A retrospective approach to examining child abuse disclosure.
Often times, a child's disclosure is the only forensic evidence available in child abuse cases. Therefore, understanding disclosure patterns of suspected child abuse victims plays a critical role in the forensic investigations of both child physical abuse (CPA) and child sexual abuse (CSA) cases. To explore adults' retrospective reports about childhood disclosure of CPA and CSA. College students (N = 907) were screened for reported histories of CSA (n = 94) or CPA (n = 109). Through an online survey, participants provided anonymous information regarding CSA and CPA experiences along with information about any disclosure events or opportunities that they have encountered since the abuse. Among the adults reporting CSA histories, 50 % indicated disclosing the abuse during childhood; 80 % indicated any lifetime disclosure. Among the adults indicating CPA histories, 32 % reportedly disclosed the abuse to someone during childhood with 52 % reporting any lifetime disclosure. For both groups, length of delay until disclosure was bimodal with many individuals reporting immediately and many waiting considerable time. Among adults reporting CSA, a minority (16 %) indicated the abuse came to the attention of authorities, with even fewer CPA cases (8%) reporting authorities were aware of their abuse. Denial and recantation in a formal setting was infrequent regardless of abuse type reported. Given that participants experiencing CSA and CPA both reported low levels of denial and recantation, forensic investigators and practitioners may benefit from considering consistent interviewing approaches and protocols, regardless of the type of abuse suspected.


Population structure and genome characterization of local pig breeds in Russia, Belorussia, Kazakhstan and Ukraine.
It is generally accepted that domestication of pigs took place in multiple locations across Eurasia; the breeds that originated in Europe and Asia have been well studied. However, the genetic structure of pig breeds from Russia, Belorussia, Kazakhstan and Ukraine, which represent large geographical areas and diverse climatic zones in Eurasia, remains largely unknown. This study provides the first genomic survey of 170 pigs representing 13 breeds from Russia, Belorussia, Kazakhstan and Ukraine; 288 pigs from six Chinese and seven European breeds were also included for comparison. Our findings show that the 13 novel breeds tested derived mainly from European pigs through the complex admixture of Large White, Landrace, Duroc, Hampshire and other breeds, and that they display no geographic structure based on genetic distance. We also found a considerable Asian contribution to the miniature Siberian pigs (Minisib breed) from Russia. Apart from the Minisib, Urzhum, Ukrainian Spotted Steppe and Ukrainian White Steppe breeds, which may have undergone intensive inbreeding, the breeds included in this study showed relatively high genetic diversity and low levels of homozygosity compared to the Chinese indigenous pig breeds. This study provides the first genomic overview of the population structure and genetic diversity of 13 representative pig breeds from Russia, Belorussia, Kazakhstan and Ukraine; this information will be useful for the preservation and management of these breeds.


Rapid differentiating colorectal cancer and colorectal polyp using dried blood spot mass spectrometry metabolomic approach.
Colorectal cancer (CRC) is the third leading causes of cancer mortality, and the early-stage detection could significantly enhance survival rates. Cancer influences the important metabolic pathways and the changes in metabolite levels had been used in many studies as the potential biomarkers. This study is aimed at screening metabolite biomarkers with CRC diagnosis potentials. The direct infusion mass spectrometry (MS) metabolomic analysis based on dried blood spot was used to distinguish CRC from polyp. The target metabolites were composed of 23 amino acids and 26 acylcarnitines. The 21 metabolites in blood were selected via multivariate analysis. A regression model was established based on parameters C16, Arg, C4/C8, C5/C3, Val, Phe/Tyr, Ala, C4/C3. Tenfold cross validation (CV) method was used to test this model and showed sensitivity of 81.18% and specificity of 83.95%. The metabolomic analysis is a practicable method for CRC detection. The use of direct MS analysis in metabolite screening could be finished in several minutes and served as a higher-throughput method to distinguish CRC and polyps. © 2017 IUBMB Life, 69(5):347-354, 2017.


[Metabolic engineering strategies for carboxylic acids production by Saccharomyces cerevisiae---a review].
Carboxylatic acids have been widely used in food, pharmaceutical and chemical industries. As a eukaryotic model organism, Saccharomyces cerevisiae is thought as cell factory to produce organic acids through manipulating metabolic pathway. In this review, we addressed the metabolic engineering strategies to construct a high titer route converting pyruvate to target carboxylate, and to explore how to divert the carbon flux to desired product from ethanol. Furthermore, we also discussed the mechanisms for carboxylate transport and energy involved in. Finally, the relevant strategies for development in future are proposed.


Student life - Professional conduct.
It is often said that we form assumptions of people within a few minutes of meeting.


[Effect of cooling on the mechanisms of myocardial contraction autoregulation in homoiothermic animals].
It has been found in experiments on isolated papillary muscles that cooling of the cat myocardium does not affect the efficacy of Starling's mechanism but decreases the chronoinotropic autoregulation of the heart muscle.


Chemical restraint in ruminants.
Physical restraint is generally required when working with food animal patients. Adding a degree of chemical restraint can make many procedures more pleasant for both practitioner and patient. The enhanced level of patient cooperation improves efficiency, offsetting the modest additional cost of the drugs used. Chemical restraint techniques used in ruminants range from mild sedation of standing patients to semianesthetized recumbency.


Comparison of differences in bone microarchitecture in adult- versus juvenile-onset type 1 diabetes Asian males versus non-diabetes males: an observational cross-sectional pilot study.
Evidence about bone microarchitecture in Asian type 1 diabetes (T1D) patients is lacking. We assessed the bone microarchitecture in T1D patients versus controls and compare the differences between juvenile-onset and adult-onset T1D patients. This cross-sectional study recruited 32 Asian males with T1D and 32 age-, sex-, and body mass index (BMI)-matched controls. Dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) for ultradistal nondominant radius and tibia were performed. The data were analyzed using Student's t test and analysis of covariance. Among the patients, 15 had juvenile-onset T1D, with a median disease duration of 11 years, and 17 had adult-onset T1D, with a median disease duration of 7 years. At the radius, adult-onset and juvenile-onset T1D patients had lower total volumetric bone mineral density (vBMD), trabecular vBMD, trabecular bone volume fraction (BV/TV), and trabecular thickness (Tb.Th) (p < 0.05) than the control subjects. After adjusting for BMI, disease duration, and insulin dose, juvenile-onset patients tended to have lower trabecular vBMD, BV/TV, Tb.Th, and intracortical porosity (Ct.Po) than adult-onset patients. At the tibia, adult-onset patients displayed lower total vBMD, lower Ct. vBMD, and higher Ct.Po (p < 0.05), while juvenile-onset patients had lower Tb.Th and standard deviation of trabecular number (1/Tb.N.SD) (p < 0.05) than control subjects. After adjustment for covariates, adult-onset patients tended to have higher cortical pore diameter (Ct.Po.Dm) than juvenile-onset patients. T1D patients were associated with compromised bone microarchitecture, adult-onset and juvenile-onset T1D patients demonstrated some differences in cortical and trabecular microarchitecture.


BCAR3 promotes head and neck cancer growth and is associated with poor prognosis.
Breast cancer anti-estrogen resistance protein 3 (BCAR3) is involved in anti-estrogen resistance and other important aspects of breast cancer. However, the role of BCAR3 in other solid tumors remains unclear. The relationship between the clinicopathologic characteristics of head and neck squamous cell carcinoma (HNSCC) patients and BCAR3 was analyzed using the Wilcoxon's signed-rank test and logistic regression. The association between BCAR3 expression and clinicopathologic features and survival was analyzed using Cox regression and the Kaplan-Meier method. In vivo and in vitro assays were performed to validate the effect of BCAR3 on HNSCC growth. BCAR3-related mRNAs were determined by calculating the Pearson's correlation coefficient based on The Cancer Genome Atlas (TCGA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and gene set enrichment analysis (GSEA) were used to predict the potential functions of BCAR3. BCAR3 expression is overexpressed in HNSCC and was shown to be associated with perineural invasion (PNI) and poor survival. BCAR3 silencing significantly attenuated the proliferation of HNSCC cells, whereas BCAR3 depletion inhibited tumor growth in vitro. GO and KEGG functional enrichment analyses, and GSEA showed that BCAR3 expression in HNSCC was associated with biological processes, such as cell adhesion, actin binding, cadherin binding, and angiogenesis. BCAR3, which promotes HNSCC growth, is associated with perineural invasion and may be a potential molecular prognostic marker of poor survival in HNSCC.


A novel multi-atlas segmentation approach under the semi-supervised learning framework: Application to knee cartilage segmentation.
Multi-atlas based segmentation techniques, which rely on an atlas library comprised of training images labeled by an expert, have proven their effectiveness in multiple automatic segmentation applications. However, the usage of exhaustive patch libraries combined with the voxel-wise labeling incur a large computational cost in terms of memory requirements and execution times. To confront this shortcoming, we propose a novel two-stage multi-atlas approach designed under the Semi-Supervised Learning (SSL) framework. The main properties of our method are as follows: First, instead of the voxel-wise labeling approach, the labeling of target voxels is accomplished here by exploiting the spectral content of globally sampled datasets from the target image, along with their spatially correspondent data collected from the atlases. Following SSL, voxels classification is boosted by incorporating unlabeled data from the target image, in addition to the labeled ones from atlas library. Our scheme integrates constructively fruitful concepts, including sparse reconstructions of voxels from linear neighborhoods, HOG feature descriptors of patches/regions, and label propagation via sparse graph constructions. Segmentation of the target image is carried out in two stages: stage-1 focuses on the sampling and labeling of global data, while stage-2 undertakes the above tasks for the out-of-sample data. Finally, we propose different graph-based methods for the labeling of global data, while these methods are extended to deal with the out-of-sample voxels. A thorough experimental investigation is conducted on 76 subjects provided by the publicly accessible Osteoarthritis Initiative (OAI) repository. Comparative results and statistical analysis demonstrate that the suggested methodology exhibits superior segmentation performance compared to the existing patch-based methods, across all evaluation metrics (DSC:88.89%, Precision: 89.86%, Recall: 88.12%), while at the same time it requires a considerably reduced computational load (>70% reduction on average execution time with respect to other patch-based). In addition, our approach is favorably compared against other non patch-based and deep learning methods in terms of performance accuracy (on the 3-class problem). A final experimentation on a 5-class setting of the problems demonstrates that our approach is capable of achieving performance comparable to existing state-of-the-art knee cartilage segmentation methods (DSC:88.22% and DSC:85.84% for femoral and tibial cartilage respectively).


