Comparison of the mid-term clinical efficacy of different fixtaion methods combined with oblique lumbar interbody fusion in treating lumbar degenerative diseases.
To compare the mid-term follow-up clinical efficacy among three treatment approaches for lumbar degenerative diseases (LDD): standalone oblique lumbar interbody fusion (SF), oblique lumbar interbody fusion combined with lateral screw fixation (LF), and oblique lumbar interbody fusion combined with posterior screw fixation (PF). This retrospective study included a total of 71 cases of single level LDD that underwent OLIF in Hospital of Chengdu University of Traditional Chinese Medicine were retrospectively collected between March 2016 and September 2017. Patients were divided into three groups: 24 cases in the SF group, 24 cases in the LF group and 23 cases in the PF group. Various parameters, such as operation time, hospitalization time, and complications, were recorded. The fusion condition was assessed at last follow up. Clinical outcomes were evaluated using the Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) from pre-operation to 5 years post-surgery. Significantly lower mean operation time and hospitalization time were observed in the SF and LF groups compared to the PF group (p < .05). However, no significant difference in fusion rate was found among the three groups. Regarding clinical outcomes, there was no statistically significant difference in VAS scores between the three groups during all follow-up periods. At the 6th month and 1st year after surgery, the SF and LF groups had significantly lower Oswestry Disability Index (ODI) scores compared to the PF group (p < .05). There was no significant difference in perioperative complication rates among the three groups (p > .05). In the LF group, one case of instrument displacement and urethra injury were reported, while in the SF, LF, and PF groups, 10, 9, and 3 cases of cage subsidence were reported, respectively. The study findings suggest that oblique lumbar interbody fusion (OLIF) is a safe and effective treatment for mid-term management of lumbar degenerative diseases (LDD). Compared to the posterior screw fixation (PF) group, both the standalone OLIF (SF) and OLIF combined with lateral screw fixation (LF) groups showed advantages in terms of reduced operation time, shorter hospitalization, and faster symptom alleviation in the short-term. However, OLIF combined with PF demonstrated comparable symptom relief in the mid-term and had the additional benefit of lower cage subsidence rates while improving fusion rates as well.


Anxiety in Geriatric Depression: Effects of Age and Cognitive Impairment.
The authors investigated the occurrence of anxiety symptomatology in a clinical sample of geriatric depressed patients and examined the effect of age and cognitive impairment on the experience of anxiety symptoms. Subjects were psychiatric patients consecutively admitted to a longitudinal study of geriatric depression. Severity of depression, antidepressant treatment, cognitive impairment, medical illness, social support, and physical environment were systematically assessed at entry and approximately every 6 months afterwards. Symptoms of anxiety and phobic anxiety were similar in older (n = 52) and younger (n = 15) subjects, although older subjects had significantly lower scores of subjectively experienced depression, interpersonal sensitivity, anger, hostility, and psychoticism. Older depressed patients with cognitive impairment corresponding to mild or moderate dementia had less anxiety than geriatric depressed patients without dementia. Findings of this study suggest the absence of an age effect on the expression of anxiety during depressive states. Although there is no age effect on anxiety, mild-to-moderate dementia appears to be associated with lower anxiety.


Correlation between serum cystatin C and lipid level in patients with chronic heart failure.
Serum cystatin C (Cys C) and blood lipid levels are related to the occurrence and development of chronic heart failure (CHF). However, there are few reports on the correlation between blood lipid level and serum Cys C level in patients with CHF. The aim of this study is to explore the correlation between serum Cys C level and blood lipid level in patients with CHF, and to provide valuable reference for clinical diagnosis and treatment of CHF. A total of 336 CHF patients who were hospitalized in the Department of Cardiovascular Medicine of Shaanxi Provincial People's Hospital from October 2017 to July 2018 were included and they were divided into a Cys C normal group (n=180) and a Cys C abnormal group (n=156) according to serum Cys C level of the patients. The general data, laboratory indicators, and cardiac ultrasound results were compared between the 2 groups. Pearson correlation analysis was used to detect the correlation between serum Cys C level and blood lipid level and other factors, and the data related to Cys C were further analyzed by multivariate logistic regression. Compared with the Cys C normal group, patients in the Cys C abnormal group had lower left ventricular ejection fraction (LVEF) (P<0.001), older age (P=0.030), higher incidence rate of diabetes and smoking index (P=0.002 and P=0.003, respectively). The levels of serum creatinine (SCr), blood urea nitrogen (BUN), and total bilirubin (TBIL) were higher (all P<0.001), while the levels of high density lipoprotein (HDL), apolipoprotein (Apo) A, and albumin (ALB) were lower (P<0.001, P=0.001, and P=0.003, respectively) in the Cys C abnormal group. Pearson correlation analysis showed that serum Cys C level was negatively correlated with platelet count, HDL, Apo A, ALB, and LVEF. It was positively correlated with smoking index, mean platelet volume, neutrophil ratio, BUN, and TBIL (all P<0.05). The results of multivariate logistic regression analysis showed that the decreased HDL level was a risk factor for the abnormality of serum Cys C in patients with CHF (OR=0.119, P=0.003), while Apo A was not a risk factor for its abnormality (P=0.337). HDL might be the only blood lipid index associated with abnormal serum Cys C in patients with CHF.


Improving Access to Specialist Palliative Care for Patients With Catastrophic Strokes Using Best Practice Advisory- a Feasibility Study.
The American Heart Association and American Stroke Association (AHA/ASA) strongly recommend specialty palliative care (PC) for all patients hospitalized with life-threatening or life-altering strokes to provide expert symptom management, improve communication, promote shared decision-making and relieve suffering. We piloted an intervention to remind physicians about high PC needs of their patients admitted with catastrophic stroke. We worked with colleagues from medical informatics to create a "Best Practice Advisory" (BPA) to recommend a goals-of-care conversation and PC consultation for patients with a National Institutes of Health Stroke Scale (NIHSS) score of 20 or more in our electronic medical record (Epic). We evaluated the impact of this BPA, after implementation, on the number and timing of PC consults and reviewed barriers to this system change. The BPA was operational in Jan 2019. Data analysis showed that it fired for all patients with an entered NIHSS score of ≥20. Though a large portion of the BPAs (more than 90%) were acknowledged without documented reason (after selecting "do not order"), PC consultations per 100 patients with triggered BPA increased from the first year of implementation (11.7 in 2019) to the next 2 years (20.7 in 2020, 15.6 in 2021). Also, the providers learned to manage BPA alerts better resulting in more than 30% reduction in the number of BPA alerts fired for each patient encounter in 2020-2021 compared to 2019.


Nonalcoholic fatty liver disease: the hepatic metabolic syndrome.
To examine a case of nonalcoholic fatty liver disease (NAFLD) and review the incidence, pathophysiology, appropriate diagnostic procedures and imaging, clinical considerations, and treatment options. Findings from the history, physical examination, and diagnostic testing of a 39-year-old man with elevated liver enzymes presenting to the hepatology clinic; a search of evidence-based literature in the PubMed and CINAHL database with the terms "fatty liver,""nonalcoholic fatty liver disease," and "nonalcoholic steatohepatitis." NAFLD is the deposition of fat in the liver that can progress to nonalcoholic steatohepatitis, resulting in fibrosis and cirrhosis. The exact pathophysiology is unknown, but risk factors can include those criteria associated with metabolic syndrome. NAFLD is a diagnosis of exclusion and can lead to serious health consequences if it is not identified and interventions are not implemented promptly. Treatment options remain limited but currently focus on weight loss, exercise, and diet. The clinician must include the spectrum of NAFLD in the differential diagnosis for any patient with elevated liver enzymes. The key actions for diagnosing NAFLD are identifying risk factors and ordering appropriate testing for confirmation. These considerations will lead to early diagnosis and implementation of treatment interventions.


Is resuscitative endovascular balloon occlusion of the aorta for computed tomography diagnosis feasible or not? A Japanese single-center, retrospective, observational study.
Advances in medical equipment have resulted in changes in the management of severe trauma. The role of resuscitative endovascular balloon occlusion of the aorta (REBOA) in this scenario is still unclear. This study aimed to evaluate the usage of REBOA and utility of computed tomography (CT) in the setting of aortic occlusion in our current trauma management. This Japanese single-tertiary center, retrospective, and observational study analyzed 77 patients who experienced severe trauma and persistent hypotension between October 2014 and March 2020. All patients required urgent hemostasis. Twenty patients underwent REBOA, 11 underwent open aortic cross-clamping, and 46 did not undergo aortic occlusion. Among patients who underwent aortic occlusion, 19 patients underwent prehemostasis CT, and 7 patients underwent operative exploration without prehemostasis CT for identifying active bleeding sites. The 24-hour and 28-day survival rates in patients who underwent CT were not inferior to those in patients who did not undergo CT (24-hour survival rate, 84.2% vs. 57.1%; 28-day survival rate, 47.4% vs. 28.6%). Moreover, the patients who underwent CT had less discordance between primary hemostasis site and main bleeding site compared with patients who did not undergo CT (5% vs. 71.4%, p = 0.001). In the patients who underwent prehemostasis CT, REBOA was the most common approach of aortic occlusion. Most of the bleeding control sites were located in the retroperitoneal space. There were many patients who underwent interventional radiology for hemostasis. In a limited number of patients whose cardiac arrests were imminent and in whom no active bleeding sites could be clearly identified without CT findings, REBOA for CT diagnosis may be effective; however, further investigations are needed. Therapeutic/care management study, level V.


Genetics of Nonalcoholic Fatty Liver Disease: A 2018 Update.
Nonalcoholic fatty liver disease (NAFLD), now the leading cause of liver damage worldwide, is epidemiologically associated with obesity, insulin resistance and type 2 diabetes, and is a potentially progressive condition to advanced liver fibrosis and hepatocellular carcinoma. However, there is huge interindividual variability in liver disease susceptibility. Inherited factors also play an important role in determining disease predisposition. During the last years, common variants in PNPLA3, TM6SF2, MBOAT7 and GCKR have been demonstrated to predispose to the full spectrum of NAFLD pathology by facilitating hepatic fat accumulation in the presence of environmental triggers. Other variants regulating inflammation and fibrogenesis then modulate liver disease progression in those at higher risk. Evidence is also accumulating that rare variants are involved in disease predisposition. In the future, evaluation of genetic risk factors may be exploited to stratify the risk of liver-related complications of the disease, and to guide hepatocellular carcinoma surveillance and choose pharmacological therapy.


