Immune-Related Hub Genes and the Competitive Endogenous RNA Network in Alzheimer's Disease.
The pathogenesis of Alzheimer's disease (AD) involves various immune-related phenomena; however, the mechanisms underlying these immune phenomena and the potential hub genes involved therein are unclear. An understanding of AD-related immune hub genes and regulatory mechanisms would help develop new immunotherapeutic targets. The aim of this study was to explore the hub genes and the mechanisms underlying the regulation of competitive endogenous RNA (ceRNA) in immune-related phenomena in AD pathogenesis. We used the GSE48350 data set from the Gene Expression Omnibus database and identified AD immune-related differentially expressed RNAs (DERNAs). We constructed protein-protein interaction (PPI) networks for differentially expressed mRNAs and determined the degree for screening hub genes. By determining Pearson's correlation coefficient and using StarBase, DIANA-LncBase, and Human MicroRNA Disease Database (HMDD), the AD immune-related ceRNA network was generated. Furthermore, we assessed the upregulated and downregulated ceRNA subnetworks to identify key lncRNAs. In total, 552 AD immune-related DERNAs were obtained. Twenty hub genes, including PIK3R1, B2M, HLA-DPB1, HLA-DQB1, PIK3CA, APP, CDC42, PPBP, C3AR1, HRAS, PTAFR, RAB37, FYN, PSMD1, ACTR10, HLA-E, ARRB2, GGH, ALDOA, and VAMP2 were identified on PPI network analysis. Furthermore, upon microRNAs (miRNAs) inhibition, we identified LINC00836 and DCTN1-AS1 as key lncRNAs regulating the aforementioned hub genes. AD-related immune hub genes include B2M, FYN, PIK3R1, and PIK3CA, and lncRNAs LINC00836 and DCTN1-AS1 potentially contribute to AD immune-related phenomena by regulating AD-related hub genes.


Does the presence of diabetes mellitus confer an increased risk of stroke in patients with atrial fibrillation on direct oral anticoagulants? A systematic review and meta-analysis.
There is limited data on clinical outcomes in high risk groups such as patients with diabetes mellitus (DM) with atrial fibrillation (AF) on direct-acting oral anticoagulants (DOACs). Using a systematic review and meta-analysis of published studies, we aimed to determine the risk of stroke and other clinical outcomes in patients with AF on DOACs, with or without DM. Observational cohort studies reporting clinical outcomes in patients with AF on DOACs, with or without DM were identified from MEDLINE, Embase, Web of Science, the Cochrane Library, and search of bibliographies to April 2020. Summary measures of effect were relative risks with 95% confidence intervals (CIs). Eight studies comprising of 4 observational cohorts (n = 76,260 participants) and 4 randomised controlled trials (RCTs) (n = 71,683 participants) were included. In RCTs, DOACs compared with warfarin reduced the risk of the composite outcome of stroke and systemic embolism, CVD death and intracranial bleeding in patients with DM: RRs (95% CIs) of 0.75 (0.62-0.90), 0.84 (0.72-0.97), and 0.57 (0.40-0.81) respectively. The corresponding estimates for patients without DM were 0.81 (0.68-0.96), 0.93 (0.80-1.08), and 0.47 (0.31-0.70) respectively. There was no evidence of interactions between DM status and effects of DOACs. The absolute reduction in clinical outcomes with DOACs compared to warfarin was greater in DM than without DM. Regardless of treatment strategy, interventional and observational evidence indicate that patients with DM had higher rates of stroke or systemic embolism, mortality and major bleeding compared to patients without DM. Patients with AF and DM have increased risk of vascular events, which is reduced with the use of DOACs. The use of DOACs should be considered as an option in reducing the risk of stroke in these populations. PROSPERO 2020: CRD42020157196.


[Treatment of advanced ovarian cancer: results of the Department of Clinical Pharmacology and Chemotherapy, N.N. Blokhin RORC from 1993-2010].
The aim of this study was to analyse the outcome of ovarian cancer depending on the type of surgical debulking, the strategy of treatment of recurrent cancer, and other clinical factors. We performed retrospective analysis of patients with stage IC-IV ovarian cancer treated at the Department of Clinical Pharmacology and Chemotherapy in 1993-2010. A total of 353 patients were included. The medians of progression-free and overall survival were 11.3 and 40.8 months respectively. The results of the treatment depended on the mode of surgical debulking, histological type and stage of the tumour, regimen of front-line chemotherapy. The main prognostic factor in recurrent ovarian cancer was the number of potentially effective anticancer agents used during the treatment.


Laboratory diagnosis, clinical management and infection control of the infections caused by extensively drug-resistant Gram-negative bacilli: a Chinese consensus statement.
Extensively drug-resistant (XDR) Gram-negative bacilli (GNB) are defined as bacterial isolates susceptible to two or fewer antimicrobial categories. XDR-GNB mainly occur in Enterobacteriaceae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia. The prevalence of XDR-GNB is on the rise in China and in other countries, and it poses a major public health threat as a result of the lack of adequate therapeutic options. A group of Chinese clinical experts, microbiologists and pharmacologists came together to discuss and draft a consensus on the laboratory diagnosis, clinical management and infection control of XDR-GNB infections. Lists of antimicrobial categories proposed for antimicrobial susceptibility testing were created according to documents from the Clinical Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the United States Food and Drug Administration (FDA). Multiple risk factors of XDR-GNB infections are analyzed, with long-term exposure to extended-spectrum antimicrobials being the most important one. Combination therapeutic regimens are summarized for treatment of XDR-GNB infections caused by different bacteria based on limited clinical studies and/or laboratory data. Most frequently used antimicrobials used for the combination therapies include aminoglycosides, carbapenems, colistin, fosfomycin and tigecycline. Strict infection control measures including hand hygiene, contact isolation, active screening, environmental surface disinfections, decolonization and restrictive antibiotic stewardship are recommended to curb the XDR-GNB spread.


Localised concentrations of elements in hamster cardiomyopathy. Electron microscopic x-ray microanalysis of normal and sick myocardia.
Localized elemental concentrations of Ca, P, Cl, S, and Zn were detected by X-ray microanalysis during viewing of ultrathin myocardial sections. Cardiomyopathic hamsters were compared with a healthy strain of the same age. Significant increases in calcium and chlorine concentrations were found in sick animals. These were highest in the hypertrophic stage of the disease. Phosphorus and zinc were more variable. Ratios between elements (especially P/Ca) in the same cells and of the same elements in different cell types were found to offer numerical criteria for estimating the degree of pathological change.


Plasticity of grasshopper vitellogenin production in response to diet is primarily a result of changes in fat body mass.
Life history plasticity is the developmental production of different phenotypes by similar genotypes in response to different environments. Plasticity is common in early post-embryonic or adult development. Later in the developmental stage, the transition from developmentally plastic to canalized (i.e., inflexible) phases is often associated with the attainment of a threshold level of storage. Thresholds are often described simply as total body mass or cumulative consumption of food. The physiological characteristics of thresholds, such as the contributions of the growth of particular organs or the production rate of proteins, are largely unstudied. To address the physiology underlying a threshold-induced developmental transition, total vitellogenin production in response to diet quality in the lubber grasshopper was studied. For individuals that differed in age or dietary protein, somatic mass, ovarian mass, fat body mass, mass-specific vitellogenin production, vitellogenin titer, and storage protein titer were measured. Age and diet strongly affected these parameters, with ovarian mass and fat body mass contributing most to the differences. During mid vitellogenesis, females were highly plastic in response to changing food quality. Only during late vitellogenesis were females unresponsive to changes in food quality. Fat body mass was a more important component of plasticity than was mass-specific vitellogenin production. Because these two variables together make up total vitellogenin production, the greater contribution of fat body mass than mass-specific vitellogenin production suggests that growth factors may be more important than tissue stimulators in producing developmental changes in total vitellogenin production. To our knowledge, this is the first study to demonstrate that mass gain of an organ is more important to developmental plasticity than is the output of that same organ.


The influence of waiting times on cost-effectiveness: a case study of colorectal cancer mass screening.
When a cost-effectiveness analysis is implemented, the health-care system is usually assumed to adjust smoothly to the proposed new strategy. However, technological innovations in health care may often induce friction in the organization of care supply, implying the congestion of services and subsequent waiting times. Our objective here is to measure how these short run rigidities can challenge cost-effectiveness recommendations favorable to an innovative mass screening test for colorectal cancer. Using Markov modeling, we compare the standard Guaiac fecal occult blood test (gFOBT) with an innovative screening test for colorectal cancer, namely the immunological fecal occult blood test (iFOBT). Waiting time can occur between a positive screening test and the subsequent confirmation colonoscopy. Five scenarios are considered for iFOBT: no further waiting time compared with gFOBT, twice as much waiting time for a period of 5 or 10 years, and twice as much waiting time for a period of 5 or 10 years combined with a 25% decrease in participation to confirmation colonoscopies. According to our modeling, compared with gFOBT, iFOBT would approximately double colonoscopy demand. Probabilistic sensitivity analysis enables concluding that the waiting time significantly increases the uncertainty surrounding recommendations favorable to iFOBT if it induces a decrease in the adherence rate for confirmation colonoscopy.


Risk Factors for Surgical Shunting in a Large Cohort With Ischemic Priapism.
Ischemic priapism is treated with a stepwise algorithm, but some patients may benefit from immediate shunt placement. To identify risk factors for surgical shunt placement in a large series of patients with ischemic priapism. We identified all patients presenting to our institution with ischemic priapism from January 2010 to December 2018. Multivariable was performed to assess risk factors for surgical shunting. Receiver operating characteristic curve analysis (Youden Index) was used to assess which cutoff time for the duration of priapism was most predictive requiring shunting. We assess risk factors for surgical shunting and what duration of priapism was most predictive of requiring a shunt. We identified a total of 169 ischemic priapism encounters from 143 unique patients, of which 26 (15%) encounters resulted in a surgical shunt. Patients treated with a shunt had longer priapism durations than those without (median 36 vs 10 hours, P < .001). Independent predictors of a surgical shunt on multivariate logistic regression were the duration of priapism in hours (odds ratio: 1.05, 95% confidence interval: 1.02-1.10; P < .001) and history of prior priapism (odds ratio: 3.15, 95% confidence interval: 1.03-9.60; P = .045). Receiver operating characteristic curve analysis using priapism duration to predict the need for shunt generated an area under curve of 0.83. A duration of 24 hours correlated to a sensitivity of 0.77 and specificity of 0.90. These results can be used to counsel future patients and assist in the decision-making process for providers. This is one of the largest series of priapism in the literature. Most (74%) of the priapism were due to intracavernosal injections so the results may not be generalizable to populations with different priapism etiologies. In this study of 169 priapism encounters, we found that the priapism duration and history of prior priapism were independent predictors of surgical shunt placement. These results can aid urologists in the counseling and decision-making process of these challenging cases. Zhao H, Dallas K, Masterson J, et al. Risk Factors for Surgical Shunting in a Large Cohort With Ischemic Priapism. J Sex Med 2020;17:2472-2477.