Usage of supplemental alternative medicine by community-based patients with gastroesophageal reflux disease (GERD).
There is an increasing trend towards alternative medicine usage by the general US population. However, the extent and type of supplemental alternative medicine used specifically by community-based patients with GERD is unknown. A previously validated questionnaire that included questions about patient demographics, 18 types of alternative medicine, and attitudes towards alternative and conventional medicine was utilized. Consecutive patients seen by community-based physicians in Arizona (Tucson, Phoenix, and Flagstaff) and Wisconsin (Milwaukee) for GERD received the questionnaire during the years 1999 and 2000. Patients completed the questionnaire and returned it to the Tucson VA Medical Center by mail. A total of 185 patients were surveyed (82 men, mean age 55.8 years). Of those, 61.6% used alternative medicine for any reason. However, only 3.8% of patients used supplemental alternative medicine for GERD. Females were twice as likely (95% CI, 1.10-3.67) to use alternative medicines for any reason (including GERD). Patients with daily acid regurgitation were 5.75 times (95% CI, 1.03-32.17) more likely than patients with less frequent acid regurgitation to use alternative medicines specifically for GERD. None of the other demographics, health characteristics, or attitudes were predictive of supplemental alternative medicine use for any reason (or specifically for GERD). In conclusion, only a small percentage of GERD patients seen by community-based practitioners use supplemental alternative medicine specifically for GERD symptoms, despite a higher usage of supplemental alternative medicine for non-GERD-related illness. Being female and having acid regurgitation daily were positively associated with alternative medicine usage for GERD.


Topical dimethylsulfoxide may prevent tissue damage from anthracycline extravasation.
The optimal management of anthracycline extravasation remains unclear. Traditional topical measures to reduce local tissue damage, including corticosteroids, sodium bicarbonate, and ice applications, have not consistently demonstrated beneficial effects. This report describes our experience with four adult patients who suffered anthracycline extravasation and were treated with a regimen of ice, local glucocorticoid injection, and dimethylsulfoxide (DMSO) 55%-99% applied topically every 2-4 h after extravasation for a minimum of 3 days. In all four cases, pain and erythema resolved within 2 days; in no case did tissue necrosis or skin ulceration occur. Topical DMSO is a safe, inexpensive agent that appears to reduce the risk of anthracycline-induced tissue damage. Further studies are needed to determine the optimal dose and schedule of DMSO application and to assess its efficacy in extravasation injuries from other vesicants.


Identification and quantification of the major volatile constituents in antidepressant active fraction of xiaoyaosan by gas chromatography-mass spectrometry.
Xiaoyaosan (XYS), a well-known formula for relieving depression, was originated from the book of "Taiping Huimin Heji Jufang" in Song Dynasty (960-1127 AD), composed of Radix Bupleuri, Radix Angelicae Sinensis, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae, Rhizoma Zingiberis Recens and Radix Glycyrrhizae with dose proportion of 6:6:6:6:6:3:2:2. It is commonly used for the treatment of depression-related syndromes in China. In the formula, Radix Bupleuri usually serves as the principal drug, Radix Angelicae Sinensis and Radix Paeoniae Alba serve as the ministerial drugs, Rhizoma Atractylodis Macrocephalae, Poria, Herba Menthae and Rhizoma Zingiberis Recens serve as adjunctive drugs, Radix Glycyrrhizae serves as messenger drug, they coordinate with each other and enhance the effect of the formula. In our previous experiments, the antidepressant effect of XYS was revealed. However, the antidepressant part (or component) of this prescription was still obscure. An experimental despair animal model: the mice tail suspension test (TST) was used to evaluate the antidepressant activity of XYS and its fractions. GC-MS method was developed to identify the volatile components and determine 4 major volatile components in active fraction. In the TST test, the effect of a low polar fraction (XY-EA) was superior to other fractions of XYS. 13 volatile compounds in the XY-EA were identified on the basis of standards, isolation and structural determination in our laboratory, NIST 05 database and literature data. The content of 4 major volatile compounds in XY-EA which is 6.703%. The petroleum ether fraction (XY-EA) appears to be the active fraction of XYS. 4 major components Z-ligustilide, palmitic acid, atractylenolide I, and atractylenolide II may be the antidepressant active compounds.


Mutation spectrum and predicted function of laforin in Lafora's progressive myoclonus epilepsy.
Lafora's disease is a progressive myoclonus epilepsy with pathognomonic inclusions (polyglucosan bodies) caused by mutations in the EPM2A gene. EPM2A codes for laforin, a protein with unknown function. Mutations have been reported in the last three of the gene's exons. To date, the first exon has not been determined conclusively. It has been predicted based on genomic DNA sequence analysis including comparison with the mouse homologue. 1) To detect new mutations in exon 1 and establish the role of this exon in Lafora's disease. 2) To generate hypotheses about the biological function of laforin based on bioinformatic analyses. 1) PCR conditions and components were refined to allow amplification and sequencing of the first exon of EPM2A. 2) Extensive bioinformatic analyses of the primary structure of laforin were completed. 1) Seven new mutations were identified in the putative exon 1. 2) Laforin is predicted not to localize to the cell membrane or any of the organelles. It contains all components of the catalytic active site of the family of dual-specificity phosphatases. It contains a sequence predicted to encode a carbohydrate binding domain (coded by exon 1) and two putative glucohydrolase catalytic sites. The identification of mutations in exon 1 of EPM2A establishes its role in the pathogenesis of Lafora's disease. The presence of potential carbohydrate binding and cleaving domains suggest a role for laforin in the prevention of accumulation of polyglucosans in healthy neurons.


The NLRP3 inflammasome and gut dysbiosis as a putative link between HIV-1 infection and ischemic stroke.
HIV-associated comorbidities, such as ischemic stroke, are prevalent in people with HIV (PWH). Several studies both in animal models and humans have revealed an association between activation of the inflammasome in HIV-1 infection and stroke. The gut microbiota is an important component in controlling neuroinflammation in the CNS. It has also been proposed to be involved in the pathobiology of HIV-1 infection, and has been associated with an increase in activation of the inflammasome. In this review, we provide an overview of the microbiota-gut-inflammasome-brain axis, focusing on the NLRP3 inflammasome and dysregulation of the microbiome as risk factors that may contribute to the outcome of ischemic stroke and recovery in PWH. We also focus on the potential of targeting the NLRP3 inflammasome as a novel therapeutic approach for PWH who are at risk of developing cerebrovascular diseases.


Dissociation of item and order spatial memory in rats following medial prefrontal cortex lesions.
In order to test whether there is a correspondence in function of prefrontal cortex in rats and humans, rats with medial prefrontal cortex lesions were tested for item and order memory for a list of items (spatial locations in a maze). Results indicate that for order memory rats with medial prefrontal cortex lesions cannot remember the order of presentation of four or eight specific spatial locations. This inability to remember order information can be seen even when animals with lesions have to remember only two spatial locations, can self-order the sequence of four or eight spatial locations, or have been presented with the same study phase on every trial. In contrast, for item memory animals with medial prefrontal cortex lesions retain the first item of the list in the variable study phase situation and remember all the items of the list in a constant study phase situation. However, there are also deficits for the last items within a list in the variable study phase situation for both win-stay and win-shift procedures. This deficit might be a function of an impairment in the utilization of appropriate temporal strategies, which normally would facilitate recognition memory in the win-stay and win-shift tasks. In general, the data suggest a partial, but not complete, dissociation of item-order memory. Furthermore, the data suggest that the medial prefrontal cortex is involved in temporal structuring of information.


Monitoring neuromuscular blockade at the vastus medialis muscle using phonomyography.
The vastus medialis muscle has been recently proposed as a new site for monitoring neuromuscular blockade (NMB). The purpose of this study is to compare NMB at the vastus medialis with the adductor pollicis muscle using phonomyography (PMG). Fifteen patients were enrolled in the study. Anesthesia was induced with remifentanil 0.25 to 0.5 microg x kg(-1) x min(-1), followed by propofol 2 to 2.5 mg(-1) x kg(-1) iv. Analgesia was provided by remifentanil 0.05 to 0.25 microg x kg (-1) x min(-1) iv throughout surgery. A small piezo-electric microphone was attached to the middle of the thenar mass of the right hand to record acoustic signals produced by the contraction of the adductor pollicis muscle. A second microphone was fixed to the medial part of the thigh, 10 cm over the patella, to record the response from the vastus medialis muscle. The ulnar nerve and the im branches of the femoral nerve were stimulated using train-of-four stimulation every 12 sec. Onset, maximum effect, and offset of neuromuscular block were measured after mivacurium 0.2 mg x kg(-1) iv and compared. At the vastus medialis muscle, the onset of NMB was significantly shorter at 1.9 +/- 0.6 min vs 2.8 +/- 0.7 min, the maximum effect less pronounced at 85 +/- 11% vs 96 +/- 2% and recovery of NMB to 25%, 75%, 90% of twitch control height more rapid than at the adductor pollicis muscle at 17 +/- 2.2 min vs 21.6 +/- 4.2 min, 26.7 +/- 6.5 vs 21 +/- 4.1 min and 30.7 +/- 6.6 vs 35.9 +/- 7.1 min, respectively. PMG can be used to measure NMB at the vastus medialis muscle. We found a shorter onset time, less pronounced maximum effect and more rapid recovery of NMB at the vastus medialis muscle than at the adductor pollicis muscle.


IL-10 Indirectly Regulates Corneal Lymphangiogenesis and Resolution of Inflammation via Macrophages.
The role of IL-10, a primarily anti-inflammatory cytokine, in the regulation of inflammatory lymphangiogenesis is undetermined. Herein, we show that IL-10 modulates corneal lymphangiogenesis and resolution of inflammation. IL-10 was not expressed in healthy corneas but was up-regulated in inflamed corneas by infiltrating macrophages. Macrophages up-regulated the expression of prolymphangiogenic vascular endothelial growth factor-C upon stimulation with IL-10. Consistently, corneal inflammation resulted in reduced expression of vascular endothelial growth factor-C and decreased corneal lymphangiogenesis in IL-10-deficient mice (IL-10(-/-)). The effect of IL-10 on lymphangiogenesis was indirect via macrophages, because IL-10 did not directly affect lymphatic endothelial cells. The expression of proinflammatory cytokines and the numbers of infiltrating macrophages increased and remained elevated in inflamed corneas of IL-10(-/-) mice, indicating that IL-10 deficiency led to more severe and prolonged inflammation. The corneal phenotype of IL-10 deficient mice was mimicked in mice with conditional deletion of Stat3 in myeloid cells (lysozyme M Cre mice Stat3(fl/fl) mice), corroborating the critical role of macrophages in the regulation of lymphangiogenesis. Furthermore, local treatment with IL-10 promoted lymphangiogenesis and faster egress of macrophages from inflamed corneas. Taken together, we demonstrate that IL-10 indirectly regulates inflammatory corneal lymphangiogenesis via macrophages. Reduced lymphangiogenesis in IL-10(-/-) and lysozyme M Cre Stat3(fl/fl) mice is associated with more severe inflammatory responses, whereas IL-10 treatment results in faster resolution of inflammation. IL-10 might be used therapeutically to terminate pathological inflammation.