SAP30 promotes breast tumor progression by bridging the transcriptional corepressor SIN3 complex and MLL1.
SAP30 is a core subunit of the transcriptional corepressor SIN3 complex, but little is known about its role in gene regulation and human cancer. Here, we show that SAP30 was a nonmutational oncoprotein upregulated in more than 50% of human breast tumors and correlated with unfavorable outcomes in patients with breast cancer. In various breast cancer mouse models, we found that SAP30 promoted tumor growth and metastasis through its interaction with SIN3A/3B. Surprisingly, the canonical gene silencing role was not essential for SAP30's tumor-promoting actions. SAP30 enhanced chromatin accessibility and RNA polymerase II occupancy at promoters in breast cancer cells, acting as a coactivator for genes involved in cell motility, angiogenesis, and lymphangiogenesis, thereby driving tumor progression. Notably, SAP30 formed a homodimer with 1 subunit binding to SIN3A and another subunit recruiting MLL1 through specific Phe186/200 residues within its transactivation domain. MLL1 was required for SAP30-mediated transcriptional coactivation and breast tumor progression. Collectively, our findings reveal that SAP30 represents a transcriptional dependency in breast cancer.


B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma.
In this report, we demonstrate that B7-H1, a B7 family molecule implicated in tumor immune evasion, is constitutively expressed on 66% of freshly isolated squamous cell carcinomas of the head and neck (SCCHN). To define the potential impact of tumor-associated B7-H1 on immunotherapy, the B7-H1-negative mouse SCC line, SCCVII, was transfected to express B7-H1. Although all of the animals succumbed to B7-H1/SCCVII tumors even after adoptive T-cell immunotherapy, the infusion of B7-H1 blocking monoclonal antibody with activated T cells cured 60% of animals. These data support B7-H1 blockade as a new approach to enhance the efficacy of T-cell immunotherapy.


Diltiazem reduces the dose requirement for nitroprusside-induced hypotension.
The efficacy of diltiazem, a calcium channel blocker, for reducing the dose requirement for nitroprusside-induced hypotension was studied in 20 healthy patients during spine fusion for scoliosis. Anesthesia included methohexital (3 mg/kg followed by 3 mg.kg-1.h-1 intravenously), nitrous oxide, and alfentanil (40 micrograms/kg, followed by 0.7 microgram.kg-1.min-1 intravenously). Patients were assigned randomly to two groups, receiving either nitroprusside alone or nitroprusside and diltiazem (bolus of 80 micrograms/kg with two consecutive infusions of 4.5 micrograms.kg-1.min-1 during the first 30 min and then 1.3 micrograms.kg-1.min-1). Nitroprusside was used to maintain mean arterial pressure at 55-60 mm Hg in both groups. Hypotension was obtained in similar times, 4 min in the group receiving nitroprusside alone (range, 1-8 min) and 2 min in the group receiving nitroprusside and diltiazem (range, 1-8 min). Nitroprusside administration lasted 186 +/- 17 min (mean +/- SEM) in the group receiving nitroprusside alone and 214 +/- 26 min (mean +/- SEM) in the other group (NS). After hypotension, arterial blood pressure returned to its initial value in a time of 7 min in the group receiving nitroprusside alone (range, 5-9 min) and 9 min in the group receiving nitroprusside and diltiazem (range, 7-13 min) (NS). Cumulative doses of nitroprusside were larger in the group receiving nitroprusside alone (0.47 +/- 0.07 mg/kg; mean +/- SEM) than in the other group (0.24 +/- 0.05 mg/kg; mean +/- SEM) (P < 0.01). Significant increase in plasma thiocyanate concentration, cardiac index, and heart rate was observed only in the group receiving nitroprusside alone, but no intergroup differences were found.(ABSTRACT TRUNCATED AT 250 WORDS)


A selective medium for recovery and enumeration of endolithic bacteria.
The study of lithic microbial communities, inhabiting rock substrates has been gathering momentum due to a growing attention of their wide importance as model systems in ecological studies and for their community structure. It is generally accepted that the success of cultivation-based technique is primarily based on suitable culture medium for isolation. The media available for enumeration and recovery of endolithic bacteria are mainly specific to particular type of rock which may not be suitable to isolate endolithic bacterial community from diverse lithobiontic niches. In this study, a new unoptimized medium was formulated, designated LM10 (unoptimized) for enumeration and recovery of endolithic bacteria by addition and/or omission of media components to the basal medium R2G, which was selected after experimental evaluation of five different existing media. The endolithic bacterial count in LM10 medium (unoptimized) was significantly higher than the R2G medium (t=-12.57, p<0.0001). The culture and nutritional parameters associated with unoptimized LM10 medium were optimized using statistical approach to maximize the recovery and enumeration of endolithic bacteria. The first phase of the study comprised of a Plackett-Burman (PB) design experiment conducted to screen thirteen medium components and two culture parameters as variables with effect on bacterial enumeration and recovery. Out of these, Yeast extract, Casein hydrolysate, Glucose, Starch and Sodium thiosulphate were found to be significantly affecting the bacterial count (p<0.05) based on PB design. On keeping rest of the media components and culture conditions at fixed value as per the PB design analyses (p>0.05 and coefficients), further optimization was carried out for significant factors using Box-Behnken design (BBD) of response surface methodology (RSM). Optimized media components obtained by BBD were Yeast extract, Casein hydrolysate, Glucose and Starch in 0.05g/l each and Sodium thiosulphate in 0.047g/l concentrations. The composition of optimized LM10 medium formulated (per litre) is 0.05g Yeast extract, 0.05g Casein hydrolysate, 0.05g Glucose, 0.05g Starch, 0.01g K2HPO4, 0.02g Sodium pyruvate, 0.2g MgSO4, 0.001g FeSO4·7H2O, 0.285g NH4Cl, 0.039g CaCl2·2H2O, 0.047g Na2S2O3·5H2O, 0.002g NaHCO3 and 11g Gellan gum (pH=7.4). Validation of optimized LM10 medium using nine different rock samples from Meghalaya clearly indicated that optimized LM10 medium was better suited for higher recovery and enumeration of endolithic bacteria under both aerobic and anaerobic conditions.


Cortical and subcortical contributions to the attentive processing of speech.
The neuroanatomical correlates of attentive listening were investigated with functional magnetic resonance imaging and an attention task in which listeners responded only to words that combined two specific attributes of voice and semantic content. This task was performed under two different attentive listening conditions: (i) diotically, with words presented sequentially, and (ii) dichotically, with male and female voices presented simultaneously but segregated to different ears. For both conditions, functional magnetic resonance imaging revealed bihemispheric but right-lateralized activity patterns in mid-prefrontal, anterior cingulate, and inferior parietal areas, as well as significant anterior insular and subcortical activation. Manipulating attentional demands under different listening conditions revealed an important role for right anterior insula, striatum, and thalamus in the regulation of attentive listening to spoken language.


Attending rounds: A patient with intradialytic hypotension.
Intradialytic hypotension is the most common adverse event that occurs during the hemodialysis procedure. Despite advances in machine technology, it remains a difficult management issue. The pathophysiology of intradialytic hypotension and measures to reduce its frequency are discussed. An accurate assessment of dry weight is crucial in all patients on dialysis and especially those patients prone to intradialytic hypotension. The presence of edema and hypertension has recently been shown to be a poor predictor of volume overload. Noninvasive methods to assess volume status, such as whole body and segmental bioimpedance, hold promise to more accurately assess fluid status. Reducing salt intake is key to limiting interdialytic weight gain. A common problem is that patients are often told to restrict fluid but not salt intake. Lowering the dialysate temperature, prohibiting food ingestion during hemodialysis, and midodrine administration are beneficial. Sodium modeling in the absence of ultrafiltration modeling should be abandoned. There is not enough data on the efficacy of l-carnitine to warrant its routine use.


Influence of the Components and Orientation of Hydroxyapatite Fibrous Substrates on Osteoblast Behavior.
Synthetic hydroxyapatite has good biocompatibility, bioactivity and osteoconductive ability because its chemical properties and biological properties are similar to those of bioapatite in bone tissue. Strontium-substituted hydroxyapatite has better degradability than hydroxyapatite and can both promote osteogenesis and inhibit adipogenesis in mesenchymal stem cells. Hence, hydroxyapatite and strontium-substituted hydroxyapatite are widely used as bone graft materials, cell carriers and drug/gene delivery carriers. In addition, osteoblasts cultured on aligned nanofibrous substrates had higher expression of osteogenesis-related genes than did those cultured on random nanofibrous substrates. However, to date, no study has explored the effects of the components and orientation of hydroxyapatite nanofibrous substrates on osteoblastic behavior. In this study, a random hydroxyapatite nanofibrous substrate (R-HANF), a random strontium-substituted hydroxyapatite nanofibrous substrate (R-SrHANF), an aligned hydroxyapatite nanofibrous substrate (A-HANF) and an aligned strontium-substituted hydroxyapatite nanofibrous substrate (A-SrHANF) were successfully fabricated by using the electrospinning technique. The effect of fiber composition on osteoblast-like MG63 cells was assessed by evaluating cell morphology, cell proliferation and osteogenesis-related gene expression. The results showed that MG63 cells cultured on A-SrHANF had higher osteogenesis-related gene expression than those cultured on A-HANF. Additionally, MG63 cells were cultured on R-SrHANF and A-SrHANF to evaluate the effects of fiber orientation on cell behavior. On A-SrHANF, the cells aligned along the direction of the nanofibers, with typical bipolar morphologies, and exhibited higher osteogenesis-related gene expression than cells on R-SrHANF. Hence, the components and orientation of hydroxyapatite nanofibrous substrates are critical parameters affecting the osteogenesis process.


KEDOP: Keratoconus early detection of progression using tomography images.
To investigate a method to identification of early progression of keratoconus using deep learning neural networks. Retrospective evaluation of medical records of patients with progressive keratoconus and had more than one followup visits. Images extracted from the single scheimplug analyzer for analysis were captured during the patient visits. The baseline progression of keratoconus is detected by a change in flat or steep K of ≥1.0D which is labeled as keratometric progression (KP) and progression detected by image based deep learning convolutional neural network (CNN) models, is labeled as latent progression (LP). Patient data consisted of model data (385 eyes of 351patients) to train and test the learning models and prediction data (1331 eyes of 828 patients) to determine the LP based on the learning models. The LP prediction model was able to identify progression at a mean of 11.1 months earlier than KP (p < 0.001). LP prediction model was able to identify progression earlier than KP irrespective of age category, gender, the severity of keratoconus, presenting visual acuity, astigmatism, and spherical equivalent (P < 0.001). When compared to the first visit the corrected distance visual acuity was more stable in 71% of the eyes at LP prediction visit compared to 50% at KP visit (p < 0.001). Through this study, we propose a possible solution to address the shortcomings noted in the current approaches of detecting progression relying only on KP. Avoiding bias towards feature selection from tomography images as done in the current study aids in identifying very subtle changes on the images between visits.