Renal Bleeding Due to Extramedullary Hematopoiesis in a Patient With Chronic Myelogenous Leukemia.
Chronic myelogenous leukemia (CML) is a myeloproliferative disorder that normally presents in middle-aged adults. Renal infiltration and extramedullary hematopoiesis in renal tissue has been rarely reported. This case report presents a patient with CML and renal insufficiency who developed gross hematuria. Efforts at controlling the hematuria led to a cascade of events propelled by the underlying disorder that ultimately led to a radical nephrectomy, multiorgan failure, and prolonged hospitalization. We suggest that management of gross hematuria in clinically stable patients with CML, suspected of having extramedullary hematopoiesis, should prioritize treatment of the myeloproliferative disorder over efforts to control bleeding.


Sonochemical reaction with microbubbles generated by hollow ultrasonic horn.
A microbubble generator with a cylindrical hollow ultrasonic horn (HUSH), gas flow path, and an orifice inside it can produce high ultrasonic pressure around the generated microbubbles. We used this microbubble generator with a HUSH as a sonochemical reactor for the degradation of indigo carmine and evaluated the sonochemical reaction by simply inserting the horn end into a liquid. The experimental results revealed that the ultrasonic irradiation around ultrasonically generated microbubbles effectively degraded indigo carmine in water. In addition, degradation experiments performed by varying the ultrasonic power and gas flow rates indicated that a continuous gas supply and ultrasonic pressure were required for generating the microbubbles, without the generation of millimeter-scale bubbles, to enhance the sonochemical reaction in water.


Prevalence and Prognostic Implications of Moderate or Severe Mitral Regurgitation in Patients with Bicuspid Aortic Valve.
Significant (moderate or greater) mitral regurgitation (MR) could augment the hemodynamic effects of aortic valvular disease in patients with bicuspid aortic valve (BAV), imposing a greater hemodynamic burden on the left ventricle and atrium, possibly culminating in a faster onset of left ventricular dilation and/or symptoms. The aim of this study was to determine the prevalence and prognostic implications of significant MR in patients with BAV. In this large, multicenter, international registry, a total of 2,932 patients (mean age, 48 ± 18 years; 71% men) with BAV were identified. All patients were evaluated for the presence of significant primary or secondary MR by transthoracic echocardiography and were followed up for the end points of all-cause mortality and event-free survival. Overall, 147 patients (5.0%) had significant primary (1.5%) or secondary (3.5%) MR. Significant MR was associated with all-cause mortality (hazard ratio [HR], 2.80; 95% CI, 1.91-4.11; P < .001) and reduced event-free survival (HR, 1.97; 95% CI, 1.58-2.46; P < .001) on univariable analysis. MR was not associated with all-cause mortality (adjusted HR, 1.33; 95% CI, 0.85-2.07; P = .21) or event-free survival (adjusted HR, 1.10; 95% CI, 0.85-1.42; P = .49) after multivariable adjustment. However, sensitivity analyses demonstrated that significant MR not due to aortic valve disease retained an independent association with mortality (adjusted HR, 1.81; 95% CI, 1.04-3.15; P = .037). Subgroup analyses demonstrated an independent association between significant MR and all-cause mortality for individuals with significant aortic regurgitation (HR, 2.037; 95% CI, 1.025-4.049; P = .042), although this association was not observed for subgroups with significant aortic stenosis or without significant aortic valve dysfunction. Significant MR is uncommon in patients with BAV. Following adjustment for important confounding variables, significant MR was not associated with adverse prognosis in this large study of patients with BAV, except for the patient subgroup with moderate to severe aortic regurgitation. In addition, significant MR not due to aortic valve disease demonstrated an independent association with all-cause mortality.


Kindling-like convulsive activities in the isolated ileum of the guinea pig. I. Electrical stimulation.
A kindling-like convulsive activity model produced by subthreshold, iterative electrical stimulation of the isolated male guinea pig ileum is described. In this model, the mechanical activity of the longitudinal muscular fibers of the ileum was systematically quantified in terms of the basic frequency, tonus, amplitude, and transient amplitude increments (A, n spikes/20 min) of "normal" contractions and presence of high-amplitude, paroxysmal, "epileptiform" contractures (B, n spikes/20 min). Changes in these parameters were statistically compared through consecutive stages of the same stimulated male ileum (I = initial activation, II = initial inhibition. IIIA = late activation, and IV = late inhibition) and equivalent stages of stimulated female and nonstimulated male ilea where "kindling-like" activities were only occasionally observed. Basic tonus, amplitude, and number of A spikes showed significant changes through consecutive stimulated male ileum "kindling" stages: increased from baseline to stage I, decreased from I to II, increased from II to III and from III to IIIA, and decreased from IIIA to IV. The number of B spikes significantly increased from II to III, III to IIIA, and IIIA to IV. No significant changes in baseline frequency were found through all stages nor in tonus, amplitude, A and B spikes between stage IV and the self-sustained activity observed 120 min after stimulation. In addition, there were significant correlations between B spikes vs. basic tonus and amplitude and A spikes when the stimulated male ileum shifted from stage II to IIIA (positive correlations) and from IIIA to IV (negative correlations). Basic tonus during stage I, basic amplitude during IIIA, A spikes during self-sustained activity and B spikes during III, IIIA, IV, and self-sustained activity were in the stimulated male ileum larger than those in both the stimulated female and the nonstimulated male ilea. Tonus and A spikes during III and IIIA in the stimulated male ileum were larger than in the nonstimulated, whereas tonus during IV and self-sustaining activity and amplitude during II in the stimulated male ileum were smaller than in the female stimulated ileum.


Starvation-inducible loci of Salmonella typhimurium: regulation and roles in starvation-survival.
Four starvation-inducible loci (stiA, stiB, stiC, and stiE) of Salmonella typhimurium have been extensively characterized as to their genetic and physiologic regulation, and their roles in survival during prolonged simultaneous phosphate (P)-, carbon (C)- and nitrogen (N)-starvation (PCN-starvation). Strains of S. typhimurium LT-2, isogenic with the exception of lacking either the stiA, stiB or stiC locus, died off more quickly and survived at much reduced levels compared with their wild-type parent. When certain sti mutations were combined in the same strain, we found that viability of these cultures declined even more rapidly, and starvation-survival was affected to levels over-and-above the additive effects of each individual mutation, indicating an epistatic relationship between these loci. All four sti loci were, directly or indirectly, under negative control by the crp gene product (cAMP receptor protein, CRP). With the exception of stiB, all were similarly regulated by the cya gene product (i.e., cAMP). This suggests that CRP acts alone, or with a signal molecule other than cAMP, to cause repression of the stiB locus. In addition, all four loci are under positive regulation by the relA gene product (i.e., ppGpp) during C- or N-starvation, but not P-starvation. Since not all relA-dependent sti loci are induced during both C- and N-starvation, we propose that two separate ppGpp-dependent pathways function during C-starvation and N-starvation, respectively. Possible models for separate P-, C- and N-starvation-induction pathways are discussed.


Intra-arterial carboplatin and intravenous etoposide for the treatment of recurrent and progressive non-GBM gliomas.
Recurrent and progressive non-GBM gliomas are a diverse group of brain tumors that often respond poorly to adjuvant chemotherapy treatment. Regional intra-arterial (IA) administration of chemotherapy may result in increased tumor uptake of drug, with improvement in response rates and time to progression (TTP). Twenty-five patients with recurrent or progressive non-GBM gliomas were treated with IA carboplatin (200 mg/m2/d) and intravenous (IV) etoposide (100 mg/m2/d) for 2 days every 4 weeks. Patients ranged in age from 22 to 68 years (mean 37.8). All but one patient had received standard irradiation, and eight patients had attempted prior chemotherapy. Five of 25 patients had objective responses (20%), while another 15 patients had stable disease (60%), receiving a total of 318 IA treatment procedures. There was one complete response (4.0%), three partial responses (12.0%), one minor response (4.0%), 15 stable diseases (60.0%), and five progressive diseases (20.0%). The median TTP was 24.2 weeks overall and 32 weeks in responders. Overall median survival was 34.2 weeks. Therapy was well tolerated, with mainly hematologic toxicity. Two patients had embolic complications. Although these are preliminary results, IA carboplatin and IV etoposide have modest activity against recurrent and progressive non-GBM gliomas and warrants further study.


The PROMIS satisfaction with social participation measures demonstrated responsiveness in diverse clinical populations.
To conduct a longitudinal evaluation of Patient-Reported Outcomes Measurement Information System (PROMIS) social function measures (satisfaction with participation in social roles and satisfaction with participation in discretionary social activities) in English-speaking people with chronic health conditions. Adults receiving treatment for chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD), chronic back pain, or depression completed PROMIS computer-based measures of social health at two time points approximately 3 months apart and global ratings of change. Linear mixed effects models and standardized response means were estimated for the two social function measures. A total of 599 people participated: 79 with stable COPD, 46 COPD exacerbation, 60 with CHF, 196 with depression, and 218 with back pain. Four groups experienced improvement over time, one (COPD stable) changed very little. Those who reported better global ratings of change in overall health experienced larger changes in social function than those who reported the same or worse global health. This study provided support for responsiveness to change for two PROMIS social function measures. These results provide further evidence of the PROMIS goal to enable comparable measurement of universally relevant symptoms and experiences that apply to people with a variety of diseases.


