Intraoperative bowel irrigation improves anastomotic collagen metabolism in the left-sided colonic obstruction but not covering colostomy.
This study investigated the effects of intraoperative colonic irrigation and proximal diverting end colostomy after segmental bowel resection in experimental left-colonic obstruction on anastomotic healing. Simple obstruction of descending colon was performed in male Sprague-Dawley rats. After 24 h we performed segmental colonic resection and anastomosis in the control group (n = 15); resection, anastomosis, and covering colostomy in the colostomy group (n = 14); resection and anastomosis after antegrade colonic lavage through cecum by using isotonic saline solution in the irrigation group (n = 13). In rats that were killed 7 days later anastomotic dehiscence and bursting pressure and tissue hydroxyproline concentration at the anastomosis were measured. No significant differences were observed between groups in terms of anastomotic dehiscence, bursting site, or pressure. The hydroxyproline concentration was significantly higher in the irrigation group than the control group (P = 0.025) and the colostomy group (P = 0.029), but no difference was noted between the control group and the colostomy group. These findings suggest that intraoperative antegrade colonic irrigation in the acute left-sided colonic obstruction positively affects collagen metabolism at the anastomotic site; if the anastomosis is performed without bowel cleansing, covering colostomy does not improve collagen metabolism.


Estimating the grid of time-points for the piecewise exponential model.
One of the greatest challenges related to the use of piecewise exponential models (PEMs) is to find an adequate grid of time-points needed in its construction. In general, the number of intervals in such a grid and the position of their endpoints are ad-hoc choices. We extend previous works by introducing a full Bayesian approach for the piecewise exponential model in which the grid of time-points (and, consequently, the endpoints and the number of intervals) is random. We estimate the failure rates using the proposed procedure and compare the results with the non-parametric piecewise exponential estimates. Estimates for the survival function using the most probable partition are compared with the Kaplan-Meier estimators (KMEs). A sensitivity analysis for the proposed model is provided considering different prior specifications for the failure rates and for the grid. We also evaluate the effect of different percentage of censoring observations in the estimates. An application to a real data set is also provided. We notice that the posteriors are strongly influenced by prior specifications, mainly for the failure rates parameters. Thus, the priors must be fairly built, say, really disclosing the expert prior opinion.


MiR-630 Inhibits Endothelial-Mesenchymal Transition by Targeting Slug in Traumatic Heterotopic Ossification.
Heterotopic ossification (HO) is the abnormal formation of mature bone in extraskeletal soft tissues that occurs as a result of inflammation caused by traumatic injury or associated with genetic mutation. Despite extensive research to identify the source of osteogenic progenitors, the cellular origins of HO are controversial and the underlying mechanisms, which are important for the early detection of HO, remain unclear. Here, we used in vitro and in vivo models of BMP4 and TGF-β2-induced HO to identify the cellular origin and the mechanisms mediating the formation of ectopic bone in traumatic HO. Our results suggest an endothelial origin of ectopic bone in early phase of traumatic HO and indicate that the inhibition of endothelial-mesenchymal transition by miR-630 targeting Slug plays a role in the formation of ectopic bone in HO. A matched case-control study showed that miR-630 is specifically downregulated during the early stages of HO and can be used to distinguish HO from other processes leading to bone formation. Our findings suggest a potential mechanism of post-traumatic ectopic bone formation and identify miR-630 as a potential early indicator of HO.


Interplay between E-box and NF-kappaB in regulation of A20 gene by DRB sensitivity-inducing factor (DSIF).
The NF-kappaB target gene A20 serves as a paradigm for gene-specific control of transcription elongation. This gene is regulated by the elongation factor DSIF (DRB sensitivity-inducing factor) under basal and NF-kappaB-activated states by two distinct mechanisms. Prior to NF-kappaB stimulation, the A20 gene is occupied by polymerase II, and elongation is inhibited by DSIF. This inhibition is mediated by an upstream promoter element termed ELIE (elongation inhibitory element). Upon NF-kappaB activation, inhibition of the A20 gene by DSIF persists, but now NF-kappaB and the core promoter regulate DSIF instead of ELIE. Here we investigated the regulation of DSIF by ELIE and the regulatory switch from ELIE to NF-kappaB following NF-kappaB induction. Electrophoretic mobility shift assays revealed two distinct protein complexes that specifically interact with ELIE, one of which is the E-box protein USF1. Interestingly, USF1 is displaced from the A20 promoter upon induction of NF-kappaB. A mutation in the E-box section of ELIE diminished the binding of USF1 and DSIF recruitment. Consistent with these findings, the E-box is crucial for DSIF inhibition in resting, but not NF-kappaB-stimulated, cells. These findings reveal a dynamic regulation of DSIF involving either E-box or NF-kappaB depending on the physiological circumstances.


Spinocerebellar projections to lobules III to V of the anterior lobe in the cat, as studied by retrograde transport of horseradish peroxidase.
Spinocerebellar tract (SCT) neurons projecting to lobules III to V of the cerebellar anterior lobe were identified by the retrograde horseradish peroxidase technique. SCT neurons projecting to lobule III with crossed ascending axons were located mainly in the central cervical nucleus (CCN), the medial part of lamina VII of L6 to the caudal segments, and the dorsal horn (lamina V) and ventral horn (lamina VIII) of the sacral-caudal segments. Spinal border cells with crossed ascending axons also projected to lobule III. SCT neurons projecting to this lobule with uncrossed ascending axons were located in the medial part of lamina VI of the cervical segments and the middle part of lamina VII of C6 to T1, lamina V of the lower cervical, thoracic and the lumbar segments, Clarke's column including marginal neurons, and the medial part of lamina VI of L5 and L6. These neuronal groups also projected to lobule IV, except for those present caudal to L6 (in the medial part of lamina VII, and laminae V and VIII of the sacral-caudal segments). A far smaller number of similar neurons projected to lobule V. Injections of HRP restricted to the vermal region labeled mainly neurons in the CCN and Clarke's column while restricted injections to the intermediate-lateral regions labeled ipsilaterally spinal border cells, lamina V neurons, and Clarke column neurons, especially of the lumbar segments as well as marginal neurons of this column.


Cardiovascular risk is similar in patients with glomerulonephritis compared to other types of chronic kidney disease: a matched cohort study.
Patients with chronic kidney disease (CKD) due to glomerulonephritis (GN) are thought to be at high risk for cardiovascular disease (CVD). However, no study has examined whether GN directly contributes to CV risk beyond the effects conferred by pre-existing traditional risk factors and level of renal function. Matched cohort study using the previously described prospective CanPREDDICT study cohort. 2187 patients with CKD (eGFR 15-45 ml/min/m2) from 25 Canadian centres were divided into GN vs non-GN cause of CKD. Patients on immunotherapy for GN were not included in the study. Standardized measures of CV risk factors, biomarkers and CV outcomes were recorded over 3 years of follow-up, with the primary outcome measure being time to first all-cause CV event. In the overall cohort, CV events occurred in 25 (8.7%) of the GN group and 338 (17.8%) of the non-GN group (HR 0.45, 95% CI 0.30-0.67, p < 0.01). In a Cox regression multivariable model that included age, sex, prior diabetes and CVD, baseline eGFR and onset of renal replacement therapy, the risk of CV events was similar in the GN and non-GN groups (HR 0.71, 95% CI 0.47-1.08, p = 0.11). GN and non-GN patients were matched by age and using a propensity score including sex, prior diabetes and CVD and baseline eGFR. In the matched group, the risk of CV events was similar in GN vs non-GN patients (N = 25/271 (9.2%) in both groups, HR 1.01, 95% CI 0.05-1.77, p = 0.9). An interaction analysis showed that CRP, ACR and troponin conferred differing amounts of CV risk in the GN and non-GN groups. Patients with advanced CKD due to GN have a high 8.7% absolute 3-year risk of CVD, attributable to prior CV risk factors and level of kidney function rather than the GN disease itself.


Dynamic global sagittal alignment evaluated by three-dimensional gait analysis in patients with degenerative lumbar kyphoscoliosis.
Sagittal vertical axis (SVA) is the most commonly used parameter for evaluating global sagittal alignment (GSA) in a static condition. However, its dynamic statuses remain unclear. The aim of this study was to evaluate dynamic GSA of degenerative lumbar kyphoscoliosis (DLKS) using three-dimensional motion analysis system (3D-MAS). Twenty-six patients with DLKS underwent gait analysis using 3D-MAS. Static (S-) and dynamic (D-) trunk angle (TA) (the angle between the vertical axis and the line connecting C7 and S1 spinous processes) and S-sagittal trunk shift (STS) and D-STS (the distance between the two vertical lines running through C7 and S1 spinous process) were recorded during treadmill walking. Pelvic angle (PA) (the angle between the horizontal axis and the line connecting the posterior and anterior superior iliac spine) were also recorded. S-PA and D-PA represent retroversion or anteversion of the pelvis, which can be substituted for pelvic tilt. As to dynamic parameters, those at the initial five steps (Di) and the final five steps (Df) of treadmill walking were also recorded. The median S-TA, S-STS, and S-PA were 16.0°, 11.9 cm, and -5.5° (retroversion). The median D parameters were Di-TA/Df-TA 21.8°/26.9°; Di-STS/Df-STS 14.1/21.1 cm; and Di-PA/Df-PA 15.7°/22.8° (anteversion). All D parameters were significantly greater than S parameters (P < 0.01) and all Df parameters were also significantly worse than Di parameters (P < 0.001). Thus, compensated GSA by pelvic retroversion in static condition was lost due to anteversion change of the pelvis immediately after start of walking and worsened over time. Dynamic GSA assessment using 3D-MAS can avoid underestimation of GSA loss that is detected by static standing full-length radiography.


The pulmonary vascular effects of dopamine, dobutamine, and isoproterenol in unilobar pulmonary edema in dogs.
Although catecholamine inotropic drugs are often used to support the circulation of critically ill patients with hypoxemic respiratory failure, their effect on the pulmonary circulation and on gas exchange is incompletely understood. In order to improve our understanding of the effects of these drugs on the pulmonary circulation, we made measurements of total and regional intrapulmonary shunt (Qs/Qt), distribution of pulmonary blood flow, and pulmonary hemodynamics before and after infusions of dopamine (n = 6, 5 micrograms/kg/min), dobutamine (n = 6, 10 micrograms/kg/min), isoproterenol (n = 6, 0.1 micrograms/kg/min), or saline in dogs with unilobar oleic acid-induced pulmonary edema. In addition to permitting determination of the overall hemodynamic and gas exchange effects of these drugs, this preparation allowed measurement of changes in distribution of pulmonary blood flow between normal and edematous lung. In 6 dogs given dobutamine, mean cardiac output (CO) increased by 1 liter/min, while pulmonary arterial pressure (PPA) increased by 2 mm Hg with no change in pulmonary vascular resistance (PVR) or distribution of pulmonary blood flow. There was a 5% increase in mean Qs/Qt which, because of the lack of evidence of pulmonary vasoactivity, was attributed to time or to increased CO. Isoproterenol produced a similar increase in CO, but reduced PPA and PVR indicating pulmonary vasodilator activity. Pulmonary vasodilation was most prominent in edematous lung, resulting in an increase in relative blood flow to the edema lung lobe and a substantial increase in Qs/Qt, exceeding the increase in all other groups. Dopamine, similarly increasing CO, did not change overall PVR but reduced fractional blood flow to the edema lobe by 3.4% of CO. Neither Qs/Qt nor PaO2 changed significantly in this group. The differing effects of these agents on pulmonary hemodynamics, intrapulmonary blood flow distribution, and gas exchange have potentially significant implications affecting the choice of drug used for circulatory support in hypoxemic respiratory failure.