Event-Triggered Learning-Based Fault Accommodation for a Class of Nonlinear Interconnected Systems.
In this article, a distributed learning-based fault accommodation scheme is proposed for a class of nonlinear interconnected systems under event-triggered communication of control and measurement signals. Process faults occurring in the local dynamics and/or propagated from interconnected neighboring subsystems are considered. An event-triggered nominal control law is used for each subsystem before detecting any fault occurrence in its dynamics. After fault detection, the corresponding event-triggered fault accommodation law is utilized to reconfigure the nominal control law with a neural-network-based adaptive learning scheme employed to estimate an ideal fault-tolerant control function online. Under the asynchronous controller reconfiguration mechanism for each subsystem, the closed-loop stability of the interconnected systems in different operating modes with the proposed event-triggered learning-based fault accommodation scheme is rigorously analyzed with the explicit stabilization condition and state upper bound derived in terms of event-triggering parameters, and the Zeno behavior is shown to be excluded. An interconnected inverted pendulum system is used to illustrate the proposed fault accommodation scheme.


Women in Selected Communities of Punjab, India Have a High Prevalence of Iron, Zinc, Vitamin B12, and Folate Deficiencies: Implications for a Multiply-Fortified Salt Intervention.
Dietary intake and biomarkers of micronutrient status of 100 non-pregnant women of reproductive age (NPWRA) were assessed to determine optimal levels of iron, zinc, vitamin B12, and folic acid to include in multiply-fortified salt (MFS) that will be evaluated in an upcoming trial. Weighed food records were obtained from participants to measure intake of micronutrients and discretionary salt, and to assess adequacy using Indian Nutrient Reference Values (NRVs). Statistical modeling was used to determine optimal fortification levels to reduce inadequate micronutrient intake while limiting intake above the upper limit. Fasting blood samples were obtained to assess iron, zinc, vitamin B12, and folate status. In usual diets, inadequate intake of iron (46%), zinc (95%), vitamin B12 (83%), and folate (36%) was high. Mean intake of discretionary salt was 4.7 g/day. Prevalence estimates of anemia (37%), iron deficiency (67%), zinc deficiency (34%), vitamin B12 insufficiency (37%), and folate insufficiency (70%) were also high. Simulating the addition of optimized MFS to usual diets resulted in percentage point (pp) reductions in inadequate intake by 29 pp for iron, 76 pp for zinc, 81 pp for vitamin B12, and 36 pp for folate. MFS holds potential to reduce the burden of micronutrient deficiencies in this setting.


Synergistic Proinflammatory Responses by IL-17A and Toll-Like Receptor 3 in Human Airway Epithelial Cells.
Viral respiratory infections activate the innate immune response in the airway epithelium through Toll-like receptors (TLRs) and induce airway inflammation, which causes acute exacerbation of asthma. Although increases in IL-17A expression were observed in the airway of severe asthma patients, the interaction between IL-17A and TLR activation in airway epithelium remains poorly understood. In this study, we demonstrated that IL-17A and polyI:C, the ligand of TLR3, synergistically induced the expression of proinflammatory cytokines and chemokines (G-CSF, IL-8, CXCL1, CXCL5, IL-1F9), but not type I interferon (IFN-α1, -β) in primary culture of normal human bronchial epithelial cells. Synergistic induction after co-stimulation with IL-17A and polyI:C was observed from 2 to 24 hours after stimulation. Treatment with cycloheximide or actinomycin D had no effect, suggesting that the synergistic induction occurred without de novo protein synthesis or mRNA stabilization. Inhibition of the TLR3, TLR/TIR-domain-containing adaptor-inducing interferon β (TRIF), NF-κB, and IRF3 pathways decreased the polyI:C- and IL-17A/polyI:C-induced G-CSF and IL-8 mRNA expression. Comparing the levels of mRNA induction between co-treatment with IL-17A/polyI:C and treatment with polyI:C alone, blocking the of NF-κB pathway significantly attenuated the observed synergism. In western blotting analysis, activation of both NF-κB and IRF3 was observed in treatment with polyI:C and co-treatment with IL-17A/polyI:C; moreover, co-treatment with IL-17A/polyI:C augmented IκB-α phosphorylation as compared to polyI:C treatment alone. Collectively, these findings indicate that IL-17A and TLR3 activation cooperate to induce proinflammatory responses in the airway epithelium via TLR3/TRIF-mediated NF-κB/IRF3 activation, and that enhanced activation of the NF-κB pathway plays an essential role in synergistic induction after co-treatment with IL-17A and polyI:C in vitro.


Influence of postoperative infectious complications on long-term survival of lung cancer patients: a population-based cohort study.
Surgery is essential to any curative plan for lung cancer, but is associated with a high complication rate. We sought to determine the impact of complications on long-term survival after a curative surgery for lung cancer, independent of the effect on early postoperative mortality. We studied a population-based cohort of patients with lung cancer who underwent curative-intent surgery in the province of Quebec, Canada, from 2000 to 2005. Kaplan-Meier survival analysis was used to compare unadjusted overall survival (OS) beyond postoperative day 90 for patients with and without complications. Cox regression was used to determine the prognostic impact of 30-day postoperative complications on the OS after adjusting for several confounders. The overall 30-day postoperative complication rate was 58.2% among 4033 eligible patients. A major infectious complication (pneumonia, empyema, or mediastinitis) occurred in 378 patients. The 5-year OS was lower for those with any postoperative complication (62.8%) than those without (73.8%; p < 0.001). Those with major infectious complications had the lowest OS (56.3%; p < 0.001). Postoperative complication was an independent prognostic factor after adjusting for several patient and treatment factors (hazard ratio = 1.37; 95% confidence interval, 1.21-1.54). Adjusted hazard ratio for major infectious complications was 1.67 (95% confidence interval, 1.39-2.01). Postoperative complications, particularly of a major infectious type, are strong negative predictors of long-term survival in lung cancer patients. The strong association between major infectious complications and survival may also open the door to investigational therapies targeting bacterial antigens in the perioperative period in patients who undergo lung cancer surgery.


[Evaluation of lymph node dissection in the central neck area in managing thyroid microcarcinoma].
To evaluate lymph node dissection in the central neck area to treat micro-sized thyroid carcinoma. The clinical data of 65 surgically treated thyroid microcarcinoma patients in our hospital were retrospectively reviewed. In this series, the positive metastasis rate of cervical lymph node was 40%. A total of 62 patients had been followed up until the data were reviewed. None was found to be dead nor having distant metastasis. Five patients were re-operated due to countralateral lobe meatstasis 3 years after initial operation, 2 of them had developed para-tracheal lymph node metastasis; another 2 cases underwent functional neck lymph node dissection due to lymph node metastasis on the operated side 2 years later. Thyroidectomy with lymph node dissection of the central neck area is more effective than the thyroidectomy alone for managing thyroid microcarcinoma. It can improve the quality of life and survival through reducing cervical lymph node metastasis.


Knowledge and attitudes of high school students related to organ donation and transplantation: a cross-sectional survey in Turkey.
We have very little information about the knowledge and attitude of high school students towards organ donation and transplantation. The aim of this study was to identify student-related factors that might affect organ donation, and then use this information to develop some essential strategies and policies. Two hundred students from one urban high school were surveyed with a questionnaire. After completing the first interview, the students underwent a training program on organ donation and transplantation. Once this was complete, the students filled out the same questionnaire in a second interview session. We then analyzed the changes from before to after the educational program in order to assess the program's effectiveness. Concerning brain-death, 66.1% of the respondents identified the correct definition of this concept before training, and 92% did so after training (p<0.001). The correct definition of transplantation was chosen by 68.3% of the respondents before training, and by 90.6% after training (p<0.001). It is clear that this educational program greatly enhanced the students' level of knowledge related to many aspects of organ donation and transplantation and significantly expanded awareness. By leading to changes in opinion, such training programs will significantly increase the number of donors and the rate of transplantation in Turkey.


Seed size: a priority trait in cereal crops.
Crop production and productivity must be increased to provide a balanced diet for the global population. The entire genome sequences of crop species allow the elucidation of genes that regulate important traits related to the final crop seed yield, which frequently depends mainly on seed size. Seed size is a major factor that controls seed quantity and it is strongly affected by various biotic, abiotic and genetic factors. Epigenetic marks in the genome and phytohormones are also important factors affecting seed growth and development. Several genes are known to be involved in the control of seed size, but their interaction and functional characterization have yet to be resolved. In this review, we discuss the different factors that govern seed size in cereal crops and Arabidopsis.


Manganese superoxide dismutase and aldehyde dehydrogenase deficiency increase mitochondrial oxidative stress and aggravate age-dependent vascular dysfunction.
Imbalance between pro- and antioxidant species (e.g. during aging) plays a crucial role for vascular function and is associated with oxidative gene regulation and modification. Vascular aging is associated with progressive deterioration of vascular homeostasis leading to reduced relaxation, hypertrophy, and a higher risk of thrombotic events. These effects can be explained by a reduction in free bioavailable nitric oxide that is inactivated by an age-dependent increase in superoxide formation. In the present study, mitochondria as a source of reactive oxygen species (ROS) and the contribution of manganese superoxide dismutase (MnSOD, SOD-2) and aldehyde dehydrogenase (ALDH-2) were investigated. Age-dependent effects on vascular function were determined in aortas of C57/Bl6 wild-type (WT), ALDH-2(-/-), MnSOD(+/+), and MnSOD(+/-) mice by isometric tension measurements in organ chambers. Mitochondrial ROS formation was measured by luminol (L-012)-enhanced chemiluminescence and 2-hydroxyethidium formation with an HPLC-based assay in isolated heart mitochondria. ROS-mediated mitochondrial DNA (mtDNA) damage was detected by a novel and modified version of the fluorescent-detection alkaline DNA unwinding (FADU) assay. Endothelial dysfunction was observed in aged C57/Bl6 WT mice in parallel to increased mitochondrial ROS formation and oxidative mtDNA damage. In contrast, middle-aged ALDH-2(-/-) mice showed a marked vascular dysfunction that was similar in old ALDH-2(-/-) mice suggesting that ALDH-2 exerts age-dependent vasoprotective effects. Aged MnSOD(+/-) mice showed the most pronounced phenotype such as severely impaired vasorelaxation, highest levels of mitochondrial ROS formation and mtDNA damage. The correlation between mtROS formation and acetylcholine-dependent relaxation revealed that mitochondrial radical formation significantly contributes to age-dependent endothelial dysfunction.


