The value of carcinoembryonic antigen stage in staging, prognosis, and management of colorectal cancer: results from two cohort studies.
Combining the carcinoembryonic antigen (CEA) level (C stage) with TNM staging can provide a more comprehensive prognostic assessment of colorectal cancer (CRC). However, the clinical value of incorporating CEA status into the TNM staging system needs to be evaluated. We used the SEER database (N = 49,350) and a retrospective cohort from China (N = 1,440). A normal CEA level was staged as C0 and an elevated CEA level was staged as C1. Restricted cubic spline analysis was used to examine the dose-response relationship between the CEA level and survival. The Kaplan-Meier method with the log-rank test was used to plot survival curves. Multivariable Cox proportional hazards regression models with forward stepwise variable selection were used to estimate the hazard ratios and 95% confidence intervals. Patients with C1 were more likely to have advanced disease than those with C0. CEA on a continuous scale was positively associated with mortality risk. Compared with patients with C0 stage, those with C1 stage had significantly lower survival rates. In the SEER dataset, C1 was independently associated with poor prognosis in patients with CRC, with an approximately 70% increased risk of mortality. Patients with C1 stage had significantly lower survival than those with C0 stage at all clinical stages. Incorporating the C stage into the TNM staging refined the prediction of prognosis of patients with CRC, with a gradual decline in prognosis from stage I C0 to stage IV C1. A similar pattern was observed in the present retrospective cohort study. At each lymph node stage, patients with C1 had significantly lower 5-year survival rates than patients with C0. Compared with lymph node positivity, CEA positivity may have a stronger correlation with a worse prognosis. Our findings not only validated the independent prognostic significance of CEA in CRC but also demonstrated its enhanced prognostic value when combined with TNM staging. Our study provides evidence supporting the inclusion of C stage in the TNM staging system.


Hemorheological and antioxidant effects of Ascovertin in patients with sclerosis of cerebral arteries.
The clinical trials on 31 patients with arteriosclerosis and I-II stage discirculatory encephalopathy to assess an ability of Ascovertin to limit hemorheology abnormalities were carried out. In patients with discirculatory encephalopathy was a distinct increase in blood viscosity which was induced by disturbances of cell rheological factors: increase in aggregation of erythrocytes and decrease in their deformability were observed in comparison with indices in the group of healthy volunteers. No difference in plasma viscosity and fibrinogen was found. The treatment with Ascovertin in patients with discirculatory encephalopathy improved their attention, memory, mental performance, normalized sleep, releaved headache, decreased fatiquebility, led to the decrease in blood viscosity values, the reduction of pathological erythrocyte hyper aggregation and the improvement of erythrocyte deformability. We partly connect this clinical effect and hemorheology activity of Ascovertin with its antioxidant property--there was found impressive lipid peroxidation suppression. No significant changes in hemorheological and lipid peroxidation indices were observed in patients without Ascovertin.


New Approaches on Quantification of Campylobacter jejuni in Poultry Samples: The Use of Digital PCR and Real-time PCR against the ISO Standard Plate Count Method.
Campylobacteriosis is the most frequently reported bacterial food-borne illness in the European Union and contaminated broiler meat is considered the most important source of infection in humans. The aim of the present study was to evaluate real-time PCR (qPCR) and digital PCR (dPCR) for quantification of Campylobacter jejuni in 75 broiler neck-skin samples collected from a poultry slaughterhouse, and to compare them with the ISO 10272-2 standard plate count method. For qPCR standard curve, C. jejuni-negative neck-skin samples were spiked with C. jejuni suspension with a known number of bacterial cells. The observed CFU/g values by qPCR correlated greatly with the expected values and qPCR showed good performance with the reliable limit of detection (rLOD) and limit of quantification (LOQ) of three and 31 target copies per reaction, respectively. However, both rLOD (1219 CFU/g) and LOQ (12,523 CFU/g) were beyond the EFSA-proposed critical limit of 500-1,000 CFU/g of neck skin. Although C. jejuni cell counts were ≤1,000 CFU/g in only 7/75 samples by plate counting, they were ≤LOQ in 60/75 and ≤rLOD in 26/75 (≤1,000 CFU/g in 24/75) samples by qPCR. A strong and statistically significant correlation was observed between qPCR and dPCR. Both PCR-based methods correlated significantly with the plate count method; however, the correlation was moderate. Using the Bland-Altman analysis, an average agreement was noted between all three methods, although with a large standard deviation. A significant bias toward overestimation in dPCR was observed, probably due to the relatively high number of false positive calls. The linear dynamic range was comparable in both PCR-based methods; however, qPCR proved to be more suitable for routine use. In the future, the establishment of a reliable molecular quantification of C. jejuni in poultry samples showing a wide range of contamination levels down to the proposed critical limit is needed to enable time- and cost-effective surveillance throughout all stages in the food production chain. As both rLOD and LOQ were beyond this limit, a modification of the procedure is suggested to include less sample dilution prior to DNA extraction to enable PCR-based quantification of C. jejuni at the proposed microbiological criteria.


Population ecology of Aspergillus flavus associated with Mississippi Delta soils.
Understanding the source of Aspergillus flavus is required to manage aflatoxin contamination of maize (Zea mays L.). Studies assessed A. flavus propagules, Fusarium spp., and total fungi associated with Mississippi Delta soils. Soils from 12 and 15 sites were collected in 2000 and 2001, respectively. The propagule density of A. flavus ranged from log(10) 2.0 to 4.3 colony-forming units (cfu) g(-1) soil, while total fusaria ranged from log(10) 3.0 to 5.4 cfu g(-1) soil. The highest populations of A. flavus were associated with soils containing higher organic matter, especially in sites under a no-tillage management. The frequency of aflatoxin production in isolates ranged from 13 to 81% depending on soil. In 2001, there was a highly significant correlation between A. flavus and the history of maize cultivation. Soil fertility factors such as organic matter content, nitrate and extractable phosphorus correlated with the density of Aspergillus, Fusarium spp., and total fungi. The relationship between soil parameters and Aspergillus populations may be useful in predicting the contribution of soil microflora to aflatoxin contamination.


Prognostic significance of miR-203 and ZEB1 expression in early-stage hepatocellular carcinoma.
Background: Approximately one-quarter of patients with early-stage hepatocellular carcinoma (HCC) suffer from tumor recurrence within the first year after hepatectomy. Identification of patients at high risk of recurrence and new therapeutic approaches are crucial to improve clinical outcome. This study aimed to assess the prognostic significance of miR-203 and Zinc finger E-box binding homeobox 1 (ZEB1) in early-stage HCC and explore the association between the expression of ZEB1 and miR-203 in HCC. Methods: Tissue microarray-based immunohistochemistry (IHC) and in situ hybridization (ISH) were performed to investigate ZEB1 and miR-203 expression in 73 patients with early-stage HCC and their correlation with clinicopathological features and prognosis of patients were analyzed. The prognostic value of the two factors was also measured by public KM plotter database. Quantitative reverse transcription PCR (qRT-PCR) assays were conducted to study the relationship between miR-203 and ZEB1. Transwell assays, Cell Counting Kit-8 (CCK-8) assays were performed to detect the roles of miR-203 in migration, invasion and proliferation of HCC cells. Results: We found low expression of miR-203 was associated significantly with tumor recurrence (P<0.001) and poor survival (P=0.020) of patients with early-stage HCC. Multivariate analysis revealed that low miR-203 expression was a poor prognostic factor for both overall survival (OS) (P=0.036) and recurrence free survival (RFS) (P=0.017). ZEB1 did not show any prognostic significance in our cohort. Correlation analysis indicated that there was no significant correlation between miR-203 and ZEB1 on both mRNA and protein levels. Furthermore, functional studies indicated that miR-203 repressed migration, invasion and proliferation of HCC cells in vitro. Conclusion: Our study suggested that miR-203 could be a novel predictor in early-stage HCC and might also be a potential molecular target for HCC therapy.


Phenotypic characterization and in vitro antifungal sensitivity of Candida spp. and Malassezia pachydermatis strains from dogs.
Yeasts of the genera Candida and Malassezia can be found as commensal microorganisms in animals. The main species of importance in veterinary medicine are Malassezia pachydermatis and Candida albicans. The objectives of this study were to conduct a phenotypic characterization and to evaluate the in vitro antifungal sensitivity of strains of C. albicans (n=5), C. tropicalis (n=3) and M. pachydermatis (n=32) isolated from dogs. The phenotyping was based on macro and micromorphological features as well as biochemical analysis. The techniques of microdilution in broth and dilution in agar were used to evaluate the in vitro sensitivity of Candida spp. and M. pachydermatis, respectively. The tested drugs were ketoconazole (KTC), itraconazole (ITC), fluconazole (FLC) and amphotericin B (AMB). The morphological analysis of the strains of Candida spp. and M. pachydermatis did not show any noteworthy alterations when compared to standard strains. On the other hand, in the biochemical tests, 34.4% of the strains of M. pachydermatis were negative for the urease test. Four strains of C. albicans were resistant to FLC with a minimum inhibitory concentration (MIC) >64microg/mL and all were resistant to KTC and ITC (MIC>16microg/mL). The MIC for two strains of C. tropicalis were >16microg/mL for KTC and ITC, and >64microg/mL for FLC. It is worth highlighting that all of the strains tested were sensitive to AMB with the MIC varying from 0.25-1.0microg/mL. All strains of M. pachydermatis were sensitive to ITC with a minimum fungistatic concentration (MFC) 0.0075microg/mL. The MIC for 29 strains was the same (MFC0.0075microg/mL) for KTC. The MFCs for FLC varied from 1 to 16microg/mL, and for AMB, the MFC interval was 0.125-8microg/mL. There were no alterations in the classic phenotypic features of the strains of Candida spp. and M. pachydermatis isolated from dogs but, unlike M. pachydermatis, Candida spp. were much more resistant to azole antifungal agents.