[Long-term follow-up of continent cystostomy with the Mitrofanoff procedure: 5 years later].
This study analyzed long-term functional outcome of continent catheterizable channels with the Mitrofanoff procedure, their continence, complications and the satisfaction of the patients. Data from patients who underwent a Mitrofanoff procedure at our institution from June 1997 to March 2015 were retrospectively collected. All patients were contacted at the end of the study, a survey was submitted to them. Sixty-seven patients underwent a continent cystostomy with the Mirtrofanoff procedure. Forty-five patients had the inclusion criteria: 18 years old or older, no previous urinary diversion with a minimum of 6 months of follow-up. The cohort comprised mainly neurologic bladder (84 %) with spinal cord injuries (54 %) or spina-bifida patients (15 %). Median age was 35 years old [22-49]. Median follow-up was 64months [39-90]. The surgical procedure used an appendicular channel: 30 patients (67 %) or a continent ileal plasty: 15 patients (33 %). At the end of follow-up: 88 % patients have a full cystostomy continence, 89 % full uretral continence. Twenty-nine patients had one (41 %) or more reinterventions. Reasons for the 58 reinterventions were: stomal stenosis (31 %), uretral incontinence (29 %), cystostomy incontinence (15 %), lithiasis (9 %). Those reinterventions were done with a local surgery (31 %) or an endoscopic surgery (35 %). Overall early adverse events (<30days) or delayed (>30days) adverse events were similar (P=0.93) in appendicovesicostomy group or continent ileal plasty group. Ninety-four percent patients described a satisfactory urinary comfort. The cystostomy was considered esthetic by 71 %, its realization allowed an improvement of the quality of life for 89 % of them. Continent channels in adults demonstrate favorable long-term outcomes even if reinterventions could be necessary to maintain a continent and catheterizable channel. Despite reinterventions, patients remain satisfied by the Mitrofanoff procedure which facilitate the process of clean intermittent catheterization. 4.


Clinical correlation between coagulation disorders and sepsis in patients with liver failure.
This study aimed to explore the clinical detection and prognosis of coagulation function in patients with liver failure and sepsis. The plasma fibrinogen (FIB), factor II, factor VII, factor V, factor IV, antithrombin III (ATIII), platelet (PLT), mean PLT volume (MPV), D-dimer, prothrombin activity (PTA), and fibrin degradation product (FDP) levels and thromboelastogram values were detected in patients with liver failure complicated with sepsis and compared with those in the liver failure and liver cirrhosis groups. The patients with liver failure complicated with sepsis were analyzed by univariate and multivariate logistic regression, and the regression equation was established. The levels of FIB, factor II, factor VII, factor V, ATIII, PLT, MPV, D-dimer, and FDP in the patients with liver failure complicated with sepsis were compared with those in the control group patients, and the differences were statistically significant (p < 0.05). Among the thromboelastography parameters in the patients with liver failure and sepsis, the differences in the K-value, R-value, angle, maximum amplitude, and coagulation index values compared with those of the control group were statistically significant (p < 0.05). The logistic regression model obtained was as follows: p = 1/(1 + e [-0.128×X1-0.058×X2 + 0.211×X3 + 0.2×X4 + 0.25]). The specificity, sensitivity, and accuracy values of the regression equation in determining the prognosis were 92%, 93.9%, and 92.8%, respectively. Among the 11 factors, factor VII, PLT, FDP, and D-dimer were included in the regression equation. Coagulation disorder is exacerbated in patients with liver failure and sepsis. Among the 11 coagulation-related factors, factor VII, PLT, FDP, and D-dimer may be the independent factors influencing the prognosis of patients with acute liver failure and sepsis.


Simultaneous determination of seven pesticides in waters using multi-walled carbon nanotube SPE and NACE.
In this work, NACE with UV detection is combined with SPE using multi-walled carbon nanotubes (MWCNT) as stationary phase to determine a group of seven pesticides (pirimicarb, pyrifenox, penconazol, carbendazim, cyromazine, pyrimethanil and cyprodinil) in mineral water samples using ametryn as internal standard. The optimized BGE, consisting of a mixture of MeOH and ACN (1:2 v/v) with 90 mM SDS and 20.5 mM HClO(4), was satisfactory to get a good resolution of the seven compounds in less than 13 min. On-line preconcentration was carried out by electrokinetic injection of the sample dissolved in 78:22 v/v MeOH/ACN, 1.11 mM HClO(4). Repeatability was studied for the same day (n=4), for nine different days (n=36) and for four different capillaries. RSD values were appropriate in all cases, i.e. in the range 4.3-9.4% between different capillaries. MWCNT of 10-15 nm od, 2-6 nm id and 0.1-10 mum length were used as SPE materials for the preconcentration of these pesticides from water samples. SPE parameters influencing the enrichment were optimized and the most favorable conditions were as follows: the amount of stationary phase, eluent, sample pH and sample volume were 40 mg MWCNT, 10 mL ACN and 10 mL dichloromethane containing 5% v/v formic acid, pH 8.0, and 750 mL, respectively. Mean recovery values ranged between 53 and 94% for Milli-Q water and between 47 and 93% for mineral waters (RSD values were in the range 2-16%). The method allowed the determination of these pesticides at concentrations below the maximum residue limits established by the European Union legislation (LOD in the range 27-58 ng/L). When the cost, amount and type of the carbon nanotubes used in this work are compared with those carbon nanotubes previously used in the literature it is clear that the proposed materials can be used as economical stationary phases, even cheaper than conventional SPE cartridges.


Renoprotective effect of curcumin against the combined oxidative stress of diabetes and nicotine in rats.
The progression of diabetic nephropathy (DN) is accelerated by smoking. The current study investigated the ability of curcumin to protect the kidneys against damage from oxidative stress induced by diabetes mellitus (DM) and nicotine (NC). A total of 24 male Wistar rats were divided into four groups of six rats each. DM was induced by a single intraperitoneal injection of streptozotocin 60 mg/kg body weight. DM rats were treated with or without NC in the absence or presence of curcumin for 8 weeks. As compared with the controls, DM rats exhibited reduced serum levels of high density lipoprotein, superoxide dismutase and glutathione peroxidase, and decreased renal mRNA expression levels of synaptopodin, connexin 43 and erythropoietin (EPO), which were further suppressed by NC and restored to normal levels by curcumin treatment. Additionally, DM rats exhibited increases in their lipid profiles (cholesterol, triacylglycerol and phospholipids), oxidative markers (malondialdehyde, γ‑glutamyltranspeptidase and nitric oxide), kidney function markers (urea and creatinine) and the mRNA expression levels of vimentin, desmin, SREBP‑1, iNOS and TGF‑β1. These effects were further enhanced by NC, but counteracted by curcumin treatment. Kidneys from DM rats displayed glomerular hypertrophy, sclerosis and tubulo‑interstitial changes represented by tubular lipid deposition, interstitial mononuclear cell infiltration and fibroplasia. Pancreatic islets exhibited cellular vacuolation, morphological irregularity and damaged or reduced in size β‑cells. These renal and pancreatic changes became more severe following NC treatment and were ameliorated by curcumin. Therefore, NC‑induced DN progression may predominantly operate by increasing oxidative stress, reducing the levels of antioxidants, suppressing EPO levels, and causing perturbations to gap junction and podocyte structure. Curcumin may ameliorate the damaging effects of DM and NC on the kidney through normalization of the mRNA expression levels of several genes important in the progression of DN.


Clinical and immunological studies of 49 cases of various types of intercellular IgA dermatosis and 13 cases of classical subcorneal pustular dermatosis examined at Kurume University.
Intercellular IgA dermatosis (IAD) is a subset of autoimmune bullous disease exclusively with IgA antikeratinocyte cell-surface antibodies. The classification and pathogenesis of this condition are still obscure. To classify IAD and study its pathogenesis. From our cohort of 5402 cases of autoimmune bullous disease, we selected 49 cases of various types of intercellular IgA dermatosis (IAD) and 13 cases of classical subcorneal pustular dermatosis (SPD), for which sera and information were available. We studied these cases clinically and immunologically. There were 17 SPD-type IAD, 12 intraepidermal neutrophilic IgA dermatosis (IEN)-type IAD, two IgA-pemphigus vegetans, four IgA-pemphigus foliaceus, six IgA-pemphigus vulgaris and eight unclassified IAD cases. There was no sex predominance, and the average age at disease onset was 45·9 years. Clinically, bullous and pustular skin lesions developed on various sites, particularly intertriginous areas. Histopathology showed intraepidermal blisters or pustules at the upper epidermis in the SPD-type and at the midepidermis in the IEN-type. Immunological studies revealed that direct immunofluorescence, indirect immunofluorescence of normal human skin and enzyme-linked immunosorbent assays (ELISAs) of recombinant proteins of desmogleins and desmocollins frequently showed positive results, although no antigens were detected in many cases. All cases of classical SPD, which showed no positive immunological results, were indistinguishable clinically and histopathologically from SPD-type IAD. The present study of the largest cohort of cases of IAD showed that the major subtypes are SPD and IEN, and that the combination of indirect immunofluorescence and ELISAs of desmogleins and desmocollins, in addition to direct immunofluorescence, was useful for the diagnosis of IAD and its subtypes.


Changes in communication of end-of-life decisions in European ICUs from 1999 to 2016 (Ethicus-2) - a prospective observational study.
We investigated changes in communication practice about end-of-life decisions in European ICUs over 16 years. This prospectively planned secondary analysis of two observational studies in 22 European ICUs in 1999-2000 (Ethicus-1) and 2015-16 (Ethicus-2) included consecutive patients who died or with limitation of life-sustaining therapy. ICUs were grouped into North, Central and South European regions. A total 4592 patients were included in 1999-2000 (n = 2807) and 2015-16 (n = 1785). Information about patient wishes increased overall (from 25.4% [570] to 51.1% [840]) and in all regions (42% to 61% [North], 22% to 56% [Central] and 20% to 32% [South], all p < 0.001). Discussions of treatment limitations with patients or families increased overall (66.0% to 76.1%) and in Northern and Central Europe (87% to 94% and 75% to 82.2%, respectively, all p < 0.001) but not in the South. Strongest predictor for discussions was the region (North>Central>South) followed by patient decision-making capacity. End-of-life decisions are increasingly discussed but communication practices vary by region and follow a North-South gradient. Despite increased availability of information, patient preferences still remain unknown in every second patient. This calls for increased efforts to assess patient preference in advance and make them known to ICU clinicians.