Differential effects of cytochalasin D and 2,3 butanedione monoxime on isometric twitch force and transmembrane action potential in isolated ventricular muscle: implications for optical measurements of cardiac repolarization.
2,3-Butanedione monoxime (BDM) has been widely used to inhibit contraction during optical recordings of cardiac membrane voltage changes, even though it markedly abbreviates cardiac action potentials. We compared the effects of BDM and of the F-actin disrupter cytochalasin D (cyto D) on isometric twitch force and transmembrane action potentials in isolated canine right ventricular trabeculae superfused with Tyrode's solution (2 mmol/L CaCl2, 37 degrees C) and stimulated at 0.5 Hz. BDM at 10 mmol/L and cyto D at 80 micromol/L were equally effective in reducing peak isometric force to 10%+/-3% (n = 6; mean+/-SEM) and 8%+/-1% (n = 8), respectively. Neither agent significantly altered resting tension. While 10 mmol/L BDM markedly shortened the action potential duration at 90% repolarization (APD90) from 198+/-7 msec to 146+/-9 msec (P < 0.001), 80 micromol/L cyto D had no significant effects on APD90 or on any other action potential parameter. The effects of BDM on peak isometric force and APD were completely reversible after 15 minutes of washout, whereas in the cyto D group contractile force continued to be reduced (13%+/-3%) and action potential characteristics did not show significant changes from control values after a 60-minute period of superfusion with cyto D-free Tyrode's solution. We conclude that cyto D should be considered an alternative excitation-contraction uncoupler for optical mapping studies of cardiac repolarization.


Exploring the Asian ethnic predisposition to dry eye disease in a pediatric population.
To investigate the differences in ocular surface characteristics, tear film parameters, and dry eye symptomology between co-located pediatric populations of Asian and Caucasian ethnicity. Seventy New Zealand-born pediatric participants, aged between 5 and 18 years, were recruited in an age and environmentally controlled cross-sectional study. Participants were classified into three groups according to ethnicity and eyelid morphology: Asian single lid (ASL), Asian double lid (ADL), and Caucasian double lid (CDL). Ocular biometry, tear film parameters, ocular surface characteristics, and dry eye symptomology were evaluated in a single clinical session. Overall, no significant intergroup differences were observed in tear film quality, dry eye symptomology, and meibomian gland dropout. A higher proportion of ASL and ADL participants exhibited incomplete blinking than the Caucasian group (both p < 0.001). Meibomian gland shortening was more frequently observed among the two Asian groups (both p < 0.05), while gland tortuosity was more common in the Caucasian group (both p < 0.001). ASL participants exhibited greater inferior lid wiper epitheliopathy grades than ADL participants (p = 0.01), and corneal astigmatism was more pronounced in the ASL than CDL group (p = 0.02). Ethnic differences in meibomian gland morphological patterns were observed in the current pediatric cohort, although overall meibomian gland dropout did not differ between groups. Asian participants exhibited a higher degree of incomplete blinking, and more marked inferior lid wiper epitheliopathy and corneal astigmatism were observed in the ASL group. These findings would suggest that eyelid anatomy and tension may potentially be implicated in the development of ethnic differences in dry eye disease later in life.


Determinants of optimal insecticide resistance management strategies.
The use of insecticides to control agricultural pests has resulted in resistance developing to most known insecticidal modes of action. Strategies by which resistance can be slowed are necessary to prolong the effectiveness of the remaining modes of action. Here we use a flexible mathematical model of resistance evolution to compare four insecticide application strategies: (i) applying one insecticide until failure, then switching to a second insecticide (sequential application), (ii) mixing two insecticides at their full label doses, (iii) rotating (alternating) two insecticides at full label dose, or (iv) mixing two insecticides at a reduced dose (with each mixture component at half the full label dose). The model represents target-site resistance. Multiple simulations were run representing different insect life-histories and insecticide characteristics. The analysis shows that none of the strategies examined were optimal for all the simulations. The four strategies: reduced dose mixture, label dose mixture, sequential application and label dose rotation, were optimal in 52%, 22%, 20% and 6% of simulations respectively. The most important trait determining the optimal strategy in a single simulation was whether or not the insect pest underwent sexual reproduction. For asexual insects, sequential application was most frequently the optimal strategy, while a label-dose mixture was rarely optimal. Conversely, for sexual insects a mixture was nearly always the optimal strategy, with reduced dose mixture being optimal twice as frequently as label dose mixture. When sequential application of insecticides is not an option, reduced dose mixture is most frequently the optimal strategy whatever an insect's reproduction.


Healthy diets, healthy hearing: National Health and Nutrition Examination Survey, 1999-2002.
A significant relationship between dietary nutrient intake and susceptibility to acquired hearing loss is emerging. Variability in the outcomes across studies is likely related to differences in the specific metrics used to quantify nutrient intake and hearing status. Most studies have used single nutrient analysis. Although this analysis is valuable, interactions between nutrients are increasingly recognized and could modify modeling of single nutrient effects. Therefore, we examined the potential relationship between diet and hearing using a metric of overall dietary quality. This cross-sectional analysis was based on healthy eating index data and audiological thresholds. Data for adults between the ages of 20 to 69 years of age were drawn from the National Health and Nutrition Examination Survey, 1999-2002. Controlling for age, race/ethnicity, sex, education, diabetes, and noise exposure, we found a significant negative relationship (Wald F = 6.54, df = 4, 29; p ≤ 0.05) between dietary quality and thresholds at higher frequencies, where higher dietary quality was associated with lower hearing thresholds. There was no statistically significant relationship between dietary quality and threshold sensitivity at lower frequencies. The current findings support an association between healthier eating and better high frequency thresholds in adults.


Treatment for lactation suppression: little progress in one hundred years.
Our goal was to characterize the postpartum symptoms experienced by women who do not breast-feed and to review data on the efficacy of nonpharmacologic methods of lactation suppression. The placebo arms of randomized clinical trials of pharmacologic methods for lactation suppression were used to characterize postpartum symptoms. A subset of the placebo arms was reviewed to assess current strategies for treatment of symptoms associated with lactation suppression. Studies of nonpharmacologic methods of lactation suppression were also reviewed to assess efficacy. Engorgement and breast pain may encompass most of the first postpartum week. Up to one third of women who do not breast-feed and who use a brassiere or binder, ice packs, or analgesics may experience severe breast pain. Specific studies of nonpharmacologic methods of lactation suppression were limited and inconclusive. Available data suggest that many women using currently recommended strategies for treatment of symptoms may nevertheless experience engorgement or pain for most of the first postpartum week.


Impact of fine-grained sediment on mountain stream macroinvertebrate communities: Forestry activities and beaver-induced sediment management.
Fine-grained sediments are a natural component of river systems. Human activities generate additional sources of fine sediment. In mountainous areas, the anthropogenic inputs of fine sediments are associated with forestry. The aim of this study was to analyse the differences in the macroinvertebrate communities between the reference and caused by forest harvesting activities increased influx of fine-sediment to mountain streams. The tested hypothesis was that the macroinvertebrate communities will differ depending on the intensity of forest harvesting practices in the stream catchment that causes excessive influx of fine sediment into the stream. The reintroduction of beavers in the study area, and the formation of in-stream beaver dams, contribute the accumulation of sediments in stream sections with slower water. Thus, it was also assumed that by capturing and storing fine sediments, may contribute to the restoration of the natural structure of the benthic communities downstream of the ponds. The study was carried out in a mountain stream catchment area (Carpathians, Poland), in which inflow of fine sediments in the stream sections varied in intensity. The study was conducted over three years (2018-2020). The extensive use of forest roads, timber skidding trails, and timber storage areas produced fine sediments that clogged the interstitial spaces between the stones in the riffles, limiting the presence of rheophilic taxa associated with coarse-grained substrates. The reduction of the number of scrapers and shredders (i.e. primary consumers) associated with the influx of fine sediments may significantly affect the entire food-web structure in stream ecosystems. The capture and deposition of fine sediments in beaver ponds may accelerate the revitalisation of the flowing sections of the stream. Beaver-induced sediment management is strongly recommended as a beneficial practice that could contribute to ecological preservation and the potential of streams, particularly in mountain areas.


Validation of Novel Fibrosis Index (NFI) for assessment of liver fibrosis: comparison with transient elastography (FibroScan).
In this study, we collated cheap and readily available non-invasive biomarkers and FibroScan score in predicting fibrosis stages in chronic hepatitis C virus (HCV) infection. We studied 1898 patients with HCV infection confirmed by presence of HCV RNA in their serum. We compared the FibroScan score and fibrosis indices (FIs): aspartate transaminase (AST) to alanine transaminase (ALT) ratio (AAR), AST to Platelet Ratio Index (APRI), FI, fibrosis-4 (FIB-4), Age-Platelet Index (API), Pohl score, Fibrosis Cirrhosis Index (FCI). We developed a new FI, named Novel Fibrosis Index (NFI) calculated by the following formula: NFI=[(bilirubin×(ALP)2)/(platelet count (albumin)2)]-n. AAR, APRI, FI, FIB-4, API, Pohl score, FCI and NFI were able to predict fibrosis stage with correlation coefficient indices 0.848, 0.711, 0.618, 0.741, 0.529, 0.360, 0.477 and 0.26, respectively. Receiver operating characteristic curves showed sensitivity and specificity for predicting F3 by NFI=75.1% and 41.1% and F4 for NFI=72.1% and 47.1%, AAR=62.8% and 37.6%, APRI=74.6% and 87.6%, FIB-4=53.2% and 72.3%, FI=78.1% and 92.3%, API=78.1% and 60%, Pohl score=38.1% and 78.1% and FCI=78.1% and 88.1%. Our NFI predicted F3 and has been found to have more sensitivity and specificity in predicting F4 fibrosis stage than other FIs.


Popliteal cysts in a pediatric patient.
A 12-year-old boy with recurrent complaints of knee pain and swelling for six months, but without diagnosed rheumatological disease, presented with calf swelling and knee pain of several days duration. Examination revealed findings consistent with juvenile rheumatoid arthritis and a ruptured Baker's cyst. This is the sixth reported case of ruptured Baker's cyst reported in a child less than 14 years old and should alert emergency physicians that calf pain and swelling secondary to a ruptured popliteal (Baker's) cyst may be an early manifestation of juvenile rheumatoid arthritis.


New Mexico safety restraint law: changing patterns of motor vehicle injury, severity, and cost.
The impact of the New Mexico safety belt law on patterns of injury, severity, and cost was evaluated (using an emergency department data base). Data collected from November 1985 through February 1986 compared the 2 months before the January 1986 law with 2 months after. Before the law, 22.2% of the 379 injuries included abrasions, contusions, and lacerations to face, neck, and head. Following the law, this category constituted only 13.8% of 356 injuries, representing a reduction of 38% (P less than .05). Cost and injury severity scores (ISS) for 436 injured patients covered by the law were not significantly different between the pre- and post-seatbelt law periods. However, significant cost and severity differences were observed after the law between belted and nonbelted occupants: +2,569 compared with +662; ISS of 3.6 compared with 2.0 (P less than .05). Methodologic problems of an emergency department-based study and the need for E coding (external causes of injury) are discussed.