A multicentre, randomized clinical trial comparing the Veriset™ haemostatic patch with fibrin sealant for the management of bleeding during hepatic surgery.
Bleeding during hepatic surgery is associated with prolonged hospitalization and increased morbidity and mortality. The Veriset™ haemostatic patch is a topical haemostat comprised of an absorbable backing made of oxidized cellulose and self-adhesive hydrogel components. It is designed to achieve haemostasis quickly and adhere to tissues without fixation. A prospective, randomized, multicentre, single-blinded study (n = 50) was performed to compare the use of a Veriset™ haemostatic patch with a fibrin sealant patch (TachoSil(®) ) (control) in the management of diffuse bleeding after hepatic surgery. Patients were randomized following the confirmation of diffuse bleeding requiring the use of a topical haemostat. Time to haemostasis was assessed at preset intervals until haemostasis was achieved. Both groups were similar in comorbidities and procedural techniques. The median time to haemostasis in the group using the Veriset™ haemostatic patch was 1.0 min compared with 3.0 min in the control group (P < 0.001; 3-min minimum application time for the control patch). This result was independent of bleeding severity and surface area. Both products had similar safety profiles and no statistical differences were observed in the occurrence of adverse or device-related events. Regardless of bleeding severity or surface area, the Veriset™ haemostatic patch achieved haemostasis in this setting significantly faster than the control device in patients undergoing hepatic resection. It was safe and easy to handle in open hepatic surgery.


Binding of nonspecific cross-reacting antigen, a granulocyte membrane glycoprotein, to Escherichia coli expressing type 1 fimbriae.
Nonspecific cross-reacting antigen (NCA) is a well-characterized membrane glycoprotein on granulocytes, macrophages, and lung epithelium. Structural studies at the protein and genomic levels have revealed that NCA is a member of the immunoglobulin supergene family, and hybridization studies showed that the transcript level of NCA is induced by treatment with gamma interferon. These studies, as well as the expression of NCA on granulocytes, suggest a role for NCA in immune response. For a first step in studying this possible role, we have examined the binding of two glycoforms of NCA designated NCA-50 (Mr, 50,000) and TEX-75 (Mr, 75,000). Here we report the results from binding assays which demonstrate carbohydrate-mediated binding of Escherichia coli expressing type 1 fimbriae and of isolated type 1 fimbriae to NCA-50. TEX-75 did not bind to the purified fimbriae but bound slightly to the bacterial strain. Inhibition studies showed that the binding to NCA-50 involved interaction of mannose moieties on NCA-50 and lectins on the fimbriae. The binding of NCA-50 to bacterial fimbriae was confirmed by electron microscopy studies, using immunolabeling techniques. In addition, we show that the surface expression of NCA-50 (and presumably of other NCA species) on isolated polymorphonuclear leukocytes is increased following activation with the bacterial peptide formylmethionyl-leucyl-phenylalanine, consistent with a role for NCA in immune response.


Direct Oxidation of Hibiscus cannabinus Stalks to Vanillin Using CeO2 Nanostructure Catalysts.
Biomass lignin can be used to produce vanillin through an oxidation process. Although its purity is high, the processing time and separation efficiency are not ideal. This research aims to produce vanillin directly from Kenaf stalks without separating the lignin first from the lignocellulosic biomass. This method is greener because it does not require the separation of cellulose and hemicellulose from the biomass, thus minimizing the use of acid and alkaline solutions and saving time. A high oxygen storage capacity and release capacity of ceria as an oxidation catalyst contribute to the reversable redox properties between Ce4+ and Ce3+ in ceria lattice. Cerium oxide nanostructures were synthesized using a hydrothermal method treated under alkaline NaOH, followed by drying at 120 °C for 16 h and calcining at different temperatures between 400 and 600 °C for the direct oxidation of Kenaf stalks to vanillin under microwave irradiation. The catalysts were characterized for their physicochemical properties using XRD, N2 adsorption-desorption isotherms and TEM. All synthesized CeO2 nanostructures showed the presence of diffraction peaks assigned to the presence of cubic fluorite. The N2 adsorption-desorption isotherms showed that all catalysts possess a Type IV isotherm, indicating a mesoporous structure. The TEM image shows the uniform shape of the CeO2 nanostructures, while HRTEM images show that the CeO2 nanostructures are single-crystalline in nature. All catalysts were tested for the direct oxidation of Kenaf stalks using H2O2 as the oxidizing agent in temperatures ranging from 160 to 180 °C for 10-30 min with 0.1-0.3 g catalyst loading under 100-500 W of microwave irradiation. The CeO2-Nps-400 catalyst produced the highest vanillin yields of 3.84% and 4.32% for the direct oxidation of Kenaf stalks and extraction of lignin from Kenaf stalks, respectively. Compared to our earlier study, the highest vanillin yields of 2.90% and 3.70% for direct biomass and extracted lignin were achieved using a Ce/MgO catalyst.


Widespread sex ratio polymorphism in Caenorhabditis nematodes.
Although equal sex ratio is ubiquitous and represents an equilibrium in evolutionary theory, biased sex ratios are predicted for certain local conditions. Cases of sex ratio bias have been mostly reported for single species, but little is known about its evolution above the species level. Here, we surveyed progeny sex ratios in 23 species of the nematode genus Caenorhabditis, including 19 for which we tested multiple strains. For the species with multiple strains, five species had female-biased and two had non-biased sex ratios in all strains, respectively. The other 12 species showed polymorphic sex ratios across strains. Female-biased sex ratios could be due to sperm competition whereby X-bearing sperm outcompete nullo-X sperm during fertilization. In this model, when sperm are limited allowing all sperm to be used, sex ratios are expected to be equal. However, in assays limiting mating to a few hours, most strains showed similarly biased sex ratios compared with unlimited mating experiments, except that one C. becei strain showed significantly reduced female bias compared with unlimited mating. Our study shows frequent polymorphism in sex ratios within Caenorhabditis species and that sperm competition alone cannot explain the sex ratio bias.


Support for Government Provision of Health Care and the Patient Protection and Affordable Care Act.
Since the 1930s, US politicians have argued about whether healthcare should be the responsibility of the federal government. Both major political parties have cited public opinion concerning Americans' support for or rejection of government provision of healthcare to support their position. With the passage of the Patient Protection and Affordable Care Act (ACA) in 2010, however, the political debate has changed. Where it had been about the government provision of healthcare as an abstract principle, it became a debate imbued with evaluations of the implementation of the ACA itself. This spawned a new line of research examining the consequences of the ACA's implementation on public attitudes toward government provision of healthcare. The change in support for government provision of healthcare and the new post-ACA research highlight a need for a long-term examination of trends in support over the past two decades that will provide context for the new studies. This study provides that examination.


MicroRNA-624-mediated ARRDC3/YAP/HIF1α axis enhances esophageal squamous cell carcinoma cell resistance to cisplatin and paclitaxel.
Development of chemoresistance remains a major challenge in treating patients suffering from esophageal squamous cell carcinoma (ESCC), despite treatment advances. MicroRNAs (miRNAs) have been shown to play critical roles in the regulation of ESCC cell chemoresistance. Here, we aimed to investigate the role of miR-624 in ESCC and its molecular mechanism in mediating the resistance of ESCC cells to two common chemotherapeutic drugs, cisplatin (CIS) and paclitaxel (PT). Expression patterns of miR-624, arrestin domain-containing 3 (ARRDC3), Yes-associated protein (YAP), and hypoxia-inducible factor-1α (HIF1α) in ESCC tissues and cell lines were identified using RT-qPCR and Western blot analysis. The binding affinities with the miR-624/ARRDC3/YAP/HIF1α axis were characterized. The chemotherapy-sensitive cell line KYSE150 and chemotherapy-resistant cell line KYSE410 were transfected with an overexpression plasmid or shRNA to study the effect of miR-624/ARRDC3/YAP/HIF1α axis on ESCC cell resistance to CIS and PT. Their in vivo effects on resistance to PT were assessed in tumor-bearing nude mice. High expression of miR-624, YAP and HIF1α, and low expression of ARRDC3 were observed in ESCC tissues and cell lines. miR-624 presented with higher expression in KYSE410 than in KYSE150 cells. miR-624 downregulated ARRDC3 to increase YAP and HIF1α expression so as to enhance ESCC cell resistance to CIS and PT in vitro and in vivo. Taken together, these data indicate an important role for miR-624 in promoting the chemoresistance of ESCC cells, highlighting a potential strategy to overcome drug resistance in ESCC treatment. miR-624 targets ARRDC3 to inhibit its expression, and consequently upregulates YAP expression by inhibiting degradation of YAP. By this mechanism, HIF1α expression is upregulated and the HIF1α signaling pathway is activated. ESCC cell chemotherapy resistance is eventually increased.


Radiofrequency ablation of normal lungs after pulmonary artery embolization with use of degradable starch microspheres: results in a porcine model.
The present study was performed to evaluate the effect of pulmonary artery embolization on radiofrequency (RF) ablation of normal porcine lungs. RF ablation zones (n=34) were created in the normal lungs of five domestic pigs (five zones in each of the first two pigs and eight zones in each of the remaining three pigs) with an expandable multitined electrode with use of bilateral thoracotomy. RF ablation was performed without pulmonary artery embolization (group 1, n=8), immediately after embolization (group 2, n=11), 15 minutes after embolization (group 3, n=7), and 30 minutes after embolization (group 4, n=8) with degradable starch microspheres. Among them, 12 ablation zones were excluded from this study because they were considerably limited by the presence of the pleura or large bronchi. The remaining 22 zones were included (n=7, n=5, n=4, and n=6 in groups 1, 2, 3, and 4, respectively). Coagulation necrosis volumes in the ablation zones were measured and compared among the groups. Coagulation necrosis volumes were 0.9+/-0.5 cm3, 2.1+/-0.4 cm3, 2.1+/-1.0 cm3, and 1.9+/-0.6 cm3 in groups 1, 2, 3, and 4, respectively. Groups 2-4 showed significantly larger coagulation volumes than group 1 (P=.012, P=.023, and P=.010 in groups 2, 3, and 4, respectively). Pulmonary artery embolization contributed to larger volumes of coagulation necrosis after RF ablation of normal lungs.


Baseline and stress-induced levels of corticosterone during different life cycle substages in a shorebird on the high arctic breeding grounds.
After a migratory flight of several thousand kilometers to their high arctic breeding grounds, red knots (Calidris canutus islandica, Scolopacidae) showed high baseline concentrations of plasma corticosterone (58 ng/mL). Such high baseline corticosterone levels may be conditional for the right behavioral and metabolic adjustments to environmental and social stresses that shorebirds experience on arrival in an unpredictable tundra breeding environment. Despite the high baseline levels of corticosterone, red knots still showed a marked stress response during the postarrival period, with corticosterone concentrations increasing significantly during a 60-min period of confinement. Baseline levels of corticosterone declined as the breeding season progressed. Red knots with brood patches, that is, birds that had completed egg laying and commenced incubation, had a reduced adrenocortical response to the stress of confinement compared with red knots with no, or with half-developed, brood patches. This is consistent with the idea that birds breeding in extreme environments with short breeding seasons may exhibit a decreased adrenocortical response to stressful events to prevent high corticosterone concentrations from inducing interruptions of reproductive behavior.