Perceived stressors and coping strategies among heart transplant candidates.
This study examined heart transplant candidates' perceived stressors and coping strategies at the time of placement on the waiting list and at 3, 6, 9, and 12 months following. Mean stress scores were relatively low at each assessment time. The 4 greatest stressors were (1) having a terminal disease, (2) needing a heart transplant, (3) worrying family members, and (4) undergoing prolonged hospitalization. Total stress scores indicated that candidates were effectively using a moderate number of coping strategies, the 5 most frequently used ones being thinking positively, trying to keep life normal, keeping a sense of humor, praying or trusting in God, and trying to distract oneself. The 5 most effective coping mechanisms were thinking positively, keeping a sense of humor, thinking of good things, praying or trusting in God, and trying to keep life normal. No significant differences were seen in coping use or effectiveness over time.


Determination of main components in the extracellular polymeric substances extracted from activated sludge using a spectral probing method.
In this study, a spectral probing method was applied to determine the content of the main components, i.e., proteins, polysaccharides and humic substances, in the extracellular polymeric substances (EPS) extracted from activated sludge. The measurement results were consistent with those obtained from the conventional methods, such as the anthrone for polysaccharide determination, the modified Lowry method for protein and humic substance determination. The recoveries for the determination of proteins, humic substances and polysaccharides in the EPS extracted from six sludge samples using standard additional method were between 92.4 and 108.9%, 84.8 and 108.9%, 75.1 and 117.2%, respectively. These results indicate that the propose method has a good accuracy and precision, and can be used as an effective approach to determine the main components in sludge EPS.


Intracorporeal versus extracorporeal anastomosis in laparoscopic right colectomy: updated meta-analysis of randomized controlled trials.
Selection of intracorporeal anastomosis (IA) or extracorporeal anastomosis (EA) in laparoscopic right colectomy (LRC) remains controversial. This meta-analysis aimed to evaluate the effectiveness and safety of IA compared with EA in LRC patients. Literature was searched systematically for randomized controlled trials (RCTs) that compared IA with EA in LRC patients until May 2021. The eligible studies for risk of bias were assessed using the Cochrane Risk of Bias Tool. Data were extracted and analysed for the following outcomes of interest: operative time, length of incision, nodal harvest, bowel function recovery, postoperative pain, postoperative complications (wound infection, anastomotic leak, ileus, obstruction, reoperation), death at 30 days, duration of hospital stay and 30-day readmission. Five RCTs, including a total of 559 patients, were eligible for meta-analysis. All of the trials reported adequate random sequence generation and allocation concealment. There were significantly better outcomes in the IA group than in the EA group in time to first flatus (mean difference (MD) -0.71 (95 per cent c.i. -1.12 to -0.31), P = 0.0005), time to first passage of stool (MD -0.53 (95 per cent c.i. -0.69 to -0.37), P < 0.00001), visual analogue scale of pain on postoperative day (POD) 3 (MD -0.76 (95 per cent c.i. -1.23 to -0.28), P = 0.002), POD 4 (MD -0.83 (95 per cent c.i. -1.46 to -0.20), P = 0.01), POD 5 (MD -0.60 (95 per cent c.i. -0.95 to -0.25), P = 0.0007), length of incision (MD -1.52 (95 per cent c.i. -2.30 to -0.74), P = 0.0001) and wound infection (relative risk 0.46 (95 per cent c.i. 0.23 to 0.91), P = 0.02). However, there were no statistically significant differences between the two groups in duration of hospital stay (P = 0.47), operative time (P = 0.07), number of lymph nodes harvested (P = 0.70), anastomotic leak (P = 0.88), postoperative ileus (P = 0.48), bleeding (P = 0.15), bowel obstruction (P = 0.24), reoperation (P = 0.34), readmission within 30 days (P = 0.26), and death (P = 0.70). Compared with EA, IA shows a faster recovery of bowel function with fewer wound infections.


Mutation of a cysteine in the first transmembrane segment of Na,K-ATPase alpha subunit confers ouabain resistance.
The cardiac glycoside ouabain inhibits Na,K-ATPase by binding to the alpha subunit. In a highly ouabain resistant clone from the MDCK cell line, we have found two alleles of the alpha subunit in which the cysteine, present in the wild-type first transmembrane segment, is replaced by a tyrosine (Y) or a phenylalanine (F). We have studied the kinetics of ouabain inhibition by measuring the current generated by the Na,K-pump in Xenopus oocytes injected with wild-type and mutated alpha 1 and wild-type beta 1 subunit cRNAs. When these mutations, alpha 1C113Y and alpha 1C113F [according to the published sequence [Verrey et al. (1989) Am. J. Physiol., 256, F1034] were introduced in the alpha 1 subunit of the Na,K-ATPase from Xenopus laevis, the inhibition constant (Ki) of ouabain increased greater than 1000-fold compared with wild-type. A more conservative mutation, serine alpha 1C113S did not change the Ki. We observed that the decreased affinity for ouabain was mainly due to a faster dissociation, but probably also to a slower association. Thus we propose that an amino acid residue of the first transmembrane segment located deep in the plasma membrane participates in the structure and the function of the ouabain binding site.


Mycotoxigenic fungi in peanuts from different geographic regions of Egypt.
To understand the importance of mycotoxigenic fungi in Egyptian peanuts, samples from five regions (Alexandria, El-Beheira, El-Sharqiya, El-Daqahelaya in northern Egypt and Asyut, southern Egypt) in two seasons (2007, 2008) were collected. Aspergillus was consistently the most frequent genus in seeds and in-shell peanuts and was the dominant mycotoxigenic component of the mycobiota. There was no direct correlation between the moisture content of the samples and the fungal populations on peanut seeds tested from different regions. The most common species were from Aspergillus section Flavi (4.7-78.3%), Aspergillus section Nigri (9.4-52.6%) and Aspergillus section Circumdati (5.1-30.9%). In the in-shell peanut samples, the lowest populations were recorded in El-Beheira and Asyut (3.7-4.0 log10 CFU g(-1)) and the highest in Alexandria and Elsharqiya (4.1-6.0 log10 CFU g(-1)). Aspergillus section Flavi and section Nigri were the most dominant, and Aspergillus section Circumdati were only found in samples in 2008. Both qualitative (coconut cream agar) and quantitative analyses (HPLC) were used to analyse the potential mycotoxin production by strains isolated from peanuts. Of a total of 88 Aspergillus section Flavi strains examined, 95% were A. flavus based on production of aflatoxin B1 on yeast extract sucrose (YES) medium and confirmation using molecular analyses. Of 64 Aspergillus section Circumdati strains only 28% produced ochratoxin A (OTA), and were identified as A. westerdijkiae. No Aspergillus section Nigri strains produced OTA, and they were identified as A. niger (uniseriate). The presence of these toxigenic fungi indicates that there is a potential risk of mycotoxin contamination in Egyptian peanuts and suggests that problems can arise from contamination with both aflatoxins and perhaps also OTA.


Detection of Ag⁺ ions and cysteine based on chelation actions between Ag⁺ ions and guanine bases.
A selective and sensitive fluorescence biosensor for Ag(+) ions and cysteine (Cys) was developed based on the chelation actions between Ag(+) ions and guanine bases of G-rich fluorogenic oligonucleotide (FAM-ssDNA) and the different electrostatic affinity between FAM-ssDNA and graphene oxide (GO). FAM-ssDNA adsorbed onto the surface of GO through π-π stacking interaction between the ring structure in the nucleobases and the hexagonal cells of GO, and the fluorescence of the dye was quenched. In the presence of Ag(+) ions, the random coil structure changed into a G-Ag(+) architecture. As a result, the binding released FAM-ssDNA signal probe from the surface of GO, which disrupted the energy transfer from FAM-ssDNA to GO, recovering the fluorescence emission of FAM-ssDNA. On the other hand, because Cys was a strong Ag(+) ions binder, it could deactivate the sensor fluorescence by rewrapping FAM-ssDNA around GO. In this way, these changes in fluorescence intensity allowed the selective detection of Ag(+) ions and Cys.


Analyzing bean extracts using time-dependent SDS trapping to quantify the kinetic stability of phaseolin proteins.
In common beans and lima bean, the storage protein phaseolin is difficult to degrade and SDS-resistant, a sign of kinetic stability. Kinetically stable proteins (KSPs) are characterized by having a high-energy barrier between the native and denatured states that results in very slow unfolding. Such proteins are resistant to proteolytic degradation and detergents, such as SDS. Here the method SDS-Trapping of Proteins (S-TraP) is applied directly on bean extracts to quantify the kinetic stability of phaseolin in lima bean and several common beans, including black bean, navy bean, and small red bean. The bean extracts were incubated in SDS at various temperatures (60-75 °C) for different time periods, followed by SDS-PAGE analysis at room temperature, and subsequent band quantification to determine the kinetics of phaseolin unfolding. Eyring plot analysis showed that the phaseolin from each bean has high kinetic stability, with an SDS-trapping (i.e. unfolding) half-life ranging from about 20-100 years at 24 °C and 2-7 years at 37 °C. The remarkably high kinetic stability of these phaseolin proteins is consistent with the low digestibility of common beans and lima bean, as well as their relatively high germination temperatures. From a practical perspective, this work exemplifies that S-TraP is a useful and cost-effective method for quantifying the kinetic stability of proteins in biological extracts or lysates. Depending on the protein to be studied and its abundance, S-TraP may be performed directly on the extract without need for protein purification.


[Factors associated with Th1 cytokine disorders in children with newly diagnosed type 1 diabetes].
To measure levels of cytokines including IL-1β, IL-12, IL-18 and TNF-α in children with newly diagnosed type 1 diabetes and to analyze their correlation with clinical indices such as infection and onset time. A total of 33 children with newly diagnosed type 1 diabetes were assigned to the case group, and 27 healthy children to the control group. The case group was further divided into increased white blood cell (WBC) and normal WBC subgroups according to peripheral WBC level. The serum levels of cytokines including IL-1β, IL-12, IL-18 and TNF-α were measured by enzyme-linked immunosorbent assay. Blood pH, blood sugar, blood lactate, fructosamine, peripheral leukocytes and neutrophils and some other clinical indices were also measured. The level of IL-12 in the case group was higher than in the control group (P<0.001). In the case group, the level of IL-18 was negatively correlated with onset time (r=0.413, P=0.015), the neutrophil count was positively correlated with IL-1β level (r=0.413, P=0.023) and the WBC count was positively correlated with IL-18 level (r=0.352, P=0.038). IL-1β, IL-12 and IL-18 levels in the increased WBC subgroup were higher than in the normal WBC subgroup (P<0.05 for all comparisons). Cytokine secretion disorders of Th1 cells exist in children with type 1 diabetes. Infections may induce cytokine secretion and might contribute to the early onset of diabetes.