Treatment Efficacy of Pharmacotherapies for Frontotemporal Dementia: A Network Meta-Analysis of Randomized Controlled Trials.
The neuropsychiatric symptoms of frontotemporal dementia (FTD) have a profound negative impact on disease outcomes and care burden. Available pharmacotherapies might be supported by small-scale randomized controlled trials (RCTs); however, clinical recommendations might not be conclusive. We systematically searched several databases from inception to April 30, 2022, for RCTs of drug therapy in patients with FTD and neuropsychiatric symptoms (primary outcome). Secondary outcomes included changes in caregiver stress, daily interactive activities, cognitive function, and acceptability (adverse event or dropout rates). The network meta-analysis (NMA) procedure was performed under the frequency model, showing effect sizes as standardized mean differences (SMD) or odds ratios (OR) with 95% confidence intervals (95% CIs). Seven RCTs with 243 participants were included. Compared with placebo, high-dose oxytocin (72 international units) was associated with the greatest improvement in patients' neuropsychiatric symptoms (SMD = -1.17, 95% CIs = -2.25 to -0.08, z = -2.10, p = 0.035). Piracetam significantly worsened neuropsychiatric symptoms (SMD = 3.48, 95% CIs = 1.58 to 5.37, z = 3.60, p < 0.001) and caregiver stress (SMD = 2.40, 95% CIs = 0.80-4.01, z = 2.94, p = 0.003). Trazodone had significantly higher rates of adverse events (OR = 9.53, 95% CIs = 1.85-49.20, z = 2.69, p = 0.007). No pharmacological intervention significantly benefited cognitive function. This study provides the first NMA for clinical recommendation to support the use of high-dose oxytocin and caution regarding the use of piracetam for neuropsychiatric symptoms in patients with FTD.


Topographical organization of olivocerebellar and corticonuclear connections in the rat--an WGA-HRP study: I. Lobules IX, X, and the flocculus.
The organization of the olivocerebellar and corticonuclear relations for vermal lobules IX and X and the flocculus has been studied in the rat by using microinjections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). This axonal tracer allowed us to study simultaneously the olivocortical connections (revealed by retrograde transport) and corticonuclear connections (revealed by anterograde transport) from a single injection in the cerebellar cortex. The results indicate that four modules can be distinguished, each of which consists of a region of cerebellar cortex receiving afferents from a single small region of the inferior olive (IO) and sending efferents to one or several portions of the cerebellar nuclei and/or vestibular nuclei. The first module includes a medial part of lobule X as well as all the flocculus. It receives afferents from the dorsal cap (dc) and sends efferents to the small cell (s) zone of the dentate nucleus as well as to the medial vestibular (VM) nucleus and subnucleus y. The second module includes a medial parasagittal region located in lobules IX and X. It receives afferents from the ventrolateral outgrowth (vlo) and/or beta nucleus (vlo + beta nucleus) and sends efferents principally to the ventrolateral part of fastigial nucleus and to the superior vestibular (VS), inferior vestibular (VI), and VM nuclei. The third module includes a lateral parasagittal region in lobules IX and X. It receives afferents from the dorsomedial cell column (dmcc) of IO and sends efferents principally to the interpositus nucleus and subnucleus y. The fourth module includes the most lateral part of lobules IX and Xa. It receives afferents from the principal olive (PO) and sends efferents to the s zone of the dentate nucleus. These results are comparable to those obtained in the cat although a few differences are discussed.


Impact of COVID-19 lockdowns on postoperative morbidity after hepatectomy: A propensity-score matching study on a national French database.
The impact of the SARS-CoV-2 pandemic on managing liver malignancies worldwide is unknown. This study aimed to determine the impact of lockdowns on patient clinical pathways and postoperative morbi-mortality. This study evaluated all adults' hospital stays for liver tumors between 2019 and 2021 from the national French discharge database. The primary outcome was the clinical pathway, especially surgical care and postoperative outcomes, between patients admitted during COVID-19 lockdown periods (lockdown group) and during the same periods of 2019 and 2021 (control groups). The overall population included 58,508 patients: 18,907 patients in the lockdown group, 20,045 in the 2019 control group, and 19,556 in the 2021 control group. Surgical activity decreased by 11.6% during lockdowns, with 1,514 (8.0%) of patients in the lockdown group treated by surgery, 1,514 (8.6%) in the 2019 control group (P < .001), and 1,466 (7.4%) in the 2021 control group. Chemotherapy was considered more during the lockdowns (P < .001). More patients were operated in small-volume centers during the lockdowns (34% vs 32% vs 32%, P = .034), and fewer were hospitalized in highly populated regions (P < .001). Postoperative morbidity (47% vs 47% vs 47%, P = .90) and mortality (3.3% vs 3.6% vs 3.1%, P = .80) were comparable in the 3 periods, with no influence of lockdowns on morbidity (risk ratio = 0.94, 95% confidence interval = 0.81-1.09, P = .40) or mortality (odds ratio = 1.12, 95% confidence interval = 0.72-1.74, P = .6). Postoperative pulmonary (17% vs 13%, P = .024) and septic complications (20% vs 15%, P = .022) were significantly higher during the first lockdown compared to the second. This study provides a French overview of liver malignancy management during the COVID-19 pandemic. Moreover, surgical activity decreased by 11.6% in high-volume centers, with no impact on postoperative morbidity and mortality.


The Lively Legs self-management programme increased physical activity and reduced wound days in leg ulcer patients: Results from a randomized controlled trial.
Investigating the effectiveness of the Lively Legs program for promoting adherence with ambulant compression therapy and physical exercise as well as effects on leg ulcer recurrence. A randomized controlled trial. Eleven outpatient clinics for dermatology in the Netherlands participated in the study. 184 patients attending the outpatient clinic with leg ulcers based dominantly on a venous aetiology. Randomization was stratified by centre, age, sex and aetiology (purely venous or mixed). The intervention group received additionally to usual care, lifestyle counselling according to the Lively Legs program, the control group received care as usual. Patient behaviour on physical activity (IPAQ), adherence to compression therapy and wound status were assessed every 6 months during a follow-up period of 18 months. Data analysis was based on the intention to treat principle, using a generalized linear model with additive link function and Bernouilli distributions. Effects on recurrence were analyzed after the first ulcer had healed using proportional hazard regression. The results showed an increase in adherence with compression therapy in both groups, with no significant difference between the groups. The intervention group performed significantly better on conducting leg exercises (p<0.01) and 10 min walks at five days a week (p<0.01). There was no difference on reaching 30 min of walking on 5 days a week. The intervention group had less wound days (p<0.01), time till recurrence did not differ significantly (p=0.07). The Lively Legs program effectively increased the use of leg exercises and walking behaviour, and decreased wound time, however it did not significantly enhance use of compression stockings. Non significant effects regarding secondary outcomes may relate to the frailty of the sample.


Baseline and on-treatment HBcrAg levels as predictors of HBeAg seroconversion in chronic hepatitis B patients treated with antivirals.
HBeAg seroconversion is an important treatment endpoint. We aimed to identify predictors of seroconversion using serum HBsAg and hepatitis B core-related antigen (HBcrAg) in HBeAg-positive patients treated with nucleos(t)ide analogs (NAs). Data and samples from 70 HBeAg-positive patients treated with entecavir or tenofovir between January 2007 and December 2017 were retrospectively analysed. The mean follow-up period was 11 years. The predictive power for HBeAg seroconversion of HBcrAg levels at baseline and 2 years after antiviral therapy was determined using receiver operating curve analysis. Twenty-one patients (30%) achieved HBeAg seroconversion at a mean of 28 (range, 12-84) months after antiviral treatment. The median baseline HBcrAg and HBsAg levels were 6.9(5.7-7.0) vs. 5.8(5.5-6.5) log10 U/mL (p = .006), 4.9(4.5-5.1) vs. 4.5(4.1-5.0) log10 IU/mL (p = .044) in the no seroconversion group and seroconversion group, respectively. In the multivariate analysis, the serum HBcrAg levels at baseline and 2 years after antiviral therapy were predictive factors for HBeAg seroconversion ([HR]; 0.326; [CI], 0.111-0.958; p = .042 and HR, 0.4555; CI, 0.211-0.984; p = .045). HBcrAg levels≤6.5log10 U/mL at baseline and ≤5.3log10 U/mL at 2 years after antiviral therapy had sensitivities of 53.1% and 69.8%, specificities of 95.2% and 70.6%, positive predictive values of 82.6% and 50.0%, and negative predictive values of 82.6% and 84.5%, respectively, with AUROCs of 0.712 (95%CI, 0.596-0.830) and 0.745 (95%CI, 0.599-0.891) for predicting HBeAg seroconversion. In chronic hepatitis B patients treated with NAs, HBcrAg levels≤6.5log10 U/mL at baseline and ≤5.3log10 U/mL at 2 years after antiviral therapy were useful predictive factors of HBeAg seroconversion.


Epidemiological and clinical evaluation of patients with a cleft in lower saxony Germany: a mono-center analysis.
The aim was to provide epidemiological and clinical data on patients with orofacial clefts in Lower Saxony in Germany. The records of 404 patients with orofacial clefts treated surgically at the University Medical Center Goettingen from 2001 to 2019 were analyzed in this retrospective study. Prevalence of orofacial clefts in general, orofacial clefts as manifestation of a syndrome, sex distribution, and prevalence of different cleft types was evaluated and associated with the need for corrective surgery, family history, pregnancy complications, and comorbidities. The prevalence of orofacial clefts for Goettingen in Lower Saxony was 1:890. 231 patients were male and 173 were female. CLP was most common (39.1%) followed by CP (34.7%), CL (14.4%), CLA (9.9%), and facial clefts (2%). The left side was more frequently affected and unilateral cleft forms occurred more often than bilateral ones. Almost 10% of the population displayed syndromic CL/P. 10.9% of all patients had a positive family history regarding CL/P, predominantly from the maternal side. Pregnancy abnormalities were found in 11.4%, most often in the form of preterm birth. Comorbidities, especially of the cardiovascular system, were found in 30.2% of the sample. 2.2% of patients treated according to the University Medical Center Goettingen protocol corrective surgery was performed in form of a velopharyngoplasty or residual hole closure. The epidemiological and clinical profile of the study population resembled the expected distributions in Western populations. The large number of syndromic CL/P and associated comorbidities supports the need for specialized cleft centers and interdisciplinary cleft care.


