Acute renal failure (ARF) in critically ill patients is currently very frequent and requires renal replacement therapy (RRT) in many patients. During the last 15 years, several studies have considered important issues regarding the use of RRT in ARF, like the time to initiate the therapy, the dialysis dose, the types of catheter, the choice of technique, and anticoagulation. However, despite an abundant literature, conflicting results do not provide evidence on RRT implementation. We present herein recommendations for the use of RRT in adult and pediatric intensive care developed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system by an expert group of French Intensive Care Society (SRLF), with the participation of the French Society of Anesthesia and Intensive Care (SFAR), the French Group for Pediatric Intensive Care and Emergencies (GFRUP), and the French Dialysis Society (SFD). The recommendations cover 4 fields: criteria for RRT initiation, technical aspects (access routes, membranes, anticoagulation, reverse osmosis water), practical aspects (choice of the method, peritoneal dialysis, dialysis dose, adjustments), and safety (procedures and training, dialysis catheter management, extracorporeal circuit set-up). These recommendations have been designed on a practical point of view to provide guidance for intensivists in their daily practice.

Since 2006, there has been a marked increase in the number of reports of severe and often fatal fungal skin infections in wild snakes in the eastern USA. The emerging condition, referred to as snake fungal disease (SFD), was initially documented in rattlesnakes, where the infections were believed to pose a risk to the viability of affected populations. The disease is caused by Ophidiomyces ophiodiicola, a fungus recently split from a complex of fungi long referred to as the Chrysosporium anamorph of Nannizziopsis vriesii (CANV). Here we review the current state of knowledge about O. ophiodiicola and SFD. In addition, we provide original findings which demonstrate that O. ophiodiicola is widely distributed in eastern North America, has a broad host range, is the predominant cause of fungal skin infections in wild snakes and often causes mild infections in snakes emerging from hibernation. This new information, together with what is already available in the scientific literature, advances our knowledge of the cause, pathogenesis and ecology of SFD. However, additional research is necessary to elucidate the factors driving the emergence of this disease and develop strategies to mitigate its impacts.This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'.

OBJECTIVE

To demonstrate that a modern theory of paraplegia prevention in thoracoabdominal aortic (TAAA) surgery is primarily non-anatomic and derives from experimentally validated interventions that prolong the ischemic tolerance, reduce reperfusion injury, and enhance the collateral perfusion of the spinal cord with or without assisted circulation.

METHODS

Using an accurate predictive model (r(2)>> 0.95) for paraplegia risk we studied the effects of protective strategies in 82 clinical series reporting more than 15,000 patients treated from 1985 to 2008. The observed/expected (O/E) ratios were calculated for each series and the results were grouped by technique. The effect of interventions such as spinal fluid drainage (SFD), systemic hypothermia, epidural cooling, and naloxone on O/E ratios were studied. We analyzed changes in O/E ratios from Era 1 (1985 to 1997) to Era 2 (1997 to 2008) and within treatment techniques over time.

RESULTS

The mean O/E ratio for paraplegia for all patients declined from 1.13 in Era 1 to 0.26 in Era 2. Adding SFD to patients treated with assisted circulation (AC) decreased the O/E ratio from 1.03 to 0.24 (P < .0001). Adding SFD to patients treated with aortic clamping without AC (XCL) decreased O/E from 0.91 to 0.23 (P = .0013). O/E for hypothermic arrest (HA) declined from 0.42 to 0.14 with SFD. The addition of SFD to AC, XCL, and HA accounted for most of the decline in O/E between Eras. Other factors which played a less defined but important role in the decline in O/E ratios were attention to higher mean arterial pressures (MAPs), more hypothermia, and neurochemical protection.

CONCLUSIONS

Paraplegia causation is anatomic but paraplegia prevention is physiologic (non-anatomic). We demonstrate that by using hypothermia, SFD, and increasing MAP, clinicians had similar improvements in paraplegia, reducing O/E deficit ratios from 1.03 to as low as 0.16, with or without intercostal reimplantation, and whether or not assisted circulation was used. Understanding the fundamental principles of paraplegia prevention and how to apply protective strategies leads to a reduction in paralysis in clinical series with or without the use of assisted circulation. This modern theory of paraplegia has significant implications for the rapidly advancing field of TAAA repair with branched endografts where the same principles apply.