Heatstroke induces liver injury via IL-1β and HMGB1-induced pyroptosis.
Liver injury is a common complication of heat stroke (HS), and often constitutes a direct cause for patient death. The cellular and molecular mechanism underlying HS-induced liver injury remains unclear. Recent evidence indicates that inflammasome plays an important role in mediating sterile inflammation triggered by tissue damage. Using a rat HS model, we identified a novel mechanism by which inflammasome-dependent interleukin-1β (IL-1β) activation and hepatocyte pyroptosis mediate HS-induced liver injury. To induce HS, rats were subjected to heat exposure. Inhibition of inflammasomes was achieved by RNA silencing and pharmacologic inhibitor prior to heat exposure. Inflammasome assembly, caspase-1 activation, histological changes, as well as serum levels of liver enzymes were measured. We demonstrated that the onset of HS activated inflammasome in the liver as evidenced by increased capase-1 activity and the association of inflammasome components NOD-like receptor family pyrin domain containing 3 (Nlrp3) and apoptosis speck-like protein containing a caspase-recruitment domain (ASC); and the activated inflammasome, in turn, induced IL-1β activation and hepatocyte pyroptosis, and subsequent augmented liver injury. HS-induced hepatocyte inflammasome activation seems to be high-mobility group box 1 (HMGB1) dependent. Inhibition of Nlrp3, caspase-1, or HMGB1 prevented HS-induced liver inflammation and ameliorated liver injury. These findings demonstrate an important role of HMGB1 in mediating inflammasome activation in the development of liver injury following HS, and suggest that targeting inflammasome may represent a novel therapeutic strategy to limit cell death and prevent liver failure after HS.


Satisfaction of life and late psycho-social outcome after severe brain injury: a nine-year follow-up study in Aquitaine.
In view of assessing their late outcome and satisfaction of life, 79 out of 158 severe traumatic brain injury (STBI) patients who received inpatient rehabilitation in Aquitaine in 1993 were followed by phone interview. Results showed that 9 years on average after their injury, 65 to 85% of these patients were independent for daily living, whereas 35 to 55% only were independent in social life. Most of the patients were satisfied with their autonomy (67%), family life (66%) and financial status (41%), but they were dissatisfied with leisures (36%), vocational adjustment (28%) and sexual life (32%). Satisfaction of life was mostly related to age, gender, physical autonomy, need of help because of cognitive impairment and functional outcome as assessed by the Glasgow Outcome Scale. Severe traumatic brain injury (STBI) stands in industrialised countries as a major Public Health problem and a dreadful human drama for the patients, their families and the community [2]. A great number of STBI patients survive with severe disability, most of them being young adults. The most severely impaired may live only with their parents or in high-cost nursing homes. From a psychological point of view, STBI causes a total and sudden breakdown of the mental states, personality and conditions of life. Life plans and projects are definitively disrupted, satisfaction of life is deeply changed. Rehabilitation aims at improving functional outcome of persons with STBI, and at improving their overall quality of life. Planning for rehabilitation and re-entry into community of STBI patients need to be provided with precise data on their late outcome and disability level. Despite that the concepts of quality and satisfaction of life are difficult to define and moreover to assess, these are also major factors to take into account. The aims of the present study were to assess the late psycho-social outcome of patients hospitalized in Aquitaine for rehabilitation of a STBI 7 to 10 years after their injury, and to ask for their satisfaction of life and subjective feeling of quality of life.


MicroRNA delivery based on nanoparticles of cardiovascular diseases.
Cardiovascular disease, especially myocardial infarction, is a serious threat to human health. Many drugs currently used cannot achieve the desired therapeutic effect due to the lack of selectivity. With the in-depth understanding of the role of microRNA (miRNA) in cardiovascular disease and the wide application of nanotechnology, loading drugs into nanoparticles with the help of nano-delivery system may have a better effect in the treatment of cardiomyopathy. In this review, we highlight the latest research on miRNAs in the treatment of cardiovascular disease in recent years and discuss the possibilities and challenges of using miRNA to treat cardiomyopathy. Secondly, we discuss the delivery of miRNA through different nano-carriers, especially inorganic, polymer and liposome nano-carriers. The preparation of miRNA nano-drugs by encapsulating miRNA in these nano-materials will provide a new treatment option. In addition, the research status of miRNA in the treatment of cardiomyopathy based on nano-carriers is summarized. The use of this delivery tool cannot only realize therapeutic potential, but also greatly improve drug targeting and reduce side effects.


Natural-clay-reinforced hydrogel adsorbent: Rapid adsorption of heavy-metal ions and dyes from textile wastewater.
In this study, two natural clay minerals were combined with hydrogels to study the influence of natural adsorbents on the adsorption performance of hydrogels. Here, we separately doped bentonite and vermiculite and discussed their mechanical properties and adsorption properties. It was found that the compressive performance of the hydrogel added with clay increased by 21.6% and the swelling performance decreased or increased to varying degrees. Regarding the adsorption performance of hydrogels, it can be seen from the adsorption Langmuir isotherm model that the adsorption capacity of clay-hydrogels is improved to varying degrees (6.6%-15.8%) compared with non-clay-hydrogels, and clay-hydrogels have different degrees of improvement (6.6%-15.8%). The hydrogel has a removal efficiency of more than 95% for low concentrations of heavy-metal ions and dyes. In addition, the clay-hydrogel has low cost and is easy to prepare, and can be recycled many times. Therefore, the material is of great significance for the treatment of pollutants. PRACTITIONER POINTS: The effect of natural clay on the adsorption performance of hydrogels was studied. Clay can enhance the compression and adsorption properties of hydrogels. The adsorption mechanism and adsorption capacity of clay hydrogels were evaluated.


Do hospitals and surgeons with higher coronary artery bypass graft surgery volumes still have lower risk-adjusted mortality rates?
Studies that are the basis of recommended volume thresholds for CABG surgery are outdated and not reflective of recent advances in the field. This study examines both hospital and surgeon volume-mortality relations for CABG surgery through the use of a population-based clinical data set. Data from New York's clinical CABG surgery registry from 1997 to 1999 (total number of procedures, 57 150) were used to examine the individual and combined impact of annual hospital volume and annual surgeon volume on in-hospital mortality rates after adjusting for differences in severity of illness. Significantly lower risk-adjusted mortality rates occurred above all annual hospital volume thresholds between 200 and 800 and above all surgeon volume thresholds between 50 and 200. The number needed to treat (NNT) at higher-volume providers to avoid a death was minimized for a hospital threshold volume of 100 (NNT=50) and a surgeon threshold volume of 50 (NNT=118). The risk-adjusted mortality rate (RAMR) for patients undergoing surgery performed by surgeons with volumes of > or =125 in hospitals with volumes of > or =600 was 1.89%. The RAMR was significantly higher (2.67%) for patients undergoing surgery performed by surgeons with volumes of <125 in hospitals with volumes of <600. Higher-volume surgeons and hospitals continue to have lower risk-adjusted mortality rates, and patients undergoing surgery performed by higher-volume surgeons in higher-volume hospitals have the lowest mortality rates.


Immunological studies in B6C3F1 mice following exposure to ethylene glycol monomethyl ether and its principal metabolite methoxyacetic acid.
Exposure to glycol ethers has been associated with adverse effects in laboratory animals including thymus atrophy and mild leukopenia. These effects may involve depletion of immunoresponsive cells. This study examined possible alterations in immune function and host resistance of B6C3F1 mice following exposure to ethylene glycol monomethyl ether (EGME) or its principal metabolite, methoxyacetic acid (MOAA). EGME and MOAA were administered by gavage to mice in 10 doses over a 2-week period at total dosages of 250, 500, and 1000 micrograms/g of body weight. Following exposure, immunopathology, humoral immunity, cell-mediated immunity, macrophage function, and host resistance to Listeria monocytogenes bacterial challenge were examined. A 48% reduction in thymus weight was observed at the intermediate and high doses of both chemicals. No significant alterations in immune function or host resistance to L. monocytogenes were observed in animals exposed to either EGME or MOAA.


Genome-wide association study reveals novel genetic loci contributing to cold tolerance at the germination stage in indica rice.
Low temperature at the germination stage is one of the major abiotic stresses limiting rice (Oryza sativa L.) production, especially in regions where rice seeds are sown directly. However, few relevant genetic loci and genes have been identified. In this study, we report the phenotypic analysis of low temperature germination (LTG) in 200 indica rice varieties and a genome-wide association study (GWAS) of LTG in this collection using 161,657 high-quality SNPs, which were identified via genotyping-by-sequencing (GBS) of all the rice varieties. A total of 159 genetic loci were detected, and they were evenly distributed on all 12 chromosomes. Among them, 51 loci were detected more than twice; in particular, 23 loci were detected repeatedly in both the wet and dry seasons, and 569 genes were predicted in the 200-kb genomic region harbouring these 23 loci. Furthermore, 14,742 differentially expressed genes (DEGs) were identified using RNA sequencing. By integrating GWAS and RNA sequencing, 179 candidate DEGs were obtained. Sequence variation in the region of loci 95 was analyzed using 20 varieties with extreme phenotype. The polymorphisms of three DEGs (Os07g0585500, Os07g0585700, Os07g0585900) were associated with their phenotypes. Haplotype analysis of the three genes demonstrated that almost all the varieties with the same haplotype as japonica Nipponbare on the three DEGs showed high LTG ability. These findings provide valuable information for understanding the genetic control of LTG and performing molecular breeding with marker-assisted selection in indica rice.


Constitutive 5-HT2C receptor knock-out facilitates fear extinction through altered activity of a dorsal raphe-bed nucleus of the stria terminalis pathway.
Serotonin 2C receptors (5-HT2CRs) are widely distributed throughout the brain and are strongly implicated in the pathophysiology of anxiety disorders such as post-traumatic stress disorder (PTSD). Although in recent years, a considerable amount of evidence supports 5-HT2CRs facilitating effect on anxiety behavior, the involvement in learned fear responses and fear extinction is rather unexplored. Here, we used a 5-HT2CR knock-out mouse line (2CKO) to gain new insights into the involvement of 5-HT2CRs in the neuronal fear circuitry. Using a cued fear conditioning paradigm, our results revealed that global loss of 5-HT2CRs exclusively accelerates fear extinction, without affecting fear acquisition and fear expression. To investigate the neuronal substrates underlying the extinction enhancing effect, we mapped the immediate-early gene product cFos, a marker for neuronal activity, in the dorsal raphe nucleus (DRN), amygdala and bed nucleus of the stria terminalis (BNST). Surprisingly, besides extinction-associated changes, our results revealed alterations in neuronal activity even under basal home cage conditions in specific subregions of the DRN and the BNST in 2CKO mice. Neuronal activity in the dorsal BNST was shifted in an extinction-supporting direction due to 5-HT2CR knock-out. Finally, the assessment of DRN-BNST connectivity using antero- and retrograde tracing techniques uncovered a discrete serotonergic pathway projecting from the most caudal subregion of the DRN (DRC) to the anterodorsal portion of the BNST (BNSTad). This serotonergic DRC-BNSTad pathway showed increased neuronal activity in 2CKO mice. Thus, our results provide new insights for the fear extinction network by revealing a specific serotonergic DRC-BNSTad pathway underlying a 5-HT2CR-sensitive mechanism with high significance in the treatment of PTSD.