SARS-CoV-2 utilization of ACE2 from different bat species allows for virus entry and replication in vitro.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to have a zoonotic origin with bats suspected as a natural host. In this work, we individually express the ACE2 of seven bat species including, little brown, great roundleaf, Pearson's horseshoe, greater horseshoe, Brazilian free-tailed, Egyptian rousette, and Chinese rufous horseshoe in DF1 cells and determine their ability to support attachment and replication of SARS-CoV-2 viruses. We demonstrate that the ACE2 receptor of all seven species made DF1 cells permissible to SARS-CoV-2. The level of virus replication differed between bat species and variants tested. The Wuhan lineage SARS-CoV-2 virus replicated to higher titers than either variant virus tested. All viruses tested grew to higher titers in cells expressing the human ACE2 gene compared to a bat ACE2. This study provides a practical in vitromethod for further testing of animal species for potential susceptibility to current and emerging SARS-CoV-2 viruses.


Primary aortic valve replacement with allografts over twenty-five years: valve-related and procedure-related determinants of outcome.
Allografts offer many advantages over prosthetic valves, but allograft durability varies considerably. From 1969 through 1993, 618 patients aged 15 to 84 years underwent their first aortic valve replacement with an aortic allograft. Concomitant surgery included aortic root tailoring (n = 58), replacement or tailoring of the ascending aorta (n = 56), and coronary artery bypass grafting (n = 87). Allograft implantation was done by means of a "freehand" subcoronary technique (n = 551) or total root replacement (n = 67). The allografts were antibiotic sterilized (n = 479), cryopreserved (n = 12), or viable (unprocessed, harvested from brain-dead multiorgan donors or heart transplant recipients, n = 127). Maximum follow-up was 27.1 years. Thirty-day mortality was 5.0%, and crude survival was 67% and 35% at 10 and 20 years. Ten- and 20-year rates of freedom from complications were as follows: endocarditis, 93% and 89%; primary tissue failure, 62% and 18%; and redo aortic valve replacement, 81% and 35%. Multivariable Cox analyses identified several valve- and procedure-related determinants: rising allograft donor age and antibiotic-sterilized allograft for mortality; donor more than 10 years older than patient for endocarditis; rising donor age minus patient age, rising implantation time (from harvest to aortic valve replacement), and donor age more than 65 years for tissue failure; and rising donor age minus patient age, young patient age, rising implantation time, and subcoronary implantation preceded by aortic root tailoring for redo aortic valve replacement. Estimated 10- and 20-year rates of freedom from tissue failure for a 70-year-old patient with a viable valve from a 30-year-old donor and no other risk factors were 91% and 64%; the figures were 71% and 20% if the donor age was 65 years. The rates of freedom from tissue failure for a 30-year-old patient with a 30-year-old donor were 82% and 39%; the figures were 49% and 3% with a 65-year-old donor. Beneficial influences of a viable valve were largely covered by short harvest time (no delay for allografts from brain dead organ donors or heart transplant recipients) and short implantation time. Primary allograft aortic valve replacement can give acceptable results for up to 25 years. The late results can be improved by the use of a viable allograft, by matching patient and donor age, and by more liberal use of free root replacement with re-implantation of the coronary arteries rather than tailoring the root to accommodate a subcoronary implantation.


3-D modeling applications in ultrasound education: a systematic review.
Ultrasound offers a real-time 2-D view of structures within the human body. While many medical education programs have already dedicated a portion of their curriculum to ultrasound, others are concerned about cost, accessibility and limits to student practice. Student benefit may be affected by cognitive errors, which are in part owing to the mental heuristics required to visualize a 3-D structure by interpreting a 2-D image. A possible solution to eliminating subjectivity in ultrasound interpretation is the use of 3-D models to augment the traditional 2-D ultrasound experience. PubMed, Embase and Web of Science were searched for primary literature exploring relationships between 3-D modeling applications and their use in ultrasound education. The search and review process was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. Overall, 14 of the included 16 studies indicated a significant improvement in medical education of ultrasound with the intervention of 3-D modeling applications. This systematic review confirms that 3-D modeling applications benefit student learning in ultrasound education while illuminating the need for more research in this field.


Detection of multiple Epstein-Barr viral strains in allogeneic bone marrow transplant recipients.
We have previously shown in 3 allogeneic bone-marrow transplant (BMT) recipients that complete replacement of recipient marrow was associated with the elimination of the pretransplant Epstein-Barr virus (EBV) strain of the recipient. To study the kinetics of EBV elimination and reinfection in more detail, we have performed a longitudinal study of BMT recipients combining serology, virus isolation from mouthwashes and peripheral blood, and EBV strain characterization. Oropharyngeal EBV excretion was found to persist after the cytoreductive therapy prior to BMT, whereas EBV-carrying cells in the blood were detected only after 5 weeks following BMT. During the first month post-BMT, 2 different EBV strains could be isolated from sequential mouth-washes of 3 patients. The initial strains were found to persist up to 7, 21, and 29 days post-BMT, whereas the subsequent strains appeared at 21, 42, and 34 days post-BMT, respectively. Thus, the original EBV strain may persist only for a limited time after BMT, and the oropharyngeal epithelium may be reinfected by a new EBV strain from the blood within 3 weeks. With respect to the coexistence of multiple EBV strains, 2 patterns were evident. From the day 62 mouthwash of 1 patient, 1 Type A and 1 Type B strain were isolated. From the day 180 mouthwash of a second patient, a dominant Type A strain was recovered, together with 6 "variant" strains that differed from each other by only a single EBNA protein (EBNA 1). This pattern may be explained by viral recombinations during replication, which may form the basis for the vast polymorphism of EBV observed in unrelated individuals.


Validity of criteria for establishing maximal O2 uptake during ramp exercise tests.
The incremental or ramp exercise test to the limit of tolerance has become a popular test for determination of maximal O(2) uptake (VO(2max)). However, many subjects do not evidence a definitive plateau of the VO(2) -work rate relationship on this test and secondary criteria based upon respiratory exchange ratio (RER), maximal heart rate (HR(max)) or blood [lactate] have been adopted to provide confidence in the measured VO(2max). We hypothesized that verification of VO(2max) using these variables is fundamentally flawed in that their use could either allow underestimation of VO(2max) (if, for any reason, a test were ended at a sub-maximal [Formula: see text]), or alternatively preclude subjects from recording a valid VO(2max). Eight healthy male subjects completed a ramp exercise test (at 20 W/min) to the limit of tolerance on an electrically braked cycle ergometer during which pulmonary gas exchange was measured breath-by-breath and blood [lactate] was determined every 90 s. Using the most widely used criterion values of RER (1.10 and 1.15), VO(2max) as determined during the ramp test (4.03 +/- 0.10 l/min) could be undermeasured by 27% (2.97 +/- 0.24 l/min) and 16% (3.41 +/- 0.15 l/min), respectively (both P < 0.05). The criteria of HR(max) (age predicted HR(max) +/- 10 b/min) and blood [lactate] (> or = 8 mM) were untenable because they resulted in rejection of 3/8 and 6/8 of the subjects, most of whom (5/8) had demonstrated a plateau of VO(2max) at VO(2max). These findings provide a clear mandate for rejecting these secondary criteria as a means of validating VO(2max) on ramp exercise tests.


Genetic and molecular analyses of lymphocyte-defined HLA-D region specificities.
Determinants encoded in the HLA-D region have been studied with both cellular (PLT) and molecular (SDS-IEF) methods. When the PLT response against a lymphoblastoid cell line was analyzed by limiting dilution culture and determination of the reactivity of individual cultures against a panel of loss mutants of the initial stimulating LCL, a large fraction of the cultures showed the same pattern, apparently recognizing a determinant associated with DR. In two-dimensional gel analysis of several DR4-positive HLA-D region homozygous cells, the IEF pattern of the DR beta chain correlated with the Dw specificity expressed by the cell. These two pieces of evidence suggest that, although many determinants may contribute to reactivity in mixed leucocyte culture or PLT, an immunodominant determinant associated with the DR beta chain may be the most important single factor in the assignment of Dw specificity.


Patterns of reciprocity in auditory thalamocortical and corticothalamic connections: study with horseradish peroxidase and autoradiographic methods in the rat medial geniculate body.
The patterns of reciprocity between retrogradely labeled thalamocortical cells of origin and anterogradely projecting corticothalamic axon terminals were studied in the subdivisions of the adult rat medial geniculate body following auditory cortical injections of mixtures of horseradish peroxidase and [3H]leucine. The labeling produced by each method was examined independently, both qualitatively and quantitatively, in adjacent series of tetramethylbenzidine-processed sections and in autoradiographs after 24-96 hour survivals. The distribution and number of labeled cells and axon terminals were assessed separately for each method and compared systematically throughout the rostro-caudal extent of the medial geniculate complex. The principal finding was that zones containing many retrogradely labeled neuronal somata are not completely coextensive with areas of heavy terminal labeling within the medial geniculate body, although there is a gross congruence of thalamocortical-corticothalamic projections. Conversely, we found many zones of autoradiographic silver grains without retrogradely labeled somata in the adjacent sections; in general, the autoradiographic zones of non-reciprocity were more extensive and marked than were retrograde zones of non-reciprocity. The rat medial geniculate complex could be subdivided on the basis of its neuronal organization, cytoarchitecture, fiber architecture, and thalamocortical and corticothalamic connections into three major parts: the ventral, dorsal, and medial divisions. This pattern of organization was comparable, though not identical, to that of the corresponding subdivisions in the cat medial geniculate body (Winer: Adv. Anat. Embryol. Cell Biol. 86:1-98, '85). While the retrograde labeling appeared to mark many of the different types of neurons in each of the three divisions, there were distinct local and quantitative and qualitative differences in the distribution of autoradiographic terminal labeling. The ventral division received the heaviest cortical input, the medial division the least labeling, while the dorsal division was intermediate. Thus, corticogeniculate projections to the ventral division often produced values 20-100 times above background (absolute values: 2,001-10,000 silver grains/14,400 micron2; background: less than 100 silver grains/14,400 micron2); the same projection to the dorsal division usually resulted in grain counts no more than 5-20 times above background (501-2,000/14,400 micron2), while in the medial division the number of silver grains rarely exceeded two to five times the background (201-500/14,400 micron2).(ABSTRACT TRUNCATED AT 400 WORDS)


Radiolarian data from the submarine Vityaz Ridge, Northwest Pacific, for biostratigraphic and paleoceanographic reconstructions.
Radiolaria are marine siliceous microfossils used to reconstruct paleoceanographic and paleoclimatic events. This report presents a dataset obtained from radiolarian analysis for the biostratigraphic and paleoceanographic reconstructions of the submarine Vityaz Ridge and the Kuril-Kamchatka Trench paraxial zone. Data were obtained from dredge samples collected during the 4th cruise of the R/V Akademik A. Nesmeyanov in 1984 and during the 37th, 41st, and 52nd cruises of the R/V Akademik M. A. Lavrentyev in 2005, 2006, and 2010, respectively. Both new and previously published data on distribution of the Pleistocene radiolarian zones in the North Pacific are presented in this report.