Stimulus dependence of orientation and direction sensitivity of cat LGNd relay cells without cortical inputs: a comparison with area 17 cells.
The cortical contribution to the orientation and direction sensitivity of LGNd relay cells was investigated by recording the responses of relay cells to drifting sinusoidal gratings of varying spatial frequencies, moving bars, and moving spots in cats in which the visual cortex (areas 17, 18, 19, and LS) was ablated. For comparison, the spatial-frequency dependence of orientation and direction tuning of striate cortical cells was investigated employing the same quantitative techniques used to test LGNd cells. There are no significant differences in the orientation and direction tuning to relay cells in the LGNd of normal and decorticate cats. The orientation and direction sensitivities of cortical cells are dependent on stimulus parameters in a fashion qualitatively similar to that of LGNd cells. The differences in the spatial-frequency bandwidths of LGNd cells and cortical cells may explain many of their differences in orientation and direction tuning. Although factors beyond narrowness of spatial-frequency tuning must exist to account for the much stronger orientation and direction preferences of cells in area 17 when compared to LGNd cells, the evidence suggests that the orientation and direction biases present in the afferents to the visual cortex may contribute to the orientation and direction selectivities found in cortical cells.


[Ophthalmological characteristics of early cerebral atherosclerosis].
The results are discussed of a complex neuro-ophthalmological investigation of 439 patients with initial cerebral atherosclerosis. Their neurological characterization and the results of elecrcto-physiological, biochemical, and psychological examination methods are indicated. The opthalmologist had performed the opthalmoscopic examination, biomicroscopy of the vessels of conjunctiva and episclera the opthalmocalibrometry and angiophotometry as well as opthalmodynamometry. The most frequent opthalmological symptoms of initial cerebral atherosclerosis are pointed out. The methods are compared for their diagnostic value.


Not All Masks Are Created Equal: Masking Success in Clinical Trials of Children and Adolescents.
The current study assessed the success of masking omega-3 (Ω3) and psychotherapy in clinical trials of youth with depression or bipolar spectrum disorder. Participants were youth ages 7-14 with DSM-IV-TR diagnosed depressive (n = 72) or bipolar spectrum (n = 23) disorders. Inclusion diagnoses were depressive disorder, cyclothymic disorder, or bipolar disorder not otherwise specified. Exclusion diagnoses included bipolar I or II disorder, chronic medical condition or autism. Youth participated in 2 × 2 randomized controlled trials, in which they received Ω3 or placebo (PBO) and psychoeducational psychotherapy (PEP) or active monitoring (AM). Participants and study staff (including independent interviewers) were masked to Ω3/PBO allocation. Besides the masked independent interviewers, one coprincipal investigator (Co-PI) was fully masked to both conditions and completed all consensus conference ratings postrandomization. At the endpoint assessment or last completed interview, interviewers and the masked Co-PI guessed whether each child was assigned to Ω3 or PBO and to PEP or AM. Masking failure was calculated using the degree of correct guesses above chance level using binomial tests across all participants for Ω3 versus PBO and PEP versus AM. For all guessers, Ω3 allocation was guessed correctly approximately half the time (50%-52.5%). Rates of correct guessing were higher for PEP, but only the interviewer guesses were correct significantly more often (58.5%-68.7%) than chance. Reporting of masking success should be an essential element of RCTs. Psychotherapy is generally more difficult to mask, but with attentive masking procedures reasonable masking can be achieved.


Adalimumab ameliorates OVA-induced airway inflammation in mice: Role of CD4(+) CD25(+) FOXP3(+) regulatory T-cells.
Asthma is a chronic inflammatory heterogeneous disorder initiated by a dysregulated immune response which drives disease development in susceptible individuals. Though T helper 2 (TH2) biased responses are usually linked to eosinophilic asthma, other Th cell subsets induce neutrophilic airway inflammation which provokes the most severe asthmatic phenotypes. A growing evidence highlights the role of T regulatory (Treg) cells in damping abnormal Th responses and thus inhibiting allergy and asthma. Therefore, strategies to induce or augment Treg cells hold promise for treatment and prevention of allergic airway inflammation. Recently, the link between Tumor necrosis factor-α (TNF-α) and Treg has been uncovered, and TNF-α antagonists are increasingly used in many autoimmune diseases. Yet, their benefits in allergic airway inflammation is not clarified. We investigated the effect of Adalimumab, a TNF-α antagonist, on Ovalbumin (OVA)-induced allergic airway inflammation in CD1 mice and explored its impact on Treg cells. Our results showed that Adalimumab treatment attenuated the OVA-induced increase in serum IgE, TH2 and TH1 derived inflammatory cytokines (IL-4 and IFN-γ, respectively) in bronchoalveolar lavage (BAL) fluid, suppressed recruitment of inflammatory cells in BAL fluid and lung, and inhibited BAL fluid neutrophilia. It also ameliorated goblet cell metaplasia and bronchial fibrosis. Splenocytes flow cytometry revealed increased percentage of CD4(+) CD25(+) FOXP3(+) Treg cells by Adalimumab that was associated with increase in their suppressive activity as shown by elevated BAL fluid IL-10. We conclude that the beneficial effects of Adalimumab in this CD1 neutrophilic model of allergic airway inflammation are attributed to augmentation of Treg cell number and activity.


Surgical outcomes in traumatic brain injuries with bilateral mass occupying lesions. Analysis of prognostic factors.
Traumatic brain injury is a silent epidemic with major impacts on national productivity as it affects the economically productive age group. Bilateral injuries are usually severe with no clearly defined predictors of outcome as per current available literature. We retrospectively assessed 102 consecutive cases of post traumatic intracranial mass lesions operated bilaterally, either simultaneously or sequentially, between January 2011 and April 2019. The primary and secondary end points of the study were to assess mortality and GCS at discharge respectively. The cohort included 102 patients. 91(89.2 %) were males, mean age was 40(±13.6) years. Median GCS at presentation was 9 with 47(46.07 %) having moderate head injury. EDH with contusion was seen in 38(37.3 %), SDH with contusion in 24(23.5 %) and 4 patients (3.9 %) had EDH, SDH and contusion. On univariate analysis, female gender(p = 0.001), poor GCS at presentation(p < 0.001), higher Rotterdam grade on initial CT scan(p < 0.001), need for blood transfusions(p = 0.026) and intraoperative hypotension(p = 0.007) were associated with significantly higher mortality. On multivariate analysis female gender(p = 0.034), poor GCS(p = 0.026) and worse Rotterdam score(p = 0.038) were associated with mortality. Among the subgroup of survivors, GCS at presentation(p < 0.001), Rotterdam grading(p = 0.003), time to surgery after trauma(p = 0.032), duration of hospital stay(<0.001), intraoperative brain bulge(p=.003) and craniotomy instead of craniectomy(p = 0.001) were associated with clinical outcome at discharge. Traumatic brain injuries with bilateral mass lesions requiring surgery have been rarely reported. In this study we have elucidated management strategies and have further studied the factors influencing mortality and clinical outcome. Careful considerations are required in decision making in such cases. Larger multicentric studies would throw more light on outcomes of this rare variety of traumatic brain injury.


The ovarian-uterine vasculature in relation to unilateral endometrial growth in flying foxes (genus Pteropus, suborder Megachiroptera, order Chiroptera).
The ovarian-uterine vasculature was examined in three Australian species of flying fox (Pteropus scapulatus, P. poliocephalus and P. alecto). Vascular casts and histological sections were used to determine the relationship between the blood supply and the localized endometrial reaction, which occurs ipsilateral to the ovulating ovary. The ovarian artery coils extensively just cranial to the ovary, gives off a branch to the ovary and continues caudally as the major vessel supplying the cranial tip of the uterus, where it anastomoses with the smaller uterine artery. The coil of the ovarian artery is completely enclosed by a venous sinus that drains the cranial pole of the ovary. The ovary is heavily encapsulated, with primordial follicles restricted to the caudal pole; thus, the corpus luteum is completely internal and placed cranially, close to the coil of the ovarian artery. This arrangement would allow countercurrent or crosscurrent transfer of ovarian steroids from ovarian vein to ovarian artery and on to the cranial tip of the ipsilateral uterine horn. The steroids could thus reach high concentrations locally and generate localized endometrial growth. Cranial to the coil, the ovarian artery is enclosed in a venous sinus that derives from uterine as well as ovarian veins. This would allow countercurrent transfer of bioactive substances from uterus to ovary.


What is straight ahead to a patient with torticollis?
Vestibular and neck proprioceptive signals are known to be used in judging the locations of objects in space and relative to the body. Given that these signals are asymmetric in patients with spasmodic torticollis, one would expect such patients to have abnormal spatial perception. We tested this idea by measuring patients' perception of visual straight ahead (VSA) under various conditions: with the body in its primary position, i.e. with the head and trunk as closely aligned as possible, and after well defined passive rotations of the head and/or trunk. In the primary body position, patients' VSA direction showed considerable variations which were similar, however, to those of normal subjects; it was independent of torticollis direction, of the head torque it produced, and of the weak spontaneous nystagmus recorded in seven of the 10 patients. After whole-body rotations, i.e. where head and trunk underwent the same motion, the VSA was shifted in both patients and normal subjects, and in both groups the shift was symmetrical after rotations to the right or left. After motions where the trunk rotated under the stationary head (neck proprioceptive stimulation) or the head on the stationary trunk (combined vestibular and neck stimulus), the VSAs of normal subjects coincided rather well with their head midsagittal planes, whereas the VSAs of patients were shifted considerably towards the trunk, again in a symmetrical way. We suggest two mechanisms to explain the findings in patients: (i) a central compensation which restores symmetry of the afferent inflow in the patients (unlike the motor efference); (ii) shifting of the reference for the VSA from the head towards the trunk, because the trunk is a more reliable egocentric reference than the head in the patients. Our findings do not support the assumption that asymmetries in afferent inflow are responsible for the asymmetry of motor output in spasmodic torticollis.