Non-invasive monitoring of reproductive and stress hormones in the endangered red panda (Ailurus fulgens fulgens).
The red panda (Ailurus fulgens fulgens) is classified as endangered due to its declining population, habitat fragmentation and poaching. Efforts are being made to breed them in captivity as part of nationwide conservation breeding program. This study aimed to standardize Enzyme immunoassays (EIAs) to monitor reproductive (Progesterone metabolite, Testosterone) and stress hormone (Cortisol) in red panda. For this purpose, we collected 1471 faecal samples from four females and one male over a period of one year from Padmaja Naidu Himalayan Zoological Park, Darjeeling, India. HPLC confirmed the presence of immunoreactive 5α-pregnan-3α-ol-20-one, testosterone and cortisol metabolites in faecal samples. Using 5α-pregnan-3α-ol-20-one EIA, we were able to monitor reproduction and detect pregnancy in one of the females, which successfully conceived and delivered during the study period. We were also able to monitor testosterone and cortisol in faecal samples of the red panda. Faecal testosterone levels were found in higher concentration in breeding season than in non-breeding season. Faecal cortisol concentrations showed a negative relationship with ambient temperature and peaked during winter months in all animals. Standardization of EIAs and faecal hormone monitoring would facilitate red panda conservation breeding programs in India and elsewhere.


Digested disorder, Quarterly intrinsic disorder digest (October-November-December, 2013).
This is the 4th issue of the Digested Disorder series that represents reader's digest of the scientific literature on intrinsically disordered proteins. The only 2 criteria for inclusion in this digest are the publication date (a paper should be published within the covered time frame) and topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the fourth quarter of 2013; i.e. during the period of October, November, and December of 2013. Similar to previous issues, the papers are grouped hierarchically by topics they cover, and for each of the included paper a short description is given on its major findings.


The human homologue of yeast ArgRIII protein is an inositol phosphate multikinase with predominantly nuclear localization.
The function of the transcription regulator ArgRIII in the expression of several genes involved in the metabolism of arginine in yeast has been well studied. It was previously reported that it is also an inositol phosphate multikinase and an important factor of the mRNA export pathway [reviewed by Shears (2000) Bioessays 22, 786-789]. In the present study we report the cloning of a full-length 1248-bp cDNA encoding a human inositol phosphate multikinase (IPMK). This protein has a calculated molecular mass of 47.219 kDa. Functionally important motifs [inositol phosphate-binding site, ATP-binding site, catalytically important SSLL (Ser-Ser-Leu-Leu) domain] are conserved between the human IPMK and yeast ArgRIII. Bacterially expressed protein demonstrated an inositol phosphate multikinase activity similar to that of yeast ArgRIII. Ins(1,4,5)P3 is phosphorylated at positions 3 and 6 up to Ins(1,3,4,5,6)P5. The human IPMK fused with a fluorescent protein tag is localized predominantly in the nucleus when transiently expressed in mammalian cells. A basic cluster in the protein's C-terminus is positively involved in nuclear targeting. These findings are consistent with the concept of a nuclear inositol phosphate signalling and phosphorylation pathway in mammalian cells.


Clinical observation of umbilical cord mesenchymal stem cell treatment of severe idiopathic pulmonary fibrosis: A case report.
Idiopathic pulmonary fibrosis (IPF) is a degenerative disease characterized by fibrosis. Cell therapy has been considered within the therapeutic options for IPF. In this study, we explored the potential benefits of human umbilical cord-derived mesenchymal stem cell (HUC-MSC) intravenous infusion in the management of IPF. We describe a case of a 56-year-old man with IPF who was receiving long-term oxygen therapy (LTOT). The patient underwent HUC-MSC intravenous infusion and was followed up for 12 months. Clinical and motor tests, as well as questionnaires assessing quality of life, were performed prior to and following the transplantation. At the end of 12 months, a relevant reduction of LTOT requirement was registered; improvements in terms of physical performance, quality of life, and respiratory parameters were observed in our patient. In conclusion, a program of HUC-MSC intravenous infusion appears to be beneficial to patients with IPF and may be considered as an additional therapeutic option.


Microsatellite instability and loss of heterozygosity in chromosomes 9 and 16 in human breast epithelial cells transformed by chemical carcinogens.
Microsatellite instability (MSI) and loss of heterozygosity (LOH) in chromosomes 9 and 16 have been reported in human breast cancers. In order to determine whether changes in these chromosomes play a role in the initiation and progression of this disease, we performed microsatellite polymorphism analyses in human breast epithelial cells (HBEC) transformed by chemical carcinogens, an in vitro system that recapitulates various stages of neoplastic transformation. In this experimental system we studied the mortal HBEC MCF-10M, immortal MCF-10F cells, derived from MCF-10M cells, and clones derived from MCF-10F cells treated with benzo[a]pyrene (B[a]P) (BP1 and BP1E) and 7,12-dimethylbenz[a]anthracene (DMBA) (D3 and D3-1). The four clones of transformed cells were injected into severe combined immunodeficient (SCID) mice. Only BP1-E cells induced the formation of tumors, designated BP1E-Tp cells. These cells originated six additional tumors, designated BP1E-Tf no. 1 through Tf no. 6. Microsatellite analyses were carried out using five markers for chromosome 9 and 20 for chromosome 16. There was no evidence of MSI or LOH in clones BP1 and BP1E when compared with the MCF-10M and MCF-10F cells, whereas BP1E-Tp cells and Bp1E-Tf no. 1-Tf no. 6 tumors exhibited MSI at loci p23 and p21, and LOH at p21-22 of chromosome 9. They also exhibited MSI and LOH at multiple loci of both the short and long arms of chromosome 16, i.e. p13.13, p13.3, p12, q12.1, q12.2, q23 and q24, to which putative tumor suppressor genes have been localized. Clones D3 and D3-1 exhibited no genomic changes in chromosome 9, but did show MSI at locus q12.1 of chromosome 16 using marker D16S285. Although the cells treated with DMBA expressed early phenotypes of neoplastic transformation, they were not tumorigenic, and also manifested fewer changes than the tumorigenic BP1E-Tp cells and the tumors BP1E-Tf. The changes in chromosomes 9 and 16 observed in these latter ones indicated an association with the expression of tumorigenesis, which represents a late event in the progression of the neoplastic transformation of HBEC. Of interest was the observation that HBEC transformed by chemical carcinogens in vitro express genomic changes similar to those found in spontaneous breast carcinomas.


Oral sensitization to food proteins: a Brown Norway rat model.
Although several in vivo antigenicity assays using parenteral immunization are operational, no adequate enteral sensitization models are available to study food allergy and allergenicity of food proteins. This paper describes the development of an enteral model for food allergy research in the Brown Norway (BN) rat. The animals were exposed to ovalbumin either ad libitum via the drinking water (0.002 to 20 mg/mL) continuously for 6 weeks or by gavage (1 mg/mL per rat). Gavage dosing was performed either daily, twice a week, once a week or once every 2 weeks during a period of 6 weeks. No adjuvants were used during the sensitization studies. After intra-gastric administration of ovalbumin once or twice a week or once every two weeks, no or only a very low frequency of ovalbumin-specific antibody responses were detected. Daily intra-gastric dosing with ovalbumin resulted in antigen-specific IgG as well as IgE responses in almost all animals tested. Upon ad libitum exposure, ovalbumin-specific IgG but no ovalbumin-specific IgE was detected. The cellular response was examined by determination of delayed-type hypersensitivity (DTH) reactions in the animals dosed by daily gavage and in the ad libitum exposed rats. Both sensitization protocols sensitized for DTH. The response was most pronounced in ad libitum exposed rats at day 28 of exposure. These studies show that the BN rat may provide a suitable animal model for inducing specific IgG and IgE responses as well as specific T-cell mediated hypersensitivity (DTH) to ovalbumin upon exposure via the enteral route without the use of adjuvants.


Attributable mortality of nosocomial candidemia, revisited.
We reexamined the attributable mortality of nosocomial candidemia 15 years after a retrospective cohort study performed at our hospital demonstrated an attributable mortality of 38%. For all episodes of nosocomial candidemia between 1 July 1997 and 30 June 2001, we matched control patients with case patients by age, sex, date of hospital admission, underlying disease(s), length of time at risk, and surgical procedure(s). We analyzed 108 matched pairs. There were no statistically significant differences in age, sex, underlying disease(s), time at risk, surgical procedure, or vital signs at admission between cases and controls. The crude mortality among case patients was 61% (66 of 108 patients), compared with 12% (13 of 108) among control patients, for an attributable mortality of 49% (95% CI, 38%-60%). Nosocomial candidemia is still associated with an extremely high crude and attributable mortality--much higher than that expected from underlying disease alone.


New Directions in the Treatment of Glioblastoma.
Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodality treatment, the median survival for GBM remains marginally better than 1 year. In the past decade, genome-wide analyses have uncovered new molecular features of GBM that have refined its classification and provided new insights into the molecular basis for GBM pathogenesis. Here, we review these molecular features and discuss major clinical trials that have recently defined the field. We describe genetic alterations in isocitrate dehydrogenase, ATRX, the telomerase promoter, and histone H3 variants that promote GBM tumorigenesis and have altered GBM categorization. We also discuss intratumoral genetic heterogeneity as one explanation for therapeutic failures and explain how ultra-long extensions of glioma cells, called tumor microtubes, mediate therapeutic resistance. These findings provide new insights into GBM biology and offer hope for the development of next-generation therapies.


A heuristic approach for the economic optimization of a series of CSTR's performing Michaelis-Menten reactions.
The estimation of the size of each reactor of a series of CSTR's performing a Michaelis-Menten reaction in the liquid phase can be obtained to advantage via an optimization technique leading to the minimum overall capital cost. The cost scaleup is assumed to be described by a power rule on the equipment capacity. Various contributions are lumped into the exponent, thus leading to values above unity. The analytical development leading to the optimal intermediate concentrations of substrate according to the foregoing criterion is presented. A short-cut method based on an empirical expression that approximates the numerical solution is reported. This correlation is found to be exact at the asymptotic behaviors, and to give accurate results within an acceptable error level for the range with physical interest. Therefore, it is particularly useful during the predesign steps of equipment for the biochemical industry.