BACKGROUND

The role of inhaled corticosteroids for the treatment of wheeze in infancy remains unclear.

OBJECTIVE

To investigate the effect of inhaled fluticasone on symptoms in a group of wheezy infants who had a high risk of progressing to childhood asthma.

METHODS

A total of 52 infants, under 1 year of age, with a history of wheeze or cough and a history (personal or first degree relative) of atopy were prescribed either 150 microg fluticasone twice daily (group F) or placebo (group P), via metered dose inhaler, for 12 weeks following a two week run in period. Symptoms were scored in a parent held diary and the mean daily symptom score (MDS) and symptom free days (SFD) calculated for each two week period.

RESULTS

Thirty seven infants completed the study. Both MDS and SFD improved significantly between the run in and final two week period in group F, but not group P, with a mean difference in change (95% CI) between groups of 1.12 (0.05 to 2.18) for MDS and median difference of 3.0 (0.002 to 8.0) for SFD.

CONCLUSIONS

Improvement of clinical symptoms in response to fluticasone can be shown in this high risk group of infants. In the absence of effective alternatives inhaled corticosteroids should be considered in this patient group.

OBJECTIVE

The objective of this study was to investigate the role of plasminogen activator inhibitor-1 (PAI-1) in adipose tissue development in vivo.

RESULTS

Transgenic (Tg) mice overexpressing murine PAI-1 under control of the adipocyte promoter aP2 and wild-type (WT) controls were kept on standard food (SFD) or on high-fat diet (HFD) for 15 weeks. The body weight and the weight of the isolated subcutaneous and gonadal fat deposits of the Tg mice kept on the HFD were significantly lower than those of the WT mice. The number of adipocytes in the adipose tissue was similar for Tg and WT mice on the HFD, but adipocyte hypotrophy and a significantly lower ratio of stroma cells/adipocytes were observed in the Tg mice. A significant negative correlation (P<0.01) was observed between expression of preadipocyte factor-1, which blocks adipocyte differentiation, and adipose tissue weight. Fasting insulin and total cholesterol levels on the HFD were lower in Tg than in WT mice.

CONCLUSIONS

High circulating PAI-1 levels attenuate nutritionally induced obesity. This may be related to modifications in adipose tissue cellularity affecting weight and plasma metabolic parameters.

The power of histology to define states of cell differentiation was used as the basis of a mutagenesis screen in zebrafish. In this screen, 7-day-old parthenogenetic half-tetrad larvae from potential carrier females were screened for mutations affecting cell differentiation in hematoxylin and eosin-stained tissue sections. Seven, noncomplementing, recessive mutations were found. Two mutations affect only the retina: segmented photoreceptors (spr) show a discontinuous photoreceptor cell layer; vestigial outer segments (vos) has fewer photoreceptor cells and degenerated outer segments within this cell layer. Three mutants have gut-specific defects: the epithelial cells of kirby (kby) are replaced by ballooned cells; the intestines of stuffy (sfy) and stuffed (sfd) contain increased luminal mucus. Two mutations affect multiple organs: disordered neural retina (dnr) has disrupted retinal layering and mild nuclear abnormalities in the gut and liver; and in huli hutu (hht), the retinal cell layers are disorganized and multiple organs have mild to severe nuclear abnormalities that are reminiscent of the atypia of human neoplasia. Each mutation appears to be homozygous lethal. This screen is proof of principle for the feasibility of histologic screens to yield novel mutations, including potential models of human disease. The throughput for this type of screen may be enhanced by automation.

A retrospective analysis was carried out of 133 patients undergoing therapeutic lymph node dissection for malignant melanoma of the lower limb. A radical ilio-obturator dissection (RID) was performed in 106 patients and a superficial femoral dissection (SFD) in the remaining 27. On univariate analysis five factors were found to be significant indicators of prognosis. These were: Clark level of the primary (P = 0.02); primary melanoma thickness (P = 0.04); total number of positive nodes (P less than 0.001); number of positive femoral nodes (P less than 0.001); and number of positive ilio-obturator nodes (P less than 0.001). On multiple regression analysis only the number of positive nodes in each compartment remained a significant independent factor (P less than 0.001). The morbidity associated with RID was not significantly greater than after SFD. RID was, however, associated with a reduction in subsequent groin recurrence. Radical nodal clearance is the operation of choice. This technique provides maximum prognostic information, reduces the likelihood of local untreatable disease and possibly improves overall survival rates--especially when only one iliac node is involved.

