling on the in vivo circumferential stretch distribution and collagen engagement in the main pulmonary artery. We found that the in vivo circumferential stretch distribution in both groups was nonuniform across the vessel wall with the largest stretch at the outer wall, suggesting that collagen at the outer wall would engage first. It was also found that the circumferential stretch was more uniform in the hypertensive group, partially due to arterial remodeling that occurred during their hypoxic treatment, and that their onset of collagen engagement occurred at a higher pressure. It is concluded that the residual stretch and arterial remodeling have strong impact on the in vivo stretch state and the collagen engagement and thus the mechanical behavior of the main pulmonary artery in calves.     

Validated SNPs for eGFR and their associations with albuminuria

Albuminuria and reduced glomerular filtration rate are manifestations of chronic kidney disease (CKD) that predict end-stage renal disease, acute kidney injury, cardiovascular disease and death. We hypothesized that SNPs identified in association with the estimated glomerular filtration rate (eGFR) would also be associated with albuminuria. Within the CKDGen Consortium cohort (n= 31 580, European ancestry), we tested 16 eGFR-associated SNPs for association with the urinary albumin-to-creatinine ratio (UACR) and albuminuria [UACR >25 mg/g (women); 17 mg/g (men)]. In parallel, within the CARe Renal Consortium (n= 5569, African ancestry), we tested seven eGFR-associated SNPs for association with the UACR. We used a Bonferroni-corrected P-value of 0.003 (0.05/16) in CKDGen and 0.007 (0.05/7) in CARe. We also assessed whether the 16 eGFR SNPs were associated with the UACR in aggregate using a beta-weighted genotype score. In the CKDGen Consortium, the minor A allele of rs17319721 in the SHROOM3 gene, known to be associated with a lower eGFR, was associated with lower ln(UACR) levels (beta = -0.034, P-value = 0.0002). No additional eGFR-associated SNPs met the Bonferroni-corrected P-value threshold of 0.003 for either UACR or albuminuria. In the CARe Renal Consortium, there were no associations between SNPs and UACR with a P< 0.007. Although we found the genotype score to be associated with albuminuria (P= 0.0006), this result was driven almost entirely by the known SHROOM3 variant, rs17319721. Removal of rs17319721 resulted in a P-value 0.03, indicating a weak residual aggregate signal. No alleles, previously demonstrated to be associated with a lower eGFR, were associated with the UACR or albuminuria, suggesting that there may be distinct genetic components for these traits.     

喘可治注射液对哮喘患者免疫功能和临床疗效的影响

目的观察喘可治注射液对哮喘患者免疫功能和临床疗效的影响。方法选取我院确诊为支气管哮喘急性发作期患者40例,随机分为对照组和喘可治组（CKZ组）,每组20例。对照组给予常规治疗（吸氧、抗感染、解痉平喘、止咳化痰、纠正水电解质平衡紊乱等）,CKZ组在常规治疗基础上加喘可治注射液肌注双足三里穴,两组疗程均为7 d。观察两组治疗前后外周血T淋巴细胞亚群百分比（CD3%、CD4%、CD8%）的变化、肺功能峰流速（peak expiratory flow,PEF）以及临床主要症状疗效。结果与对照组比较,治疗后CKZ组T淋巴细胞亚群CD4%、CD8%均明显升高（P〈0.05）,肺功能PEF%明显改善（P〈0.05）,且治疗组主要症状改善情况也较对照组更显著（P〈0.05）。结论喘可治注射液能够调节哮喘急性发作期患者外周血T淋巴细胞亚群的紊乱状态,使之恢复平衡,而且能够有效改善肺功能和临床症状。     

A new technique for multiple re-use of planar patch clamp chips

The patch clamp technique is widely used for recording the activity of ion channels in single cells and lipid bilayers. Most platforms utilize borosilicate glass configured as a pipette, however more recently planar patch clamp chips have been developed that require less technical expertise. Planar patch clamp chips in systems like the Nanion Port-a-Patch are useful in that they allow more rapid throughput in drug screening studies. This technique also has the ability to perform rapid solution changes from the intracellular side. A current drawback with the planar patch clamp chips is the need to utilize a separate chip for each experiment. This increases the cost of each experiment and is due to the fact that the ～1μm aperture used for cell attachment is thought to retain cellular debris thereby preventing subsequent cell attachment and formation of GΩ seals. In the present study we have for the first time solved the technical problem of developing a simple protocol for re-use of Nanion planar patch clamp chips. The re-use methodology is demonstrated in whole cell patch clamp studies of HEK-293 cells expressing the electrogenic sodium bicarbonate cotransporter NBCe1-A in protocols involving external and internal solution changes, and CHO-K1 cells with incorporated gramicidin channels.     

An unusual cause of dyspnea in a patient with cervical herpes zoster

Motor involvement in acute herpes zoster does occur,but is rare. Most causes of zoster paresis are due to the extension of the inflammation to the anterior horn and/or anterior motor roots. We report a female patient with an unusual diaphragmatic paralysis caused by cervical herpes zoster. The lesion, diagnosed by MRI, involved the anterior horn of the cervical spinal cord.     

Neuroethologically delineated differences in the seizure behavior of Synapsin 1 and Synapsin 2 knock-out mice

The highly homologous nerve terminal phosphoproteins synapsin I and synapsin II have been linked to the pathogenesis of epilepsy through associations between synapsin gene mutations and epileptic disease in humans and to the observation of handling induced seizures in mice genetically depleted of one or both of these proteins. Whereas seizure behavior in mice lacking both synapsin I and synapsin II is well characterized, the seizure behavior in mice lacking either is less well studied. Through so called neuroethologically based analyses of fully established seizure behavior in Synapsin 1 and 2 knock-out mice (Syn1KO and Syn2KO mice) aged 4 1/2 months, this study reveals significant differences in the seizure behavior of the two genotypes: whereas Syn1KO mice show both partial and generalized forebrain seizure activity, Syn2KO mice show only fully generalized forebrain seizures. Analysis of seizure behavior at earlier stages shows that the mature seizure pattern in Syn2KO mice establishes rapidly from the age of ～2 months, when Syn1KO partial seizures are rare, and Syn1KO generalized seizures are almost absent. The specific behavioral phenotypes of the two strains suggest that the slight differences in structure, function and expression of these highly related proteins could be important factors during seizure generating neural activity.