[Femoroacetabular impingement as a cause of inguinal pain].
Femoro-acetabular impingement is an anatomical disturbance of the hip, caused by a deformity of the acetabulum, femur or both that causes an abnormal contact between both structures during certain movements. Its prevalence is 10 to 15% and causes chronic inguinal pain. It can be confused with several other causes of inguinal pain such as hernias, facet syndromes, a renal colic, etc. Patients with this condition are usually young individuals with inguinal pain that may appear after a minor trauma. During examination, pain may be elicited by infernal rotation and abduction movements of hip, flexed in 90 degrees . Plain hip X ray is the most commonly used diagnostic method. Non-steroidal anti-inflammatory drugs and physical therapy can be used to alleviate pain, but the definitive treatment is surgical.


Reversible Charge-Carrier Trapping Slows Förster Energy Transfer in CdSe/CdS Quantum-Dot Solids.
The dynamics of photoluminescence (PL) from nanocrystal quantum dots (QDs) is significantly affected by the reversible trapping of photoexcited charge carriers. This process occurs after up to 50% of the absorption events, depending on the type of QD considered, and can extend the time between the photoexcitation and relaxation of the QD by orders of magnitude. Although many optoelectronic applications require QDs assembled into a QD solid, until now, reversible trapping has been studied only in (ensembles of) spatially separated QDs. Here, we study the influence of reversible trapping on the excited-state dynamics of CdSe/CdS core/shell QDs when they are assembled into close-packed "supraparticles". Time- and spectrally resolved photoluminescence (PL) measurements reveal competition among spontaneous emission, reversible charge-carrier trapping, and Förster resonance energy transfer between the QDs. While Förster transfer causes the PL to red-shift over the first 20-50 ns after excitation, reversible trapping stops and even reverses this trend at later times. We can model this behavior with a simple kinetic Monte Carlo simulation by considering that charge-carrier trapping leaves the QDs in a state with zero oscillator strength in which no energy transfer can occur. Our results highlight that reversible trapping significantly affects the energy and charge-carrier dynamics for applications in which QDs are assembled into a QD solid.


[Aortic valve surgery in a patient with cold agglutinin disease; effectiveness of continuous retrograde cardioplegia].
A 76-year-old female was hospitalized because of congestive heart failure and anemia. A thorough examination led to a diagnosis of severe aortic stenosis and cold agglutinin disease. The critical temperature for hemagglutination was 27 °C, which caused particular problems with regard to the myocardial protection temperature during surgery. Aortic valve replacement was performed safely by increasing the normal myocardial protection temperature from 15 °C to 32 °C and using 3 times the normal volume of cardioplagic fluid. As a result of strict perioperative thermal management, the operation was completed without any complications.


[Tuberculosis in indigenous peoples in the Brazilian Amazon: an epidemiological study in the Upper Rio Negro region].
To describe the sociodemographic, clinical, and epidemiological characteristics of reported tuberculosis cases among indigenous individuals of São Gabriel de Cachoeira, State of Amazonas, Brazil, and to identify the factors associated with mortality during treatment; and to estimate the prevalence of latent tuberculosis infection (LTBI) and associated factors and obtain information on the therapeutic course and the individual perceptions regarding acquistion of tuberculosis in the district of Iauaretê. Firstly, a retrospective epidemiological study (1997 to 2007) was conducted using data from the Brazilian Notifiable Diseases Surveillance System (SINAN). Next, a cross-sectional study (2010) was conducted with respiratory symptomatic subjects and contacts of Iauaretê. Seven hundred and twenty-three new cases were reported, with incidence of 273.4/100 000 and mortality of 13.2/100 000. There was a predominance of males (57%), aged > 45 years (37.6%), people with no schooling (42.7%), and cases from rural areas (76.9%). Patients aged 0 to 20 years were at lower risk of death when compared to those aged > 45 years (OR = 0.3; IC95%: 0.1 a 0.9). In Iauaretê, with 15.3% of the reported cases, 184 people were interviewed. A prevalence of LTB of 76.1% was reported. Tuberculin skin test > 5 mm was associated with the > 15-year old age group, history of active tuberculosis, and radiological alterations. A previous history of tuberculosis was cited by 54 people (29.3%). The main explanation for the disease was "puffing/poisoning" (24.1%). The therapeutic course included industrialized drugs (42.6%), medicinal plants/roots, shamanism, and prayer (42.7%). The risk of tuberculosis infection and disease in this population was high. Despite the reduced incidence resulting from recent efforts, tuberculosis control requires closer surveillance of contacts and improvement in communication strategies between health teams and indigenous populations.


Fetal esophagus: normal sonographic appearance.
Our objective was to describe the sonographic appearance of the normal fetal esophagus and to determine the rate of its visualization. The fetal esophagus has a tubular echogenic appearance. Two patterns of the tubular structure were observed: two parallel echogenic lines or several parallel echogenic lines (the so-called "multilayered pattern"). A cannula was placed in the stomach of three stillborns and removed under ultrasonographic monitoring, confirming its location. In 155 consecutive pregnancies examined, the thoracic part of the fetal esophagus was easy to visualize (about 90% of cases); the cervical and abdominal segments were more difficult to visualize (19 and 30%, respectively). The multilayered pattern was observed in 49% of cases before and in 87% of cases after 26 weeks' gestation. A direct sonographic demonstration of the fetal esophagus is possible and could help to exclude esophageal malformations.


Actomyosin-driven force patterning controls endocytosis at the immune synapse.
An important channel of cell-to-cell communication is direct contact. The immune synapse is a paradigmatic example of such type of interaction: it forms upon engagement of antigen receptors in lymphocytes by antigen-presenting cells and allows the local exchange of molecules and information. Although mechanics has been shown to play an important role in this process, how forces organize and impact on synapse function is unknown. We find that mechanical forces are spatio-temporally patterned at the immune synapse: global pulsatile myosin II-driven tangential forces are observed at the synapse periphery while localised forces generated by invadosome-like F-actin protrusions are detected at its centre. Noticeably, we observe that these force-producing actin protrusions constitute the main site of antigen extraction and endocytosis and require myosin II contractility to form. The interplay between global and local forces dictated by the organization of the actomyosin cytoskeleton therefore controls endocytosis at the immune synapse.


Hanseniaspora thailandica BC9 β-Glucosidase for the Production of β-D-Hexyl Glucoside.
For biotechnological production of high-valued β-D-hexyl glucoside, the catalytic properties of Hanseniaspora thailandica BC9 β-glucosidase purified from the periplasmic fraction were studied, and the transglycosylation activity for the production of β-D-hexyl glucoside was optimized. The constitutive BC9 β-glucosidase exhibited maximum specific activity at pH 6.0 and 40ºC, and the activity of BC9 β-glucosidase was not significantly inhibited by various metal ions. BC9 β-glucosidase did not show a significant activity of cellobiose hydrolysis, but the activity was rather enhanced in the presence of sucrose and medium-chain alcohols. BC9 β-glucosidase exhibited enhanced production of β-D-hexyl glucoside in the presence of DMSO, and 62% of β-D-hexyl glucoside conversion was recorded in 4 h in the presence of 5% 1-hexanol and 15% DMSO.


L-shaped association between dietary coenzyme Q10 intake and high-sensitivity C-reactive protein in Chinese adults: a national cross-sectional study.
Background: Chronic inflammation contributes to the occurrence and progression of many diseases. Most previous clinical studies have explored the effect of high-dose CoQ10 supplements on inflammation. Food is another important source of CoQ10, but the relationship between the intake of CoQ10 from dietary sources and inflammation was unknown. We aimed to explore the dose-response association between the intake of dietary-derived CoQ10 and inflammation-related biomarkers. Methods: Seven thousand nine hundred and fifty-three Chinese adults from the China Health and Nutrition Survey (CHNS) were the subjects of this cross-sectional investigation. Dietary CoQ10 intake was assessed using dietary information from three days. High-sensitivity C-reactive protein (hsCRP) and white blood cell count (WBC) were assessed using fasting venous blood. Results: In an adjusted linear regression model, CoQ10 consumption from dietary sources was inversely associated with hsCRP, with effect sizes in each group: Q2 (β = -0.85 mg L-1, 95% CI: -1.43 to -0.28 mg L-1, P = 0.004), Q3 (β = -0.70 mg L-1, 95% CI: -1.28 to -0.12 mg L-1, P = 0.017), and Q4 (β = -0.79 mg L-1, 95% CI: -1.39 to -0.19 mg L-1, P = 0.010). Moreover, restricted cubic splines (RCS) revealed a non-linear L-shaped association between dietary-derived CoQ10 consumption and hsCRP (Pnonlinear < 0.001). According to subgroup analyses, these relationships were more significant in males, or >45 years old (Ptrend < 0.05). Nevertheless, no significant relationship was found between dietary-derived CoQ10 intake and WBC. Conclusions: These findings suggested a significant negative association between dietary-derived CoQ10 and hsCRP levels.


Using the Chinese version of Memorial Delirium Assessment Scale to describe postoperative delirium after hip surgery.
Memorial Delirium Assessment Scale (MDAS) assesses severity of delirium. However, whether the MDAS can be used in a Chinese population is unknown. Moreover, the optimal postoperative MDAS cutoff point for describing postoperative delirium in Chinese remains largely to be determined. We therefore performed a pilot study to validate MDAS in the Chinese language and to determine the optimal postoperative MDAS cutoff point for delirium. Eighty-two patients (80 ± 6 years, 21.9% male), who had hip surgery under general anesthesia, were enrolled. The Confusion Assessment Method (CAM) and Mini-Mental State Examination (MMSE) were administered to the patients before surgery. The CAM and MDAS were performed on the patients on the first, second and fourth postoperative days. The reliability and validity of the MDAS were determined. A receiver operating characteristic (ROC) curve was used to determine the optimal Chinese version MDAS cutoff point for the identification of delirium. The Chinese version of the MDAS had satisfactory internal consistency (α = 0.910). ROC analysis obtained an average optimal MDAS cutoff point of 7.5 in describing the CAM-defined postoperative delirium, with an area under the ROC of 0.990 (95% CI 0.977-1.000, P < 0.001). The Chinese version of the MDAS had good reliability and validity. The patients whose postoperative Chinese version MDAS cutoff point score was 7.5 would likely have postoperative delirium. These results have established a system for a larger scale study in the future.