Sorsby's fundus dystrophy (SFD) is a rare autosomal dominant macular disorder with age of onset usually in the fourth decade. It is characterised by loss of central vision owing to subretinal neovascularisation and disciform macular degeneration. In an effort to identify the SFD gene, the disease locus was first mapped to chromosome 22q13-qter by genetic linkage analysis, the same chromosomal region as the gene encoding the tissue inhibitor of metalloproteinases-3 (TIMP3). Subsequently, two separate mutations in TIMP3 were found in affected members of two unrelated SFD pedigrees (Tyr168Cys and Ser181Cys). More recently, two additional SFD related mutations, Ser156Cys and Gly167Cys, have provided further confirmation that heterozygous mutations in TIMP3 are causally responsible for the SFD phenotype. We now report the occurrence of the Tyr168Cys mutation in an SFD patient of Austrian descent and show that this mutation found earlier in an American SFD family arose independently. The new findings add to an emerging pattern of SFD mutations which all seem to affect the C-terminal region of the mature TIMP3 protein. In addition, all known mutations cause a change of an amino acid to a cysteine residue. This suggests a critical role for the additional C-terminal free thiol group in SFD pathogenesis.

Until a few years ago, griseofulvin and ketoconazole were the only 2 oral agents available for the treatment of dermatophyte onychomycosis of the toenails. With the availability of the newer antifungal agents, such as itraconazole, terbinafine and fluconazole, the armamentarium of drugs available to treat onychomycosis has expanded. The objective of this study was to determine the relative cost effectiveness of the most commonly used oral antifungal agents in the US for the treatment of dermatophyte onychomycosis of the toenails from the perspective of a third-party payer. The time horizon was 3 years. A 5-step approach was used in this pharmacoeconomic analysis. First, the purpose of the study, the comparator drugs and their dosage regimens were defined. In step II, the medical practice and resource-consumption patterns associated with the treatment of onychomycosis were identified. In step III, a meta-analysis was performed on all studies meeting prespecified criteria, and the mycological cure rates of the comparator drugs were determined. In step IV, the treatment algorithm for the management of onychomycosis was constructed for each drug. The cost-of-regimen analysis for each comparator incorporated the drug acquisition cost, medical-management cost and cost of managing adverse drug reactions. The expected cost per patient, number of symptom-free days (SFDs), cost per SFD and the relative cost effectiveness for the comparator drugs were calculated. In step V, a sensitivity analysis was performed. The drug comparators for this study were griseofulvin, itraconazole (continuous and pulse), terbinafine and fluconazole. The mycological cure rates [mean +/- standard error (SE)] from the meta-analysis were griseofulvin 24.5 +/- 6.7%, itraconazole (continuous) 66.4 +/- 6.1%, itraconazole (pulse) 76 +/- 9.3%, terbinafine 74 +/- 7% and fluconazole 59%. The cost per mycological cure was griseofulvin $US8089, itraconazole (continuous) $US1877, itraconazole (pulse) $US991, terbinafine $US1125 and fluconazole $US1506. The corresponding cost per SFD was griseofulvin $US7.05, itraconazole (continuous) $US2.18, itraconazole (pulse) $US1.26, terbinafine $US1.28 and fluconazole $US2.12. The resulting ratios of cost per SFD relative to itraconazole (pulse) [1.00] were terbinafine 1.02, itraconazole (continuous) 1:73, fluconazole 1.69 and griseofulvin 5.62. In conclusion, in this analysis, itraconazole (pulse) and terbinafine were the most cost-effective therapies for dermatophyte onychomycosis of the toenails, both being substantially more cost effective than griseofulvin.

