Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH ...Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.
Accurate measurement of the position of features in an image is subject to a fundamental compromise: The features must be both small, to limit the effect of nonlinear distortions, and large, to limit ...the effect of noise and discretization. This constrains both the accuracy and the robustness of image measurements, which play an important role in geometric camera calibration as well as in all subsequent measurements based on that calibration. In this paper, we present a new geometric camera calibration technique that exploits the complete camera model during the localization of control markers, thereby abolishing the marker size compromise. Large markers allow a dense pattern to be used instead of a simple disc, resulting in a significant increase in accuracy and robustness. When highly planar markers are used, geometric camera calibration based on synthetic images leads to true errors of 0.002 pixels, even in the presence of artifacts such as noise, illumination gradients, compression, blurring, and limited dynamic range. The camera parameters are also accurately recovered, even for complex camera models.
The small GTP binding protein Rho is implicated in cytoskeletal responses to extracellular signals such as lysophosphatidic acid to form stress fibers and focal contacts. Here we have purified a ...Rho‐interacting protein with a molecular mass of approximately 164 kDa (p164) from bovine brain. This protein bound to GTPgammaS (a non‐hydrolyzable GTP analog).RhoA but not to GDP.RhoA or GTPgammaS.RhoA with a mutation in the effector domain (RhoAA37).p164 had a kinase activity which was specifically stimulated by GTPgammaS.RhoA. We obtained the cDNA encoding p164 on the basis of its partial amino acid sequences and named it Rho‐associated kinase (Rho‐kinase). Rho‐kinase has a catalytic domain in the N‐terminal portion, a coiled coil domain in the middle portion and a zinc finger‐like motif in the C‐terminal portion. The catalytic domain shares 72% sequence homology with that of myotonic dystrophy kinase and the coiled coil domain contains a Rho‐interacting interface. When COS7 cells were cotransfected with Rho‐kinase and activated RhoA, some Rho‐kinase was recruited to membranes. Thus it is likely that Rho‐kinase is a putative target serine/threonine kinase for Rho and serves as a mediator of the Rho‐dependent signaling pathway.
For the real-time recognition of unspecified gestures by an arbitrary person, a comprehensive framework is presented that addresses two important problems in gesture recognition systems: selective ...attention and processing frame rate. To address the first problem, we propose the Quadruple Visual Interest Point Strategy. No assumptions are made with regard to scale or rotation of visual features, which are computed from dynamically changing regions of interest in a given image sequence. In this paper, each of the visual features is referred to as a visual interest point, to which a probability density function is assigned, and the selection is carried out. To address the second problem, we developed a selective control method to equip the recognition system with self-load monitoring and controlling functionality. Through evaluation experiments, we show that our approach provides robust recognition with respect to such factors as type of clothing, type of gesture, extent of motion trajectories, and individual differences in motion characteristics. In order to indicate the real-time performance and utility aspects of our approach, a gesture video system is developed that demonstrates full video-rate interaction with displayed image objects.
Hepatic failure has been treated successfully with clinical extracorporeal perfusions of porcine livers. However, dog-to-pig and pig-to-baboon liver xenotransplant models have resulted in severe ...bleeding secondary to liver xenograft-induced thrombocytopenia. Kupffer cells (KC) are abundant phagocytic cells in the liver. KC express the CD11b/CD18 receptor, which has been implicated in chilled platelet binding and phagocytosis through interaction with platelet surface proteins and carbohydrates. We sought to identify the role of KC CD18 in liver xenograft-induced thrombocytopenia.
Primary pig KC were characterized by flow cytometry, immunoblots, and quantitative polymerase chain reaction. Pig KC were used in inhibition assays with fluorescently labeled human platelets. The CD18 receptor was targeted for siRNA knockdown.
Domestic and α1,3-galactosyltransferase double knockout porcine KC cultures were approximately 92% positive for CD18 as detected by quantitative polymerase chain reaction and flow cytometry. Use of CD18 blocking antibodies resulted in reduction of human platelet binding and phagocytosis. Additionally, asialofetuin, not fetuin, inhibited platelet phagocytosis suggesting the involvement of an oligosaccharide-binding site. Furthermore, reduced CD18 expression by siRNA resulted in decreased human platelet binding.