Optically-generated focused ultrasound for noninvasive brain stimulation with ultrahigh precision.
High precision neuromodulation is a powerful tool to decipher neurocircuits and treat neurological diseases. Current non-invasive neuromodulation methods offer limited precision at the millimeter level. Here, we report optically-generated focused ultrasound (OFUS) for non-invasive brain stimulation with ultrahigh precision. OFUS is generated by a soft optoacoustic pad (SOAP) fabricated through embedding candle soot nanoparticles in a curved polydimethylsiloxane film. SOAP generates a transcranial ultrasound focus at 15 MHz with an ultrahigh lateral resolution of 83 µm, which is two orders of magnitude smaller than that of conventional transcranial-focused ultrasound (tFUS). Here, we show effective OFUS neurostimulation in vitro with a single ultrasound cycle. We demonstrate submillimeter transcranial stimulation of the mouse motor cortex in vivo. An acoustic energy of 0.6 mJ/cm2, four orders of magnitude less than that of tFUS, is sufficient for successful OFUS neurostimulation. OFUS offers new capabilities for neuroscience studies and disease treatments by delivering a focus with ultrahigh precision non-invasively.


Mice exhibit stochastic and efficient action switching during probabilistic decision making.
In probabilistic and nonstationary environments, individuals must use internal and external cues to flexibly make decisions that lead to desirable outcomes. To gain insight into the process by which animals choose between actions, we trained mice in a task with time-varying reward probabilities. In our implementation of such a two-armed bandit task, thirsty mice use information about recent action and action–outcome histories to choose between two ports that deliver water probabilistically. Here we comprehensively modeled choice behavior in this task, including the trial-to-trial changes in port selection, i.e., action switching behavior. We find that mouse behavior is, at times, deterministic and, at others, apparently stochastic. The behavior deviates from that of a theoretically optimal agent performing Bayesian inference in a hidden Markov model (HMM). We formulate a set of models based on logistic regression, reinforcement learning, and sticky Bayesian inference that we demonstrate are mathematically equivalent and that accurately describe mouse behavior. The switching behavior of mice in the task is captured in each model by a stochastic action policy, a history-dependent representation of action value, and a tendency to repeat actions despite incoming evidence. The models parsimoniously capture behavior across different environmental conditionals by varying the stickiness parameter, and like the mice, they achieve nearly maximal reward rates. These results indicate that mouse behavior reaches near-maximal performance with reduced action switching and can be described by a set of equivalent models with a small number of relatively fixed parameters.


Co-MOF-67 derived hollow double-shell core Co3O4 with Zn0.5Cd0.5S to construct p-n heterojunction for efficient photocatalytic hydrogen evolution.
It is an effective way to improve the photocatalytic hydrogen evolution activity by constructing a unique structure and tuning the morphology of catalysts. On the one hand, ZIF-67 was used as a precursor to prepare Co3O4 derivatives with different morphologies [Co3O4 (Porous Polyhedron) and Co3O4db (Hollow Double-Shelled Polyhedron)]. The hollow polyhedron have the advantages of large specifie surface area, low density, stable three-dimensional spatial structure and excellent electron transport channels, which provide great advantages for the enhancement of photocatalytic activity in photocatalytic reactions. On the flip side, p-type Co3O4 polyhedron and n-type Zn0.5Cd0.5S nanoparticles are successfully coupled to construct a p-n heterojunction, which accelerated the transfer and separation of electrons and holes, thus enhancing the photocatalytic hydrogen production efficiency. Therefore, the composite catalyst (Zn0.5Cd0.5S-Co3O4db-20 %) exhibits excellent hydrogen evolution activity (33885 μmol·h-1·g-1), which is 9.17 times that of pure Zn0.5Cd0.5S (3695 μmol·h-1·g-1) and 1.21 times that of Zn0.5Cd0.5S-Co3O4-20 % (27903 μmol·h-1·g-1). This work provides a new idea for tuning the photocatalytic morphology to enhance the hydrogen evolution activity.


Recovery from water stress affects grape leaf petiole transcriptome.
Fast and efficient recovery from water stress is a key determinant of plant adaptation to changing meteorological conditions modulating transpiration, i.e. air temperature and humidity. We analysed transcriptomic responses during rehydration after water stress in grapevine leaf petioles, where embolism formation and repair commonly take place, and where metabolic changes related to embolism recovery are expected to be particularly important. We compared gene expression of recovering plants with irrigated controls, upon high and low transpiration conditions, using cDNA microarrays. In parallel, we assessed the daily dynamics of water relations, embolism formation and repair, and leaf abscisic acid concentration. In recovering plants, the most affected gene categories were secondary metabolism, including genes linked to flavonoid biosynthesis; sugar metabolism and transport, and several aquaporin genes. The physiological dynamics of recovery were lower and the number of differentially expressed probes was much lower upon low transpiration than found in actively transpiring grapevines, suggesting the existence of a more intense metabolic reorganization upon high transpiration conditions and of a signal eliciting these responses. In plants recovering under high transpiration, abscisic acid concentrations significantly increased, and, in parallel, transcripts linked to abscisic acid metabolism and signalling (ABA-8'-hydroxylase, serine-threonine kinases, RD22 proteins) were upregulated; a trend that was not observed upon low transpiration. Our results show that recovery from water stress elicits complex transcriptomic responses in grapevine. The increase observed in abscisic acid cellular levels could represent a signal triggering the activation of responses to rehydration after stress.


Vascular Signalling.
In all vertebrates, closed blood and open lymph circulatory systems are essential for the delivery of nutrients and oxygen to tissues, waste clearance, and immune function [...].


Pyk2 deficiency enhances bone mass during midpalatal suture expansion.
To determine if Pyk2 deficiency increases midpalatal suture bone mass and preserves sutural integrity after maxillary expansion. Thirty-six male Pyk2 knockout (KO) and control (WT) mice at 6 weeks of age. Mice received nickel-titanium spring expanders delivering 0 g (no intervention control), 10 or 20 g force for 14 days. High-resolution micro-CT was used to determine bone volume/tissue volume (BV/TV), sutural width and intermolar width. Effects on osteoclasts, chondrocytes and suture morphology were determined by histomorphometry. Pyk2-KO controls (0 g) had 7% higher BV/TV compared with WT controls. Expanded Pyk2-KO maxillae also exhibited 12% (10 g) and 18% (20 g) higher BV/TV than WT mice. Although bone loss following expansion occurred in both genotypes, BV/TV was decreased to a greater extent in WT maxillae (-10% at 10g; -22% at 20 g) compared with Pyk2-KO maxillae (-11% only at 20 g). Expanded WT maxillae also showed a greater increase in sutural width, intermolar width and fibrous connective tissue width compared with expanded Pyk2-KO maxillae. Moreover, osteoclast number was increased 77% (10 g) and 132% (20 g) in expanded WT maxillae, but remained unchanged in expanded Pyk2-KO, compared to their respective controls. Cartilage area and chondrocyte number were increased to the same extent in expanded WT and Pyk2-KO sutures. These findings suggest that midpalatal suture expansion increases osteoclast formation in WT but not Pyk2-KO mice, leading to higher BV/TV in expanded Pyk2-KO maxillae. These studies suggest Pyk2-targeted strategies may be beneficial to increase bone density and preserve sutural integrity during maxillary expansion.


Hidden grief reactions on a psychiatric consultation service.
Assessment of the family and social relationships of 123 medical and surgical patients consecutively referred to the psychiatric consultation-liaison service revealed that acute or unresolved grief was present in 15% of patients. Patients with unresolved grief often presented with depression and/or conflict with the medical or nursing staff. The referring physician in most cases recognized the presence of acute grief; however, all cases of unresolved grief presented as "hidden" grief reactions. Patients with acute grief rarely had associated psychiatric illness, whereas all patients with unresolved grief had concurrent psychiatric disorders. The management of acute and unresolved grief in hospitalized medical or surgical patients is discussed, and illustrative cases are presented.


Amphetamine-induced dopamine release and post-synaptic specific binding in patients with mild tardive dyskinesia.
Several lines of evidence suggest that changes in dopamine release and/or post-synaptic sensitivity may be involved in the pathogenesis of tardive dyskinesia (TD). Preclinically, increased D(2) receptor sensitivity and dopamine turnover are associated with D(2) receptor antagonism. Clinically, development of TD is associated with D(2) receptor antagonist administration. Eight patients with mild evidence of TD (AIMS ratings > or =14) and six without (AIMS = 10), underwent [(11)C]raclopride PET scans. Baseline and amphetamine-induced decrements in striatal specific binding were assessed. Baseline and amphetamine-induced decrements in specific binding did not differ between patients with and without evidence of mild TD (p =.53). AIMS ratings did not significantly correlate with baseline (p =.76) or decrements in specific binding (p =.45). This study provides evidence that TD is not associated with increased amphetamine-induced presynaptic dopamine release and/or D(2) receptor binding as measured by [(11)C]raclopride PET. More research is needed to unravel the neurobiology of this debilitating disorder.


Malformation of the epididymis in undescended testis.
During a 6-year period, 312 boys (mean age 4.7 years) underwent orchidopexy for cryptorchidism. A total of 388 epididymides were examined and the configurations were recorded as a prospective trial. This study consists of 166 ectopic testes and 222 undescended testes. The observed configurations of epididymides in the ectopic testes were: type 1a in 99 cases (59.6%), type 1b in 35 (21.1%), type 2 in 24 (14.5%), type 3 in 7 (4.2%), and type 4 in 1 (0.6%). There were no patients in the study with type 5 and 6 anomalies. The configurations of epididymides in the undescended testes were: type 1a in 105 (47.3%), type 1b in 63 (28.4%), type 2 in 26 (11.7%), type 3 in 13 (5.9%), type 4 in 5 (2.3%), type 5 in 7 (3.2%), and type 6 in 3 (1.4%). The data revealed that the incidence of epididymal abnormalities in undescended testes (41%) was higher than that in the ectopic testes (25.9%) (P < 0.05).