Toll-like Receptor 2-Melatonin Feedback Loop Regulates the Activation of Spinal NLRP3 Inflammasome in Morphine-Tolerant Rats.
Morphine is amongst the most effective analgesics available for the management of severe pain. However, prolonged morphine treatment leads to analgesic tolerance which limits its clinical usage. Previous studies have demonstrated that melatonin ameliorates morphine tolerance by reducing neuroinflammation. However, little is known about the relationship between Toll like receptor 2 (TLR2) and neuroinflammation in morphine tolerance. The aim of this study was to explore the role of TLR2 in morphine tolerance and its connections with melatonin and Nod-like receptor protein 3 (NLRP3) inflammasome. Sprague-Dawley rats were treated with morphine for 7 days and tail-flick latency test was performed to identify the induction of analgesic tolerance. The roles of TLR2 in microglia activation and morphine tolerance were assessed pharmacologically, and the possible interactions between melatonin, TLR2 and NLRP3 inflammasome were investigated. Morphine tolerance was accompanied by increased TLR2 expression and NLRP3 inflammasome activation in spinal cord. whereas melatonin level was down-regulated. Chronic melatonin administration resulted in a reduced TLR2 expression and NLRP3 inflammasome activation. Moreover, the analgesic effect of morphine was partially restored. Inhibition of TLR2 suppressed the microglia and NLRP3 inflammasome activation, as well as restored the spinal melatonin level while attenuated the development of morphine tolerance. Furthermore, the inhibition of microglia activation ameliorated morphine tolerance via inhibiting TLR2-NLRP3 inflammasome signaling in spinal cord. In this study, we directly demonstrate a TLR2-melatonin negative feedback loop regulating microglia and NLRP3 inflammasome activation during the development of morphine tolerance.


The formulation of buffers and media for enzyme histochemistry.
Buffer solutions and incubating media for enzyme histochemistry are discussed in terms of pH, ionic strength and buffering capacity. A specially written program is presented. This program enables (i) buffers and media of known pH and ionic strength to be formulated; (ii) the ionic strength of a buffer solution of known molarity, and (iii) the thermodynamic acid dissociation constant of a buffer substance, to be calculated.


Gap junctions between non-pyramidal cell dendrites in the rat hippocampus (CA1 and CA3 regions).
In thin sections of the rat hippocampus, gap junctions were observed between dendrites of non-pyramidal cells in the stratum radiatum and the stratum oriens in CA1 and CA3 regions. Gap junctions were seen on dendritic shafts, sessile and/or pedunculated spine-like appendages, and on varicose parts of dendrites.


Physical and biological removal of Microcystin-LR and other water contaminants in a biofilter using Manganese Dioxide coated sand and Graphene sand composites.
Sand as a filter media is often challenged by the presence of organics in the form of natural organic matter, metal ions, and various micropollutants in the source water. It is mainly due to the presence of limited active adsorption sites and low surface area that governs an ineffective adsorption potential of the sand material. Herein, graphitized sand was synthesized to tackle the above limitations using two sugar solution sources: a) brewery effluent (as a low-cost solution) (GS1) and; b) sucrose solution (GS2). GS1 showed 68%, 60%, and 99% higher maximum adsorption constant (qmax) for divalent metal ions: iron, copper, and manganese, respectively as compared to raw sand (RS). Coating of MnO2 over the graphitized sand (GSMs: GS1M and GS2M) further helped in Microcystin-LR (MC-LR) removal (3%-9%) when inoculated with MC-LR-degraders, but was not as effective in removing metals, organic carbon and nitrogen when compared to just graphitized sand (GS1 or GS2). Inoculating GS and GSMs (for both sugar sources) not only helped in higher MC-LR removal (10%-15% more) but also enhanced the removal of other water contaminants including metals, organic nitrogen, and carbon. GS1 showed 20% and 50% more MC-LR removal than the sand material when tested at a low and high initial concentration of MC-LR (5 µg/L and 50 µg/L). The highest breakthrough period was obtained for GS1 filter using 1 mg/L Rhodamine-B dye, which was 12 times (48 min) more than the raw sand filter and almost 2.5 times (second best, 21 min) than GS1M. After three cycles of regeneration and reuse of GS1 filter, a decrease of just 14% in saturation adsorption capacity indicated its high reusability aspects.


A new surgical technique using steel suture for trans-scleral fixation of posterior chamber intraocular lenses.
A new emerging complication of trans-scleral fixation of posterior chamber (PC) intraocular lens (IOL) with polypropylene suture is high rates of spontaneous dislocation of the IOL due to disintegration or breakage of suture. We report a new surgical technique of trans-scleral fixation of posterior chamber intraocular lens (SF PCIOL) with steel suture to eliminate the complication of dislocation of IOL fixed with polypropylene suture in one adult and a child. We successfully achieved stable fixation and good centration of IOL after SF PCIOL with steel suture in these patient having inadequate posterior capsular support. Both eyes achieved best corrected visual acuity 20/40 at 18 months follow-up. Steel suture is a viable option for trans-scleral fixation of posterior chamber intraocular lens.


Early response of lung in breast cancer irradiation: radiologic density changes measured by CT and symptomatic radiation pneumonitis.
To quantify radiologic changes in the lung with CT after radiotherapy (RT) for breast cancer (BC) and to study their association with treatment techniques and symptomatic radiation pneumonitis (RP). CT scans of the lungs were performed before and 4 months after RT in 121 BC patients treated with four different RT techniques. The changes in mean density (MDCs) were analyzed at two lung levels (i.e., the central and apical CT slice). The central CT slice was also analyzed with respect to the MDCs in the anterior third and anterior half of the ipsilateral lung area. In mastectomized patients who received chest wall RT with an en-face electron beam, the maximal depths for a range of isodose curves were measured. The occurrence of mild/moderate symptomatic RP was assessed prospectively 1, 4, and 7 months after RT. Data on covariates with potential confounding effect on RT-induced lung toxicity were also collected prospectively. In the entire study population, an association between the MDCs in the anterior third of the central CT slice and treatment technique (p <0.001) and symptomatic RP (p <0.001) was found. Among patients with chest wall treatment consisting of an en-face electron beam, the MDCs of the anterior third of the central CT slice correlated with the 35% isodose curve (16-30 Gy) (p = 0.046) and age (p <0.001). No association between post-RT lung density changes and pre-RT chemotherapy, concurrent tamoxifen intake, or smoking habits was found. Among patients treated with locoregional RT, an association was found between the MDCs in the anterior third of the central CT slice and the incidence of RP. MDCs in the apical CT slice, however, were not associated with RP. The results imply that short-term post-RT lung density changes and symptomatic RP were associated with RT techniques, total doses as low as 16-30 Gy, and increasing age. Structural changes in the central part of lung appeared to be more important for the development of RP than changes in the apex.


Left pulmonary artery sling in the adult: case report and review of the literature.
The aberrant left pulmonary artery is a serious anomaly in neonates; in the adult it is most often an incidental finding. One case is reported, incidentally discovered in the diagnostic workup of a patient with a vertebral lytic lesion. This vascular anomaly, mimicking a mediastinal adenopathy on the chest roentgenogram, which also showed a peripheral lung malignancy, was better assessed by an esophagogram (indentation on the posterior tracheal wall as well as on the anterior esophageal wall) along with fluoroscopy which showed the lesion to be pulsating. Its thorough anatomic evaluation was allowed by computed tomography (CT), performed for the staging of the lung tumor. The latter proves the choice modality due to its capability to provide precise information on all the different structures existing in a given cross-section.


[The experiences of atresia surgery under the direction of HRCT].
To probing the efficacy and safety of the utility of HRCT in the auditory rehabilitation surgery for the treatment of congenital aural atresia. HRCT were performed before the operation in 21 (22 ears) congenital aural atresia cases, one stage reconstruction surgery of auricle , external auditory meatus and middle ear were performed under the direction of HRCT. The 21 cases were followed up for 8 months to 4 years after operation and hearing improvement was 28 dB, no canal restenosis complications were occurred. The shape of auricle were satisfy. It is efficacious and safe to perform auditory rehabilitation surgery under the direction of HRCT.


Psychosocial predictors of hepatitis B vaccination among young African-American gay men in the deep south.
Despite recommendations for vaccination against hepatitis B virus (HBV) of men who have sex with men (MSM), most remain unvaccinated. The goal of this study was to identify attitudes and beliefs associated with vaccination against HBV among black MSM. The Birmingham Vaccine Acceptance Questionnaire was used to collect data from gay bar patrons. Of the 143 participants, nearly 42% reported at least one dose of HBV vaccine. In multivariable analysis, characteristics associated with vaccination were a decreased perception of barriers to HBV vaccination (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.22-0.61; P = 0.001); increased perceived medical severity (OR, 5.34; 95% CI, 2.38-11.96; P = 0.001) and personal severity (OR, 2.22; 95% CI, 1.38-3.56; P = 0.006) of HBV infection; and increased perceived general medical self-efficacy (OR, 9.22; 95% CI, 3.52-24.11; P = 0.0001) and personal self-efficacy (OR, 2.3; 95% CI, 1.14-4.63; P = 0.008) to complete the three-dose series. Our findings underscore the need to increase vaccination through innovative approaches to reduce perceived barriers to vaccination while increasing perceived severity of HBV infection and self-efficacy to complete the vaccine series.


Phase II trial of the histone deacetylase inhibitor vorinostat (Zolinza, suberoylanilide hydroxamic acid, SAHA) in patients with recurrent and/or metastatic head and neck cancer.
This phase II trial was initiated to assess the efficacy and safety of oral vorinostat (Zolinza, suberoylanilide hydroxamic acid, SAHA) in patients with recurrent and/or metastatic head and neck cancer. Eligible patients must have recurrent and/or metastatic head and neck cancer unresponsive to or intolerant of conventional chemotherapy. Patients must have measurable disease, adequate hematologic, hepatic, and renal function, and be able to swallow capsules. Four or more weeks must have elapsed since prior chemotherapy, radiation therapy, major surgery or investigational anticancer therapy, and patients must have recovered from prior toxicities. Study endpoints included response rate, duration of stable disease and progression-free survival. Thirteen patients were enrolled (9 males); 1 withdrew consent prior to starting therapy. Twelve patients received oral vorinostat 400 mg once daily and were evaluable for response. The median age was 54 years (range 40-82). All patients had received prior chemotherapy (including 10 with platinum- or taxane-based combination therapy), and 9 had prior radiation therapy. No confirmed partial or complete responses were observed. One unconfirmed partial response was seen. Three patients had stable disease ranging from 9 to 26 weeks. Nine patients discontinued due to progressive disease, two withdrew consent, and one discontinued therapy for grade 3 anorexia. Grades 3-4 drug-related toxicities included thrombocytopenia (n=3), anorexia (n=2), and dehydration (n=2). Oral vorinostat 400 mg qd was generally well tolerated but did not demonstrate efficacy as defined by tumor response in this small group of heavily pre-treated patients.