Ambulatory activity of older adults hospitalized with acute medical illness.
To describe the amount and patterns of ambulatory activity in hospitalized older adults over consecutive hospital days. Observational cohort study. University teaching hospital Acute Care for Elderly (ACE) unit. Adults aged 65 and older (N = 239) who wore a step activity monitor during their hospital stay. Total number of steps per 24-hour day. Mean daily steps were calculated based on number of days the step activity monitor was worn. Mean age was 76.6 ± 7.6; 55.1% of participants were female. Patients took a mean number of 739.7 (interquartile range 89-1,014) steps per day during their hospital stay. Patients with shorter stays tended to ambulate more on the first complete day of hospitalization and had a markedly greater increase in mobility on the second day than patients with longer lengths of stay. There were no significant differences in mean daily steps according to illness severity or reason for admission. Objective information on patient mobility can be collected for hospitalized older persons. Findings may increase understanding of the level of ambulation required to maintain functional status and promote recovery from acute illness.


Descriptive Study of Gender Dysphoria and Sexual Behavior in a Disorder of Sex Development Group.
Disorder of Sex Development (DSD) refers to a heterogeneous group of congenital conditions in which chromosomal, gonadal, and anatomical sex are atypical. Typically, the diagnosis is made at birth or infancy and interventional actions are necessary in many cases. The repercussions in adult life, more specifically in the field of sexuality, have not been not widely studied yet. This study shows research data that seek to identify in a group of individuals with DSD (XX DSD, XY DSD, Chromosomal DSD), who are being monitored in the departments of pediatric surgery and urology of a hospital in the period from 2000 to 2019, and to verify the consequences on sex life after puberty. The sample has 16 participants (7 XY DSD, 4 XX DSD, and 5 Chromosomal DSD), aged between 16 and 50 years, single, with high school education, residents of the state capital and countryside of the state. The results depict the presence of a case of Gender Dysphoria; postponement of sexual debut for almost 3 years compared to the national average; a single sexual relationship for those who have already had a sexual experience with penetration; penis size below the general population average; presence of masturbatory activity in most participants. The presence of sexual attraction and masturbation indicate sexual desire. The group has a late onset of sexual life (almost 3 years after the national average). A recurrent feature in this group is that, even having already performed a penetrative sexual act, there is no continuation in their sexual life. The main noticeable aspect about Gender Dysphoria is the presence of only one case of incongruence in the Chromosomal DSD group. The limited sample prevents us from sufficient statements for generalization.


Prognostic significance of glycaemic control in patients with HBV and HCV-related cirrhosis and diabetes mellitus.
Diabetes mellitus (DM) is frequently observed in patients with cirrhosis, particularly that due to hepatitis C virus (HCV) infection. However, no studies have focused on the clinical significance of glycaemic control in cirrhotic patients because of their short life expectancy and poor hepatic function. The aim of this study was to evaluate the prognostic impact of glycaemic control in patients with hepatitis B virus (HBV) and HCV-related cirrhosis and DM. A total of 434 patients with HCV-related (HCV group, n = 88) or HBV-related (HBV group, n = 346) cirrhosis were studied retrospectively. We determined the prevalence of DM and treatment methods for hyperglycaemia and status of glycaemic control, and the patients' outcome. The prevalence of DM was 43.2% (38/88) in the HCV group and 19.7% (68/346) in the HBV group. Patients in the HCV group were older with a female preponderance. DM was detected before the diagnosis of cirrhosis or simultaneously in 92% and 79% in the HCV and HBV groups, respectively. Most patients were treated with insulin or oral hypoglycaemic agents. However, blood glucose levels were maintained within the normal range in 34.2% of the HCV group and in 23.5% of the HBV group. Forty-six patients died during the observation period in both groups. Hepatic failure was the most common cause of death, and sepsis and variceal bleeding were more frequent in the HCV group than in the HBV group. Multivariate analysis showed that Child-Pugh class was the most important factor for survival in both groups. In the HCV group, the status of glycaemic control was a significant independent factor of survival (P = 0.018). In the HBV group, age and the development of spontaneous bacterial peritonitis were significant. DM is more frequent in patients with HCV-related cirrhosis than in patients with HBV. Strict control of blood glucose levels could improve survival in HCV patients. A precise assessment of the risks and benefits of glycaemic control is required to reduce the mortality and morbidity of patients with cirrhosis and DM.


Phage-Directed Synthesis of Photoluminescent Zinc Oxide Nanoparticles under Benign Conditions.
Biological systems, especially bacteriophages and peptides, are an attractive green alternative to other known methods of nanoparticle synthesis. In this work, for the first time, bacteriophages were employed to synthesize a specific peptide, capable of producing nanoparticles (NPs). Derivatives of M13 bacteriophage exposing a ZnO-binding peptide (TMGANLGLKWPV) on either pIII or pVIII phage coat protein were constructed and used as a biotemplate. The exposition of the ZnO-binding peptide, synthesized by phages during their propagation in bacteria, on M13 virions provided a groundwork for growing ZnO nanostructures. Depending on the recombinant phage type used (M13-pIII-ZnO or M13-pVIII-ZnO), well separated ZnO NPs or complex 3D structures of ZnO NPs of ca. 20-40 nm were synthesized at room temperature. The synthesized ZnO nanoparticles served as a luminescent material that emitted light near the short wavelength end of the visible region (at ca. 400 nm). The next very low intensity emission band at 530 nm demonstrated that the ZnO material obtained is characterized by a low concentration of surface defects.


Histoplasmosis: recognition and treatment.
Histoplasmosis has become an important mycosis in regions of endemicity in North and Central America. Traditionally, treatment has been reserved for patients with disseminated or chronic pulmonary histoplasmosis. The availability of safe and effective oral regimens, however, has offered alternatives to amphotericin B. Administration of amphotericin B is highly effective as therapy and produces a rapid clinical response; it remains the treatment of choice for patients with severe or moderately severe manifestations of histoplasmosis. Ketoconazole and itraconazole are well tolerated and are effective alternatives to amphotericin B for treatment of patients with milder illnesses or for use following response to amphotericin B. The determination of fluconazole's role in therapy for histoplasmosis awaits completion of ongoing trials. Continued research is needed to develop better-tolerated fungicidal alternatives to amphotericin B and oral agents with better absorption and drug interaction profiles than those of itraconazole and ketoconazole. Preventive strategies should be explored to reduce the frequency of histoplasmosis among individuals from regions of endemicity who are at high risk for more severe manifestations of histoplasmosis.


Identification of V-type nerve agents in vapor samples using a field-portable capillary gas chromatography/membrane-interfaced electron ionization quadrupole mass spectrometry instrument with Tri-Bed concentrator and fluoridating conversion tube.
A field-portable gas chromatography-mass spectrometry (GC-MS) system (Hapsite ER) was evaluated for the detection of nonvolatile V-type nerve agents (VX and Russian VX (RVX)) in the vapor phase. The Hapsite ER system consists of a Tri-Bed concentrator gas sampler, a nonpolar low thermal-mass capillary GC column and a hydrophobic membrane-interfaced electron ionization quadrupole mass spectrometer evacuated by a non-evaporative getter pump. The GC-MS system was attached to a VX-G fluoridating conversion tube containing silver nitrate and potassium fluoride. Sample vapors of VX and RVX were converted into O-ethyl methylphosphonofluoridate (EtGB) and O-isobutyl methylphosphonofluoridate (iBuGB), respectively. These fluoridated derivatives were detected within 10 min. No compounds were detected when the VX and RVX samples were analyzed without the conversion tube. A vapor sample of tabun (GA) was analyzed, in which GA and O-ethyl N,N-dimethylphosphoramidofluoridate were detected. The molar recovery percentages of EtGB and iBuGB from VX and RVX vapors varied from 0.3 to 17%, which was attributed to variations in the vaporization efficiency of the glass vapor container. The conversion efficiencies of the VX-G conversion tube for VX and RVX to their phosphonate derivatives were estimated to be 40%. VX and RVX vapors were detected at concentrations as low as 0.3 mg m-3 . Gasoline vapor was found to interfere with the analyses of VX and RVX. In the presence of 160 mg m-3 gasoline, the detection limits of VX and RVX vapor were increased to 20 mg m-3 . Copyright © 2017 John Wiley & Sons, Ltd.


Deoxyribonucleic acid vaccines encoding antigens with rapid proteasome-dependent degradation are highly efficient inducers of cytolytic T lymphocytes.
We generated plasmid expression vectors encoding ubiquitin and beta-galactosidase (beta-gal) with different intervening amino acids, allowing for the production of processed protein products that have either stabilizing or destabilizing residues at their N-termini. P815 cells transfected with plasmids encoding beta-gal with a destabilizing N-terminus did not have detectable expression beta-gal unless they were treated with inhibitors specific for the proteasome. Inhibitors of other proteolysis pathways had no such effect. Nevertheless, transfectants expressing beta-gal with different amino acid residues were equally sensitive to cytolysis by a CTL clone specific for a beta-gal peptide presented in the context of H-2Ld. In contrast to vectors encoding native beta-gal, plasmid vectors encoding beta-gal with a destabilizing residue did not induce detectable anti-beta-gal Abs when injected into skeletal muscle of BALB/c mice. However, such vectors were significantly more effective than vectors encoding native beta-gal or beta-gal with a stabilizing residue in stimulating CTL specific for P13.2, a lacZ transfectant of P815. We conclude that incorporation of strategies that enhance proteasome-dependent degradation may generate DNA vaccines that are more effective in inducing cellular immunity against targeted Ags.


Stone attenuation value and cross-sectional area on computed tomography predict the success of shock wave lithotripsy.
To identify the parameters on noncontrast computed tomography (NCCT) that best predict the success of shock wave lithotripsy (SWL). We reviewed the records of 75 patients who underwent SWL for urinary calculi measuring 5 to 20 mm. Using NCCT images, we estimated the largest stone cross-sectional area and contoured the inner edge of the stone. Clinical outcome was classified as successful (stone-free or <4 mm in diameter) or failed (stone fragments, ≥4 mm). The impact of preoperative parameters was evaluated by univariate and multivariate analysis. The overall success rate was 73.3%. Average stone attenuation value, stone length, and stone cross-sectional area in the success and failure groups were 627.4±166.5 HU (Hounsfield unit) vs. 788.1±233.9 HU (p=0.002), 11.7±3.8 mm vs. 14.2±3.6 mm (p=0.015), and 0.31±0.17 cm(2) vs. 0.57±0.41 cm(2) (p<0.001), respectively. In the multivariate analysis, stone attenuation value was the only independent predictor of SWL success (p=0.023), although stone cross-sectional area had a tendency to be associated with SWL success (p=0.053). Patients were then classified into four groups by using cutoff values of 780 HU for stone attenuation value and 0.4 cm(2) for cross-sectional area. By use of these cutoff values, the group with a low stone attenuation value and a low cross-sectional area was more than 11.6 times as likely to have a successful result on SWL as were all other groups (odds ratio, 11.6; 95% confidence interval, 3.9 to 54.7; p<0.001). Stone attenuation value and stone cross-sectional area are good predictors of extracorporeal SWL outcome.