Placentas from pregnancies complicated by pre-eclampsia, essential hypertension, hypertension complicated by pre-eclampsia and from normotensive pregnancies resulting in the birth of a singleton small-for-dates (SFD) infant have been studied by quantitative morphometry. The findings have been compared with those from placentas of uncomplicated pregnancies. The placentas from pregnancies complicated by pre-eclampsia and those resulting in a SFD baby had a significantly lower total volume, volume of parenchyma and villous surface area when compared with normal pregnancies of comparable gestation. They also had an increase in areas of multiple infarction and in the volume proportions occupied by fetal capillaries. The placentas from women with essential hypertension uncomplicated by pre-eclampsia were as large as those from normal pregnancies and the villous surface areas were as high. Villous surface area measurements in the different groups were related to gestation and to fetal weight.

The evidence is compelling for a role of inflammation in cardiovascular diseases; however, the chronic use of anti-inflammatory drugs for these indications has been disappointing. The recent study compares the effects of two anti-inflammatory agents [cyclooxygenase 2 (COX2) and p38 inhibitors] in a model of cardiovascular disease. The vascular, renal, and cardiac effects of 4-(4-methylsulfonylphenyl)-3-phenyl-5H-furan-2-one (rofecoxib; a COX2 inhibitor) and 6-{5-[(cyclopropylamino)carbonyl]-3-fluoro-2-methylphenyl}-N-(2,2-dimethylpropyl)-3-pyridinecarboxamide [GSK-AHAB, a selective p38 mitogen-activated protein kinase (MAPK) inhibitor], were examined in the spontaneously hypertensive stroke-prone rat (SHR-SP). In SHR-SPs receiving a salt-fat diet (SFD), chronic treatment with GSK-AHAB significantly and dose-dependently improved survival, endothelial-dependent and -independent vascular relaxation, and indices of renal function, and it attenuated dyslipidemia, hypertension, cardiac remodeling, plasma renin activity (PRA), aldosterone, and interleukin-1beta (IL-1beta). In contrast, chronic treatment with a COX2-selective dose of rofecoxib exaggerated the harmful effects of the SFD, i.e., increasing vascular and renal dysfunction, dyslipidemia, hypertension, cardiac hypertrophy, PRA, aldosterone, and IL-1beta. The protective effects of a p38 MAPK inhibitor are clearly distinct from the deleterious effects of a selective COX2 inhibitor in the SHR-SP and suggest that anti-inflammatory agents can have differential effects in cardiovascular disease. The results also suggest a method for evaluating long-term cardiovascular efficacy and safety.

OBJECTIVE

Idiopathic environmental intolerance (IEI), also known as multiple chemical sensitivity, is a chronic, polysymptomatic condition that cannot be explained by an organic disease. Physical and psychological complaints are believed to be sustained by low levels of chemically unrelated substances in the environment. At present, it is unclear whether IEI is an environmental illness or a variant of somatoform disorders (SFD). This study examined whether IEI can be distinguished from SFD with respect to self-reported symptoms, trait anxiety, body-related cognitions, and symptom attributions.

METHODS

We compared 54 subjects with IEI, 54 subjects with SFD but without IEI, and 44 subjects with neither IEI nor SFD on symptom scales, psychological questionnaires, and structured interviews for IEI, depression, anxiety, and SFD.

RESULTS

More than half of the IEI subjects met Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria of SFD. This group shared both symptoms and psychological features of somatization with the SFD group. IEI subjects who did not fulfill criteria for a specific SFD were less impaired by their chemical sensitivity but differed nevertheless from nonsomatoform controls by significantly higher symptom scores, higher trait anxiety, a focus on autonomic sensations, and more pronounced somatic symptom attributions. These psychological features were significantly associated with the burden of somatic symptoms in both SFD and IEI. Furthermore, self-reported allergy but not total immunoglobulin E correlated with symptom burden in the total sample.

CONCLUSIONS

The similarity of IEI and SFD regarding symptoms and psychological features of somatization support the hypothesis that IEI is a variant of SFD.

BACKGROUND

The Inhaled Steroid as Regular Therapy in Early Asthma (START) study reported that early intervention with budesonide in mild persistent asthma reduces severe asthmatic events and improves symptom outcomes and lung function in adults and children.

OBJECTIVE

We sought to estimate the incremental cost-effectiveness of early intervention with budesonide, as observed within the START study.