Equipment failures in laparoscopic surgery: Causes and consequences.
The aim of this study was to assess incidence, causes and consequences of equipment failures in a high volume, advanced endoscopic surgery department. This is a prospectical observational single centre study between April and July of 2019 in the Gynecological surgery department of the Estaing University Hospital of Clermont-Ferrand, France. During the study period, 171 laparoscopies were observed. Data were collected real time by three supernumerary observers. In total, 66 (38.6%) laparoscopies were complicated by equipment failures. The bipolar cable and forceps accounted for 31% of the total amount of malfunctions in laparoscopy. Causes of malfunctions were in 45% due to the instrument per se and in 43% due to the incorrect combination of elements. Less commonly, the equipment was not available or a mismatched was reported. The total length of the surgery increased by 1.35% due to the malfunctions. Human error was identified in 50% of cases. No morbility, neither mortality was reported in this series; however we observed 34 malfunctions that could have led to serious consequences for the patients and 3 incidents induced a real consequence on the operation workflow. Equipment failure is a common event in endoscopy. On the opposite, time wasted for the malfunctions is low in laparoscopy, as it only accounts for 1.35% of the overall surgical time. Human decisions contributed to malfunctions in almost half of cases. This alarming finding may advise for intensification in training on instruments of the whole surgical team.


Renal length discrepancy by ultrasound is a reliable predictor of an abnormal DMSA scan in children.
A renal length discrepancy (RLD) of more than 10 mm by ultrasound (US) is accepted as a potential indicator of an underlying renal pathology; however, there are few supporting data for this in children. Our objective was to determine a cutoff at which RLD on US is a reliable predictor of dimercaptosuccinate acid (DMSA) scan abnormality. We present data from 90 patients who had both renal US and a DMSA scan, as well as DMSA scan results compared with bipolar RLD by US. Positive (PPV) and negative (NPV) predictive values were calculated for renal RLD from 6 to >10 mm. The left kidney was longer in 56%, whereas the right kidney was longer in 37%; their lengths were equal in 8%. For children at all ages, a left kidney longer than the right by >or=10 mm or a right kidney longer than the left by >or=7 mm gave a PPV for DMSA abnormality of 79% and 100%, respectively. In children older than 4 years, if the right kidney was longer by >or=7 mm or if the left kidney was longer by >or=10 mm, the PPVs for DMSA abnormality were 100% and 63%, respectively. In children younger than 4 years, when the right kidney was longer by >or=6 mm or the left was kidney longer by >or=10 mm, the PPV were 86% and 100%, respectively. Thus, children with a right kidney longer than the left by even <10 mm is a reliable predictor of an abnormal DMSA scan.


Metagenomic analysis of Fe(II)-oxidizing bacteria for Fe(III) mineral formation and carbon assimilation under microoxic conditions in paddy soil.
Microbially mediated Fe(II) oxidation is prevalent and thought to be central to many biogeochemical processes in paddy soils. However, we have limited insights into the Fe(II) oxidation process in paddy fields, considered the world's largest engineered wetland, where microoxic conditions are ubiquitous. In this study, microaerophilic Fe(II) oxidizing bacteria (FeOB) from paddy soil were enriched in gradient tubes with FeS, FeCO3, and Fe3(PO4)2 as iron sources to investigate their capacity for Fe(II) oxidation and carbon assimilation. Results showed that the highest rate of Fe(II) oxidation (k = 0.836 mM d-1) was obtained in the FeCO3 tubes, and cells grown in the Fe3(PO4)2 tubes yielded maximum assimilation amounts of 13C-NaHCO3 of 1.74% on Day 15. Amorphous Fe(III) oxides were found in all the cell bands with iron substrates as a result of microbial Fe(II) oxidation. Metagenomics analysis of the enriched microbes targeted genes encoding iron oxidase Cyc2, oxygen-reducing terminal oxidase, and ribulose-bisphosphate carboxylase, with results indicated that the potential Fe(II) oxidizers include nitrate-reducing FeOB (Dechloromonas and Thiobacillus), Curvibacter, and Magnetospirillum. By combining cultivation-dependent and metagenomic approaches, our results found a number of FeOB from paddy soil under microoxic conditions, which provide insight into the complex biogeochemical interactions of iron and carbon within paddy fields. The contribution of the FeOB to the element cycling in rice-growing regions deserves further investigation.


Interchromosomal duplication for the short arm of chromosome no. 9: report of three cases due to a familial translocation t(9; 11) and one case with a de novo 47, XX, +9p karyotype.
Four cases of the 9p duplication syndrome are described. Three affected sibs resulted from a maternal t(9;11) translocation and have a duplication of the segment 9p13 leads to 9pter. They have the typical facies, hands and other features of the syndrome but are relatively mildly retarded. The fourth case has a de novo duplication of the short arm of chromosome 9. Her features are also typical although she is more retarded, particularly in expressive speech, than the other three individuals and had club feet. These observations further confirm the distinctive clinical features of this type of duplication, and support previous suggestions that the severity is roughly correlated with the length of the duplicated segment.


Tools to combat food fraud - A gap analysis.
A complex legal and institutional framework exists in the EU to ensure the safety of the feed-food chain, while such an integrated system for combating food fraud is under development. The European Commission (EC) Knowledge Centre for Food Fraud and Quality is charged with the provision of scientific insight for the policy making of EC services dealing with food fraud, and the creation of expert networks with the competent authorities of the EU Member States. To flag gaps in the existing infrastructure needed for effectively and efficiently fighting food fraud, the Centre together with the competent authorities and several EC services undertook a stocktaking exercise of what works well and which areas will need improvement. Out of several focus areas, (i) the development of early warning systems, (ii) the availability of compositional databases of vulnerable foods, and (iii) the creation of centres of competence were prioritised for further action.


Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: an under-recognized entity-a report of two cases.
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare pulmonary disorder that is classified as a pre-invasive lesion. It can also be present in association with chronic lung diseases. We present two cases of DIPNECH, which were picked up incidentally only on histopathology. A 29-year-old male presented with a history of longstanding cough with expectoration. A computed tomography (CT) scan showed bronchiectasis in the left lung. Histopathological evaluation of the pneumonectomy specimen revealed nests of proliferating, non-infiltrating neuroendocrine cells. Our second patient was a 38-year-old female with chronic cough and expectoration with recent exacerbation. CT scan showed cystic bronchiectasis in the left lower lobe; hence, a lobectomy was performed. On histopathology, nests of non-infiltrating neuroendocrine cells were noted. A diagnosis of DIPNECH with bronchiectasis was offered to both patients, and they have been on follow-up ever since. DIPNECH is a diagnostic and therapeutic quandary requiring a high index of suspicion for its detection and effective surveillance.


The early results of treatment of stricture of the male urethra using the Sachse optical urethrotome.
Thirty-nine male patients with urethral stricture have undergone urethrotomy using the Sachse optical urethrotome. Post-operatively a urethral catheter was used for 24 to 72 h. The technique is simple, the stay in hospital is short and complications are uncommon. Eighty-two per cent of the patients are now symptom-free and further 13% are sufficiently improved to be able to void satisfactorily at follow-up varying from 4 months to 2 1/2 years (mean 12 months). The 2 patients in whom unsatisfactory results were obtained had long strictures. We feel that direct vision urethrotomy should be considered as a treatment for urethral stricture.


"It is something that gives us hope": Lived experience among parents to children with cerebral palsy who are non-ambulant of the phenomenon physical activity, with or without the use of a novel dynamic standing device.
Regular physical activity confers health benefits for all. Parents commonly want their children to be physically active, and want to be physically active themselves, but children with cerebral palsy (CP) who are non-ambulant face challenges, and they need support to be physically active. Dynamic standing in the novel motorized assistive device Innowalk has positive effects in children who are non-ambulant-it gives them a chance to be physically active. The aim of this study was to explore the lived experience of physical activity of parents themselves and for their children with cerebral palsy who are non-ambulant. A descriptive inductive design with a hermeneutic phenomenological approach was used for the analysis of interviews with 11 parents of children with CP who are non-ambulant who participated in a study of exercise effects of dynamic standing. The parents experienced physical activity for their children as being important but difficult, especially for their child, as described in Theme 1: "Being aware of health benefits while struggling with family time." The children were perceived as being dependent on other people, the environment, and equipment for participating in physical activity, referring to Theme 2: "Being dependent." The opportunity for their children to become physically active on a regular basis through an assistive device gave the parents hope for a better life, which formed Theme 3: "Getting hope in a challenging life situation." Physical activity for children with CP who are non-ambulant is possible through an elaborate network of social relations and environmental conditions. Limiting the degree of dependence and containing the negative consequences of high a degree of dependence are vital in the support of physical activity. Relations, support, and assistive devices that strengthen empowerment and autonomy should be prioritized, and if this works, the experience of physical activity can be positive, giving families hope.