Quality of care indicators for population-based primary care in New Zealand.
To develop a set of non-invasive, evidence-based, population-based quality of care indicators for primary care in New Zealand and to test their feasibility. New Zealand, British and Australian publications were reviewed and a set of quality of care indicators was constructed. These were trialed on data collected from seventeen fully computerised practices from the FirstHealth network of general practices. 28 indicators are proposed in five categories: smoking cessation, preventive health activities, prescribing quality, chronic disease management and data quality. We were able to calculate ten indicators from data already collected routinely, a further twelve could be calculated now with more sophisticated data queries and six would require the trial practices to collect further data. While any set of indicators is arbitrary there are sufficient research data to support a set of evidence-based, population-focused, quality of care indicators in New Zealand primary health care. In computerised practices these indicators can be calculated from routinely collected data.


Evaluation of Muscle Performance in Mice by Treadmill Exhaustion Test and Whole-limb Grip Strength Assay.
In vivo muscle function testing has become of great interest as primary phenotypic analysis of muscle performance. This protocol provides detailed procedures to perform the treadmill exhaustion test and the whole-limb grip strength assay, two methods commonly used in the neuromuscular research field.


[GISE (Italian Society of Interventional Cardiology) Position paper: Short-term hospitalization for percutaneous coronary intervention; a helpful tool to manage post-COVID-19 backlogs].
Minimization of hospital lengths of stay has always been a key goal for healthcare systems. More so during the current COVID-19 pandemic. In fact, we have faced a reduction in no-COVID-19 admissions with the generation of huge backlogs. Low-risk patients undergoing elective percutaneous coronary intervention (PCI) can be candidate for short-term hospitalization, with consequent reduction of waiting lists. Several single-center and multicenter observational studies, multiple randomized trials and some meta-analyses have addressed this topic.In this position paper, we present a proposal for short hospitalization for elective PCI procedures in selected patients who present complications only exceptionally and exclusively immediately after the procedure, if the inclusion and exclusion criteria are met. Each Center can choose between admission in day surgery or one day surgery, extending hospital length of stay only for patients who present complications or who are candidate for urgent surgery. Short-term hospitalization considerably reduces costs even if, with the current model, it generally results in a parallel reduction in reimbursement. Hence, we present an actual model, already tested successfully in an Italian hospital, that warrants sustainability. This approach can then be tailored to single Centers.


Effect of in situ synthesized Fe2O3 and Co3O4 nanoparticles on electroactive β phase crystallization and dielectric properties of poly(vinylidene fluoride) thin films.
A simple and low cost in situ process has been developed to synthesize Fe2O3-Co3O4 nanoparticles (NPs) loaded poly(vinylidene fluoride) (PVDF) thin films. The electroactive β phase nucleation mechanism and the dielectric properties of the films have been investigated by X-ray diffraction spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry and using an LCR meter. Results confirmed that the electroactive β phase crystallization in the PVDF matrix is due to the fast nucleating or catalytic effect of the in situ NPs. Homogenous dispersion of in situ Fe2O3-Co3O4 NPs in the polymer matrix leads to strong interfacial interaction between the NPs and the polymer resulting in enhanced β phase nucleation in PVDF and a large dielectric constant of the thin films. The observed variation in the electroactive β phase nucleation by NPs (Fe2O3-Co3O4) and the dielectric properties of the thin films have been explained on the basis of surface charge, size, geometrical shape and extent of agglomeration of the NPs in the polymer matrix.


The effect of n-3 fatty acids on levels of methylarginines in patients with end-stage renal disease.
Patients with end-stage renal disease (ESRD) have a very high mortality mainly caused by cardiovascular disease (CVD). It has been suggested that plasma concentrations of asymmetric dimethyl arginine (ADMA), an endogenous nitric oxide synthase inhibitor, are markedly elevated in patients with ESRD. Elevation of ADMA is linked to CVD and an adverse prognosis. Supplementation with n-3 fatty acids has previously been shown to prevent CVD, but there is very little data regarding the effect of n-3 fatty acids on levels of ADMA. Patients with ESRD and documented CVD were randomized to treatment with 1.7 g of n-3 fatty acids (n=103, 34% women) or olive oil (n=103, 38% women) for three months. ADMA, symmetric dimethyl arginine (SDMA), L-arginine, and the relative content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in serum phospholipids were measured before and after treatment. ADMA was normally distributed with a mean value of 0.56+/-0.13 micromol/L (range 0.21-1.01) and only 14/206 (6.8 %) had elevated levels of ADMA. SDMA was generally elevated with a mean value of 1.88+/-0.64 micromol/L (range 0.67-4.56). Supplementation with n-3 fatty acids for three months did not change plasma levels of ADMA, SDMA or L-arginine. The present data do not support a beneficial effect of n-3 fatty acids on methylarginines in patients with ESRD.


A randomized controlled trial testing an adherence-optimized Vitamin D regimen to mitigate bone change in adolescents being treated for acute lymphoblastic leukemia.
Adolescents with acute lymphoblastic leukemia (ALL) develop osteopenia early in therapy, potentially exacerbated by high rates of concurrent Vitamin D deficiency. We conducted a randomized clinical trial testing a Vitamin D-based intervention to improve Vitamin D status and reduce bone density decline. Poor adherence to home supplementation necessitated a change to directly observed therapy (DOT) with intermittent, high-dose Vitamin D3 randomized versus standard of care (SOC). Compared to SOC, DOT Vitamin D3 successfully increased trough Vitamin 25(OH)D levels (p = .026) with no residual Vitamin D deficiency, 100% adherence to DOT Vitamin D3, and without associated toxicity. However, neither Vitamin D status nor supplementation impacted bone density. Thus, this adherence-optimized intervention is feasible and effective to correct Vitamin D deficiency in adolescents during ALL therapy. Repletion of Vitamin D and calcium alone did not mitigate osteopenia, however, and new, comprehensive approaches are needed to address treatment-associated osteopenia during ALL therapy.


Out-of-Pocket Costs for Patients Diagnosed with Tuberculosis in Different Healthcare Settings in Bandung, Indonesia.
Costs related to tuberculosis (TB) can impose a significant burden on patients and their families and create barriers to diagnosis and treatment. Our study aimed to quantify out-of-pocket costs expended by TB patients in Bandung, Indonesia. This cross-sectional study recruited adults with TB from community health centers (CHCs), public and private hospitals, and private practitioners (PPs). An interview was completed at the time of diagnosis or at their return for 2- or 6-month treatment. Costs were converted to U.S. dollars (US$)-presented as median and interquartile range (IQR). Of 469 TB patients recruited, the mean age was 38 years and 57% were male. The median pretreatment direct cost per person was $37.51 (IQR 20.79-71.24). Hospitalization, diagnostic tests, and travel costs were predominant. Higher pretreatment costs were associated with no health insurance ($41.88 versus $27.41, P < 0.001), ≥ 6 visits to a healthcare provider ($39.91 versus $24.32, P < 0.001), ≥ 60 days pretreatment ($36.35 versus $26.25, P = 0.02), and presenting first to a PP ($40.71) or informal provider ($32.72) compared with private hospital ($21.26), public hospital ($19.63), or CHC ($13.52) (P = 0.01). For a subsample of 106 patients with total pre- and posttreatment costs available, the median total cost was $243.66 (IQR 128.46-550.71). For 26.5% of these patients, total costs were ≥ 20% of their annual household income. Despite having a good network of free TB diagnostic and treatment services throughout Bandung, patients experienced significant out-of-pocket costs. Increased uptake of the National Health Insurance, and systems for early recognition and diagnosis of TB, will contribute toward reducing costs.


[Long-term effects of different management strategies on Larix gmelinii forests in Great Hing' an Mountains after the catastrophic fire in 1987].
In this paper, LANDIS model was used to study the effects of different management strategies on the larch (Larix gmelinii) forests of Tuqiang Forest Bureau on the northern slopes of Great Hing' an Mountains after the catastrophic fire in 1987. Three management strategies, i. e., natural regeneration if the catastrophic fire in 1987 was not happened (M1), natural regeneration after the catastrophic fire in 1987 (M2), and current management strategy after the catastrophic fire in 1987 (M3), were compared over a 300-year period. The results showed that the abundance of larch forests over 300 simulation years under the three management strategies had significant difference. In the whole Bureau, the abundance of larch forests under M2 was obviously lower than that under M1 and M3 over 300 years, and the abundance under M3 was lower than that under M1 at the beginning. Due to the reforestation after the catastrophic fire in 1987, the abundance of larch under M3 increased rapidly, and caught up with that under M1 after about 100 years. In addition, different forest management strategies also had significant influence on the age structure of larch forests, especially for mature and over-matured larch forests. The abundance of mature and over-matured larch forests under M1 was higher than that under M2. This abundance under M3 had tremendous decrease because of forest harvesting for about 10 years, and then, increased with time and would exceed that under M1 and M2 for over 100 years. Furthermore, in unburned areas and burned areas, the abundance of mature and over-matured larch forests also had significant difference over 300 simulation years under the three management strategies.


[Microscope and endoscope-assisted surgery of inflammatory diseases of the paranasal sinuses. Value of the Messerklinger infundibulotomy].
Insights into the importance of the infundibulum of the anterior ethmoid bone in the etiology and pathogenesis of chronic paranasal sinusitis, based above all on the studies of Messerklinger, have resulted in a fundamental change in our concept of therapy: the main objective of any treatment must be the restoration of ventilation and drainage of the paranasal sinuses in the region of the semilunar hiatus. Its function in the healing of paranasal sinus diseases parallels the significance of the Eustachian tube for the healing of inflammatory lesions of the middle ear. In many cases, the objective is attained by infundibulotomy, using Messerklinger's technique. Our technique differs from that described by Messerklinger and Wigand: we use the surgical microscope and a self-retaining nasal speculum. It is thus possible to operate with both hands, as in microsurgery of the ear and the larynx. Moreover, the operations can be taught and learned via an observation tube. Since the introduction of this technique which can be extended at any time to complete endonasal surgery of the maxillary, ethmoid and sphenoid sinuses, extranasal operations on the paranasal sinuses have become exceedingly rare. The results have been checked in a newly established paranasal sinus clinic.