Hypofractionated Postprostatectomy Radiation Therapy for Prostate Cancer to Reduce Toxicity and Improve Patient Convenience: A Phase 1/2 Trial.
The phase 1 portion of this multicenter, phase 1/2 study of hypofractionated (HypoFx) prostate bed radiation therapy (RT) as salvage or adjuvant therapy aimed to identify the shortest dose-fractionation schedule with acceptable toxicity. The phase 2 portion aimed to assess the health-related quality of life (QoL) of using this HypoFx regimen. Eligibility included standard adjuvant or salvage prostate bed RT indications. Patients were assigned to receive 1 of 3 daily RT schedules: 56.6 Gy in 20 Fx, 50.4 Gy in 15 Fx, or 42.6 Gy in 10 Fx. Regional nodal irradiation and androgen deprivation therapy were not allowed. Participants were followed for 2 years after treatment with outcome measures based on prostate-specific antigen levels, toxicity assessments (Common Terminology Criteria for Adverse Events, v4.0), QoL measures (the Expanded Prostate Cancer Index Composite [EPIC] and EuroQol EQ-5D instruments), and out-of-pocket costs. There were 32 evaluable participants, and median follow-up was 3.53 years. The shortest dose-fractionation schedule with acceptable toxicity was determined to be 42.6 Gy in 10 Fx, with most patients (23) treated with this schedule. Grade 3 genitourinary (GU) and gastrointestinal (GI) toxicities occurred in 3 patients and 1 patient, respectively. There was 1 grade 4 sepsis event. Higher dose to the hottest 25% of the rectum was associated with increased risk of grade 2+ GI toxicity; no dosimetric factors were found to predict for GU toxicity. There was a significant decrease in the mean bowel, but not bladder, QoL score at 1 year compared with baseline. Prostate-specific antigen failure occurred in 34.3% of participants, using a definition of nadir plus 2 ng/mL. Metastases were more likely to occur in regional lymph nodes (5 of 7) than in bones (2 of 7). The mean out-of-pocket cost for patients during treatment was $223.90. We identified 42.6 Gy in 10 fractions as the shortest dose-fractionation schedule with acceptable toxicity in this phase 1/2 study. There was a higher than expected rate of grade 2 to 3 GU and GI toxicity and a decreased EPIC bowel QoL domain with this regimen. Future studies are needed to explore alternative adjuvant/salvage HypoFx RT schedules after radical prostatectomy.


Presence of plasma endotoxin is correlated with tumour necrosis factor receptor levels and disease activity in alcoholic cirrhosis.
Cytokines and plasma endotoxin were measured in a consecutive series of patients with alcoholic cirrhosis (AC). Endotoxaemia was found to be strongly correlated to increased plasma levels of functionally active tumour necrosis factor (TNF) receptors -p55 and -p75, TNF-alpha and the Child-Pugh stage of the disease. Our data support the hypothesis of the pathogenic role of lipopolysaccharide in hepatocellular damage of patients with AC.


Ambrosius Holbein's memento mori map for Sir Thomas More's Utopia. The meanings of a masterpiece of early sixteenth century graphic art.
This paper describes how, and asks why, the Renaissance artist Ambrosius Holbein hid a skull within the overall design of his woodcut map of Sir Thomas More's Utopia. (Fig. 2) This map was prepared for the 1518 Froben edition of the book, and was probably commissioned by Erasmus of Rotterdam. Its identification now is made easier by the habits of interpretation with which all dentists are equipped thanks to their skill in dental radiology, and by the recognition of teeth appearing in an unlikely disguise.


Red Blood Cell-Facilitated Photodynamic Therapy for Cancer Treatment.
Photodynamic therapy (PDT) is a promising treatment modality for cancer management. So far, most PDT studies have focused on delivery of photosensitizers to tumors. O2, another essential component of PDT, is not artificially delivered but taken from the biological milieu. However, cancer cells demand a large amount of O2 to sustain their growth and that often leads to low O2 levels in tumors. The PDT process may further potentiate the oxygen deficiency, and in turn, adversely affect the PDT efficiency. In the present study, a new technology called red blood cell (RBC)-facilitated PDT, or RBC-PDT, is introduced that can potentially solve the issue. As the name tells, RBC-PDT harnesses erythrocytes, an O2 transporter, as a carrier for photosensitizers. Because photosensitizers are adjacent to a carry-on O2 source, RBC-PDT can efficiently produce 1O2 even under low oxygen conditions. The treatment also benefits from the long circulation of RBCs, which ensures a high intraluminal concentration of photosensitizers during PDT and hence maximizes damage to tumor blood vessels. When tested in U87MG subcutaneous tumor models, RBC-PDT shows impressive tumor suppression (76.7%) that is attributable to the codelivery of O2 and photosensitizers. Overall, RBC-PDT is expected to find wide applications in modern oncology.


Percutaneous radiofrequency ablation using internally cooled wet electrodes for treatment of colorectal liver metastases.
To evaluate the efficacy and safety of internally cooled wet (ICW) electrodes, which provide interstitial infusion of saline and intra-electrode cooling simultaneously, in the percutaneous radiofrequency ablation (RFA) of liver metastases from colorectal cancer. From February 2008 to October 2010, 27 patients with 35 hepatic metastatic lesions (mean size 1.99cm; range 0.7-3.8cm) underwent RFA using ICW electrodes. Of these 35 tumours, 32 had diameters ≤3cm, and three had diameters of 3-4cm. Moreover, 18 tumours were non-subcapsular and 17 were subcapsular. No patients (0%) had major complications after RFA. During follow-up (median 27 months; range 4.5-36 months), 14 of the 35 treated lesions (40%) showed local tumour progression. The local tumour progression-free survival rates at 1 and 3 years were 73 and 56%, respectively. The local tumour progression-free survival period was significantly longer in patients with tumours ≤2cm than >2cm (p<0.001), but did not differ significantly between patients with non-subcapsular and subcapsular tumours (p=0.454). The overall 1 and 3 year survival rates after RFA were 100 and 77%, respectively. Percutaneous RFA using ICW electrodes is safe and technically feasible for the treatment of liver metastases from colorectal cancer. It provides effective local tumour control with low complication rates and reduced number of needle placements.


[Demonstration of an enzyme inhibiting coagulation of blood ingested by the blood-sucking insect, Rhodnius prolixus (Heteroptera, Reduviidae)].
A new fibrinolytic enzyme, "the prolixase", was isolated and purified from the haemolymph of Rhodnius Prolixus. The mode of action of the enzyme was studied and compared to that of extracts from salivary glands and midgut of the insect. It appears that the prolixase is involved in inhibiting the coagulation of the blood ingested by Rhodnius during its blood meal. The mode of action of the enzyme in this phenomenon is discussed.


Analysis of reproducibility of respiration-triggered gated radiotherapy for lung tumors.
Respiration-gated radiotherapy (RGRT) can decrease the toxicity of chemo-radiotherapy (CT-RT) by allowing use of smaller treatment fields. RGRT requires a predictable relationship between tumor position and external surrogate, which must be verified during treatment. Time-integrated electronic portal imaging (TI-EPI) identifies mean intra-fractional positions of moving structures, and was used to study reproducibility of anatomy during RGRT for lung tumors. TI-EPIs were acquired using an amorphous silicon-based electronic portal imaging system (EPID, aS500) in continuous image acquisition mode in 11 patients treated with audio-coached RGRT at end-inspiration. The Varian Real-time Position Management (RPM) system was used for 4DCT imaging and RGRT delivery. All TI-EPI portals were co-registered to corresponding digitally reconstructed radiographs (DRR) of the planning 4DCT using the spinal column. Displacements in tumor position or that of an adjacent bronchus during RGRT was measured relative to the reference structure on the DRR. Vertebra-matched portals revealed systematic (Sigma) and random (sigma) errors of 1.8 and 1.3mm in medial-lateral direction and 1.7 and 1.7 mm in cranial-caudal direction, indicating a reproducible tumor/bronchus position during the RPM-triggered gates. RGRT delivery at end-inspiration can achieve reproducible internal anatomy in 'gated' fields delivered with audio-coaching.


A novel hybrid platform of g-C3N4 nanosheets /nucleic-acid-stabilized silver nanoclusters for sensing protein.
The fabrication of nanomaterials-based sensing platform has attracted a great deal of interest due to their unique properties. Here, we report a novel hybrid platform of g-C3N4 nanosheets/DNA-stabilized Ag nanoclusters (CNNS/AgNCs) for sensing application. In this platform, the fluorescent AgNCs was synthesized using a pair of double-functional ssDNA sequence as a template, including the aptamer segment against thrombin and C-rich segment for AgNCs. Next, the interaction between the fluorescent Apt-AgNCs and CNNS was investigated. It is verified that DNA-stabilized AgNCs could absorb on the CNNS surface via the stronger π-π interaction to form the hybrid platform, whose fluorescence is quenched by CNNS through the photoelectron transfer effect (PET). When targets are introduced into the system, target/Apt-AgNCs complex will fall off from the CNNS surface, resulting in the fluorescence recovery. This hybrid platform can achieve the detection of biomolecule with high sensitivity and selectivity. Considering the fluorescence variability of DNA scaffold AgNCs, this hybrid platform is promising to extend to other target and even multi-target detection.


Carbonaceous Nanomaterials-Mediated Defense Against Oxidative Stress.
The concept of nanoscale materials and their applications in industrial technologies, consumer goods, as well as in novel medical therapies has rapidly escalated in the last several years. Consequently, there is a critical need to understand the mechanisms that drive nanomaterials biocompatibility or toxicity to human cells and tissues. The ability of nanomaterials to initiate cellular pathways resulting in oxidative stress has emerged as a leading hypothesis in nanotoxicology. Nevertheless, there are a few examples revealing another face of nanomaterials - they can alleviate oxidative stress via decreasing the level of reactive oxygen species. The fundamental structural and physicochemical properties of carbonaceous nanomaterials that govern these anti-oxidative effects are discussed in this article. The signaling pathways influenced by these unique nanomaterials, as well as examples of their applications in the biomedical field, e.g. cell culture, cell-based therapies or drug delivery, are presented. We anticipate this emerging knowledge of intrinsic anti-oxidative properties of carbon nanomaterials to facilitate the use of tailored nanoparticles in vivo.