Outcomes of the 2021-2022 APDS General Surgery Recruitment Process Recommendations.
In recent years, mounting challenges for applicants and programs in resident recruitment have catapulted this topic into a top priority in medical education. These challenges span all aspects of recruitment-from the time an applicant applies until the time of the Match-and have widespread implications on cost, applicant stress, compromise of value alignment, and holistic review, and equity. In 2021-2022, the Association of Program Directors in Surgery (APDS) set forth recommendations to guide processes for General Surgery residency recruitment. This work summarizes the APDS 2021-2022 resident recruitment process recommendations, along with their justification and program end-of-cycle program feedback and compliance. This work also outlines the impact of these data on the subsequent 2022-2023 recommendations. After a comprehensive review of the available literature and data about resident recruitment, the APDS Task Force proposed recommendations to guide 2021-2022 General Surgery resident recruitment. Following cycle completion, programs participating in the categorical General Surgery Match were surveyed for feedback and compliance. About 122 of the 342 programs (35.7%) participating in the 2022 categorical General Surgery Match responded. Based on available data in advance of the cycle, recommendations around firm application and interview numbers could not be made. About 62% of programs participated in the first round interview offer period with 86% of programs limiting offers to the number of slots available; 95% conducted virtual-only interviews. Programs responded they would consider or strongly consider the following components in future cycles: holistic review (90%), transparency around firm requirements (88%), de-emphasis of standardized test scores (54%), participation in the ERAS Supplemental application (58%), single first round interview release period (69%), interview offers limited to the number of available slots (93%), 48-hour minimum interview offer response time (98%), operationalization of applicant expectations (88%), and virtual interviews (80%). There was variability in terms of the feedback regarding the timing of the single first round offer period as well as support for a voluntary, live site visit for applicants following program rank list certification. The majority of programs would consider implementing similar recommendations in 2022-2023. The greatest variability around compliance revolved around single interview release and the format of interviews. Future innovation is contingent upon the ongoing collection of data as well as unification of data sources involved in the recruitment process.


Scaled free-energy based reinforcement learning for robust and efficient learning in high-dimensional state spaces.
Free-energy based reinforcement learning (FERL) was proposed for learning in high-dimensional state- and action spaces, which cannot be handled by standard function approximation methods. In this study, we propose a scaled version of free-energy based reinforcement learning to achieve more robust and more efficient learning performance. The action-value function is approximated by the negative free-energy of a restricted Boltzmann machine, divided by a constant scaling factor that is related to the size of the Boltzmann machine (the square root of the number of state nodes in this study). Our first task is a digit floor gridworld task, where the states are represented by images of handwritten digits from the MNIST data set. The purpose of the task is to investigate the proposed method's ability, through the extraction of task-relevant features in the hidden layer, to cluster images of the same digit and to cluster images of different digits that corresponds to states with the same optimal action. We also test the method's robustness with respect to different exploration schedules, i.e., different settings of the initial temperature and the temperature discount rate in softmax action selection. Our second task is a robot visual navigation task, where the robot can learn its position by the different colors of the lower part of four landmarks and it can infer the correct corner goal area by the color of the upper part of the landmarks. The state space consists of binarized camera images with, at most, nine different colors, which is equal to 6642 binary states. For both tasks, the learning performance is compared with standard FERL and with function approximation where the action-value function is approximated by a two-layered feedforward neural network.


A visualized probe method for localization of surface oxygen vacancy on TiO2: Au in situ reduction.
Surface oxygen vacancy has been investigated extensively due to its great influence on photocatalysis in recent years. Among these investigations, the location of surface defects is found to be a key factor during the photocatalytic procedure. Especially when a crystal facet is involved, the synergistic action between these two factors may greatly increase the photocatalytic efficiency. Location of defects would greatly help in understanding the mechanism of this coupling action. Without an available technique, however, it is very difficult to gain the position information directly. In this paper, we provide a low-cost and visualized method to solve this problem via in situ reduction of Au. TiO2 with surface oxygen vacancy on a specific area is synthesized via a photochemical reaction. Then the Au ion was reduced at the place where oxygen vacancy exists on the TiO2 surface. Hence, the localization of surface vacancy will be determined by examining the location of Au particles. Moreover, application of this method can be extended to other surface defects such as oxygen vacancy on oxide semiconductors, Ti(3+) in TiO2, Zn vacancy on ZnO, etc. This technique is helpful for understanding how surface defects affect the properties of semiconductors.


Allogeneic fetal bone cranioplasty in Macaca mulatta.
Teratogen-induced herniation of the occipital lobes (encephalocele) associated with cranium bifidum in monkey fetuses (Macaca mulatta) were repaired by amputation and cranioplasty in utero or postnatally. Fetal allogeneic cranial bone which had been fresh frozen was used in conjunction with a bone paste to provide a protective covering of the neural tissue following repair of the encephalocele. The bone graft in those animals treated in utero or 1-2 weeks post-partum developed a strong union with the calvarium, provided good protection for the underlying dura and neural tissue, had a smooth surface, and provided good cosmetic-reconstructive results. In contrast, when the cranioplasty procedure was performed on infant monkeys at 2-3 months of age the bone graft was rejected.


Medial Malleoli Fractures: Clinical Comparison Between Newly Designed Sled Device and Conventional Screws.
The Trimed Medial Malleolar Sled is a newer device designed to treat medial malleolus fracture. The purpose of this study was to compare the outcome of medial malleolar fractures treated with the sled and conventional malleolar screws. After obtaining an institutional review board approval, we conducted a retrospective study to identify all skeletally mature patients who sustained an ankle fracture with medial malleolar involvement treated with the sled and we identified a matched cohort treated with conventional malleolar screws. The patients were divided into 2 groups: group A included patients treated with malleolar screws and group B included patients treated with the sled device. The outcomes measured included rate of union, implant removal, and pain over the implant site. Eighty-five medial malleolar ankle fractures were divided into 2 groups: group A included patients (n = 64) treated with malleolar screws and group B included patients (n = 21) treated with the sled device. In group A (n = 64), 62 patients (96.8%) achieved radiological union with a mean union rate of 11 weeks and 10 (15%) patients underwent repeat surgery for implant removal of which 3 patients (4.6%) had pain specifically over the medial implant. In group B (n = 21), all of the patients (100%) achieved radiological union with a mean union rate of 10.8 weeks and 3 patients (14.2%) underwent repeat surgery of which 1 (4.7%) was related to the medial pain. There is no significant difference between the groups for the outcomes measured, including rate of union ( P = .93), visual analog scale score for pain ( P = .07), implant removal ( P = .41), and pain over the implant site ( P = .88). Based on the data from our study, we conclude that there are no major differences between the sled devices and conventional screws relating to union rate and complications. Level III: Observational study.


Tyrosinase-generated quinones induce covalent modification, unfolding, and aggregation of human holo-myoglobin.
The present study describes the pattern of protein modification undergone by human holo-myoglobin by reactive fluoroquinones enzymatically produced by oxidation of 3-fluorophenol in mild conditions (pH 7.4, 25 degrees C). The fluoroquinones react with a number of histidine residues. Surface residues H24, H36, H48, and H82 and the heme distal histidine H64 were all found to be modified to a significant extent. In contrast, cysteine C110 is not appreciably affected, possibly because it is not accessible to the fluoroquinones. The sites of protein modification were assessed by mass spectrometry analysis of the peptide fragments resulting from controlled proteolysis of the apoprotein. As a consequence of the reaction with quinones, the globular structure of myoglobin becomes more prone to denaturation by the partial loss of its secondary structure. As a more intriguing consequence, the fluoroquinones promote the formation of structured aggregates of moderate size that lack the typical morphology of fibrillar structures.


Intra- and inter-day reproducibility of low-flow mediated constriction response in young adults.
When assessing brachial endothelial function by reactive hyperaemia, stopping blood flow creates a period of low-flow-mediated constriction (L-FMC). As little is known about how this parameter influences flow-mediated vasodilation (FMD), the purpose of this study was to better understand this relationship and to determine the intra- and interday reproducibility of brachial L-FMC. Brachial L-FMC and FMD were measured on 26 healthy, young adults (13 males, 13 females; 24·6 ± 2·7 years). Each participant had two assessments conducted on two separate visits, separated by a minimum of seven days. Brachial artery baseline diameter was imaged during rest. Continuous imaging of the artery was performed during the last 20 s of cuff-occlusion to 180 s postcuff release. An L-FMC was considered present if the relative change from pre-occlusion baseline to L-FMC artery diameter was less than -0·1%. Overall, there was a strong, positive correlation between increased brachial L-FMC and blunted FMD (visit 1 test 1: r = 0·758, P<0·001; visit 1 test 2: r = 0·706, P<0·001; visit 2 test 1: r = 0·836, P<0·001; visit 2 test 2: r = 0·857, P<0·001). The reproducibility of intra- and interday L-FMC diameter was intraclass correlation coefficients (ICC) = 0·627, coefficient of variation (CV) = 54·4% and ICC = 0·734, CV = 43·5%, respectively. Vasoconstriction to low-flow conditions influences the subsequent maximal dilation during reactive hyperaemia. However, L-FMC is variable as evidenced by the weak intra- and interday reproducibility of the measure. Further research should study brachial L-FMC reproducibility among varying populations and the implications L-FMC has on the interpretation of FMD results.


Discovery of common Asian copy number variants using integrated high-resolution array CGH and massively parallel DNA sequencing.
Copy number variants (CNVs) account for the majority of human genomic diversity in terms of base coverage. Here, we have developed and applied a new method to combine high-resolution array comparative genomic hybridization (CGH) data with whole-genome DNA sequencing data to obtain a comprehensive catalog of common CNVs in Asian individuals. The genomes of 30 individuals from three Asian populations (Korean, Chinese and Japanese) were interrogated with an ultra-high-resolution array CGH platform containing 24 million probes. Whole-genome sequencing data from a reference genome (NA10851, with 28.3x coverage) and two Asian genomes (AK1, with 27.8x coverage and AK2, with 32.0x coverage) were used to transform the relative copy number information obtained from array CGH experiments into absolute copy number values. We discovered 5,177 CNVs, of which 3,547 were putative Asian-specific CNVs. These common CNVs in Asian populations will be a useful resource for subsequent genetic studies in these populations, and the new method of calling absolute CNVs will be essential for applying CNV data to personalized medicine.