Our data suggest that primary pig KC bind and phagocytose human platelets with involvement of CD18. Further understanding and modification of CD18 expression in pigs may result in a liver xenograft with reduced thrombocytopenic effects, which could be used as a bridge to allogeneic liver transplantation.
The Lung Cancer Study Group has shown that lobectomy provides the best survival in patients with non-small cell lung cancer. However, as patients become older, lobectomy may not provide a survival ...advantage compared with sublobar resection.
We analyzed the National Cancer Database for octogenarians with pathologic stage I lung cancer from 2004 to 2016. We then evaluated the patients who underwent lobectomy or sublobar (segmentectomy or wedge) resection for the treatment of cancer. We analyzed the 5-year survival rates of the groups as well as a cubic spline plot to determine age cutoffs where lobectomy does not provide improved survival.
Among the octogenarians (227 134), there were 25 362 (26%) who had pathologic stage I lung cancer. There were 6370 (30%) patients who had sublobar resections (segmentectomy n = 1192 and wedge resection n = 5178), whereas 14 594 (70%) patients had a lobectomy. There was significantly improved survival at 5 years with lobectomy compared with sublobar resection (48.5% vs 41.1%; P < .001). The cubic spline plot provided evidence that there was no age at which sublobar resection provided survival better than or equal to lobectomy (P < .001).
In octogenarians with pathologic stage I lung cancer, lobectomy provided better 5-year survival compared with sublobar resection regardless of the age at surgical procedure. Hence, all patients with stage I cancer should be considered for a lobectomy if they are medically able to tolerate such a procedure.
GLYCOGEN SYNTHASE KINASE3 (GSK3) is a highly conserved serine/threonine kinase involved in a variety of developmental signaling processes. The Arabidopsis (Arabidopsis thaliana) genome encodes 10 ...GSK3-like kinases that are clustered into four groups. Forward genetic screens have so far uncovered eight mutants, all of which carry gain-of-function mutations in BRASSINOSTEROID-INSENSITIVE2 (BIN2), one of the three members in group II. Genetic and biochemical studies have implicated a negative regulatory role for BIN2 in brassinosteroid (BR) signaling. Here, we report the identification of eight ethyl methanesulfonate-mutagenized loss-of-function bin2 alleles and one T-DNA insertional mutation each for BIN2 and its two closest homologs, BIN2-Like1 and BIN2-Like2. Our genetic, biochemical, and physiological assays revealed that despite functional redundancy, BIN2 plays a dominant role among the three group II members in regulating BR signaling. Surprisingly, the bin2bil1bil2 triple T-DNA insertional mutant still responds to BR and accumulates a more phosphorylated form of a BIN2 substrate than the wild-type plant. Using the specific GSK3 inhibitor lithium chloride, we have provided strong circumstantial evidence for the involvement of other Arabidopsis GSK3-like kinases in BR signaling. Interestingly, lithium chloride treatment was able to suppress the gain-of-function bin2-1 mutation but had a much weaker effect on a strong BR receptor mutant, suggesting the presence of a BIN2-independent regulatory step downstream of BR receptor activation.
Statins possess pleiotropic effects in several tissues. Among them, their bone anabolic actions have been recently noted. We have proposed that Smad3, a TGF-beta-signaling molecule, is a promoter of ...bone formation. However, whether statins would affect TGF-beta-Smad3 pathway in osteoblasts is still unknown. The present study was performed to examine the effects of statin on Smad3 expression and cell apoptosis by employing mouse osteoblastic MC3T3-E1 and rat osteoblastic UMR-106 cells. Statins (pitavastatin, mevastatin, and simvastatin) as well as alendronate increased the levels of Smad3 in MC3T3-E1 cells. The effects of pitavastatin on Smad3 levels were observed from 3 hours and later. Pitavastatin induced the expression of TGF-beta, and cycloheximide, a protein synthesis inhibitor, antagonized the increased levels of pitavastatin on Smad3. On the other hand, pitavastatin antagonized dexamethasone- or etoposide-induced apoptosis in a dose-dependent manner, and Smad3 inactivation by dominant negative Smad3 or an inhibition of endogenous TGF-beta action by SB431542 antagonized anti-apoptotic effects of pitavastatin, indicating that pitavastatin suppressed osteoblast apoptosis partly through TGF-beta-Smad3 pathway. In conclusion, the present study has demonstrated for the first time that statin suppressed cell apoptosis partly through TGF-beta-Smad3 pathway in osteoblastic cells.