Taking time out: a study of women dentists who have experienced career breaks.
Data on the careers and work patterns of women dentists were established in 1975. Social and economic changes, as well as change within the profession, such as the fact that almost half the students entering dental schools are now female, pointed to the necessity of a further survey in 1985. Questionnaires were sent off to 4513 women dentists resident in England and Wales, with a resultant response of 76 per cent. Part of the questionnaire concentrated on the length of career breaks experienced by/taken by women dentists in order to determine whether there has been any change in the pattern of taking time out in dentistry over the decade. At the time of the survey, 388 women (12 per cent) were retired, in addition, just over half of the women who replied had experienced a break at some stage during their career. These breaks from practice are described and discussed.


Validity of using annual mean particulate matter concentrations as measured at fixed site in assessing personal exposure: an exposure assessment study in Japan.
From 2003 through 2005, we compared annual mean particulate matter (PM) and nitrogen dioxide (NO₂) concentrations as measured at fixed-site monitoring stations in 6 Japanese cities with those measured inside and outside subject residences and during personal monitoring. A total of 65 households participated in indoor and outdoor residential exposure monitoring. In summer and autumn, we also performed personal monitoring of one resident of each household. On each day, personal samplers were used to collect 24-h samples of PM and NO₂ simultaneously from the fixed sites, indoor and outdoor, and from those undergoing personal monitoring. We found good correlations between the fixed-site and outdoor measurements for annual mean (average of 7-day × 4-season) concentrations of PM₂.₅, PM₁₀₋₂.₅, PM10 and NO₂ (Spearman's rank correlation coefficients (ρ) ≥ 0.75). However, the correlations between the fixed-site and indoor measurements were moderate to low. In summer and autumn, the correlations between the fixed-site and personal mean concentrations of PM₂.₅ (ρ = 0.62), PM10 (ρ = 0.58), and NO₂ (ρ = 0.70) were acceptable. However, because people spend most of their time indoors, these correlations for annual mean concentrations were not estimated to be high. Our results are important in allowing researchers to estimate the effects of resulting measurement errors of PM and NO₂.


Identification of in vivo metabolites of a potential anti-rheumatoid arthritis compound, the quinazolinone derivative PD110, using ultra-high performance liquid chromatography coupled with Q-Exactive plus mass spectrometrys.
The objective of this study was to identify metabolites of PD110 by UHPLC-Q-Exactive Plus MS and determine its metabolic pathways in vivo.Mouse urine, faeces, and plasma samples were collected after an intraperitoneal administration of PD110 at a single dose of 30 mg·kg-1.The metabolites were detected and identified by UHPLC-Q-Exactive Plus MS and Compound DiscovererTM 2.0 software.In total, 44 metabolites (including 31 phase-I and 13 phase-II metabolites) were preliminarily identified according to the mass accuracy (<5 ppm) and comparison of their mass spectrometry profiles. Oxidation, glucuronide conjugation, and glucoside conjugation were the main metabolic pathways of PD110 in mice.This research first focussed on the biotransformation of PD110 in mice, and its metabolites may provide pivotal information for further pharmacological and clinical studies.


Reducing the cadmium, inorganic arsenic and dimethylarsinic acid content of rice through food-safe chemical cooking pre-treatment.
Cadmium, inorganic arsenic and, potentially, dimethyl arsenic acid are carcinogens widely elevated in rice. Here it was identified that the food-safe and common cadmium chelator citric acid efficiently removed cadmium from intact grain via pre-soaking procedure, while also reducing arsenic species. A twostep pre-soaking stage was developed whereby rice was first incubated, at ambient temperature, in 1 M citric acid for 12 h, and then in 1 M calcium carbonate for another 12 h, the latter step to neutralize pH, followed by cooking. When 10 different individual types of rice were processed in such a way this resulted in removal rates of 79% for cadmium, 81% for inorganic arsenic and a 66% for DMA. The technology is particularly suitable for bulk food processing and could be deployed in the most cadmium and arsenic impacted regions where rice is a staple.


Organic solvent-free extraction of carotenoids from carrot bio-waste and its physico-chemical properties.
The bio-wastes (like peels, seeds, etc.) from food industry are rich source of bio-active components, but are poorly managed. In present study, carotenoids were extracted from carrot pomace using ultrasonication and high shear dispersion techniques and flaxseed oil as green solvent (green biorefinery approach). Various combinations of time and temperature were used and final selection was made on the basis of maximum recovery of carotenoids. High shear disperser yielded maximum carotenoids (recovery 94.8 ± 0.08%). The total carotenoid content, antioxidant activity as ABTS, DDPH and FRAP and β-carotene of carotenoid rich extract from carrot pomace (CREP) were 82.66 ± 0.06 μg/g, 1596.04 ± 69.45 μg Trolox eq./ml, 380.21 ± 39.62 μg Trolox eq./ml, 941.20 ± 19.91 μM Trolox eq./ml, 78.37 μg/g, respectively were significantly higher (p < 0.05) when compared with the extracting medium. The L*, a* and b* values of CRE were 18.65 ± 0.037, 19.42 ± 0.21, 27.947 ± 0.65 and were significantly higher than extracting medium. The CRE could be used as a natural source of β-carotene and natural colorant for food applications.


Identification of multiple rare variants associated with a disease.
Identifying rare variants that are responsible for complex disease has been promoted by advances in sequencing technologies. However, statistical methods that can handle the vast amount of data generated and that can interpret the complicated relationship between disease and these variants have lagged. We apply a zero-inflated Poisson regression model to take into account the excess of zeros caused by the extremely low frequency of the 24,487 exonic variants in the Genetic Analysis Workshop 17 data. We grouped the 697 subjects in the data set as Europeans, Asians, and Africans based on principal components analysis and found the total number of rare variants per gene for each individual. We then analyzed these collapsed variants based on the assumption that rare variants are enriched in a group of people affected by a disease compared to a group of unaffected people. We also tested the hypothesis with quantitative traits Q1, Q2, and Q4. Analyses performed on the combined 697 individuals and on each ethnic group yielded different results. For the combined population analysis, we found that UGT1A1, which was not part of the simulation model, was associated with disease liability and that FLT1, which was a causal locus in the simulation model, was associated with Q1. Of the causal loci in the simulation models, FLT1 and KDR were associated with Q1 and VNN1 was correlated with Q2. No significant genes were associated with Q4. These results show the feasibility and capability of our new statistical model to detect multiple rare variants influencing disease risk.


A Zfp609 circular RNA regulates myoblast differentiation by sponging miR-194-5p.
Skeletal muscle development and growth regulatory mechanism is the focus of both animal genetics and medicine. The recent studies indicate that covalently closed circular RNAs (circRNAs) also play important role on muscle development through sequestering specific miRNAs. The present study was conducted to determine the functional roles of circZfp609, a recently identified circRNA, in the regulation of myogenesis in mouse myoblast cell line (C2C12). circZfp609 is predicted to has binding sites of miR-194-5p. circZfp609 knockdown increased the expression of Myf5 and MyoG, which indicated that circZfp609 suppressed myogenic differentiation. Via a luciferase screening assay, circZfp609 is observed to sponge to miR-194-5p with four potential binding sites. Specifically, we show that circZfp609 can sponge miR-194-5p to sequester its inhibition on BCLAF1 so as to repress the myogenic differentiation. Modulation of circZfp609 expression in muscle tissue may emerge as a potential target in breeding strategies attempting to control muscle development.


Cholangiocarcinoma cell proliferation is enhanced in primary sclerosing cholangitis: A role for IL-17A.
Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the biliary tree and a risk factor for development of cholangiocarcinoma (CCA). The pathogenesis of PSC-related CCA is largely unclear, although it is assumed that chronic inflammatory environment plays a pivotal role. We aimed to investigate the effect of inflammation-related cytokines in PSC on the proliferation rate of cancer cells. For this, the proliferation index in PSC-CCA and sporadic CCA was determined by Ki-67 immunohistochemistry. The percentage of Ki-67 positivity in cancer cells was significantly higher in PSC-CCA than in sporadic CCA (41.3% ± 5.7% vs 25.8% ± 4.1%; P = .038). To assess which cytokines in the inflammatory environment have the potential to stimulate cancer cell proliferation, patient-derived CCA organoids (CCAOs) were exposed to five cytokines related to PSC (Interleukin (IL)-1β, IL-6, IL-17A, interferon gamma and tumor necrosis factor alpha). Only IL-17A showed a significant stimulatory effect on cell proliferation in CCAOs, increasing organoid size by 45.9% ± 16.4% (P < .01) and proliferation rate by 38% ± 16% (P < .05). IL-17A immunohistochemistry demonstrated that PSC-CCA might express more IL-17A than sporadic CCA. Moreover, correlation analysis in sporadic CCA and PSC-CCA found a significant correlation between IL-17A expression and proliferation. In conclusion, tumor cell proliferation is increased in PSC-CCA cells compared with sporadic CCA cells. IL-17A increases CCA cell proliferation in vitro and may contribute to the high proliferation rate in PSC-CCA in situ. Therefore, IL-17A represents a new potential therapeutic target in (PSC-)CCA, to be tested in future trials.


Comparative effectiveness of hypothermia rewarming techniques: radio frequency energy vs. warm water.
The purpose of this study was to compare the rewarming effectiveness of a radio frequency coil (13.56 MHz) at a specific absorption rate (SAR) of 2.5 W/kg (RF) with warm water immersion (40 degrees C) (WW) and an insulated mummy-type insulating sack (IS) under simulated field conditions. Four male subjects, ages 24-35, were immersed in 10 degrees C water for up to 90 min or until their rectal temperatures (Tre) decreased to 35 degrees C. Each subject had 3 trials in which they were immersed. After each immersion, rewarming was accomplished with either RF, WW, or IS, so that each subject was rewarmed once with each method. Comparisons of the 3 rewarming methods were based on the rate of increase of Tre during rewarming (Tre/t), Tre 60 min after the start of rewarming (Tre60), the time-interval measured from extraction from the water to the end of afterdrop (tad), and the magnitude of any observed Tre afterdrop (Tad). WW had significantly greater Tre/t and Tre60 than either RF or IS (P < 0.03) and a smaller tad than IS (P < 0.05). IS had significantly greater Tad than either WW or RF (P < 0.05). No significant differences in Tre/t, Tre60, or tad were observed between IS and RF. The results of this study indicate that for mildly hypothermic individuals, active rewarming with RF at a SAR of 2.5 W/kg is less effective than WW and roughly equivalent to passive rewarming with IS.