Intrinsically disordered linker and plasma membrane-binding motif sort Ist2 and Ssy1 to junctions.
Membrane junctions or contact sites are close associations of lipid bilayers of heterologous organelles. Ist2 is an endoplasmic reticulum (ER)-resident transmembrane protein that mediates associations between the plasma membrane (PM) and the cortical ER (cER) in baker's yeast. We asked the question what structure in Ist2 bridges the up to 30 nm distance between the PM and the cER and we noted that the region spacing the transmembrane domain from the cortical sorting signal interacting with the PM is predicted to be intrinsically disordered (ID). In Ssy1, a protein that was not previously described to reside at membrane junctions, we recognized a domain organization similar to that in Ist2. We found that the localization of both Ist2 and Ssy1 at the cell periphery depends on the presence of a PM-binding domain, an ID linker region of sufficient length and a transmembrane domain that most probably resides in the ER. We show for the first time that an ID amino acid domain bridges adjacent heterologous membranes. The length and flexibility of ID domains make them uniquely eligible for spanning large distances, and we suggest that this domain structure occurs more frequently in proteins that mediate the formation of membrane contact sites.


Cimetidine use and risk of breast, prostate, and other cancers.
Purpose - The study was conducted to examine whether use of cimetidine is associated with the risk of cancer, with special attention to cancers of the breast and prostate because cimetidine increases estradiol levels and interferes with androgen binding. Methods - Individuals who received a prescription of cimetidine were identified from two computerized pharmacy databases of medications dispensed at Northern California Kaiser Permanente between 1982 and 1987. Users of ranitidine, a histamine-2 receptor antagonist that does not appear to influence estrogen levels or androgen binding, and non-users of either cimetidine or ranitidine, were also identified from these databases. Study subjects were followed through December 1995 for new diagnoses of cancer. Cox regression was used to estimate relative risks of cancer associated with use of cimetidine and ranitidine. Non-users of cimetidine and ranitidine were the referent group for all analyses. Result - While there were very modest increases and decreases in risk for some cancer sites among cimetidine users, most were within the limits of chance given no true association. Furthermore, similar risks of these cancers were also observed among ranitidine users. Conclusions - Although our results do not support an association between cancer risk and cimetidine use, it is one of the most widely prescribed drugs in the US and may now be purchased over-the-counter. The potential effect of cimetidine on risk of cancer, especially those that are hormone-related, should continue to be monitored, preferably in larger study populations. Copyright (c) 2000 John Wiley & Sons, Ltd.


Carcinoma ex pleomorphic adenoma of the palate composed of invasive micropapillary salivary duct carcinoma and adenoid cystic carcinoma components: an unusual case with immunohistochemical approach.
Carcinoma ex pleomorphic adenoma (CXPA) is an unusual epithelial malignancy that develops from a primary or recurrent pleomorphic adenoma (PA), the most common tumor of salivary glands, and constitutes about 11.5% of all carcinomas that affect these glands. Intraoral minor salivary glands and seromucous glands of the oropharynx are uncommon locations of CXPA. On histopathological examination, the tumor comprises a wide morphological spectrum with a variable proportion between the benign and malignant components with the latter often predominating and overlapping the PA, which may cause misdiagnosis. Here, we report a case of palatal minor salivary gland CXPA composed of invasive micropapillary salivary duct carcinoma and adenoid cystic carcinoma components with multiple nodal metastases in a 74-year-old woman. Neoplastic cells showed heterogeneous immunohistochemical profile with both luminal and myoepithelial differentiation. The invasive micropapillary salivary duct carcinoma component demonstrated overexpression of the oncoprotein human epidermal growth factor receptor-2. This feature should be considered and evaluated as a possible target for adjuvant therapy in case of metastatic disease.


Three-vessel view of the fetal upper mediastinum: an easy means of detecting abnormalities of the ventricular outflow tracts and great arteries during obstetric screening.
The three-vessel view is a transverse view of the fetal upper mediastinum is as simple to obtain as the four-chamber view. It demonstrates the main pulmonary artery, ascending aorta and superior vena cava in cross- or oblique sections. The purposes of this study were to describe the normal anatomy of the three-vessel view and to analyze what anatomical changes would occur in this view when there are lesions of the ventricular outflow tracts and/or great arteries. Sonograms of 29 fetuses with lesions involving the ventricular outflow tracts and/or great arteries were reviewed. Three-vessel views were evaluated in terms of vessel size, number, arrangement and alignment. Twenty-eight of 29 fetuses showed an abnormal three-vessel view that included abnormal vessel size (n = 12), abnormal alignment (n = 8), abnormal arrangement (n = 7) and abnormal vessel number (n = 3). The vessel size was abnormal in obstructive lesions of the right (n = 4) or the left (n = 8) side of the heart. An abnormal alignment was seen in tetralogy of Fallot (n = 6) and double-outlet right ventricle (n = 2) that showed anterior displacement of the aorta. An abnormal arrangement was seen in complete (n = 4) and corrected (n = 1) transposition, double-outlet right ventricle (n = 1) and pulmonary atresia with ventricular septal defect (n = 1). Only two vessels were seen in truncus arteriosus (n = 1). Four vessels were seen in persistent left superior vena cava (n = 2). A fetus with pulmonary atresia and intact ventricular septum showed a normal three-vessel view. In conclusion, most of the lesions involving the ventricular outflow tracts and/or great arteries showed an abnormal three-vessel view.


Early contact stage of apoptosis: its morphological features and function.
Apoptosis has been a biological phenomenon of intense interest for 20 years, but the earlier morphological features of apoptosis have not been determined hitherto. Using the methods of semi- and ultrathin sections, the livers of intact embryos and young rats have been studied under the effect of cycloheximide to determine morphological features of an early stage of apoptosis. It is discovered that both in hepatoblasts and hepatocytes, apoptosis, besides the well-known stages, also includes an early contact stage, distinguishing features of which are agglutination of bound ribosomes (breaking of translation), elimination of the nucleolus, reduction of free polysomes (and in hepatocytes, reduction of cisterns of rough endoplasmic reticulum), formation of cytoplasmic excrescences, and cell shape changes. The early stage of apoptosis is characterized by close contact with neighboring cells. At a certain phase of the contact stage of apoptosis, the nucleolus reappears in the nucleus and the number of free polysomes in the cytoplasm increases, which suggests the renewal of synthesis of new RNA and proteins. Close contact of differentiating and mitotic hepatoblasts with apoptotic cells indicates a certain functional relationship between these cells that is realized not only by micropinocytosis, but through gap junctions as well. We assume that the apoptotic cell, besides proteolytic products, can contain newly synthesized, low-molecular substances, the relocation of which from apoptotic to neighboring cells may contribute to both functional activity and proliferation of adjacent hepatoblasts and, therefore, the function of apoptosis may not be limited only to the elimination of harmful, damaged, and unwanted cells.


A nitroreductase-MOF biocatalyst for the degradation of nitroaromatic contaminants and fluorescent labeling of carbohydrates.
NfsB (nitroreductase fromEscherichia coli) can catalyze nitroaromatic compounds to aromatic amines under mild conditions. Compared with the purified enzyme NfsB, we found that the crude enzyme demonstrated better thermal stability and tolerance against a wide pH range, rendering it convenient to use and cost-effective as it did not require any downstream processing. In addition, we introduced metal-organic frameworks to immobilize the crude-NfsB. The resulting composite, crude-NfsB@ZIF-90, showed excellent catalytic performance and reusability, and it also demonstrated good catalytic activity in organic solvents, rendering it more efficient for the removal of nitroaromatic contaminants in complex environments. The nitroreductase-ZIF-90 biocatalyst can be used for fluorescent labeling of carbohydrates, which is favorable for the study of the function of carbohydrates.


Tapping the potential of synthetic riboswitches: reviewing the versatility of the tetracycline aptamer.
Synthetic riboswitches are a versatile class of regulatory elements that are becoming increasingly established in synthetic biology applications. They are characterized by their compact size and independence from auxiliary protein factors. While naturally occurring riboswitches were mostly discovered in bacteria, synthetic riboswitches have been designed for all domains of life. Published design strategies far exceed the number of riboswitches found in nature. A core element of any riboswitch is a binding domain, called an aptamer, which is characterized by high specificity and affinity for its ligand. Aptamers can be selected de novo, allowing the design of synthetic riboswitches against a broad spectrum of targets. The tetracycline aptamer has proven to be well suited for riboswitch engineering. Since its selection, it has been used in a variety of applications and is considered to be well established and characterized. Using the tetracycline aptamer as an example, we aim to discuss a large variety of design approaches for synthetic riboswitch engineering and their application. We aim to demonstrate the versatility of riboswitches in general and the high potential of synthetic RNA devices for creating new solutions in both the scientific and medical fields.


[Assessment of preoperative anxiety in patients entering the operating room on foot using state-trait anxiety inventory].
The purpose of this prospective study was to assess the effect of walking into the operating room on preoperative anxiety level. Sixty non-premedicated patients scheduled for elective surgery were randomly divided into two groups based on how they were transported into the operating room. One group was carried on a stretcher (n = 30) and the other entered on foot under their own power (n = 30). A subjective assessment of anxiety was performed using a state-trait anxiety inventory (STAI) the day before surgery and on arrival at the operating room. STAI values were not increased in the operating room as compared to the day before surgery for either group and did not differ between groups, though they showed a high level of anxiety throughout the preoperative period. We conclude that walking into the operating room has no significant influence on preoperative anxiety level.


Agenesis of the gallbladder without extrahepatic biliary atresia.
Agenesis of the gallbladder without extrahepatic biliary atresia is a rare disorder. At the UCLA-affiliated hospitals, 12 patients were classified in the following groups: (1) multiple fetal anomaly, (2) asymptomatic, and (3) symptomatic. All four patients in the multiple fetal anomaly group died of their other congenital defects. In the three patients in the asymptomatic group, the absent gallbladder was an incidental finding at autopsy. The five patients in the symptomatic group underwent operations for symptoms suggestive of biliary tract disease, with no gallbladder found; all were symptom free postoperatively. Operative strategy should include a complete exploration, operative cholangiography, and common bile duct exploration as necessary. Possible mechanisms responsible for symptoms include primary duct stones, biliary dyskinesia, or nonbiliary disorders. Computed tomography, biliary manometry, upper gastrointestinal tract endoscopy, and endoscopic cholangiography (with or without sphincterotomy) could be employed if symptoms continue.