Reverse T3 in rainbow trout, Salmo gairdneri.
Plasma levels, peripheral metabolism and extrathyroidal in vivo production of reverse T3 (rT3 = 3,3',5'-triiodo-L-thyronine) were studied in rainbow trout at 12 degrees C. Plasma rT3 levels (less than 40 pg/ml) corresponded to the detection limit of the radioimmunoassay. By in vitro analysis, a high proportion (0.95%) of rT3 added to plasma existed in the free (dialyzable) form. Injected [125I]rT3 was cleared more rapidly from plasma (minimum MCR = 7.7 ml/hr/100 g) than T3. No phenolic (outer ring) rT3 deiodination was observed. rT3 rapidly entered the liver and up to 70% of the injected [125I]rT3 was lost via the biliary route, mainly as unidentified derivatives; about 10% of the biliary-excreted 125I label was identified as rT3 or its glucuronide conjugate. Using Sephadex column chromatography combined with specific antibody separations, it was not possible to demonstrate in vivo [125I]rT3 production from [125I]T4. It is concluded that in laboratory trout, in contrast to the situation in mammals, the T4 to rT3 pathway is not prominent and that iodothyronine deiodination is restricted to T3 formation. These findings may relate to differences in extrathyroidal iodine metabolism between trout and mammals.


Proteomic and transcriptional analyses of Arthrobotrys oligospora cell wall related proteins reveal complexity of fungal virulence against nematodes.
The nematode-trapping fungus Arthrobotrys oligospora is the best-studied fungus for understanding the interaction between fungi and nematodes. The fungus uses three-dimensional adhesive networks to capture nematodes and then penetrates into the worms through their cuticle. Here we examine the effects of fungal cell wall related proteins on morphogenesis and virulence of the fungi. We focused on the changes in its proteomic and transcriptional profiles during its transition from saprophytic to predatory phase. Isobaric tags for relative and absolute quantitation (iTRAQ) proteomics using the liquid chromatography/mass spectrometry (LC/MS) method revealed an extended set of virulence related proteins, such as adhesins and serine proteases, on the cell wall of A. oligospora. Transcription analyses of their coding genes revealed an important set of candidate virulence factors. Our analyses also show that glycosyl hydrolases likely play important roles in trap formation of A. oligospora. The adhesins on the three-dimensional adhesive networks may have two functions: to enable the mycelia to stick to nematodes and to serve as important constituents of the extracellular matrix that harbors many secreted virulence related proteins. This study is the first to systematically identify cell wall related proteins that are important in the trap formation and infection of the fungus against nematode hosts.


A novel method for the rapid purification of human and rat fibrin(ogen) degradation products in high yields.
A novel method is described for the preparation and purification of fibrin(ogen) degradation products in high yields. The high yields are due to two factors: a) an improved preparation method in which the heterogeneity in the size of the degradation products D is greatly reduced by performing the digestion with plasmin at well-controlled calcium concentrations (see ref.[22]). b) a new purification method, which includes Sephadex G-200 filtration and separation of D and E fragments by preparative isoelectric focusing. The latter step gives a complete separation of D and E fragments, without any overlap, and with a nearly 100% recovery in a short period of time. The properties of human and rat fibrin(ogen) degradation products are very similar.


Widespread aluminium deposition in extracerebral organ systems of patients with dialysis-associated encephalopathy.
We have described new silver-staining methods for the demonstration of lesions in senile dementia of the Alzheimer type. The same procedure was used to visualize characteristic aluminium (Al)-containing inclusions in choroid epithelium, glia and neurons of the central nervous system in dialysis-associated encephalopathy (DAE). Here we describe the patterns and degree of Al deposition in extracerebral tissues of 12 DAE autopsy cases. Light microscopy of silver-stained paraffin sections demonstrated autonomic ganglion cells filled with numerous intracytoplasmic black-stained fine granular inclusions, which were also seen in endocrine tissues (pituitary, parathyroid and adrenal) and in Leydig cells. Heart, liver cells and the testicular tubules were involved, but decalcified bones, haematopoetic elements, hyperplastic epithelium and one case of malignant epithelium lacked inclusions. Laser microprobe mass analysis revealed prominent Al-related mass signals within the en-bloc silver-stained inclusions which were seen at low intensity in adjacent non-stained structures. Electron microscopy demonstrated accumulations of small electron-dense granules intermingling with lipopigments.


Morphological analysis of subchondral talar cysts on microCT.
Osteochondral talar defects often present in conjunction with subchondral bone cysts. The exact aetiology of these cysts is unknown. Recently was shown in a computational bone model that pressurized fluid and osteocyte death could lead to cyst growth, through mechanoregulated bone adaptation. However, a difference in cyst morphology was present between the mechanisms. The purpose of this study was to evaluate and compare the cyst morphology of human cadaveric tali by using microCT with the morphological simulation results previously reported. Sixty-six fresh-frozen human cadaveric tali were screened in a regular CT for subchondral bone cysts, radiologically defined as unexpected rounded radiolucent area. Subsequently, the tali with a cyst were scanned in a microCT. The shape of the cysts, the presence of an opening through the subchondral bone plate, and the bone volume fraction around and next to the cyst were analysed. In total, six tali were found to have a single cyst. Four cysts had an irregular shape, and two cysts were rounded. A clear opening from the cyst through the subchondral bone plate was found (diameter 0.5-1.7 mm) in four cysts. The bone volume fraction was higher (p = 0.025) around the cyst then next to the cyst. The morphological findings that we found are only compatible with the previously reported simulation results of cyst growth in response to pressurized fluid, or pressurized fluid in combination with osteocyte death. It is therefore most likely that pressurized fluid plays a role in the pathoaetiology of cyst growth. A better understanding of cyst growth may improve treatment and prevent further cyst formation.


Role of cysteine residues in human angiotensinogen. Cys232 is required for angiotensinogen-pro major basic protein complex formation.
The M235T polymorphism of human angiotensinogen is associated with essential and pregnancy-induced hypertension. A covalent complex is formed between angiotensinogen and the proform of the eosinophil major basic protein (proMBP) during pregnancy. The sequence of human angiotensinogen contains four cysteines. Their function was analyzed. Presence of free cysteines was demonstrated by their alkylation with iodo[14C]acetic acid. A disulfide bond between Cys18 and Cys138 using a fully N-deglycosylated mutant of human angiotensinogen was identified by tryptic digestion and mass spectrometry. We produced angiotensinogen. proMBP complex by co-transfection of COS-7 cells and by co-culturing transfected CHO-K1 cells. Experiments with 8 mutated recombinant angiotensinogen, in which one or more of the four cysteines were replaced by alanine, demonstrated that Cys232 is involved in complex formation and could interact with the M235T variant. The angiotensinogen.proMBP complex was isolated by molecular sieving. Hydrolysis of the complex by human renin was 7 times slower than hydrolysis of monomeric form, whatever the M235T genotype. The complex:monomeric angiotensinogen ratio was greater for Met235 (72%) than for Thr235 (58%) angiotensinogen. These data suggest a new pathophysiological explanation for the genetic association between M235T angiotensinogen polymorphism and pregnancy-induced hypertension.


Hybrid transileocecal portal vein embolization associated with staging laparoscopy for planned major hepatectomy in advanced hepatobiliary cancers.
Portal vein embolization (PVE) is widely used to promote the hypertrophy of a future liver remnant (FLR) and reduce posthepatectomy liver failure. The aim of this study was to evaluate the efficacy of transileocecal portal embolization (TIPE) associated with staging laparoscopy (hybrid lap-TIPE) for a planned hepatectomy in advanced hepatobiliary cancers. The hybrid lap-TIPE procedure consisted of staging laparoscopy for complete screening of the abdominal cavity with cytoreductive surgery and subsequent TIPE. Data on hybrid lap-TIPE, performed between March 2013 and February 2020, were collected retrospectively. Hybrid lap-TIPE was conducted for 52 patients, and a subsequent TIPE was accomplished in 42 patients (80.8%), since staging laparoscopy detected latent or unresectable factors in 13 patients (25.0%), among which 2 patients with hepatocellular carcinoma and 1 with colorectal liver metastasis received laparoscopic cytoreductive surgery for latent lesions in the FLR. Finally, radical hepatectomy was completed in 36 patients (69.2%), including 3 patients who underwent cytoreductive surgery. The most common operation was an extended right hepatectomy (50.0%), followed by right hepatectomy (30.6%), including 3 hepatopancreatoduodenectomies. The overall morbidity associated with hybrid lap-TIPE and hepatectomy was 7.1% and 41.7%, respectively. The mortality associated with hybrid lap-TIPE and hepatectomy was 0% and 5.6%, respectively. The rates of 2-year survival and 2-year disease-free survival were 64.8% and 61.9%, respectively, after hepatectomy. Hybrid lap-TIPE is safe and could be a useful treatment option for patients with advanced hepatobiliary cancer because it can help to identify optimal candidates for PVE followed by a planned hepatectomy.


Ligand interactions with the kringle 5 domain of plasminogen. A study by 1H NMR spectroscopy.
The binding of small molecules to the kringle 5 domain fragment of human plasminogen has been investigated by 1H NMR spectroscopy at 300 MHz. The compounds tested as potential ligands include L-arginine, L-lysine, and a number of aliphatic and aromatic analogs of similar size but different ionic charge configurations. Ligand/kringle 5 association constant (Ka) values were obtained from ligand titration experiments at 22 degrees C, pH 7.2. Neither L-arginine nor N alpha-acetyl-L-arginine and N alpha-acetyl-L-arginine methyl ester bind measurably to kringle 5 (Ka approximately less than 0.05 mM-1). In contrast, binding of hexylamine or epsilon-aminocaproic acid (epsilon ACA) is favored (Ka approximately 2.9 and 10.5 mM-1, respectively). Benzamidine and p-benzylaminesulfonic acid associate with kringle 5 with similar affinities (Ka approximately 3.4 and 2.2 mM-1, respectively) while benzylamine binds about twice as tightly (Ka approximately 6.3 mM-1). The higher affinities toward both benzylamine and epsilon ACA indicate that a free carboxylate group is not, by itself, a main determinant of ligand-binding to kringle 5. The experiments also reveal a definite affinity for L-arginine methyl ester, L-lysine, and N alpha-acetyl-L-lysine methyl ester. It is suggested that, although weak (0.1 approximately less than Ka approximately less than 0.6 mM-1), these interactions could be of physiological relevance in the context of plasminogen binding to the fibrin clot. Ligand-induced shifts of kringle 5 proton resonances indicate that the Trp25, His33, Tyr50, Trp62, and Tyr72 (kringle numbering convention) side chains form or neighbor the kringle 5-binding site. Benzamidine-kringle 5 magnetization transfer (Overhauser) experiments verify a close proximity of the bound ligand to these aromatic groups. A model of the binding site is proposed in which the above residues interact closely with each other and define a lipophilic surface which is accessible to the free ligand.