[Standing and walking with walking aids - an electromyokinesigraphic examination (author's transl)].
Study of the variations of the automatic electrical activity of the shoulder, trunk and lower extremities muscles with different types of walking aids (Cane, elbow-crutches, shoulder-crutches, tricycle). Electromyocinesigraphic recordings have been made in 10 normal men and women age 24 to 35. The variations of their posture and walking pattern according to the weightbearing with different types of aids have been studied and are discussed.


Stream detritus dynamics: Regulation by invertebrate consumers.
Insecticide treatment of a small, Appalachian forest stream caused massive downstream insect drift and reduced aquatic insect densities to <10% of an adjacent untreated reference stream. Reduction in breakdown rates of leaf detritus was accompanied by differences in quantity and composition of benthic organic matter between the two streams. Following treatment, transport of particulate organic matter was significantly lower in the treated stream than in the reference stream whereas no significant differences existed prior to treatment. Our results indicate that macroinvertebrate consumers, primarily insects, are important in regulating rates of detritus processing and availability to downstream communities.


An in vitro brain slice preparation to study the pharmacology of central vestibular neurons.
The purpose for development of this preparation was to allow detailed studies of the pharmacological and electrophysiological properties of individual central vestibular neurons. The pharmacology of the central afferent synapses of the vestibular system has not been examined at the level of the neuronal membrane, and as a result few definitive reports are available. The best studies have used in situ extracellular recording techniques that are difficult to interpret. For instance, recent literature still supports the concept that excitatory transmission at the N. VIII to vestibular nuclei synapse is cholinergic. Our data refute this hypothesis and suggest that an excitatory amino acid is the most likely candidate for the eighth nerve to medial vestibular nucleus in the rat. We believe this preparation combined with an intracellular electrophysiological approach will shed information of value to both the basic scientist and the clinician with interest in the vestibular system.


Subitizing object parts reveals a second stage of individuation.
Humans can efficiently individuate a small number of objects. This subitizing ability is thought to be a consequence of limited attentional resources. However, how and what is selected during the individuation process remain outstanding questions. We investigated these in four experiments by examining if parts of objects are enumerated as efficiently as distinct objects in the presence and absence of distractor objects. We found that distractor presence reduced subitizing efficiency. Crucially, parts connected to multiple objects were enumerated less efficiently than independent objects or parts connected to a single object. These results argue against direct individuation of parts and show that objecthood plays a fundamental role in individuation. Objects are selected first and their components are selected in subsequent steps. This reveals that individuation operates sequentially over multiple levels.


INTERMOLECULAR INTERACTIONS IN THE SOLUTIONS OF SERUM ALBUMIN.
The mechanisms of intermolecular protein complex formation were studied by the example of monomers, oligomers and aggregates of bovine serum albumin (BSA) depending on the protein concentration, pH and urea concentration. Using dynamic light scattering (DLS), analytical ultracentrifugation (AUC) and PAG electrophoresis, we have shown that there is dynamic equilibrium between monomers and aggregates in BSA solution. Decreasing pH of the solution (4.0—1.0) resulted in increasing sizes of the aggregates. In the solutions with low urea concentrations (below 2 M), the sizes of aggregates decreased, while higher urea concentrations induced formation of larger aggregates due to the unfolding of the protein.


Role of spinal neurons in the maintenance of elevated sympathetic activity: a novel therapeutic target?
The control of sympathetic vasomotor activity involves a complex network within the brain and spinal circuits. An extensive range of studies has indicated that sympathoexcitation is a common feature in several cardiovascular diseases and that strategies to reduce sympathetic vasomotor overactivity in such conditions can be beneficial. In the present mini-review, we present evidence supporting the spinal cord as a potential therapeutic target to mitigate sympathetic vasomotor overactivity in cardiovascular diseases, focusing mainly on the actions of spinal angiotensin II on the control of sympathetic preganglionic neuronal activity.


[Oral venous lakes: a clinicopathologic analysis of 20 cases].
To improve the recognization and treatment for oral venous lakes (OVL). Clinicopathologically analysis of 20 cases of oral venous lakes was performed. All the samples were removed by surgically. All the lesions occurred in senile persons and located under the mucosa. Among the 20 cases, 11 were male patients and 9 were female; 18 of 20 occurred in the lower lip, another two in the upper lip and buccal mucosa. The lesions were 0.3 approximately 1.2 cm in size. Pathologically, the oral venous lake was composed of single or a few large, dilated and irregular veins. Thrombosis and organization were found within the lesions sometimes. Oral venous lakes are a kind of focal anomalies of venous structure. All the 20 cases (with a follow-up time from 8 months to 4 years) has no recurrence after surgical treatment.


CpG methylation recruits sequence specific transcription factors essential for tissue specific gene expression.
CG methylation is an epigenetically inherited chemical modification of DNA found in plants and animals. In mammals it is essential for accurate regulation of gene expression and normal development. Mammalian genomes are depleted for the CG dinucleotide, a result of the chemical deamination of methyl-cytosine in CG resulting in TpG. Most CG dinucleotides are methylated, but ~15% are unmethylated. Five percent of CGs cluster into ~20,000 regions termed CG islands (CGI) which are generally unmethylated. About half of CGIs are associated with housekeeping genes. In contrast, the gene body, repeats and transposable elements in which CGs are generally methylated. Unraveling the epigenetic machinery operating in normal cells is important for understanding the epigenetic aberrations that are involved in human diseases including cancer. With the advent of high-throughput sequencing technologies, it is possible to identify the CG methylation status of all 30million unique CGs in the human genome, and monitor differences in distinct cell types during differentiation and development. Here we summarize the present understanding of DNA methylation in normal cells and discuss recent observations that CG methylation can have an effect on tissue specific gene expression. We also discuss how aberrant CG methylation can lead to cancer. This article is part of a Special Issue entitled: Chromatin in time and space.


Wraparound Stitch: A Contemporary Twist to the Bruner's Traditional Stay Stitch in Hand Surgery.
Bruner's incision has provided surgical exposure for elective and traumatic hand procedures since 1973.We present a modification of the stay stitch - the Wraparound stitch - using a single suture and single tie. The technique is safe, simple and cost effective, and is the authors' preferred method of surgical exposure during hand surgery.


Land use change detection and impact assessment in Anzali international coastal wetland using multi-temporal satellite images.
Anzali is one of the 18 Iranian wetlands of international importance listed in Ramsar Convention. This unique ecosystem in the world with high ecological diversity is highly threatened by various factors such as pollutants, sedimentation, unauthorized development of urban infrastructure, over-harvesting of wetland resources, land use changes, and invasive species. Among which, one of the most challenging destructive factors, land use change, was scrutinized in this study. For this, remotely sensed data and Geographical Information System (GIS) were used to detect land changes and corresponding impacts on the study area over a 38-year period from 1975 to 2013.. Changes in the study area were traced in five dominant land-use classes at four time intervals of 1975, 1989, 2007, and 2013. Accordingly, changes in different categories were quantified using satellite images. The methodology adopted in this study includes an integrated approach of supervised classification, zonal and object-oriented image analyses. According to the Kappa coefficient of 0.84 for the land use map of 2013, the overall accuracy of the method was estimated at 89%, which indicated that this method can be useful for monitoring and behavior analysis of other Iranian wetlands. The obtained results revealed extensive land use changes over the study period. As the results suggest, between the years 1975 to 2013, approximately 6500 ha (∼69%) rangeland area degraded. Further, urban and agricultural areas have been extended by 2982 ha (∼74%) and 2228 ha (∼6%), respectively. This could leave a negative impact on water quality of the wetland.


Dietary intake of total polyphenols and the risk of all-cause and specific-cause mortality in Japanese adults: the Takayama study.
Several epidemiological studies have demonstrated the health benefits of polyphenols, but the associations between polyphenol intake and mortality including total and major causes of death remain unclear. We investigated the associations between subjects' total polyphenol intake and their mortality from all causes, cardiovascular disease (CVD), cancer, and other causes of death in a population-based cohort study in Japan. A total of 29,079 residents of Takayama City, Japan were analyzed. Their dietary intake was assessed using a validated semi-quantitative food-frequency questionnaire (FFQ) in 1992. Mortality was ascertained over the subsequent 16 years. The dietary polyphenol intake was calculated by matching the subjects' food consumption data with our original polyphenol content database. A total of 5339 deaths occurred during the follow-up. After multivariable adjustment, the highest quartile of total polyphenol intake compared with the lowest quartile was significantly associated with a lower risk of all-cause mortality (HR: 0.93, 95% CI: 0.82-0.99, p trend = 0.003). The subjects in the highest quartile showed significantly lower CVD mortality compared to those in the lowest quartile, and among the types of CVD mortality, a strong inverse association was observed for stroke mortality. Inverse associations were also observed for mortality from other causes, specifically digestive disease. The total polyphenol intake was not significantly associated with the risk of cancer mortality. The results of this prospective study indicate that dietary total polyphenol intake in Japanese is inversely associated with all-cause mortality and mortality from cardiovascular and digestive diseases.


Association Between Time to Rehabilitation and Outcomes After Traumatic Spinal Cord Injury.
To examine the relations between time to rehabilitation after spinal cord injury (SCI) and rehabilitation outcomes at discharge and 1-year postinjury. Retrospective cohort study. Facilities designated as Spinal Cord Injury Model Systems. Patients (N=3937) experiencing traumatic SCI between 2000 and 2014, who were 18 years or older, and who were admitted to a model system within 24 hours of injury. Not applicable. Rasch-transformed FIM motor score at discharge and 1-year postinjury, discharge to a private residence, and the Craig Handicap Assessment and Reporting Technique (CHART) Physical Independence and Mobility scores at 1-year postinjury. After accounting for health status, a 10% increase in time to rehabilitation was associated with a 1.50 lower FIM motor score at discharge (95% confidence interval [CI], -2.43 to -0.58; P=.001) and a 3.92 lower CHART Physical Independence score at 1-year postinjury (95% CI, -7.66 to -0.19; P=.04). Compared to the mean FIM motor score (37.5) and mean CHART Physical Independence score (74.7), the above-mentioned values represent relative declines of 4.0% and 5.3%, respectively. There was no association between time to rehabilitation and discharge to a private residence, 1-year FIM motor score, or the CHART mobility score. Earlier rehabilitation after traumatic SCI may improve patients' functional status at discharge.