METHODS

START was a randomized, 3-year controlled trial of budesonide in early onset mild asthma among 7165 subjects ages 5 to 66 years. Three age groups (5-10, 11-17, and>>or=18 years) were studied separately and overall. Differences in the probability of emergency treatments, symptom-free days (SFDs), and costs of health care were determined. Incremental cost-effectiveness ratios were estimated from the health care payer and societal perspectives.

RESULTS

Compared with usual therapy, patients receiving budesonide experienced an average of 14.1 (SE, 1.3) more SFDs per year (P <.001), fewer hospital days (69%, P <.001), and fewer emergency department visits (67%, P <.05). From the health care payer perspective, the net cost of early use of budesonide was an additional US dollars 0.42 (SE, dollars 0.04) per day, and the resultant cost-effectiveness ratio was US dollars 11.30 (95% CI, US dollars 8.60-US dollars 14.90) per SFD gained. From the societal perspective, the cost offsets of lower absence from school or work reduced the net cost of early budesonide to US dollars 0.14 (SE, US dollars 0.07) per day and decreased the cost-effectiveness ratio to US dollars 3.70 (95% CI, US dollars 0.10-US dollars 8.00). Early intervention was more effective and cost saving in the youngest age group.

CONCLUSIONS

Long-term treatment with budesonide appears to be cost-effective in patients with mild persistent asthma of recent onset.

The combined use of nonlinear optical microscopy and broadband reflectance techniques to assess melanin concentration and distribution thickness in vivo over the full range of Fitzpatrick skin types is presented. Twelve patients were measured using multiphoton microscopy (MPM) and spatial frequency domain spectroscopy (SFDS) on both dorsal forearm and volar arm, which are generally sun-exposed and non-sun-exposed areas, respectively. Both MPM and SFDS measured melanin volume fractions between (skin type I non-sun-exposed) and 20% (skin type VI sun exposed). MPM measured epidermal (anatomical) thickness values ~30-65 μm, while SFDS measured melanin distribution thickness based on diffuse optical path length. There was a strong correlation between melanin concentration and melanin distribution (epidermal) thickness measurements obtained using the two techniques. While SFDS does not have the ability to match the spatial resolution of MPM, this study demonstrates that melanin content as quantified using SFDS is linearly correlated with epidermal melanin as measured using MPM (R² = 0.8895). SFDS melanin distribution thickness is correlated to MPM values (R² = 0.8131). These techniques can be used individually and/or in combination to advance our understanding and guide therapies for pigmentation-related conditions as well as light-based treatments across a full range of skin types.

Relative risks were calculated to assess the potency of different factors associated with the two extremes of the birthweight distribution. Maternal height affected the chances of having a small-for-dates (SFD) or large-for-dates (LFD) baby to an equal and opposite extent; but the risks associated with maternal weight were greater for LFD than SFD infants. Smoking increased the SFD risk by 3.5 times, whereas the LFD risk was only reduced by a half. Pre-eclampsia was associated with a very high SFD risk (14.6); in the LFD group it was insignificantly raised. The LFD relative risk steadily rose with increasing parity, but in the SFD group it fluctuated around unity. Among multiparae the risks of an SFD or LFD infant when previous siblings had been of relatively low or high birthweight for gestational age, respectively, were much increased. Estimates of attributable risk showed that if pathological factors such as smoking, hypertensive disorders and congenital abnormalities could be completely eliminated the number of SFD babies in this population would be reduced by about 60%; conversely the number of LFD babies would be increased by about 30%.

BACKGROUND

The SILK flow diverter (SFD) is used for the treatment of complex intracranial aneurysms. Small case series have been reported in the literature but few studies with a large number of patients have been published. We present our experience with the SFD for the treatment of intracranial aneurysms in Canada.

METHODS

Centers across Canada using SFDs were contacted to fill out a case report form for patients treated with an SFD in their center. Individual centers were responsible for approval from their ethics committee. Image analysis was performed by individual operators. The case report forms were collected and the final analysis was performed.