Self-reported morbidity and health service utilization in rural Tamil Nadu, India.
In Tamil Nadu, India, improvements have been made toward developing a high-quality, universally accessible healthcare system. However, some rural residents continue to confront significant barriers to obtaining healthcare. The primary objective of this study was to investigate self-reported morbidity, health literacy, and healthcare preferences, utilization, and experiences in order to identify priority areas for government health policies and programs. Drawing on 66 semi-structured interviews and 300 household surveys (including 1693 individuals), administered in 26 rural villages in Tamil Nadu's Krishnagiri district, we found that the prevalence of self-reported major health conditions was 22.3%. There was a large burden of non-communicable and chronic diseases, and the most common major morbidities were: connective tissue problems (7.6%), nervous system and sense organ diseases (5.0%), and circulatory and respiratory diseases (2.5%). Increased age and decreased education level were associated with higher odds of reporting most diseases. Low health literacy levels resulted in individuals seeking care only once pain interfered with daily activities. As such, individuals' health-seeking behaviour depended on which strategy was believed to result in the fastest return to work using the fewest resources. Although government facilities were the most common healthcare access point, they were mistrusted; 48.8% and 19.2% of respondents perceived inappropriate treatment protocols and corruption, respectively, at public facilities. Conversely, 93.3% of respondents reported high treatment cost as the main barrier to accessing private facilities. Our results highlight that addressing the chronic and non-communicable disease burdens amongst rural populations in this context will require health policies and village-level programs that address the low health literacy and the issues of rural healthcare accessibility and acceptability.


Neural circuits of fear and defensive behavior.
Innate fear-related behavioral responses have evolved as strategies for survival. The neural circuits responsible for defensive responses, studied mainly in rodents, have been substantially preserved across evolution. Amygdala collects sensory information (visual, auditory and olfactory) in the cortical division and conveys it to the striatal output division. Distinct amygdala nuclei/subnuclei are activated by different fearful stimuli, such as exposure to a predator or to an aggressive conspecific. The same stimuli segregation is observed in downstream structures, i.e., hypothalamus and PAG. In guinea pigs, the circuits underlying Tonic Immobility (TI) and freezing in response to a natural predator, have been mapped in different subnuclei of the same amygdala area. In the PAG circuits, defensive responses are differentially represented along the dorso-ventral and rostro-caudal axis. The coordination of behavioral, anti-nociceptive and autonomic responses is due to the overlapping of the involved neurons in longitudinal columns.


Neutrophil-to-lymphocyte ratio is associated with survival and sentinel lymph node positivity in invasive cutaneous squamous cell carcinoma: A retrospective study.
The neutrophil-to-lymphocyte ratio (NLR) is a known prognostic biomarker for survival and is predictive of sentinel lymph node (SLN) positivity in some cancers. However, its usefulness as a prognostic biomarker for cutaneous squamous cell carcinoma (cSCC) has not been fully investigated. Our objective was to investigate the relationship between the NLR and the disease-specific survival and SLN positivity in patients with cSCC. In this single-center retrospective case series, we analyzed patients with cSCC who underwent blood tests prior to the initiation of treatment at our oncology hospital. The relationship between the patients' clinical characteristics (including the NLR) and the disease-specific survival and SLN positivity was evaluated using univariate and multivariate analyses. An elevated NLR was an independent prognostic factor for poor disease-specific survival and a predictive factor for SLN positivity. Limitations include the small number of participants and selection bias due to the large proportion of high-risk cases in our patient population. NLR is a useful biomarker in cSCC because it is simple to measure and can predict prognosis.


Complete genome sequence of Streptomyces malaysiensis HNM0561, a marine sponge-associated actinomycete producing malaymycin and mccrearamycin E.
Streptomyces malaysiensis HNM0561 is a marine sponge-associated actinomycete with the potential to produce potential anti-androgens against prostate cancer cells, including malaymycin and mccrearamycin E. Here, we present the complete genome sequence of S. malaysiensis HNM0561, which consists of a linear chromosome of 11,656,895 bp and a circular plasmid of 32,797 bp, 9849 protein coding genes, 18 rRNA genes, 66 tRNA genes, and 191 sRNA genes. Genomic annotations revealed that 72.03% of the protein-coding genes were assigned to the COG database, among which the abundant genes were predicted to be involved in transcription, replication, carbohydrate transport and metabolism, and amino acid transport and metabolism. Forty-nine putative secondary metabolite biosynthetic gene clusters were found in the genome. Among them, the potential biosynthetic gene clusters of malaymycin and mccrearamycin E have been described respectively. The complete genome information presented here will enable us to investigate the biosynthetic mechanism of two novel structures of malaymycin and mccrearamycin E and to discover novel secondary metabolites with potential against prostate cancer cell activities.


Trace analysis of rimantadine in human urine after dispersive liquid liquid microextraction followed by liquid chromatography-post column derivatization.
The first dispersive liquid liquid microextraction scheme followed by liquid chromatography-post column derivatization for the determination of the antiviral drug rimantadine in urine samples is demonstrated. The effect of the type and volume of organic extraction solvent, type and volume of disperser solvent, sample pH, ionic strength, extraction time, and centrifugation speed on the extraction efficiency were studied. Rimantadine and the internal standard (amantadine) were chromatographed using a reversed phase monolithic stationary phase with a mixture of equal volumes of methanol and phosphate buffer (pH = 3) as mobile phase. On-line post-column derivatization of the analyte was performed using a "two-stream" manifold with o-phthalaldehyde and N-acetyl-cysteine at alkaline medium. Under the optimized extraction conditions, the enrichment factor of rimantadine was 58. The linear range was 5-100 µg/L with correlation coefficient r of 0.9984 while the limit of detection achieved was 0.5 µg/L. The within-day and between-day precision for the tested concentration levels were less than 14.3% and the mean recoveries obtained from the spiked samples were ranged between 87.5 and 113.9%. The main advantages of the proposed method are the simplicity of operation, rapidity, low cost, and low limit of detection of the analyte.


Altered chromatin higher-order structure in cells infected by herpes simplex virus type 1.
In cells infected by herpesviruses chromosomal aberrations such as breaks and constrictions are commonly observed. Previous studies have shown that chromatin modifications in cells infected by herpes simplex virus type 1 (HSV-1) are not due to extensive breakdown of host-cell DNA or disruption of nucleosomal structure. We have previously shown that infection by HSV-1 induces single-stranded breaks in the host-cell DNA in a time-dependent fashion. Here we report that the early DNA damage observed in virus-infected cells is related to modifications in the higher-order structure of host-cell chromatin. Such modifications seem to be of a more permanent nature than the DNA single-stranded breaks.


Prophylactic use of anti-emetic medications reduced nausea and vomiting associated with exenatide treatment: a retrospective analysis of an open-label, parallel-group, single-dose study in healthy subjects.
Transient nausea and, to a lesser extent, vomiting are common adverse effects of exenatide that can be mitigated by dose titration and usually do not result in treatment discontinuation. This retrospective analysis of data from a phase 1, open-label, parallel-group, single-dose study in healthy subjects evaluated the effect of oral anti-emetics on exenatide-associated nausea and vomiting and on the pharmacokinetics of exenatide. A single subcutaneous dose (10 μg) of exenatide was administered to 120 healthy subjects (19-65 years, BMI 23-35 kg/m(2) ). Incidences of nausea and vomiting were compared between 60 subjects premedicated with two oral anti-emetics 30 min before the exenatide dose and 60 non-premedicated subjects. Similarly, the area under the concentration-time curve (AUC) and the maximum observed concentration (C(max) ) of plasma exenatide concentrations over 8 h post-dose were compared. Among all subjects [61% male, 32 ± 12 years, body mass index (BMI) 29.1 ± 3.4 kg/m(2) (mean ± sd)], mild to moderate nausea was the most frequent adverse event after exenatide dosing. Vomiting was also observed. Subjects premedicated with anti-emetics experienced significantly less nausea and vomiting (16.7 and 6.7%, respectively) vs. non-premedicated subjects (61.7 and 38.3%, respectively; P-value <0.0001 for both nausea and vomiting). The mean area under the concentration-time curve and the maximum observed concentration AUC and C(max) of plasma exenatide concentrations during 8 h post-dose were not significantly different between groups. Administration of oral anti-emetics before a single 10-μg exenatide dose was associated with significant reductions in treatment-emergent nausea and vomiting, with no discernible effect on the pharmacokinetics of exenatide. Use of anti-emetic therapy may provide a short-term strategy to minimize the nausea and vomiting associated with exenatide treatment.


Pulse injection analysis of the binding of serum proteins to porous polymer gels modified with formyl groups.
Highly porous spherical polymer gels were modified with formyl groups by a modified Friedel-Crafts reaction and the interaction of serum proteins with the modified gels were examined by pulse injection analysis. The introduction of formyl groups into the polymer greatly increases its protein-binding capacity, and the protein bound to the gel is not eluted by washing with acid, alkali or urea solution. The effects of temperature and the percentage of formyl group substitution on the binding capacity indicate that the binding process can be interpreted as initial approach of the protein to the polymer surface, caused by the hydrophobic interaction, followed by formation of a stable Schiff base between the polymer gel and the protein. Theoretical treatment of the elution behaviour of the protein from the polymer-packed column is also examined, with the assumption that there are three kinds of binding site in the polymer gel: surface, macropore and micropore regions. These polymers are shown to be useful for the removal of proteins from biological samples in clinical assays using immobilized enzymes.


Double average parallel steady-state free precession imaging: optimized eddy current and transient oscillation compensation.
Balanced steady-state free precession (SSFP) imaging is sensitive to off-resonance effects, which can lead to considerable artifacts during a transient phase following magnetization preparation or steady-state interruption. In addition, nonlinear k-space encoding is required if contrast-relevant k-space regions need to be acquired at specific delays following magnetization preparation or for transient artifact reduction in cardiac-gated k-space segmented CINE imaging. Such trajectories are problematic for balanced SSFP imaging due to nonconstant eddy current effects and resulting disruption of the steady state. In this work, a novel acquisition strategy for balanced SSFP imaging is presented that utilizes scan time reduction by parallel imaging for optimized "double average" eddy current compensation and artifact reduction during the transient phase following steady-state storage and magnetization preparation. Double average parallel SSFP imaging was applied to k-space segmented CINE SSFP tagging as well as nongated centrically encoded SSFP imaging. Phantom and human studies exhibit substantial reduction in steady-state storage and eddy current artifacts while maintaining spatial resolution, signal-to-noise ratio, and similar total scan time of a standard SSFP acquisition. The proposed technique can easily be extended to other acquisition schemes that would benefit from nonlinear reordering schemes and/or rely on interruption of the balanced SSFP steady state.