Background
We postulated that the use of robotics may improve outcomes in hiatal hernia repair.
Methods
We performed a retrospective analysis of a prospectively collected Society of Thoracic Surgery ...database at a single institution of patients who underwent elective hiatal hernia repair from 2012 to 2017 using either laparoscopy or the da Vinci Xi robot. We compared patient characteristics and outcomes and then performed univariate and multivariate logistic regression modeling to determine the factors associated with postoperative morbidity.
Results
There were 293 consecutive patients who underwent elective hiatal hernia repair using either a laparoscopic (
n
= 151) or a robotic (
n
= 142) technique. There were no significant differences in age, gender, BMI, smoking history, presence of comorbidity, or hiatal hernia type. Seventy percent of the cases were a repair of either type III or type IV hiatal hernia. There were significantly higher ASA III and IV (7.9% vs. 4.2%,
P
= 0.03), higher Toupet fundoplication (83.4% vs. 44.4%,
P
< 0.001), and lower redo-repair (7.3% vs. 20.4%,
P
= 0.001) in the laparoscopic group compared to the robotic group. The hospital length of stay was significantly shorter (1.3 ± 1.8 vs. 1.8 ± 1.5 days,
P
= 0.003) and there were significantly lower rates of complications (6.3 vs. 19.2%,
P
= 0.001) after robotic compared to laparoscopic hiatal hernia repair. There was no difference in readmission rate and mortality. Multiple logistic regression analysis showed that older age and laparoscopic technique were associated with higher complications after surgery.
Conclusion
The use of the Da Vinci Xi robot in our institution was associated with improved outcomes compared to laparoscopic hiatal hernia repair despite a higher incidence of re-operative cases in the robotic group. Thus, short-term outcomes of Da Vinci Xi robot-assisted hiatal hernia repair are not inferior to laparoscopic hiatal hernia repair. Further studies are needed to determine if Da Vinci Xi robot provides superior short-term and long-term outcome in treatment of symptomatic hiatal hernia.
Background
Manometry is the gold standard diagnostic test for achalasia. However, there are incidences where manometry cannot be obtained preoperatively, or the results of manometry is inconsistent ...with the patient's symptomatology. We aim to determine if intraoperative use of EndoFLIP can provide a diagnosis of achalasia and provide objective information during Heller myotomy and Dor fundoplication.
Methods
To determine the intraoperative diagnostic EndoFLIP values for patients with achalasia, we determined the optimal cut-off points of the distensibility index (DI) between patients with a diagnosis of achalasia and patients with a diagnosis of hiatal hernia. To evaluate the usefulness of EndoFLIP values during Heller myotomy and Dor fundoplication, we obtained a cohort of patients with EndoFLIP values obtained after Heller myotomy and after Dor fundoplication as well as Eckardt score before and after surgery.
Results
Our analysis of 169 patients (133 hiatal hernia and 36 achalasia) showed that patients with DI < 0.8 have a >99% probability of having achalasia, while DI > 2.3 have a >99% probability of having hiatal hernia. Patients with a DI 0.8–1.3 have a 95% probability of having achalasia, and patients with a DI of 1.4–2.2 have a 94% probability of having a hiatal hernia. There were 40 patients in the cohort to determine objective data during Heller myotomy and Dor fundoplication. The DI increased from a median of 0.7 to 3.2 after myotomy and decreased to 2.2 after Dor fundoplication (
p
< 0.001). The median Eckardt score went down from a median of 4.5 to 0 (
p
< 0.001).
Conclusions
Our study shows that intraoperative use of EndoFLIP can facilitate the diagnosis of achalasia and is used as an adjunct to diagnose achalasia when symptoms are inconsistent. The routine use of EndoFLIP during Heller myotomy and Dor fundoplication provides objective data during the operation in a group of patients with excellent short-term outcomes.
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