RESULTS

A total of 92 patients were treated with SFDs in eight centers in Canada between January 2009 and August 2013. The aneurysms were located in the posterior circulation in 16 patients and in the anterior circulation in 76 patients. Most aneurysms (75%) were saccular in shape; 22% were fusiform and 3% were blister aneurysms. The size of the aneurysms varied from 2 to 60 mm with the neck varying from 2 to 60 mm. Perioperative morbidity and mortality were 8.7% and 2.2%, respectively. At the last available follow-up, 83.1% of the aneurysms were either completely or near-completely occluded. The rate of complications was higher for fusiform aneurysms (p<0.001).

CONCLUSIONS

The SFD appears to be an important tool for the treatment of complex intracranial aneurysms. Treatment outcomes and complication rates remain a problem, but should be considered in the context of available alternative interventions. Ongoing analysis of flow-diverting stents for radiographic and clinical performance is required.

Interfamilial phenotypic variations in Sorsby fundus dystrophy (SFD) have given rise to controversy as to whether SFD constitutes more than 1 nosologic entity. The recent identification of the tissue inhibitor of metalloproteinases-3 (TIMP3) as the gene causing SFD has made it possible to readdress the question of genetic and clinical heterogeneity. In this study, we have extended previous findings on a Ser181Cys founder mutation in SFD families from the British Isles and show that carriers of this mutation residing in Canada, the United States, and South Africa likewise are descendants of the British ancestor. In addition, we have reevaluated the question of variable SFD phenotypes by analyzing the available clinical data on carriers of the Ser181Cys mutation.

OBJECTIVE

Impoverished urban children suffer disproportionately from asthma and underuse preventive asthma medications. The objective of this study was to examine cost-effectiveness (CE) of the School-Based Asthma Therapy (SBAT) program compared with usual care (UC).

METHODS

The analysis was based on the SBAT trial, including 525 children aged 3 to 10 years attending urban preschool or elementary school who were randomized to either UC or administration of 1 dose of preventive asthma medication at school by the school nurse each school day. The primary outcome was the mean number of symptom-free days (SFDs). The impact of the intervention on medical costs was estimated by using parent-reported child health services utilization data and average national reimbursement rates. We estimated the cost of running the program using wages for program staff. Productivity costs were estimated by using value of parent lost time due to child illness. CE of the SBAT program compared with UC was evaluated based on the incremental CE ratio.

RESULTS

The health benefit of the intervention was equal to ∼158 SFD gained per each 30-day period (P < .05) per 100 children. The programmatic expenses summed to an extra $4822 per 100 children per month. The net saving due to the intervention (reduction in medical costs and parental productivity, and improvement in school attendance) was $3240, resulting in the incremental cost-savings difference of $1583 and CE of $10 per 1 extra SFD gained.

CONCLUSIONS

The SBAT was effective and cost-effective in reducing symptoms in urban children with asthma compared with other existing programs.

Sorbsy fundus dystrophy (SFD) is an autosomal dominant disorder that is characterized by bilateral loss of central vision secondary to choroidal neovascularization and/or pigment epithelial atrophy in the macula, with onset of visual symptoms usually in the fourth or fifth decade. Drusenlike changes may occur, with impaired dark adaptation and abnormal electroretinographic results.

C-terminal domain tissue inhibitor of metalloproteinases-3 (TIMP-3) mutations cause the rare hereditary blindness Sorsby's fundus dystrophy (SFD), which involves loss of retinal pigment epithelial (RPE) cells. Since wild-type TIMP-3 causes apoptosis, we investigated whether SFD TIMP-3 might kill RPE and other cells. Plasmid-mediated overexpression of Ser-156, Gly-167, Tyr-168 and Ser-181 SFD mutant TIMP-3 decreased RPE viability to 22+/-8, 20+/-6, 32+/-5, 30+/-12% (SFD mutants all P<0.01 versus wild-type 50+/-8%) and similarly increased propidium iodide staining and in situ end labelling. Adenovirus-mediated overexpression of the Gly-167 mutant also caused RPE apoptosis dose-dependently. Apoptosis of RPE cells might therefore contribute to the pathology of SFD.