Micro-relief characterization of benign and malignant skin lesions by polarization speckle analysis in vivo.
A recent direction in skin disease classification is to develop quantitative diagnostic techniques. Skin relief, colloquially known as roughness, is an important clinical feature. The aim of this study is to demonstrate a novel polarization speckle technique to quantitatively measure roughness on skin lesions in vivo. We then calculate the average roughness of different types of skin lesions to determine the extent to which polarization speckle roughness measurements can be used to identify skin cancer. The experimental conditions were set to target the fine relief structure on the order of ten microns within a small field of view of 3 mm. The device was tested in a clinical study on patients with malignant and benign skin lesions that resemble cancer. The cancer group includes 37 malignant melanomas (MM), 43 basal cell carcinomas (BCC), and 26 squamous cell carcinomas (SCC), all categories confirmed by gold standard biopsy. The benign group includes 109 seborrheic keratoses (SK), 79 nevi, and 11 actinic keratoses (AK). Normal skin roughness was obtained for the same patients (301 different body sites proximal to the lesion). The average root mean squared (rms) roughness ± standard error of the mean for MM and nevus was equal to 19 ± 5 μm and 21 ± 3 μm, respectively. Normal skin has rms roughness of 31 ± 3 μm, other lesions have roughness of 35 ± 10 μm (AK), 35 ± 7 μm (SCC), 31 ± 4 μm (SK), and 30 ± 5 μm (BCC). An independent-samples Kruskal-Wallis test indicates that MM and nevus can be separated from each of the tested types of lesions, except each other. These results quantify clinical knowledge of lesion roughness and could be useful for optical cancer detection.


Toxoplasmosis, old stories and new facts.
In this introductory paper some general opinions are presented regarding the parasite Toxoplasma gondii, toxoplasma infection and toxoplasmosis. The transmission of the parasite through oocysts and/or infected meat is discussed with regard to possible prevention. Old stories have been replaced by new facts in the epidemiology of toxoplasma infection. Veterinary measurements in the field of prevention are not likely to be accepted in the near future. It is stressed that laboratory diagnosticians should clearly differentiate between diagnostic support in suspected cases of clinical toxoplasmosis or screening for certain characteristics such as IgG antibodies to toxoplasma in a healthy population.


[Analysis of hand function deficit due to the limitation of forearm rotational movements].
An influence of the forearm rotational movements limitation on everyday and professional life has been presented. The investigation has been carried out with an apparatus simulating various degrees of supination or pronation loss. It almost impossible to compensate for the loss of supination so it affects the function of the hand more then the loss of pronation.


Small and Thin Oral Squamous Cell Carcinomas may Exhibit Adverse Pathologic Prognostic Features.
We set out to record the frequency of recognised adverse pathologic features in early oral squamous cell carcinoma (OSCC) and correlate with neck disease, in particular in small and thin carcinomas, a group that might be assumed to behave less aggressively. We also examined the possibility of a biopsy site interfering with assessment of WPOI5 in small tumors. We reviewed all OSCCs ≤ 20 mm size and ≤ 10 mm depth reported at our institution over a 5-year period. Tumor maximum dimension, depth, perineural invasion (PNI), lymphovascular invasion (LVI), worst pattern of invasion (WPOI), and nodal status were recorded. Out of 95 cases, there were 44 (46.3%) small and 78 (82.1%) thin OSCCs. Depth and WPOI were significant factors in predicting nodal disease. There were 41 (43.2%) OSCC that were small and thin, of which 9.8% had PNI, none had LVI, and 61% had WPOI 4 or 5. Their rate of PNI and of nodal disease was similar to the other early OSCC. Assessment of WPOI5 at a biopsy site was only a problem in 2/38 cases. In early OSCC, depth and WPOI are important factors in predicting nodal disease. The very earliest OSCC (small and thin) have a similar rate of PNI and of nodal disease to other early OSCC, suggesting that while there may be a tendency to de-escalate treatment, these small tumours should be managed in the same way as for all early OSCC. In addition, the presence of scarring due to a biopsy in very small carcinomas rarely affects assessment of WPOI5.


Novel LSS variants in alopecia and intellectual disability syndrome: New case report and clinical spectrum of LSS-related rare disease traits.
Pathogenic biallelic variants in LSS are associated with three Mendelian rare disease traits including congenital cataract type 44, autosomal recessive hypotrichosis type 14, and alopecia-intellectual disability syndrome type 4 (APMR4). We performed trio research exome sequencing on a family with a four-year-old male with global developmental delay, epilepsy and striking alopecia, and identified novel compound heterozygous LSS splice site (c.14+2T>C) and missense (c.1357 G>A; p.V453L) variant alleles. Rare features associated with APMR4 such as cryptorchidism, micropenis, mild cortical brain atrophy and thin corpus callosum were detected. Previously unreported APMR4 findings including cerebellar involvement in the form of unsteady ataxic gait, small vermis with prominent folia, were noted. A review of all reported variants to date in 29 families with LSS-related phenotypes showed an emerging genotype-phenotype correlation. Our report potentially expands LSS-related phenotypic spectrum and highlights the importance of performing brain imaging in LSS-related conditions.


Adverse outcomes in patients with venous thromboembolic disease from a rural population.
To study the adverse outcomes and its predictors during anticoagulant therapy in patients with venous thromboembolic disease (VTD) from a rural population. This is a prospective observational study of 94 consecutive patients. The patients were diagnosed in a first-level hospital from a rural Spanish area using objective methods of VTD. The mean follow-up with anticoagulant therapy was 7.1 months (range: 0-29 months). Eighteen patients (19.1%) had an adverse outcome: 10 (10.6%) during the first month and 8 (8.5%) after the first month. Sixteen patients (17%) died, 6 (6.4%) had a major hemorrhage, and 4 (4.3%) had a thromboembolic recurrence. Comorbidity, cancer, nonidiopathic VTD, and pulmonary thromboembolism were significantly associated with adverse outcomes. Adverse outcomes during anticoagulant therapy are frequent in patients from a rural population with VTD. These adverse outcomes occur frequently during the first month of treatment and are associated with the patient's prior status and the presence of pulmonary thromboembolism.


Non-infectious morphologically altered nucleocapsids of measles virus from persistently infected cells.
Persistent measles virus infection of human HEp-2 or L-41 cells was accompanied by pronounced structural and functional changes of isolated intracellular viral nucleocapsids (NCs). The bulk of persistent NCs possessed altered conformation and a "string-of-beads" appearance, contained substantial amounts of subgenomic size RNAs, exhibited reduced transcriptase activity in vitro and lacked infectivity on transfection of susceptible cells. Immunogold staining revealed negligible binding of anti-P protein monoclonal antibodies to the "string-of-beads" type NCs, thus suggesting their non-functional state.


Depression in bulimia at 2- to 5-year followup.
Previous research has indicated a strong association between bulimia and affective disorder at the time of initial clinical assessment. To investigate this relationship from a long-term perspective, 30 normal weight female bulimics were evaluated 2 to 5 years posthospital admission with psychometric measures and clinical interviews. Contrary to previous reports, the depression scores of the bulimics were surprisingly low, even though 26 of the 30 continued to fulfill DSM-III criteria for bulimia. Higher depression scores were associated with more intense bulimic symptomatology and attitudes, and greater psychiatric disturbance at followup. Although these data demonstrate a relationship between bulimic symptomatology and depression at long-term followup, they do not support recent assertions that bulimia is a variant of an underlying affective disorder.


Habitual fish consumption, fatty acids of serum phospholipids and platelet function.
To clarify whether the inverse relation between habitual fish consumption and cardiovascular mortality in the Dutch town of Zutphen could be explained by changes in platelet function or fibrinolysis, 40 healthy elderly men were selected from the Zutphen study population on the basis of their fish consumption over the last 26 years. In the high-fish group (n = 25) fish consumption was on average 33 g per person per day; in the low-fish group (n = 15) it was on average 2 g per person per day. This difference was reflected by significant differences in the concentrations of timnodonic acid (20:5n - 3) and cervonic acid (22:6n - 3) in the serum phospholipids of the participants. Between both groups no significant differences were observed in cutaneous bleeding time, platelet number, and collagen-induced platelet aggregation and ATP-release in whole blood. The same holds for the actual as well as the potential thromboxane B2 formation of activated platelets and for the activity of the plasminogen activator inhibitor. For most of the platelet-related variables a trend was found for a lower activity in the high-fish group. Therefore changes in platelet function might not explain, but may have slightly contributed to the inverse relationship between coronary heart disease and fish consumption, as observed in Zutphen.


Correction to: Don't Drive Blind: Driving Pressure to Optimize Ventilator Management in ECMO.
The original version of this article unfortunately contained a mistake. The spelling of the Hitoshi Hirose name was incorrect. It was corrected in this erratum.


A randomized-controlled trial to evaluate the app-based multimodal weight loss program zanadio for patients with obesity.
This study aimed to evaluate the effectiveness of the app-based, multimodal weight loss program zanadio. A randomized-controlled trial was conducted from January 2021 to March 2022. A total of 150 adults with obesity were randomized into an intervention group and used zanadio for 1 year or into a wait list control group. The primary end point, weight change, and the secondary end points, quality of life, well-being, and waist to height ratio, were assessed every 3 months for up to 1 year via telephone interviews and online questionnaires. After 12 months, participants of the intervention group lost, on average, -7.75% (95% CI: -9.66% to -5.84%) of their initial weight, achieving a clinically relevant and statistically stronger weight reduction than the control group (mean = 0.00% [95% CI: -1.98% to 1.99%]). All secondary end points improved significantly in the intervention group, with significantly greater improvements in well-being and waist to height ratio than in the control group. This study showed that adults with obesity who have used zanadio achieved a significant and clinically relevant weight loss within 12 months and improved further obesity-related health variables compared with a control group. Because of its effectiveness and flexible applicability, the app-based multimodal treatment zanadio might alleviate the present care gap for patients with obesity in Germany.