A New Expander for Schlemm Canal Surgery in Primary Open-angle Glaucoma-Interim Clinical Results.
To evaluate a new canal expander in circumferential viscocanalostomy (canaloplasty) for whites with primary open-angle glaucoma (POAG). Prospective, single-center, noncomparative study. Twenty-two eyes of 22 consecutive patients with medically uncontrolled POAG underwent primary viscocanalostomy and implantation of the Stegmann Canal Expander into Schlemm canal with a follow-up time of at least 1 year. Schlemm canal was unroofed ab externo, and dilated with viscoelastic material and microcatheter. The Stegmann Canal Expander is a flexible, fenestrated hollow implant of 9 mm in length. One expander was implanted into either side of the surgically created of ostium to keep the Schlemm canal permanently open. The superficial scleral flap was closed watertight. Laser goniopuncture of the trabeculo-Descemet membrane window was performed if postoperative intraocular pressure (IOP) exceeded 16 mm Hg. Complete successes were defined as a confirmed IOP≤21, ≤18, and ≤16 mm Hg without medications, respectively, combined with a 30% IOP reduction. Number of antiglaucomatous medications, best-corrected visual acuity, and intraoperative and postoperative complications were recorded. The mean IOP dropped from 27.1±5.3 mm Hg preoperatively to 13.6±1.6 mm Hg at 6 months, 13.0±1.5 mm Hg at 9 months, and 13.1±2.2 mm Hg at 12 months (P<0.001). The complete success rates for an IOP≤21, ≤18, and ≤16 mm Hg combined with a 30% IOP reduction were 91% [95% confidence interval (CI), 0.80-1.0], 91% (95% CI, 0.80-1.0), and 91.0% (95% CI, 0.80-1.0) at 6 months, and 86% (95% CI, 0.73-1.0), 82% (95% CI, 0.67-1.0), and 82.0% (95% CI, 0.67-1.0) at 12 months. The success rate of an IOP≤16 mm Hg without medications did not depend on age [hazard ratios (HR) 1.02; 95% CI, 0.85-1.12; P=0.74], preoperative IOP (HR 0.97; 95% CI, 0.83-1.23; P=0.89), and mean visual defect (HR 1.05; 95% CI, 0.72-1.27; P=0.76). Laser goniopuncture was performed on 2 eyes (9%) 4.1 months postoperatively; the mean IOP was 19.5 mm Hg before and 13.6 mm Hg after goniopuncture. The number of medications dropped from 2.9±0.6 before surgery to 0.05±0.2 after surgery (P<0.001). The postoperative best-corrected visual acuity at last visit (0.12±0.09; range, 0 to 0.39) was comparable to preoperative values (mean±SD, 0.16±0.10; range, 0 to 0.39) (P=0.35). Minor intraoperative or postoperative complications included microhyphema (8 eyes) and transient elevated IOP (steroid responder; 2 eyes). Implantation of the Stegmann Canal Expander in canaloplasty lowered IOP significantly in POAG without complications related to the device in this 1-year observation period.


The role of TREM1 in regulating microglial polarization in sevoflurane-induced perioperative neurocognitive disorders.
Microglia-mediated neuroinflammatory responses play a key role in perioperative neurocognitive disorders (PND). Triggering receptor expressed on myeloid cells-1 (TREM1) has been shown to be a key regulator of inflammation. However, its role in PND remains largely unknown. This study aimed to evaluate the role of TREM1 in sevoflurane-induced PND. We applied AAV knockdown TREM1 in hippocampal microglia in aging mice. The mice were then subjected to neurobehavioral and biochemical testing after the intervention of sevoflurane. We found that sevoflurane inhalation can cause PND in mice, increase hippocampal TREM1 expression, polarize microglia to M1 type, upregulate TNF-α and IL-1β expression (pro-inflammatory), and inhibit TGF-β and IL-10 expression (anti-inflammatory). Knocking down TREM1 can improve sevoflurane-induced cognitive dysfunction, reduce M1 type marker iNOS, and increase M2 type marker ARG, improving the neuroinflammation. TREM1 is a target for sevoflurane-induced PND prevention.


The role of histamine in burn, tourniquet and endotoxin shock in mice.
The release of histamine and mortality was studied in mice after various types of experimental shock. In burn shock, serum histamine rose significantly after injury, but there was no correlation between increased serum histamine and high mortality as a consequence of several therapy regimens. For example, after treatment with histamine or Compound 48/80 before burning, there was a rise of serum histamine, yet shock mortality fell significantly. Although separate administration of antagonists of H1 - or H2 - histamine receptors had no effect on mortality, pretreatment with both diphenhydramine and burimamide significantly increased shock mortality. In tourniquet shock, serum histamine rose significantly, and treatment with both antagonists before trauma produced a significant elevation of shock mortality. In endotoxin shock, prior treatment with one or both drugs did not change mortality. These results suggest that endogenous histamine is not a lethal factor in burn and tourniquet trauma, but rather it appears to have a compensatory, beneficial effect.


Effects of mentally induced fatigue on balance control: a systematic review.
The relationship between cognitive demands and postural control is controversial. Mental fatigue paradigms investigate the attentional requirements of postural control by assessing balance after a prolonged cognitive task. However, a majority of mental fatigue research has focused on cognition and sports performance, leaving balance relatively underexamined. The purpose of this paper was to systematically review the existing literature on mental fatigue and balance control. We conducted a comprehensive search on PubMed and Web of Science databases for studies comparing balance performance pre- to post-mental fatigue or between a mental fatigue and control group. The literature search resulted in ten relevant studies including both volitional (n = 7) and reactive (n = 3) balance measures. Mental fatigue was induced by various cognitive tasks which were completed for 20-90 min prior to balance assessment. Mental fatigue affected both volitional and reactive balance, resulting in increased postural sway, decreased accuracy on volitional tasks, delayed responses to perturbations, and less effective balance recovery responses. These effects could have been mediated by the depletion of attentional resources or impaired sensorimotor perception which delayed appropriate balance-correcting responses. However, the current literature is limited by the number of studies and heterogeneous mental fatigue induction methods. Future studies are needed to confirm these postulations and examine the effects of mental fatigue on different populations and postural tasks. This line of research could be clinically relevant to improve safety in occupational settings where individuals complete extremely long durations of cognitive tasks and for the development of effective fall-assessment and fall-prevention paradigms.


The use of anti-factor Xa monitoring in a selection of patients receiving enoxaparin at a large academic medical center.
Therapeutic enoxaparin is commonly used over heparin because of its favorable pharmacokinetic profile and ease of administration. Monitoring of the anticoagulant response, if necessary, is done with anti-factor Xa levels. Currently, it is suggested that monitoring may be beneficial in patients who are overweight and those with renal dysfunction. This study aimed to characterize the use of enoxaparin at a large-academic medical center in patients >150 kg, <45 kg and in those with renal dysfunction, and to describe the rate of anti-factor Xa monitoring in these patients. There were 273 patients included in the study: n = 96 for <45 kg arm, n = 111 for >150 kg arm and n = 66 for renal dysfunction arm. Less than 30 % of patients in each arm had low molecular weight heparin anti-factor Xa levels drawn. Of these only half were drawn as peak levels (4 h post dose). Overall rates of anti-factor Xa monitoring was low. It was found that obese patients achieved therapeutic anticoagulation with lower than recommended doses; underweight patients were often subtherapeutic on the recommended doses; and patients with renal dysfunction tended to have therapeutic to subtherapeutic anti-factor Xa levels. Ultimately, this evaluation showed that enoxaparin has unpredictable pharmacokinetics in these three high-risk patient populations and anti-factor Xa monitoring may be necessary to ensure therapeutic levels and appropriate dosing.


FOLD-RATE: prediction of protein folding rates from amino acid sequence.
We have developed a web server, FOLD-RATE, for predicting the folding rates of proteins from their amino acid sequences. The relationship between amino acid properties and protein folding rates has been systematically analyzed and a statistical method based on linear regression technique has been proposed for predicting the folding rate of proteins. We found that the classification of proteins into different structural classes shows an excellent correlation between amino acid properties and folding rates of two and three-state proteins. Consequently, different regression equations have been developed for proteins belonging to all-alpha, all-beta and mixed class. We observed an excellent agreement between predicted and experimentally observed folding rates of proteins; the correlation coefficients are, 0.99, 0.97 and 0.90, respectively, for all-alpha, all-beta and mixed class proteins. The prediction server is freely available at http://psfs.cbrc.jp/fold-rate/.


Adsorptive desulfurization and denitrogenation using metal-organic frameworks.
With the increasing worldwide demand for energy, utilization of fossil fuels is increasing proportionally. Additionally, new and unconventional energy sources are also being utilized at an increasing rate day-by-day. These sources, along with some industrial processes, result in the exposal of several sulfur- and nitrogen-containing compounds (SCCs and NCCs, respectively) to the environment, and the exposure is one of the greatest environmental threats in the recent years. Although, several methods were established for the removal of these pollutants during the last few decades, recent advancements in adsorptive desulfurization and denitrogenation (ADS and ADN, respectively) with metal-organic frameworks (MOFs) make this the most promising and remarkable method. Therefore, many research groups are currently involved with ADS and ADN with MOFs, and the results are improving gradually by modifying the MOF adsorbents according to several specific adsorption mechanisms. In this review, ADS and ADN studies are thoroughly discussed for both liquid-phase and gas-phase adsorption. The MOF modification procedures, which are important for improved adsorption, are also described. To improve the knowledge among the scientific community, it is very important to understand the detailed chemistry and mechanism involved in a chemical process, which also creates the possibility and pathway for further developments in research and applications. Therefore, the mechanisms related to the adsorption procedures are also discussed in detail. From this review, it can be expected that the scientific community will obtain an understanding of the current state of ADS and ADN, their importance, and some encouragement and insight to take the research knowledge base to a higher level.


Cisplatin induced reversible bilateral vocal cord paralysis: an undescribed complication of cisplatin.
Bilateral vocal cord paralysis is uncommon. Most cases occur secondary to trauma, malignancy, surgery, or intubation. Also, it was reported as a side effect of Vinca alkaloids. We report a patient with small cell lung cancer who developed bilateral vocal cord paralysis and needed to be intubated after treatment with cisplatin and etoposide. All workups excluded metastases as a cause of bilateral vocal cord paralysis. The patient required tracheostomy; she did not receive any further chemotherapy. After 11 weeks, vocal cord paralysis disappeared, tracheostomy was reversed, and the patient remained symptom free; however, 6 months later, the patient developed brain and liver metastases and died from her disease with no evidence of vocal cord paralysis. We report a case of reversible bilateral vocal cord paralysis that we believe to be secondary to cisplatin toxicity, which is an undescribed complication of this drug. Cisplatin can induce reversible bilateral vocal cord paralysis. The concurrent use of cisplatin and etoposide might have contributed to this complication in our patient.


Evaluation of Patient-Reported Outcomes (PROs) Protocol Content and Reporting for Clinical Trials that Lead to the approval of frontline Immune Checkpoint Blockade Combination for Patients with Advanced Renal Cell Carcinoma - The Patients' Voice or a Missed Opportunity.
Immune checkpoint blockade (ICB) is a rapidly emerging field of oncology that has revolutionized the metastatic renal cell carcinoma (mRCC) treatment. Four recent treatment regimens Nivolumab-Ipilimumab, Pembrolizumab-Axitinib, Nivolumab-Cabozantinib, and Pembrolizumab-Lenvatinib-have demonstrated improved clinical endpoints compared to standard of care and are endorsed by NCCN (2021). However, data on patient-reported outcomes (PROs) for patients receiving these regimens are limited. We conducted a comparative assessment of the quality and standardization of PROs endpoints and data reported for these randomized controlled trials (RCTs). We systematically identified all RCTs evaluating combination ICB for ccRCC. PROs-specific data were abstracted from the final version of 4 RCT protocols, as well as clinical and PROs specific manuscripts published between April 2018 and April 2021. We used 3 previously published guides standardizing PROs research to objectively score the data: (i) 24-point PROEAS; (ii) 12-point SPIRIT-PRO; and (iii) 14-point CONSORT-PRO. The CheckMate 214, KEYNOTE 426, CheckMate 9ER, and CLEAR studies had PROEAS scores of 88% (21/24), 37% (9/24), 83% (20/24), and 16% (4/24), respectively, and SPIRIT-PRO scores of 50% (6/12), 75% (9/12), 66% (8/12), and 41% (5/12) respectively. The CONSORT-PRO scores were 86% (12/14) for CheckMate 214 and 43% (6/14) for CheckMate 9ER, but scores were not available for the CLEAR and KEYNOTE 426 studies because of a lack of sufficient data. The average SPIRIT-PRO score across the 4 RCTs was 58%, indicating a reasonable adoption of PROs research in data management and analysis. The CheckMate 214 trial had the longest follow-up and most comprehensive published PROs data. Our analysis identified the limitations of current PROs data in combination ICB approved for mRCC. This analysis will enable clinicians to better interpret the current PROs results and emphasize the importance of better incorporation of PROs endpoints in future mRCC trial design.