A novel derivative for the assessment of urinary and salivary nitrate using gas chromatography/mass spectrometry.
Previous gas chromatography/mass spectrometry (GC/MS) methods for determining nitrate in biological samples involve either hazardous chemicals or produce multiple isomers that can be difficult to quantitate. Modification of these methods, by the nitration of mesitylene instead of benzene and in the presence of trifluoroacetic anhydride rather than sulphuric acid, should enable simple isotopic quantitation for use in tracer studies, for example, in the measurement of nitric oxide production. Desiccated urine and saliva samples, in addition to aqueous labelled and unlabelled nitrate standards, were treated with trifluoroacetic anhydride and mesitylene at 70 degrees C for 1 h, cooled, then sequentially washed with deionised water and aqueous sodium bicarbonate. The solution of nitromesitylene in mesitylene was separated, dried and analysed by GC/MS. The full mass spectra exhibited abundant ions at m/z 165 and 166 corresponding to the unlabelled and labelled molecular species of nitromesitylene, respectively. Selected ion monitoring of these masses for a series of gravimetrically prepared standards indicated good agreement with isotopic enrichments in the range 0.0625-5 mole % excess, and at nitrate concentrations within the physiological range of 0.078-2 mmol/L. Derivatised samples were stable with respect to isotopic enrichments and nitrate concentrations at -20 degrees C for up to 21 days and exhibited excellent repeatability. Nitration of mesitylene proved to be a simple and rapid method for the measurement of isotope ratios in aqueous nitrates by GC/MS, which has applications in tracer studies and in concentration determinations by isotope dilution techniques for nitric oxide production.


A novel description of the Vastus lateralis morphology of the Temminck's ground pangolin (Manis temminckii).
The pangolin (Manidae family) is the world's most trafficked animal, yet very little is known about its physiology and metabolism primarily due to its inconspicuous and solitary nature. Skeletal muscle samples from the Vastus lateralis were collected postmortem from a single female Temminck's ground pangolin (Manis temminckii). Samples were analyzed for fiber type composition, fiber size and myosin heavy chain isoform content. The oxidative and glycolytic metabolic capacity was determined through citrate synthase, 3-hydroxyacetyl co A dehydrogenase, creatine kinase, lactate dehydrogenase, phosphofructokinase and glycogen phosphorylase enzyme activities. Lastly, antioxidant capacity was determined through superoxide dismutase and catalase enzyme activities, and the total antioxidant capacity. The pangolin metabolic profile was then compared to other endurance and nonendurance mammals, in which data were standardized relative to human endurance athletes in order to provide context. Slow twitch type I fibers, rich in mitochondria were the predominant fiber type within the pangolin indicating a reliance on oxidative derived energy from fats and carbohydrates. This suggests that the pangolin has a high endurance capability when compared to other wild animals and human endurance athletes. This is the first study to investigate the skeletal muscle physiology and metabolism of any pangolin species, in an attempt to further understand this endangered animal and aid with conservation efforts.


Explicitly correlated second-order Møller-Plesset perturbation theory employing pseudospectral numerical quadratures.
We implemented explicitly correlated second-order Møller-Plesset perturbation theory with numerical quadratures using pseudospectral construction of grids. Introduction of pseudospectral approach for the calculation of many-electron integrals gives a possibility to use coarse grids without significant loss of precision in correlation energies, while the number of points in the grid is reduced about nine times. The use of complementary auxiliary basis sets as the sets of dealiasing functions is justified at both theoretical and computational levels. Benchmark calculations for a set of 16 molecules have shown the possibility to keep an error of second-order correlation energies within 1 milihartree (mH) with respect to MP2-F12 method with dense grids. Numerical tests for a set of 13 isogyric reactions are also performed.


An overview of traditional Chinese medicine affecting gut microbiota in obesity.
Obesity, a chronic metabolic disease with a complex pathophysiology, is caused by several variables. High-fat diets lead to the disruption of the gut microbiota and impaired gut barrier function in obese people. The dysbiosis and its metabolites through the intestinal barrier lead to an imbalance in energy metabolism and inflammatory response, which eventually contributes to the development of chronic diseases such as diabetes, hypertension, and cardiovascular disease. Current medicines are therapeutic to obesity in the short term; however, they may bring significant physical and emotional problems to patients as major side effects. Therefore, it is urgent to explore new therapeutic methods that have definite efficacy, can be taken for a long time, and have mild adverse effects. Numerous studies have demonstrated that traditional Chinese medicine (TCM) can control the gut microbiota in a multi-targeted and comprehensive manner, thereby restoring flora homeostasis, repairing damaged intestinal mucosal barriers, and eventually curbing the development of obesity. The active ingredients and compounds of TCM can restore the normal physiological function of the intestinal mucosal barrier by regulating gut microbiota to regulate energy metabolism, inhibit fat accumulation, affect food appetite, and reduce intestinal mucosal inflammatory response, thereby effectively promoting weight loss and providing new strategies for obesity prevention and treatment. Although there are some studies on the regulation of gut microbiota by TCM to prevent and treat obesity, all of them have the disadvantage of being systematic and comprehensive. Therefore, this work comprehensively describes the molecular mechanism of obesity mediated by gut microbiota based on the research state of obesity, gut microbiota, and TCM. A comprehensive and systematic summary of TCM targeting the regulation of gut microbiota for the treatment of obesity should be conducted in order to provide new strategies and ideas for the treatment of obesity.


The role of quality improvement initiatives in healthcare operational environments: changes, challenges and responses.
The purpose of this paper is to shed some light on the utilization of quality improvement initiatives in healthcare operational environments. In the process, environmental changes and strategic responses are examined for a sample of healthcare organizations. A survey-based research methodology is utilized in this study. Factor analysis is used to extract relevant factors representing environmental changes and strategic options relevant to healthcare organizations. In addition, simple percentages are utilized to assess the extent of implementation and effectiveness of quality improvement initiatives. In general, the findings appear to indicate that the studied organizations have achieved both operational and strategic benefits due to the effective implementation of quality improvement initiatives. The implementation of quality improvement initiatives appears to be in response to environmental changes and challenges faced by healthcare organizations. Based on the findings of this study, decision-makers are encouraged to commit organizational resources toward the effective implementation of quality improvement initiatives. Investing in quality improvement not only is justified, but also appears to be very much needed in a changing competitive environment. This study contributes to enhancing one's practical and theoretical understanding of the competitive impact of quality improvement initiatives in different operational settings.


Fate Characterization of Benzene Kresoxim-Methyl (a Strobilurin Fungicide) in Different Aerobic Soils.
Benzene kresoxim-methyl (BKM) is a promising broad-spectrum strobilurin fungicide widely used to control fungal pathogens in crops. However, information on its environmental fate is limited. To broaden our understanding of this fungicide's kinetic fate in aerobic soils, we labeled BKM with C on its benzoate ring and used ultralow-level liquid scintillation counting coupled with high-performance liquid chromatography analysis. Results show that degradation, mineralization, and bound residue (BR) formation of BKM was controlled by soil type and microbial community composition. Degradation of BKM followed first-order dynamics, and the half-lives () were 51.7, 30.8, and 26.8 d for clay, loamy, and saline soils, respectively. After 100 d, about 0.13, 4.35, and 5.94% of the initial C-BKM was mineralized, and 14.43, 19.90, and 28.81% was formed as BRs in the clay, loamy, and saline soils, respectively. About 60 to 85% of the C-BKM residue in soil was extractable; of this fraction, 30 to 50% was composed of incomplete degradation intermediates. Up to 40% of extractable C-BKM in soil was readily available. Our results suggest that BKM and its incomplete intermediates had a relatively long persistence in soil, which may lead to exposure for nontarget organisms. Soil microbes may play a dominant role in controlling the fate of BKM in soil as sterilization sharply decreased its mineralization rate from 4.35 to 0.03%, increased from 30.8 to 85.6 d, and decreased the BR fraction from 19.90 to 3.25%.


VR1 receptor modulators as potential drugs for neuropathic pain.
The involvement of VR(1) in the endogenous pain signalling has converted this receptor into a promising therapeutic target for the development of a new family of potent analgesics devoid of the shortcomings of other analgesics commonly used. The desensitisation induced after VR(1) activation points to the utility of VR(1) agonists for the treatment of various nociceptive disorders including mitigation of neuropathic pain, inhibition of neurogenic inflammation and suppression of urinary bladder hyperreflexia, whereas VR(1) antagonists have been described as valuable agents for the treatment of inflammatory hyperalgesia and pain. Structure of the main classes of VR(1) ligands developed to date, their molecular mechanisms of action and their promising utility for the management of diverse nociceptive alterations, specially neuropathic pain, are discussed in this review.


Going through the wine fining: Intimate dialogue between organics and clays.
Wine chemistry inspires and challenges with its complexity and intriguing composition. In this context, the composites based on the use of a model protein, a polyphenol of interest and montmorillonite in a model hydroalcoholic solution have been studied. A set of experimental characterization techniques highlighted the interactions between the organic and the inorganic parts in the composite. The amount of the organic part was determined by ultraviolet-visible (UV-VIS) and thermal analysis. X-ray diffraction (XRD) and transmission electronic microscopy (TEM) informed about the stacking/exfoliation of the layers in the composites. Vibrational and nuclear magnetic resonance spectroscopies methods stressed on the formation of a complex between the protein and the polyphenol before adsorption on the clay mineral. The mobility/rigidity of the organic parts were determined by fluorescence time resolved spectroscopy. Changes in the secondary structure of the protein occured upon complexation with polyphenol on clay mineral due to strong interactions. Although not representating faithfully enological conditions, these results highlight the range and nature of mechanisms possibly involved in wine fining.


A survey on anthelmintic resistance in nematode parasites of sheep in Lusaka, Zambia.
While surveys in Southern Africa indicate anthelmintic resistance of gastrointestinal nematodes to be common in small ruminants in South Africa, Kenya and Zimbabwe there have been no reports of resistance in Zambia. The objective of this study was to determine whether anthelmintic resistance occurs in Zambia, and to obtain information on nematode control practices in the country. During the rainy season six commercial sheep farms were selected in and around Lusaka and Chisamba. Worm control practices were gauged by means of a questionnaire, and the Faecal Egg Count Reduction Test was performed for assessing anthelmintic efficacy of albendazole, levamisole and ivermectin. On all farms anthelmintic treatment was the only approach used to control nematode infections. Frequency of treatment varied from twice a year to every 6 weeks and drugs of different anthelmintic groups were alternated within the same year. There was a wide range in faecal egg counts of individual sheep before treatment, with some individual counts of up to 87000. Larval identification showed that Haemonchus was almost the only genus recovered from the faecal cultures before and after treatment. Albendazole resistance was found on five of the six farms. On each of the four farms where ivermectin gave less than 95% reduction in egg counts, there was resistance to albendazole as well. Levamisole showed an efficacy of 95% or higher on all six farms.