Obesity and type 2 diabetes constitute leading public health problems worldwide. Studies have shown that insulin resistance affiliated with these conditions is associated with skeletal muscle lipid accumulation, while the latter is associated with mitochondrial dysfunctions. However, the initiation and regulation of mitochondrial biogenesis rely heavily on approximately 1000 nuclear-encoded mitochondrial regulatory proteins. In this study, we targeted the ubiquinol-cytochrome c reductase core protein I gene, a nuclear-encoded component of mitochondrial complex III, for its association with subcutaneous fat depth (SFD) and skeletal muscle lipid accumulation (SMLA) using cattle as a model. Four promoter polymorphisms were identified and genotyped on approximately 250 Wagyu x Limousin F2 progeny. Statistical analysis revealed that two completely linked polymorphic sites, g.13487C>T and g.13709G>C (r2 = 1), were significantly associated with both SFD (p < 0.01) and SMLA (p < 0.0001). The difference between TTCC and CCGG haplotypes was 0.178 cm for SFD and 0.624 scores for SMLA. Interestingly, the former haplotype produced higher promoter activities than the latter by 43% to 49% in three cell lines (p < 0.05). In addition to Rett syndrome and breast/ovarian cancer observed in other studies, we report evidence for the first time, to our knowledge, that overexpression of ubiquinol-cytochrome c reductase core protein I might affect mitochondrial morphology and/or physiology and lead to development of obesity and related conditions.

The tissue inhibitors of metalloproteinases (TIMPs) play a crucial role in the physiological turnover of the extracellular matrix (ECM) by tightly regulating matrix metalloproteinase (MMP) activities. Disturbances in the TIMP/MMP system have been implicated in many disease processes where loss of ECM integrity is a principal feature. More recently, we have shown that mutations in TIMP3 cause the autosomal dominant disorder Sorsby's fundus dystrophy (SFD). This is a macular degeneration disorder with characteristic ECM irregularities in Bruch's membrane. To further facilitate mutational analysis and to provide a basis for functional studies, we now report the genomic organization of the human TIMP3 gene.

BACKGROUND

Recently, a wide variety of bandages have been formulated to attempt to improve the effectiveness of emergency intervention in situations of uncontrolled bleeding. The best of these dressings contain a mixture of human thrombin and fibrinogen. The presence of human components in these bandages, although effective, increases the cost of the dressing and raises questions of availability of raw materials and transmission of pathogens. The purpose of this study was to investigate the efficacy of dressings composed of salmon thrombin and fibrinogen in a swine aortotomy model.

METHODS

A 4.4-mm aortotomy was produced in the abdominal aorta of 19 anesthetized, splenectomized swine. The United States Army standard field gauze was applied to 8 animals, and the salmon thrombin-fibrin dressing (SFD) was applied to 11 animals. Survival, blood loss, and other parameters were measured over a 60-minute period.

RESULTS

All 11 animals that received the SFD survived the aortotomy injury, and bleeding stopped within 7.5 +/- 1.5 min. Seven of 8 animals in the control group were killed when bleeding continued and blood pressures decreased to the cutoff values as outlined in the animal protocol. Bleeding was significantly less in the SFD group compared with the gauze group (241 +/- 65.3 vs. 932.7 +/- 142.4 mL).

CONCLUSIONS

Fibrin dressing using salmon-derived thrombin and fibrinogen is effective in controlling severe, uncontrolled bleeding. This dressing may offer an alternative to dressings composed of human coagulation proteins.

Electromyographic (EMG) pattern classification has been widely investigated for neural control of external devices in order to assist with movements of patients with motor deficits. Classification performance deteriorates due to inevitable disturbances to the sensor interface, which significantly challenges the clinical value of this technique. This study aimed to design a sensor fault detection (SFD) module in the sensor interface to provide reliable EMG pattern classification. This module monitored the recorded signals from individual EMG electrodes and performed a self-recovery strategy to recover the classification performance when one or more sensors were disturbed. To evaluate this design, we applied synthetic disturbances to EMG signals collected from leg muscles of able-bodied subjects and a subject with a transfemoral amputation and compared the accuracies for classifying transitions between different locomotion modes with and without the SFD module. The results showed that the SFD module maintained classification performance when one signal was distorted and recovered about 20% of classification accuracy when four signals were distorted simultaneously. The method was simple to implement. Additionally, these outcomes were observed for all subjects, including the leg amputee, which implies the promise of the designed sensor interface for providing a reliable neural-machine interface for artificial legs.