Comparative in vitro activities of new fluorinated quinolones and other antibiotics against coagulase-negative Staphylococcus blood isolates from neutropenic patients, and relationship between susceptibility and slime production.
We evaluated the in vitro antibiotic susceptibilities of 31 coagulase-negative Staphylococcus isolates causing septicemia in neutropenic patients undergoing norfloxacin prophylaxis. All the strains but one were resistant to 1 microgram of norfloxacin per ml. At the same concentration, ciprofloxacin, ofloxacin, imipenem, and pefloxacin were inhibitory for 19 (61%), 19 (61%), 18 (58%), and 14 (45%) of the evaluated strains, respectively. Imipenem had an MBC/MIC ratio of greater than or equal to 32 against 19 (61%) of the evaluated isolates, and resistant subpopulations were detected at 5 micrograms/ml in 16 of 17 oxacillin-resistant strains and in 3 of 14 oxacillin-susceptible or -tolerant strains. Resistance to gentamicin was seen with increased frequency among slime-producing strains.


Isolation, partial characterization and biological activity of mannosyl glycopeptides from seminal plasma.
Affinity chromatography on Concanavalin-A Sepharose, followed by gel filtration and hydrophobic interaction chromatography, permits the isolation of low molecular weight N-glycosidically linked oligomannosidic glycopeptides (MGp) from the autoproteolysis products of human seminal plasma. The monosaccharide composition of MGp showed only mannose, N-acetylglucosamine and a small amount of galactose. Structural studies were carried out by methylation analysis and chromium trioxide oxidation, and results were consistent with the structures accepted for high-mannose N-glycans. MGp was capable of inhibiting the sperm acrosomal exocytosis mediated by sperm-surface receptors. These data suggest that MGp act as a "decapacitation" factor preventing premature sperm exocytosis.


Removal of an atypical region from a staphylococcal cyclophilin affects its structure, function, stability, and shape.
SaCyp, a cyclophilin having 197 amino acid residues, acts both as a protein-folding catalyst and a virulence factor in Staphylococcus aureus. Interestingly, a region, homologous to the SaCyp region carrying 121-148 amino acid residues, is present in many putative cyclophilins but absent in well-studied cyclophilins. To determine the exact roles of this unusual region in SaCyp and related proteins, we have investigated a deletion mutant (rCypΔ) of a recombinant SaCyp (rCyp) using various probes. The data reveal that rCypΔ has significantly less catalytic activity and possesses altered structure and hydrophobic surface compared to rCyp. Conversely, the deletion substantially increased inhibitor binding affinity and altered the shape of rCyp. However, both proteins were unfolded by a non-two-state mechanism in the presence of urea. Additionally, the stability of rCyp was significantly reduced due to the deletion of the residues 121-148. Our MD simulation study also indicated the considerable alteration in structure, shape, and fluctuations of SaCyp due to the removal of the region carrying 121-148 residues. Hence, the atypical region located in SaCyp might be vital for maintaining its unique structure, function, stability, and shape.


Bipolar loop device versus bipolar diathermy for tonsillectomy: A pilot randomized controlled trial.
Tonsillectomy is one of the most common surgeries performed in the pediatric population. Although different forms of instruments and various methods are used to perform tonsillectomy, none of them is still recognized as the best global technique. This study aimed to compare the outcomes of the new Bipolar Loop tonsillectomy versus bipolar diathermy technique. This study is a pilot randomized clinical trial and was conducted on 40 pediatric patients who were the candidate of tonsillectomy. Patients were divided into two groups of Bipolar Loop or bipolar diathermy. Operation time, intraoperative bleeding, tonsillar fossa wound, postoperative complications, and duration of return to normal diet were evaluated in the current study. In both of the Bipolar Loop and bipolar diathermy groups, no significant difference was found in terms of sex, age, and weight. The average amount of the operative time, intra-operative blood loss, and postoperative pain loss were significantly less in the Bipolar Loop group (P < .001). In addition, the tonsillar fossa wound healing scores were significantly better (on the 14th day, P = 0.009). However, there was no significant difference between the two groups in terms of postoperative bleeding, duration of return to a normal diet, and postoperative symptoms of fever, otalgia, or voice change between the groups. The study showed that blood loss and postoperative pain through day 7 were significantly less in the Bipolar Loop group. Tonsillectomy with Bipolar Loop can be recommended as one of the methods for tonsillectomy, especially in pediatric patients.


[Orthognathic surgery: corrective bone operations].
The article reviews the history of orthognathic surgery from the middle of the last century up to the present. Initially, mandibular osteotomies were only performed in cases of severe malformations. But during the last century a precise and standardized procedure for correction of the mandible was established. Multiple modifications allowed control of small fragments, functionally stable osteosynthesis, and finally a precise positioning of the condyle. In 1955 Obwegeser and Trauner introduced the sagittal split osteotomy by an intraoral approach. It was the final breakthrough for orthognathic surgery as a standard treatment for corrections of the mandible. Surgery of the maxilla dates back to the nineteenth century. B. von Langenbeck from Berlin is said to have performed the first Le Fort I osteotomy in 1859. After minor changes, Wassmund corrected a posttraumatic malocclusion by a Le Fort I osteotomy in 1927. But it was Axhausen who risked the total mobilization of the maxilla in 1934. By additional modifications and further refinements, Obwegeser paved the way for this approach to become a standard procedure in maxillofacial surgery. Tessier mobilized the whole midface by a Le Fort III osteotomy and showed new perspectives in the correction of severe malformations of the facial bones, creating the basis of modern craniofacial surgery. While the last 150 years were distinguished by the creation and standardization of surgical methods, the present focus lies on precise treatment planning and the consideration of functional aspects of the whole stomatognathic system. To date, 3D visualization by CT scans, stereolithographic models, and computer-aided treatment planning and simulation allow surgery of complex cases and accurate predictions of soft tissue changes.


Response of the ECG to short-term diuresis in patients with heart failure.
Increase in the amplitude of electrocardiogram (ECG) QRS complexes has been observed in patients treated for heart failure (HF), but the underlying mechanism has not been delineated. Also, correlation of augmentation of the QRS potentials with loss of weight has been noted in patients recovering from anasarca of varying etiology, or after hemodialysis. We assessed the effect of diuresis-based fluid loss in patients treated for HF on the amplitude of ECG QRS complexes. This is a cohort study based on ECG and other data from a previously published investigation of patients with HF conducted at a university affiliated hospital, which used new measurements and analysis, performed by a totally blinded investigator based at another institution. Twenty-one patients (10 men) aged 70.5+/-12.7 years, 13 with ischemic, and 8 with nonischemic cardiomyopathy, were admitted to the hospital for management of exacerbated HF and were observed for 48 hours. The patients received diuresis, and had routine laboratory testing, documentation of the net fluid lost, and recording of ECGs prior to the initiation of therapy and at 24 and 48 hours. Percent change (%Delta) over the course of observation in the sums of the amplitude of QRS complexes from 12 leads (SigmaQRS12), 6-limb leads (SigmaQRS6), and leads 1+2 (SigmaQRS2) in mm of standard ECGs were correlated with net fluid loss corrected for admission weight in mL/kg. Fluid loss amounted to 3204.9+/-1399.5 mL in the course of 40+/-23 hours of diuresis. SigmaQRS12 was 160.9+/-42.3 mm before and 170.0+/-50.7 mm after diuresis (P=0. 024). Percent change in SigmaQRS12, SigmaQRS6, and SigmaQRS2 correlated well with the net fluid loss (r=-0.70, -0.82, -0.61, and P=0.002, 0.0005, 0.001) correspondingly. Changes in sums of the amplitude of QRS complexes of the standard ECG correlates well with net fluid loss in response to short-term diuresis in patients with HF. Change in the SigmaQRS12, SigmaQRS6, and SigmaQRS2 from ECGs before and after diuresis can be used as an easily obtainable and universally available bedside index of the net fluid loss experienced by bedridden patients with HF undergoing therapy.


The product of the mammalian orthologue of the Saccharomyces cerevisiae HBS1 gene is phylogenetically related to eukaryotic release factor 3 (eRF3) but does not carry eRF3-like activity.
We describe here the cloning and sequencing of human and mouse cDNAs encoding a putative GTP binding protein. Sequence comparison shows that these cDNAs (named eRFS) are likely to represent the orthologues of the yeast Saccharomyces cerevisiae HBS1 gene and that the C-terminal domains of the encoded proteins share structural features with eukaryotic elongation factor eEF-1A and release factor 3 (eRF3) families. The phylogenetic analysis suggests that eRFS proteins and Hbs1p form a cluster of orthologous sequences branching with the eRF3 family. Nevertheless, in yeast, the human eRFS protein and Hbs1p do not complement eRF3/Sup35p thermosensitive mutation and do not interact with eRF1.


Semen copper in normal and infertile subjects.
Concentration of copper in seminal plasma was found to be less than that of normal in cases of oligospermia and azoospermia. It was more in oligoasthenospermia and asthenospermia when compared with that of normal. Chances of initiation of sperm motility by copper is discussed alongwith the inhibitory role it plays.


Quantitation of talinolol and other beta-blockers by capillary electrophoresis for in vitro drug absorption studies.
A capillary zone electrophoresis method is described for the enantioseparation of talinolol using heptakis(2,3-diacetyl-6-sulfo)-beta-cyclodextrin (HDAS-beta-CD) as a chiral selector. After liquid-liquid extraction of talinolol from physiological solution, electrokinetic injection was employed to improve the sensitivity. The use of a coated capillary was necessary to achieve stable and reproducible enantioseparations. A baseline separation of the talinolol enantiomers was achieved in less than 10 min using 100 mM phosphate solution as background electrolyte and pH 3.5, at the presence of 3.0 mM HDAS-beta-CD and at 20 degrees C. In addition, this analytical condition proved to be useful for the enantioseparation of a number of other beta-blocking agents such as alprenolol, atenolol, bisoprolol, celiprolol, metipranolol, oxprenolol, and sotalol. For determining talinolol, the method could be validated in terms of precision, accuracy and linearity, and was found to be suitable in determination of talinolol enantiomers in highly diluted samples obtained from in vitro experiments.