Avoiding alar necrosis with post-nasal packs.
Foley's catheter is used for post-nasal packing in severe epistaxis. Various methods have been described for securing the catheter in position, all of which can be associated with patient discomfort, risk of alar necrosis or unsightliness. We describe a new method to secure the Foley's catheter without these problems. The ribbon gauze used for anterior nasal packing is tied over the catheter in multiple knots to secure it in place. This has been successfully tried on over 50 patients.


Direct repression of prdm1 by Bcl-6 inhibits plasmacytic differentiation.
We have identified two intronic regions of mouse prdm1, the gene encoding B lymphocyte-induced maturation protein-1 (Blimp-1), which confer transcriptional repression in response to Bcl-6. The Bcl-6 response element in intron 5, which is conserved between mice and humans, was studied in detail. It binds Bcl-6 in vitro and was shown by chromatin immunoprecipitation to be occupied by Bcl-6 in vivo. Neither Bcl-6 response element functions as a STAT3-response element, showing that STAT3 does not compete with Bcl-6 at these sites. Bcl-6(-/-) mice confirm the biological importance of Bcl-6-dependent repression of prdm1. These mice have elevated Ab response, increased Ig-secreting cells, and increased Blimp-1(+) cells in spleen following immunization and their splenic B cells show accelerated plasmacytic development in vitro.


Antibiotic treatment to prevent postextraction complications: a monocentric, randomized clinical trial. Preliminary outcomes.
Tooth extraction is a very common procedure in oral surgery. Despite this, very little information is available in the literature as to the antibiotic management of the patient. The aim of this study is to evaluate whether the antibiotic prophylaxis could be beneficial in preventing postextraction local complications and whether the use of a probiotic could help reduce the antibiotic gastro-intestinal side effects. One hundred eleven patients meeting the inclusion criteria were initially included in this randomized clinical trial and randomly allocated to one of the three experimental groups according to a computer-generated randomization list. Patients allocated to the group 1 were given amoxicillin+clavulanic acid (2 g/day for 6 days), patients allocated to the group 2 received antibiotic + probiotic (Bifidobacterium longum+lactoferrin) and patients allocated to the group 3 received no antibiotic therapy after the extraction. To evaluate post-extractive complications, controls were performed at days 7, 14 and 21 after the extraction. At T1 pain at the surgical site was present in the 48%, 30% and 71.4% of the patients belonging respectively to the antibiotic alone group, to the antibiotic+probiotic group and to the control group. The mean Numeric Rating Score (NRS) score was 1.56±1.91, 1.08±1.93, 2.02±2.27 respectively (P=0.0498). Two patients belonging to the control group experienced dry socket. In addition, 9 patients (33.3%) in the antibiotic-alone group and 1 patient (2.7%) in the antibiotic+probiotic group reported intestinal distension (P=0.0012), 7 days after surgery. Finally, diarrhea was recorded in 5 patients of the antibiotic alone group (18.5%), on the other hand, no patients of the antibiotic+probiotic group and the control group reported diarrhea. Postextractive complications observed in each group have been mild and fast to resolve. The antibiotic administration showed a decrease in pain suffered by patients but a higher incidence of gastrointestinal side effects, such as abdominal distension and diarrhea, which seemed to be relieved by the concomitant use of the probiotic.


Higher frequencies of HLA DQB1*05:01 and anti-glycosphingolipid antibodies in a cluster of severe Guillain-Barré syndrome.
Few regional and seasonal Guillain-Barré syndrome (GBS) clusters have been reported so far. It is unknown whether patients suffering from sporadic GBS differ from GBS clusters with respect to clinical and paraclinical parameters, HLA association and antibody response to glycosphingolipids and Campylobacter jejuni (Cj). We examined 40 consecutive patients with GBS from the greater Munich area in Germany with 14 of those admitted within a period of 3 months in fall 2010 defining a cluster of GBS. Sequencing-based HLA typing of the HLA genes DRB1, DQB1, and DPB1 was performed, and ELISA for anti-glycosphingolipid antibodies was carried out. Clinical and paraclinical findings (Cj seroreactivity, cerebrospinal fluid parameters, and electrophysiology) were obtained and analyzed. GBS cluster patients were characterized by a more severe clinical phenotype with more patients requiring mechanical ventilation and higher frequencies of autoantibodies against sulfatide, GalC and certain ganglioside epitopes (54 %) as compared to sporadic GBS cases (13 %, p = 0.017). Cj seropositivity tended to be higher within GBS cluster patients (69 %) as compared to sporadic cases (46 %, p = 0.155). We noted higher frequencies of HLA class II allele DQB1*05:01 in the cluster cohort (23 %) as compared to sporadic GBS patients (3 %, p = 0.019). Cluster of severe GBS was defined by higher frequencies of autoantibodies against glycosphingolipids. HLA class II allele DQB1*05:01 might contribute to clinical worsening in the cluster patients.


Microbiota-dependent activation of the myeloid calcineurin-NFAT pathway inhibits B7H3- and B7H4-dependent anti-tumor immunity in colorectal cancer.
Bacterial sensing by intestinal tumor cells contributes to tumor growth through cell-intrinsic activation of the calcineurin-NFAT axis, but the role of this pathway in other intestinal cells remains unclear. Here, we found that myeloid-specific deletion of calcineurin in mice activated protective CD8+ T cell responses and inhibited colorectal cancer (CRC) growth. Microbial sensing by myeloid cells promoted calcineurin- and NFAT-dependent interleukin 6 (IL-6) release, expression of the co-inhibitory molecules B7H3 and B7H4 by tumor cells, and inhibition of CD8+ T cell-dependent anti-tumor immunity. Accordingly, targeting members of this pathway activated protective CD8+ T cell responses and inhibited primary and metastatic CRC growth. B7H3 and B7H4 were expressed by the majority of human primary CRCs and metastases, which was associated with low numbers of tumor-infiltrating CD8+ T cells and poor survival. Therefore, a microbiota-, calcineurin-, and B7H3/B7H4-dependent pathway controls anti-tumor immunity, revealing additional targets for immune checkpoint inhibition in microsatellite-stable CRC.


HK2 contributes to the proliferation, migration, and invasion of diffuse large B-cell lymphoma cells by enhancing the ERK1/2 signaling pathway.
Hexokinase 2 (HK2) has been associated with carcinogenic growth in numerous kinds of malignancies as essential regulators during the processing of glucose. This study aimed to explore the effects of HK2 on diffuse large B-cell lymphoma (DLBCL) cells via the ERK1/2 signaling. Expressions of HK2 and ERK1/2 were examined in DLBCL cell lines using quantitative reverse transcription polymerase chain reaction and western blotting. HK2 and ERK1/2 were attenuated through HK2 small-interfering RNA (siRNA) and ERK inhibitor FR180204, respectively, in U2932 and SU-DHL-4 cells. Cell Counting Kit-8, clone formation, transwell, and flow cytometry assays were used in evaluating the effects of HK2 and ERK1/2 on cell proliferation, migration, and apoptosis. Moreover, a xenograft model was created to assess the roles of HK2 in vivo. HK2 and ERK1/2 were evidently up-regulated in DLBCL cell lines. HK2 knockdown and FR180204 markedly suppressed the proliferation and clonogenesis of U2932 and SU-DHL-4 cells and promoted cell apoptosis in vitro. We also found that HK2 silencing suppressed tumor growth in vivo. Notably, HK2 knockdown inactivated the ERK1/2 signaling pathway both in vitro and in vivo. These data indicate that inhibition of HK2 may suppress the proliferation, migration, and invasion of DLBCL cells, partly via inhibiting the ERK1/2 signaling pathway.


FT-IR spectroscopy as an emerging method for rapid characterization of microorganisms.
Statistical methods such as principal component analysis and cluster analysis were used to analyze ATR-FT-IR spectra obtained from bacterial whole cells. Both methods gave satisfactory results and are conclusive in showing that they can discriminate and classify bacterial strains of clinical origin exhibiting different resistance mechanisms. This approach places FT-IR spectroscopy at the forefront of those new potential techniques that could be used in the rapid screening of microorganisms.


HCRP1 inhibits TGF-β induced epithelial-mesenchymal transition in hepatocellular carcinoma.
Hepatocellular carcinoma-related protein 1 (HCRP1), also known as human vacuolar protein sorting 37 homologue A (hVps37A), has not been detected or is significantly downregulated in hepatocellular carcinoma (HCC) tissues. However, information on the regulatory mechanisms of HCRP1 in HCC remains unclear. Here we found that the downregulation of HCRP1 in HepG2 cells (with low invasion capacity) significantly enhanced migration and invasion, whereas HCRP1 upregulation in SMMC-7721 cells (with high invasion capacity) generated the opposite result. Interestingly, the morphology of HepG2 cells significantly changed from an epithelial to mesenchymal phenotype after HCRP1 knockdown. Moreover, we observed a decrease in the expression of epithelial cell markers E-cadherin and β-catenin, and an increase in the expression of mesenchymal cell markers N-cadherin and vimentin. We also observed that the downregulation of HCRP1 induced epithelial-mesenchymal transition (EMT) through the transforming growth factor-β pathway. Together, our findings define a novel function for HCRP1 from the perspective of EMT, which is closely associated with the migration and invasion of HCC cells.


Real-time traffic sign recognition based on a general purpose GPU and deep-learning.
We present a General Purpose Graphics Processing Unit (GPGPU) based real-time traffic sign detection and recognition method that is robust against illumination changes. There have been many approaches to traffic sign recognition in various research fields; however, previous approaches faced several limitations when under low illumination or wide variance of light conditions. To overcome these drawbacks and improve processing speeds, we propose a method that 1) is robust against illumination changes, 2) uses GPGPU-based real-time traffic sign detection, and 3) performs region detecting and recognition using a hierarchical model. This method produces stable results in low illumination environments. Both detection and hierarchical recognition are performed in real-time, and the proposed method achieves 0.97 F1-score on our collective dataset, which uses the Vienna convention traffic rules (Germany and South Korea).


[Papillary carcinoma in a thyroglossal duct cyst: report of two cases].
Thyroglossal duct cyst is the most common congenital anomaly of thyroid gland development. However, papillary carcinoma is described only in 1-2% of cases and the clinical appearance is indistinguishable from a benign thyroglossal duct cyst. We report two females aged 15 and 27 years consulting for a cervical mass. In both, a solid cystic lesion was found and excised using the Sistrunk procedure. The biopsy disclosed a papillary carcinoma in both. The postoperative evolution of both patients was uneventful.