Forced and Voluntary Aerobic Cycling Interventions Improve Walking Capacity in Individuals With Chronic Stroke.
To determine the efficacy of high-intensity cycling to improve walking capacity in individuals with chronic stroke, identify variables that predict improvement in walking capacity, and quantify the relationship between the 6-minute walk test (6MWT) and cardiopulmonary exercise (CPX) test variables. Secondary analysis of data from 2 randomized controlled trials. Research laboratory. Individuals with chronic stroke (N=43). Participants were randomized to 1 of the following time-matched interventions, occurring 3 times per week for 8 weeks: (1) forced aerobic exercise and upper extremity repetitive task practice (FE+RTP [n=16]), (2) voluntary aerobic exercise and upper extremity repetitive task practice (VE+RTP [n=14]), or (3) a non-aerobic control group (n=13). Change in walking capacity as measured by the 6MWT from baseline to the end of treatment (EOT). Significant increases were observed in distance traveled during the 6MWT at the EOT compared with baseline in the FE+RTP (P<.001) and VE+RTP (P<.001) groups, but not in the control group (P=.21). Among aerobic exercise participants, a multivariate regression analysis revealed that cycling cadence, power output, and baseline 6MWT distance were significant predictors of change in walking capacity. An 8-week aerobic cycling intervention prescribed at 60% to 80% of heart rate reserve and moderate to high cadence and resistance led to significant improvements in walking capacity in our cohort of individuals with chronic stroke. Individuals with low baseline walking capacity levels may benefit most from aerobic cycling to improve over ground locomotion. Although the 6MWT did not elicit a cardiorespiratory response comparable to the maximal exertion CPX test, the 6MWT can be considered a valid and clinically relevant submaximal test of cardiorespiratory function in individuals with chronic stroke.


Intake of vegetables and fruits rich in provitamin A is positively associated with aryl hydrocarbon receptor repressor DNA methylation in a Japanese population.
DNA methylation can be affected by numerous lifestyle factors, including diet. Tobacco smoking induces aryl hydrocarbon receptor repressor (AHRR) DNA hypomethylation, which increases the risk of lung and other cancers. However, no lifestyle habits that might increase or restore percentage of AHRR DNA methylation have been identified. We hypothesized that dietary intakes of vegetables/fruits and serum carotenoid concentrations are related to AHRR DNA methylation. A total of 813 individuals participated in this cross-sectional study. A food frequency questionnaire was used to assess dietary intake of vegetables and fruits. AHRR DNA methylation in peripheral blood mononuclear cells were measured using pyrosequencing method. In men, dietary fruit intake was significantly and positively associated with AHRR DNA methylation among current smokers (P for trend = .034). A significant positive association of serum provitamin A with AHRR DNA methylation was observed among current smokers (men: standardized β = 0.141 [0.045 to 0.237], women: standardized β = 0.570 [0.153 to 0.990]). However, compared with never smokers with low provitamin A concentrations, percentages of AHRR DNA methylation were much lower among current smokers, even those with high provitamin A concentrations (men: β = -19.1% [-33.8 to -19.8], women: β = -6.0% [-10.2 to -1.7]). Dietary intake of vegetables and fruits rich in provitamin A may increase percentage of AHRR DNA methylation in current smokers. However, although we found a beneficial effect of provitamin A on AHRR DNA methylation, this beneficial effect could not completely remove the effect of smoking on AHRR DNA demethylation.


Using Google Earth™ and Geographical Information System data as method to delineate sample domains for an urban household surveys: the case of Maroua (Far North Region-Cameroon).
Getting a random household sample during a survey can be expensive and very difficult especially in urban area and non-specialist. This study aimed to test an alternative method using freely available aerial imagery. A gridded map and random selection method was used to select households for interviews. A hundred numbered of points were put along the edges of an updated map of Maroua. Then two numbers were randomly draw at a time and a line was drawn between those two numbers. A lot of different kinds of shapes of different sizes obtained were numbered. Ten shapes were randomly draw and the one selected were considered as 'neighbourhoods'. A grid of 30 m × 30 m was drawn over each and then numbered. 202 grids considered here as households were randomly selected from the ten neighbourhoods for interviews. Out of 202 households visited, only 4 were found to be something other than a house. In addition, 30 sampled households (14.85%) were abandoned or the occupants had relocated elsewhere. This method resulted in an accuracy level of 72%, its advantage is the ability to generate efficient random sample at relatively low cost as well the time required. The method proposed in this study was efficient and cost-effective when compared to the infield generation of a household inventory or Global Positioning System (GPS) tracking of households. It can then be used by researchers in low-incomes countries where funding for research is a challenge. However, this method needs to train the investigators on how to use the GPS.


Modifying the Microenvironment of Epoxy Resin to Improve the Activity of Immobilized 7α-Hydroxysteroid Dehydrogenases.
7α-Hydroxysteroid dehydrogenase (7α-HSDH) is one of the key enzymes in the catalytic reaction of taurochenodeoxycholic acid (TCDCA). To improve the activity of immobilized 7α-HSDH, the microenvironment of immobilized 7α-HSDH was modified with epoxy resin and ethanediamine (EDA). The amino-epoxy support was characterized by Fourier transform infrared (FTIR), Spectrometer elemental analysis (EA), scanning electron microscopy (SEM), contact angle (CA), and Zetasizer. The effects of the immobilization of 7α-HSDH on the amino-epoxy resin and epoxy resin were studied. The results indicated that the relative activity of immobilized 7α-HSDH on the amino-epoxy resin increased by approximately 80%. Meanwhile, the immobilized 7α-HSDH showed favorable thermal stability and operational stability. The thermal stability of immobilized 7α-HSDH increased at temperatures ranging from 15 to 35 °C, while the relative activities of 7α-HSDH immobilized on the amino-epoxy resin and epoxy resin retained 56.4% and 61.0%. After 6 cycles, the residual activities of the 7α-HSDH immobilized on the amino-epoxy resin and epoxy resin were 81.4% and 89.5%, respectively.


A tool for teaching the B-Lynch brace suture method: an inexpensive new simulator allows obstetricians to polish an essential technique.
The B-Lynch brace suture is invaluable in the surgical management of postpartum hemorrhage, particularly as a fertility-sparing alternative to hysterectomy. In this video, we show how to create a low-cost simulator to teach the B-Lynch brace suture technique, followed by the intraoperative application of the same technique.


Olfactory desensitization requires membrane targeting of receptor kinase mediated by beta gamma-subunits of heterotrimeric G proteins.
Olfaction is mediated by G protein-coupled receptors. In isolated rat olfactory cilia, odorants such as citralva stimulate a burst of cAMP, which peaks in 50 ms and returns almost to base-line level within 150 ms in the continuing presence of odorant. This desensitization is mediated by the cAMP dependent protein kinase and a specialized G protein-coupled receptor kinase originally termed beta ARK2 (GRK3). In vitro experiments suggest that the prenylated beta gamma-subunits of heterotrimeric G proteins target the cytosolic beta ARK1 (GRK2) enzyme to its membrane bound receptor substrate by binding to sites in its carboxyl terminus. Here we demonstrate that odorants stimulate translocation of GRK3 from cytosol to membranes in isolated rat olfactory cilia. We introduced a glutathione S-transferase-GRK3ct fusion protein, containing the carboxyl-terminal 222 amino acid residues of GRK3, which includes the beta gamma binding site, or a 28-amino acid peptide derived therefrom, into permeabilized cilia preparations. These reagents block odorant-mediated enzyme translocation and desensitization while markedly attenuating odorant-stimulated phosphorylation of olfactory proteins. These findings suggest that beta gamma-subunits may physiologically regulate a G protein-coupled receptor kinase and that enzyme translocation may be a general and required feature of the activity of some members of this enzyme family.


Efferent projections of the visual Wulst upon the nucleus of the basal optic root in the pigeon.
Efferent projections of the visual Wulst upon the nucleus of the basal optic root (nBOR) were investigated using various neuroanatomical approaches: optical and EM orthograde degeneration methods (following visual Wulst ablation), radioautographic and HRP techniques (following injection of various tracers within the visual Wulst). The radioautographic and electron microscope degeneration experiments clearly demonstrated a visual Wulst projection upon the ipsilateral nBORl and the lateral portions of nBORd and nBORp. The pigeon's hyperstriato-nBOR projection is compared to a similar descending visual cortico-accessory optic pathway in mammals and its possible role in the control of oculomotor function is discussed.


Changes in visual sensitivity with age in rats with heredity retinal degeneration.
Hereditary retinal degeneration in the Royal College of Surgeons (RCS) strain of rat has been shown to produce extensive loss of photoreceptors and a corresponding decline of the electroretinogram, ganglion cell sensitivity, and the sensitivity of the pupillary light reflex. The behaviorally measured thresholds of RCS rats, on the other hand, are reported to be comparable to those for age-matched controls. We report here, that our own behavioral measurements show a clear difference between RCS rats and age-matched controls between four to twelve months of age. The difference in thresholds between RCS and control rats is about three long units at four months of age, and this difference progressively increases until at twelve months, we measure threshold differences of over seven log units.


Combination of radiation therapy-immunotherapy for head and neck cancers: Promises kept?
Chemoradiotherapy with concurrent cisplatin has been the standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC) for over 20 years. Recently, immunotherapy, a new therapeutic class, has emerged for patients with recurrent or metastatic HNSCC and has significantly extended their survival. Will it bring the same benefit to patients with localized tumors? There is a strong rationale for combining radiation therapy and checkpoint inhibitors for HNSCC. Indeed, radiation therapy can have both immunostimulatory and immunomodulatory effects. This is what explains the famous abscopal effect. The aim of this review is to present the data available on the combination of radiation therapy and immunotherapy for HNSCC.


An Update on Appendiceal Neuroendocrine Tumors.
The mainstay of appendiceal neuroendocrine neoplasm (aNEN) treatment is surgery, based on simple appendectomy or right-sided hemicolectomy with lymphadenectomy (RHC). The majority of aNENs are adequately treated with appendectomy, but current guidelines have poor accuracy in terms of selecting patients requiring RHC, especially in aNENs 1-2 cm in size. Simple appendectomy is curative for appendiceal NETs (G1-G2) < 1 cm (if the resection status is R0), whereas RHC with lymph node dissection is recommended in tumors ≥ 2 cm in diameter, based on the high risk of nodal metastases in these cases. The clinical management of aNENs 1-2 cm in size is more controversial because lymph node or distant metastases are uncommon but possible. In our opinion, patients with tumor size > 15 mm or with grading G2 (according to WHO 2010) and/or lympho-vascular invasion should be referred for radicalization with RHC. However, decision-making in these cases should include discussion within a multidisciplinary tumor board at referral centers with the aim of offering each patient a tailored treatment, also considering that relatively young patients with long-life expectancy represent the majority of cases.