Flash burns to the face.
A characteristic 'crow's foot' pattern is seen around the eye in many flash burns. The protective blink reflex underlies this, and the injury is due to convected rather than radiant energy.


The relationship between CAM use and adherence to antiretroviral therapies among persons living with HIV.
The use of complementary and alternative medicine (CAM) among people living with HIV and AIDS (PLWHA) may undermine other adaptive illness management behaviors, such as treatment adherence. The present study tests the hypothesis that CAM use is associated with intentional lapses in adherence (e.g., "medication vacations"), perhaps due to negative beliefs about antiretroviral therapy (ART). Cross-sectional interviews with 116 PLWHA were completed using a computerized assessment of self-reported CAM use and ART adherence. Almost half of participants used CAM to treat or manage HIV-related health concerns in the past month, and 78% had used CAM since being diagnosed with HIV. Seventy-one percent of participants endorsed at least one domain of intentional nonadherence since starting HIV treatment. As hypothesized, CAM users did not differ from nonusers on overall ART adherence. Contrary to hypotheses, CAM users were less likely to report taking medication vacations or having stopped taking HIV medications without their doctor's approval compared with nonusers. CAM intensity was also related to intentional nonadherence, such that patients who engaged in more CAM tended to report fewer skipped doses and fewer nonprescribed adjustments to their medication regimen in the past month. Findings suggest that PLWHA use CAM as an adjunct to ART and that CAM use does not undermine ART adherence. Needed now is longitudinal research to determine how a proactive, holistic approach to HIV care interacts with conventional HIV treatment over time, and whether CAM use impacts long-term quality of life and health outcomes.


Magnitude of rise in proneurotensin is related to amount of triglyceride appearance in blood after standardized oral intake of both saturated and unsaturated fat.
In rodents, neurotensin contributes to high fat diet induced obesity by facilitation of intestinal fat absorption. The effect of oral lipid load on plasma proneurotensin and relationship with plasma triglycerides in humans is unknown. To investigate the acute effects of an oral lipid load on proneurotensin and plasma triglycerides and their interrelationships in healthy individuals. Twenty-two healthy subjects were given 150 mL of full milk cream (54 g fat) and 59 mL of pure olive oil (54 g fat) in the fasted state at two different occasions separated by at least 1 week in random order. Venous blood was drawn at fasted before 0 h (h) and at 1 h, 2 h and 4 h after ingestion. Post-ingested values of proneurotensin and plasma triglycerides were compared with fasting levels and post ingestion Area Under the Curve (AUC) of proneurotensin was correlated with that of plasma triglycerides. An immediate rise of plasma proneurotensin and plasma triglycerides were observed after ingestion of cream with maximum increase at 2 h for proneurotensin [mean (95% confidence interval)] of 22 (12-31) pmol/L (P < 0.001) and at 3 h for triglycerides of 0.60 (0.43-0.78) mmol/L (P < 0.001). Similarly, plasma proneurotensin and plasma triglycerides increased after ingestion of olive oil with maximum increase of proneurotensin at 3 h of 62 (46-78) pmol/L (P < 0.001) and plasma triglycerides at 3 h of 0.32 (0.18-0.45) mmol/L (P < 0.001). The post lipid load AUC for proneurotensin correlated significantly with the AUC for plasma triglycerides both after cream (r = 0.49, P = 0.021) and olive oil (r = 0.55, P = 0.008), respectively. Proneurotensin increases after an oral lipid load of both cream and olive oil and the rise of post-ingestion plasma triglycerides is significantly related to the rise of post-ingestion proneurotensin.


[Practice-oriented pain therapy in dermatology : Concept with special emphasis on pain quality].
In order to avoid chronification of pain, appropriate treatment has to be started as early as possible. Inpatient dermatology patients not only suffer from old age and associated multimorbidities but also from characteristic pain due to distinct dermatological diseases. In many cases clinicians have little experience with specific pain treatment but instead have many concerns about how to deal with analgesics. So far chronic pain has been treated according to the pain ladder of the World Health Organization (WHO), which prioritizes the intensity of pain. This article presents an easily implementable concept of pain therapy with special emphasis on the quality of pain. This provides information on whether it is neuropathic or nociceptive pain, which can ultimately be differentially treated. The primary aim is to provide treating dermatologists with a concept to assist in the initiation of an efficient and correct pain therapy. This brief introduction of an individualized pain treatment can reduce the risk of chronification of pain, which can severely impair the quality of life particularly in dermatology patients and also the frequent stigmatization due to the dermatosis.


Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche.
Satellite cells are situated beneath the basal lamina that surrounds each myofiber and function as myogenic precursors for muscle growth and repair. The source of satellite cell renewal is controversial and has been suggested to be a separate circulating or interstitial stem cell population. Here, we transplant single intact myofibers into radiation-ablated muscles and demonstrate that satellite cells are self-sufficient as a source of regeneration. As few as seven satellite cells associated with one transplanted myofiber can generate over 100 new myofibers containing thousands of myonuclei. Moreover, the transplanted satellite cells vigorously self-renew, expanding in number and repopulating the host muscle with new satellite cells. Following experimental injury, these cells proliferate extensively and regenerate large compact clusters of myofibers. Thus, within a normally stable tissue, the satellite cell exhibits archetypal stem cell properties and is competent to form the basal origin of adult muscle regeneration.


Prostate high dose-rate brachytherapy as monotherapy for prostate cancer: Late toxicity and patient reported outcomes from a randomized phase II clinical trial.
Long-term toxicity of high dose-rate brachytherapy as monotherapy for prostate cancer is not well defined. We report late toxicity and health related quality of life (HRQOL) changes from a randomized phase II clinical trial of two different fractionation schemes. Eligible patients had NCCN low or intermediate risk prostate cancer. 170 patients were randomized to receive either a single 19 Gy or two-fractions of 13.5 Gy one week apart. Toxicity was measured using Common Terminology for Adverse Events (CTCAE) v4.0, and HRQOL was measured using the Expanded Prostate Index Composite (EPIC). Median follow-up was 63 months. The 5-year cumulative incidence of Grade 2 or higher genitourinary (GU) and gastrointestinal (GI) toxicity was 62% and 12% in the single-fraction arm, and 47% and 9% in the two-fraction arm, respectively. Grade 3 GU toxicity was only seen in the single fraction arm with a cumulative incidence of 2%. The 5-year prevalence of Grade 2 GU toxicity was 29% and 21%, in the single- and two-fraction arms, respectively, with Grade 2 GI toxicity of 1% and 2%. Beyond the first year, no significant differences in mean urinary HRQOL were seen compared to baseline in the two-fraction arm, in contrast to the single-fraction arm where a decline in urinary HRQOL was seen at 4 and 5 years. Sexual HRQOL was significantly reduced in both treatment arms at all timepoints, with no changes in the bowel domain. HDR monotherapy is well tolerated with minimal impact on HRQOL.


Ultrasound evaluation of foot deformities in infants.
Foot deformity in infants is the most common congenital musculoskeletal condition. A precise diagnosis can sometimes be impossible to establish clinically. Radiologic imaging plays a major role in the evaluation of musculoskeletal abnormalities. However conventional imaging techniques, such as plain radiographs of the foot, are of very little help in this age group because of the lack of ossification of the tarsal bones. US presents a significant advantage because it permits the visualization of cartilaginous structures. This leads to the detailed assessment of foot deformities in infants. Furthermore, US can also be used as a dynamic imaging modality. Different scanning views are beneficial to evaluate the complete anatomy of the foot; depending on the suspected clinical diagnosis, some planes are more informative to display the pathological features of a specific deformity. We describe the US findings of five of the most common foot deformities referred to our pediatric orthopedic clinic (clubfoot, simple metatarsus adductus, skewfoot, and oblique and vertical talus). For each deformity we propose a specific imaging protocol based on US to provide an accurate diagnosis. US is a complementary tool to the clinical examination for determining the diagnosis and the severity of the deformity and also for monitoring the efficacy of treatment. Radiologists investigating foot deformities in infants should consider using US for the detailed assessment of the foot in this age group.


Usefulness and pitfalls of MAA SPECT/CT in identifying digestive extrahepatic uptake when planning liver radioembolization.
Identifying gastroduodenal uptake of (99m)Tc-macroaggregated albumin (MAA), which is associated with an increased risk of ulcer disease, is a crucial part of the therapeutic management of patients undergoing radioembolization for liver tumours. Given this context, the use of MAA single photon emission computed tomography (SPECT)/CT may be essential, but the procedure has still not been thoroughly evaluated. The aim of this retrospective study was to determine the effectiveness of MAA SPECT/CT in identifying digestive extrahepatic uptake, while determining potential diagnostic pitfalls. Overall, 139 MAA SPECT/CT scans were performed on 103 patients with different hepatic tumour types. Patients were followed up for at least 6 months according to standard requirements. Digestive, or digestive-like, uptake other than free pertechnetate was identified in 5.7% of cases using planar imaging and in 36.6% of cases using SPECT/CT. Uptake sites identified by SPECT/CT included the gastroduodenal region (3.6%), gall bladder (12.2%), portal vein thrombosis (6.5%), hepatic artery (6.5%), coil embolization site (2.1%) as well as falciform artery (5.0%). For 2.1% of explorations, a coregistration error between SPECT and CT imaging could have led to a false diagnosis by erroneously attributing an uptake site to the stomach or gall bladder, when the uptake actually occurred in the liver. SPECT/CT is more efficacious than planar imaging in identifying digestive extrahepatic uptake sites, with extrahepatic uptake observed in one third of scans using the former procedure. However, more than half of the uptake sites in our study were vascular in nature, without therapeutic implications. The risk of coregistration errors must also be kept in mind.


The spectrum of cavitary optic disc anomalies in a family.
The current classification of cavitary optic disc anomalies including the morphologically related entities--optic nerve pit, morning glory disc anomaly, coloboma of the optic nerve, and retinochoroidal coloboma involving the optic nerve--is inexact and confusing. Traditionally, these disc abnormalities have been regarded as distinct morphologic anomalies. Thirty-five members of a five-generation kindred with autosomal dominantly inherited optic disc anomalies were examined. Observed abnormalities in this pedigree comprised a spectrum of morphologic variants ranging from large anomalous discs to typical pits and colobomas. The findings in this family suggest a variable expression of a single autosomal dominant defect rather than the chance occurrence of three separate, distinct, but morphologically similar entities occurring in a single pedigree.