Spotlight on avian coronaviruses.
Coronaviruses (CoVs) mainly cause enteric and/or respiratory signs. Mammalian CoVs including COVID-19 (now officially named SARS-CoV-2) belong to either the Alphacoronavirus or Betacoronavirus genera. In birds, the majority of the known CoVs belong to the Gammacoronavirus genus, whilst a small number are classified as Deltacoronaviruses. Gammacoronaviruses continue to be reported in an increasing number of avian species, generally by detection of viral RNA. Apart from infectious bronchitis virus in chickens, the only avian species in which CoV has been definitively associated with disease are the turkey, pheasant and guinea fowl. Whilst there is strong evidence for recombination between gammacoronaviruses of different avian species, and between betacoronaviruses in different mammals, evidence of recombination between coronaviruses of different genera is lacking. Furthermore, the recombination of an alpha or betacoronavirus with a gammacoronavirus is extremely unlikely. For recombination to happen, the two viruses would need to be present in the same cell of the same animal at the same time, a highly unlikely scenario as they cannot replicate in the same host!


Glycerin laxatives for prevention or treatment of feeding intolerance in very low birth weight infants.
Feeding intolerance is a common clinical problem among preterm infants. It may be an early sign of necrotising enterocolitis, sepsis or other serious gastrointestinal conditions, or it may result from gut immaturity with delayed passage of meconium. Glycerin laxatives stimulate passage of meconium by acting as an osmotic dehydrating agent and increasing osmotic pressure in the gut; they stimulate rectal contraction, potentially reducing the incidence of feeding intolerance. To assess the effectiveness and safety of glycerin laxatives (enemas/suppositories) for prevention or treatment of feeding intolerance in very low birth weight (VLBW) infants. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 4), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We restricted our search to all randomised controlled trials and applied no language restrictions. We searched the references of identified studies and reviews on this topic and handsearched for additional articles. We searched the database maintained by the US National Institutes of Health (www.clinicaltrials.gov) and European trial registries to identify ongoing trials. We considered only randomised or quasi-randomised controlled trials that enrolled preterm infants < 32 weeks' gestational age (GA) and/or < 1500 g birth weight. We included trials if they administered glycerin laxatives and measured at least one prespecified clinical outcome. We used standard methods of The Cochrane Collaboration and its Neonatal Group to assess methodological quality of trials, to collect data and to perform analyses. We identified three trials that evaluated use of prophylactic glycerin laxatives in preterm infants. We identified no trials that evaluated therapeutic use of glycerin laxatives for feeding intolerance. Our review showed that prophylactic administration of glycerin laxatives did not reduce the time required to achieve full enteral feeds and did not influence secondary outcomes, including duration of hospital stay, mortality and weight at discharge. Prophylactic administration of glycerin laxatives resulted in failure of fewer infants to pass stool over the first 48 hours. Included trials reported no adverse events. Our review of available evidence for glycerin laxatives does not support the routine use of prophylactic glycerin laxatives in clinical practice. Additional studies are needed to confirm or refute the effectiveness and safety of glycerin laxatives for prevention or treatment of feeding intolerance in VLBW infants.


Targeting One Carbon Metabolism with an Antimetabolite Disrupts Pyrimidine Homeostasis and Induces Nucleotide Overflow.
Antimetabolites that affect nucleotide metabolism are frontline chemotherapy agents in several cancers and often successfully target one carbon metabolism. However, the precise mechanisms and resulting determinants of their therapeutic value are unknown. We show that 5-fluorouracil (5-FU), a commonly used antimetabolite therapeutic with varying efficacy, induces specific alterations to nucleotide metabolism by disrupting pyrimidine homeostasis. An integrative metabolomics analysis of the cellular response to 5-FU reveals intracellular uracil accumulation, whereas deoxyuridine levels exhibited increased flux into the extracellular space, resulting in an induction of overflow metabolism. Subsequent analysis from mice bearing colorectal tumors treated with 5-FU show specific secretion of metabolites in tumor-bearing mice into serum that results from alterations in nucleotide flux and reduction in overflow metabolism. Together, these findings identify a determinant of an antimetabolite response that may be exploited to more precisely define the tumors that could respond to targeting cancer metabolism.


Poly(ethylene glycol)-alpha-chymotrypsin complex catalytically active in anhydrous isooctane.
Enzymatic catalysis in predominantly organic media has undergone rapid expansions, particularly over the past decade. There are numerous potential advantages in employing enzymes in organic media. However, there are some crucial defects in the native enzyme-catalyzed biocatalyses, such as a decrease in their reaction rate due to diffusional limitations of substrates. To overcome these defects, enzymes modified chemically with polymers and physically with surfactants, which were soluble in organic solvents, were often used. However, they had inherent drawbacks. On the other hand, the enzymes modified physically with polymers were found to be soluble and catalytically active in organic media. To date, however, the effect of the amount of added polymers on the enzyme activity has not been clarified, even though this may be an important factor governing the activity of polymer-enzyme complexes in organic media. In this study, we obtained a complex of an enzyme and a hydrophilic polymer by lyophilizing an aqueous solution containing a polymer and an enzyme. We found that the polymer-enzyme complex was catalytically active in organic media even when the molar ratio of polymer/enzyme in its preparation stage was unity, and that the activity of the polymer-enzyme complex increased with an increase in the molar ratio of polymer/enzyme, reached the maximum activity (ca. 7200-fold higher than that of the native enzyme suspended in organic media) and then gradually decreased.


Analyses of Pneumocystis fatty acids.
The major ester-linked fatty acids of the total lipids extracted from Pneumocystis carinii isolated from the lungs of corticosteroid-treated rats were 16:0, 18:0, 18:1, 18:2 and 20:4. Others detected included 14:0, 16:1 and 22:4. The major sphingolipid fatty acids were 16:0, 18:0, 22:0, 24:0 and 24:1; others included 14:0, 18:1, 20:0, 23:0, 24:2 and 26:0. The total lipid fatty acid compositions of preparations from appropriate lung controls were similar to those of the organism.


Interleukin 6 effects on the pituitary-thyroid axis in the rat.
It has been postulated recently that cytokines, and in particular interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), may have a role in the pathogenesis of the changes of serum thyroid hormone concentrations that are encountered in patients with non-thyroidal illness (NTI). Many of the IL-1 and TNF-alpha effects are believed to be mediated by the induction of IL-6 synthesis, which might, therefore, represent an important mediator of thyroid hormone changes in NTI. To address this problem, male Wistar rats were injected subcutaneously with 2.5 micrograms of recombinant human IL-6 (rhIL-6, in 500 microliters of saline solution), with 2.5 micrograms of rhIL-6 preincubated with 100 microliters of anti-IL-6 neutralizing antibody or with saline solution alone (control group). Administration of rhIL-6 resulted in a significant decrease of thyroxine (T4) from 82 +/- 4 nmol/l (mean +/- SEM) to a nadir of 33 +/- 3 nmol/l (p < 0.0001) after 48 h, and of triiodothyronine (T3) from 1.6 +/- 0.1 to 0.8 +/- 0.1 nmol/l after 48 h (p < 0.0001). A slight decrease in serum T4 and T3 concentrations also was observed in the control group, but the lowest values (T4, 66 +/- 3 nmol/l; T3, 1.2 +/- 0.1 nmol/l) were significantly higher (p < 0.0001) than in IL-6-treated rats. The IL-6-induced changes could be prevented by preincubation of rhIL-6 with its neutralizing antibody.(ABSTRACT TRUNCATED AT 250 WORDS)


Selection of the tagged photons by off axis heterodyne holography in ultrasound-modulated optical tomography.
Ultrasound-modulated optical tomography (UOT) is a technique that images optical contrast deep inside scattering media. Heterodyne holography is a promising tool that is able to detect UOT-tagged photons with high efficiency. In this work, we describe theoretically the detection of the tagged photon in heterodyne holography-based UOT, show how to filter the untagged photon, and discuss the effect of shot noise. The discussion also considers speckle decorrelation. We show that optimal detection sensitivity can be reached, if the frame exposure time of the camera used to perform the holographic detection is on the order of the decorrelation time.


Relationship between the nuclear morphology of the sperm of 10 bulls and their fertility.
The relationships between the fertility and nuclear morphology, chromatin maturity and chromatin condensation of the sperm of three bulls with a calving rate over a year of more than 65 per cent, four bulls with a calving rate between 65 per cent and 35 per cent, and three bulls with a calving rate of less than 35 per cent were studied. The sperm nuclei were stained with the Feulgen reaction, and chromatin condensation and maturation were evaluated in situ by staining with toluidine blue and acid aniline blue. Nuclear chromatin decondensation was induced with dithiothreitol; this showed that in the bulls with low fertility, more than 35 per cent of nuclei were decondensed, and that one of them had the lowest percentage of normal nuclei (64.9 per cent) and stronger positive reactions to the acid aniline blue and toluidine blue stains than the other bulls.


Enteral formula use in children after small bowel transplant.
The ultimate goal of intestinal transplantation (ITx) is the maintenance of nutritional status enterally/orally. We retrospectively identified children who had received ITx since the inception of our Intestinal Care Center in December 1996 (n = 24; median age, 2.6 years). Two patients died within 2 months of transplant. Enteral formulas used in the remaining 22 patients included the following: amino acid, trace long chain fatty acids (LCT; n = 4); amino acid, medium chain fatty acids (MCT)/LCT fat mix (n = 13); amino acid, LCT fat (n = 1); and peptide, MCT/LCT fat mix (n = 3). Feedings were initiated on an average of 13 days after ITx. The median number of days to complete the total parenteral nutrition (TPN) wean was 30 days, and stoma output measured on an average of 37 mL/kg per day at 1 month posttransplant. Nine patients (41%) advanced to oral intake alone within 2 to 30 months, and 5 patients (23%) were diagnosed with milk allergy through the RAST test (Pharmacia, Uppsala, Sweden). No differences in the initiation of therapy, advancement to oral intake, stoma output, or TPN weaning were observed by the type of formula used. Using z-score statistics, positive linear growth was achieved in 7 of 21 children (33%) over the 1-year period, whereas linear growth velocity was maintained in an additional 6 patients (29%). Successful advancement to total enteral/oral intake and positive growth after ITx can be achieved with either an amino acid- or peptide-based, partial MCT enteral formula initiated within 2 weeks of transplant. Monitoring for posttransplant allergy is recommended because of the high rate of postoperative allergy symptomology.