Bolus administration of esmolol for controlling the haemodynamic response to tracheal intubation: the Canadian Multicentre Trial.
A multicentre trial was designed to determine the dose-response and side-effects of esmolol when administered as a single iv bolus prior to induction of anaesthesia for controlling the haemodynamic response to tracheal intubation. Five hundred and forty-eight patients from 12 university-affiliated centres across Canada were randomized prospectively to receive either placebo (PLAC) or esmolol (E) in a dose of 100 mg (E100) or 200 mg (E200). Study medication was given immediately before induction of anaesthesia with thiopentone 3-5 mg.kg-1 and succinylcholine 1.5 mg.kg-1. Low-dose narcotic (fentanyl 2-3 micrograms.kg-1 or sufentanil 0.3 micrograms.kg-1) or moderate dose narcotic (fentanyl 4-7 micrograms.kg-1) was also given at five of the participating centres, whereas patients in the remaining seven centres received no narcotic. Patients who received PLAC and no narcotic had greater HR and SBP values after tracheal intubation than patients who received either E100 or E200 (P less than 0.005). The proportion of patients whose maximum HR exceeded 110 min-1 was also greater in the PLAC group (22/180) than in either the E100 (10/187) or E200 (9/181) groups (P less than 0.05), but was not different when comparing E100 with E200. Esmolol was less effective in controlling blood pressure, but, in combination with low-dose narcotic, esmolol suppressed the SBP response to tracheal intubation. In the presence of moderate-dose narcotic, however, a decrease in SBP occurred in all three groups following induction of anaesthesia (P less than 0.003), with the largest decrease (17 +/- 4%) occurring in patients who had received E200. The overall incidence of hypotension (SBP less than 90 mmHg) was greater in the E200 group (33%) than either the E100 (25%) or PLAC (16%) groups (P less than 0.05). Other side-effects, such as bradycardia, bronchospasm or pain on injection, occurred no more frequently in either esmolol group than with placebo. It is concluded that a 100 mg bolus of esmolol is safe and effective for controlling the haemodynamic response to tracheal intubation. This dose of esmolol combined with a low dose of narcotic (fentanyl 2-3 micrograms.kg-1 or equivalent) results in effective control of both heart rate and blood pressure, while avoiding important side-effects.


The application of optical coherence tomography angiography in retinal diseases.
Optical coherence tomography angiography (OCTA) is a new, noninvasive imaging technique that generates real-time volumetric data on chorioretinal vasculature and its flow pattern. With the advent of high-speed optical coherence tomography, established enface chorioretinal segmentation, and efficient algorithms, OCTA generates images that resemble an angiogram. The principle of OCTA involves determining the change in backscattering between consecutive B-scans and then attributing the differences to the flow of erythrocytes through retinal blood vessels. OCTA has shown promise in the evaluation of common ophthalmologic diseases such as diabetic retinopathy, age-related macular degeneration, and retinal vascular occlusions. It quantifies vascular compromise reflecting the severity of diabetic retinopathy. OCTA detects the presence of choroidal neovascularization in exudative age-related macular degeneration and maps loss of choriocapillaris in nonexudative age-related macular degeneration. We describe principles of OCTA and findings in common and some uncommon retinal pathologies. Finally, we summarize its potential future applications. Its current limitations include a relatively small field of view, inability to show leakage, and a tendency for image artifacts. Further larger studies will define OCTAs utility in clinical settings and establish if the technology may offer its utility in decreasing morbidity through early detection and guide therapeutic interventions in retinal diseases.


Development of a novel 3-degrees of freedom flexure based positioning system.
Flexure mechanisms have been widely used for nanometer positioning systems. This article presents a novel conceptual design of an ultra-precision 3-degrees of freedom (XYθ(Z)) positioning system with nanometer precision. The main purpose of this novel stage design is for the application of measurement equipment, in particular biological specimens. The stage was designed as a hollow type and with a compact size for the inverted microscope. This stage includes piezoelectric transducer actuators, double compound amplification mechanisms, moving plate, and capacitor sensors. The double compound amplification mechanism was designed using a mathematical model and analyzed by the finite element method. Since the relationship between the variables of the hinge parameters and system performances are complicated, an optimization procedure was used to obtain the optimal design parameters, which maximized the system bandwidth. Based on the solution of the optimization problem, the design of the stage and FEM simulation results are presented. Finally, the stage was manufactured and tested.


Surgery of hyperparathyroidism: a conservative approach.
The extent of surgery in the treatment of primary hyperparathyroidism should be based on the pathologic entity of the disease. In neoplasia (either the common adenoma or the rare carcinoma), excision of the diseases parathyroid will generally suffice to cure the disease, but in primary hyperplasia, the removal of all the diseased glands except for a small amount of glandular tissue is required. The pathologic diagnosis of primary hyperparathyroidism can usually be made by a macroscopic assessment of the parathyroid. It is further delineated by the density test and confirmed by Sudan fat-frozen section examination.


Bolus Administration of Fentanyl and Midazolam for Colonoscopy Increases Endoscopy Unit Efficiency and Safety Compared With Titrated Sedation.
Guidelines recommend slow titration of sedatives for moderate sedation. Bolus sedation, in which a larger weight-based dose of medication is given upfront, has been shown in a single trial to be beneficial. We evaluated the effects of bolus sedation on procedural safety, efficiency, and patient experience. We performed a retrospective analysis of colonoscopies performed between April 2010 and April 2011 at Duke Medical Center. Colonoscopies before October 2010 were performed with nurse-directed titration of sedative (n = 966); colonoscopies performed after October 2010 were performed with physician-directed administration of bolus sedative (n = 699). We compared sedation and recovery times, medication doses, and adverse events between groups. We also compared patient satisfaction in a subset of patients from each group. Data were compared using the chi-square test for categorical variables and Wilcoxon rank sum test for continuous and ordinal categorical variables. Patients in the bolus group had a shorter sedation time (6.0 min) than patients in the titration group (13.0 min; P < .01) and a slightly longer colonoscopy time (25.0 min vs 24.0 min in the titration group; P < .01). Recovery time did not differ significantly between groups (53.0 min in the bolus group vs 52.1 min in the titration group; P = .07). Patients in the bolus group received lower weight-adjusted doses of fentanyl (1.71 μg/kg vs 1.89 μg/kg in the titration group) and midazolam (0.065 mg/kg vs 0.075 mg/kg in the titration group). A smaller proportion of patients in the bolus sedative group developed hypotension (12.7% vs 17.9% in the titration group; P < .01). These findings persisted even after adjustment for baseline patient age, race, sex, smoking status, alcohol use, body mass index, and American Society of Anesthesiologists' classification. In a retrospective study of patients undergoing colonoscopy, we found that compared with titrated administration of sedative, bolus dosing improves endoscopy unit efficiency and safety and decreases the amount of sedative required. This benefit does not come at the expense of the patient experience.


Role of substance P and bradykinin in acute pancreatitis induced by secretory phospholipase A2.
Secretory phospholipases A2 (sPLA2s) induce acute pancreatitis when injected into the common bile duct of rats. Substance P via neurokinin 1 (NK-1) receptors and bradykinin via B2 receptors are described to play important roles in the pathophysiology of acute pancreatitis. This study was undertaken to evaluate the role of substance P and bradykinin in the sPLA2-induced pancreatitis. Rats were submitted to the common bile duct injection of sPLA2 obtained from Naja mocambique mocambique venom at 300 microg/kg. At 4 hours thereafter, measurement of pancreatic plasma extravasation, pancreatic and lung myeloperoxidase (MPO), serum amylase, and serum tumor necrosis factor alpha levels were evaluated. Injection of sPLA2 significantly increased all parameters evaluated. Pretreatment with either the NK-1 receptor antagonist SR140333 or the B2 receptor antagonist icatibant largely reduced the increased pancreatic plasma extravasation and circulating levels of tumor necrosis factor alpha. Both treatments partly reduced the MPO levels in the pancreas, whereas in the lungs, icatibant was more efficient to reduce the increased MPO levels. In addition, icatibant largely reduced the serum levels of amylase, whereas SR140333 had no significant effect. We concluded that NK-1 and B2 receptors can regulate important steps in the local and remote inflammation during acute pancreatitis induced by sPLA2.


Evaluation of a novel quantitative canine species-specific point-of-care assay for C-reactive protein.
Species-specific point-of-care tests (POCT) permit a rapid analysis of canine C-reactive protein (CRP), enabling veterinarians to include CRP in clinical decisions. Aim of the study was to evaluate a novel POCT for canine CRP (Point Strip™ Canine CRP Assay) run on a small in-house-analyzer (Point Reader™ V) using lithium heparin plasma and to compare assay performance to an already established canine CRP assay (Gentian Canine CRP Immunoassay) run on two different bench top analyzers serving as reference methods (ABX Pentra 400, AU 5800). Linearity was assessed by stepwise dilution of plasma samples with high CRP concentrations. Limit of quantification (LoQ) was determined by repeated measurements of samples with low CRP concentrations. Coefficient of variation (CV) at low (10-50 mg/l), moderate (50-100 mg/l), and high (100-200 mg/l) CRP concentrations was investigated as well as possible interferences. Method comparison study was performed using 45 samples of healthy and diseased dogs. Quality criteria were fulfilled if the total observed error (TEobs = 2CV% + bias%) was below the minimal total allowable error of 44.4% (TE min). Additionally, a reference range (n = 60 healthy dogs) was established. Linearity was present at CRP concentrations of 10-132 mg/l (≙ 361 mg/l CRP with reference method) with a LoQ set at 10 mg/l. At moderate to high CRP concentrations, intra- and inter-assay CVs were ≤ 8% and ≤ 11% respectively, while CVs ≤ 22% and ≤ 28% were present at low concentrations. No interferences were observed at concentrations of 4 g/l hemoglobin, 800 mg/l bilirubin and 8 g/l triglycerides. Method comparison study demonstrated an excellent correlation with both reference methods (r = 0.98 for ABX Pentra 400; 0.99 for AU 5800), though revealing a proportional bias of 19.7% (ABX Pentra 400) and 10.7% (AU 5800) respectively. TEobs was 26.7-31.9% and 16.7-21.9% and thus < TEmin. Healthy dogs presented with CRP values ≤11.9 mg/l. The POCT precisely detects canine CRP at clinically relevant moderate and high CRP concentrations. The assay correlates well with both reference methods. Due to the bias, however, follow-up examinations should be performed with the same assay and analyzer.