The development of metabolic tolerance in the alcohol-preferring P rats: comparison of forced and free-choice drinking of ethanol.
Experiments were performed to determine whether metabolic tolerance to alcohol develops in the alcohol-preferring P rats during free-choice drinking. In Experiment 1, alcohol elimination rates (AERs) in female Wistar and P rats were measured as a function of age from 26 to 180 days old. AERs calculated as mmol hr-1 per kg body weight fell with age, whereas AERs expressed as mmol hr-1 per rat increased to reach a constant value after 60 days of age. These data indicate that the chronic effects of ethanol on AER are most easily interpreted if experiments are performed in animals 60 days of age or older and AERs are calculated as mmol hr-1 per rat. In Experiments 2 and 3, P female rats were exposed to alcohol for 6-7 weeks either by free-choice drinking or by forced feeding with liquid diets. With free-choice drinking of alcohol, solid food containing 31 percent of the calories as protein, 10 percent ethanol (v/v) and water were made available ad lib. The liquid diets used for forced ethanol feeding were the Bio-Serv-711 diet, a protein-supplemented Bio-Serv-711 diet and the AIN diet and they contained 18, 32 and 22 percent calories as protein, respectively. When compared with pair-fed or ad lib controls, all the P rats exposed to alcohol by either free-choice or forced-feeding exhibited increased AERs (i.e., metabolic tolerance) after 6-7 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)


Diploid-aneuploid mosaicism in human embryos cultured to the blastocyst stage.
To examine diploid-aneuploid mosaicism in human in vitro cultured blastocysts. A laboratory study on spare blastocysts from an IVF program. University hospital laboratory. Forty-three couples undergoing IVF or intracytoplasmic sperm injection. Ninety-one blastocysts were spread for fluorescence in situ hybridization using the HCl-Tween 20 method. A total of 6,664 nuclei were analyzed for aneuploidy using fluorescent DNA probes specific to chromosomes 2, 7, and 18. The proportion of aneuploid cells within each blastocyst. The incidence of diploid-aneuploid mosaicism among 91 blastocysts examined was 17.6%. All of the mosaic blastocysts were abnormal for only one of the three chromosomes tested, with the incidence of involvement of chromosomes 2, 7, and 18 being 3.3%, 8.8%, and 5.5%, respectively. The majority of the mosaic blastocysts had low proportions of aneuploid cells. Ten of the 16 (62.5%) affected blastocysts were of morphology compatible with implantation. A considerable proportion of human IVF blastocysts show a form of mosaicism that has been observed in fetal and placental tissues. This mosaicism often arises at the final stage of preimplantation development in vitro and is present in blastocysts of morphology compatible with implantation.


Comment on Küppers et al. Percutaneous Anorectoplasty (PARP)-An Adaptable, Minimal-Invasive Technique for Anorectal Malformation Repair. Children 2022, 9, 587.
I read the above-mentioned article with a great deal of interest [...].


Effect of N-acetyl-cysteine on liposomal and muscle model oxidation induced by reactive oxygen, nitrogen, and sulfur.
N-acetyl-cysteine (NAC), a naturally occurring thiol, is found in some fruits and vegetables, sometimes in concentrations higher than glutathione. The objective of this research was to determine the antioxidative effect of NAC in liposomal and muscle models challenged by different oxidizing systems, three that produce reactive oxygen species, two that produce reactive nitrogen species, and two that produce reactive sulfur. The antioxidative effect of cysteine and NAC was compared in the liposomes and NAC and BHT were compared in the muscle homogenates. Lipid hydroperoxides (LOOH), TBARS, and sulfydryls (protein and non-protein) were analyzed. Results indicated that NAC is a more effective inhibitor of lipid oxidation in systems induced by free radicals and reactive nitrogen than those that are induced by peroxides. NAC appears to be at least mildly antioxidative in both liposomal and muscle models, although it did not completely inhibit oxidation in liposomes and generally was not as effective as BHT in the muscle models.


Consistently low levels of histidine-rich glycoprotein as a new prognostic biomarker for sepsis: A multicenter prospective observational study.
Few sepsis biomarkers accurately predict severity and mortality. Previously, we had reported that first-day histidine-rich glycoprotein (HRG) levels were significantly lower in patients with sepsis and were associated with mortality. Since the time trends of HRG are unknown, this study focused on the time course of HRG in patients with sepsis and evaluated the differences between survivors and non-survivors. A multicenter prospective observational study was conducted involving 200 patients with sepsis in 16 Japanese hospitals. Blood samples were collected on days 1, 3, 5, and 7, and 28-day mortality was used for survival analysis. Plasma HRG levels were determined using a modified quantitative sandwich enzyme-linked immunosorbent assay. First-day HRG levels in non-survivors were significantly lower than those in survivors (mean, 15.7 [95% confidence interval (CI), 13.4-18.1] vs 20.7 [19.5-21.9] μg/mL; P = 0.006). Although there was no time × survivors/non-survivors interaction in the time courses of HRG (P = 0.34), the main effect of generalized linear mixed models was significant (P < 0.001). In a univariate Cox proportional hazards model with each variable as a time-dependent covariate, higher HRG levels were significantly associated with a lower risk of mortality (hazard ratio, 0.85 [95% CI, 0.78-0.92]; P < 0.001). Furthermore, presepsin levels (P = 0.02) and Sequential Organ Function Assessment scores (P < 0.001) were significantly associated with mortality. Harrell's C-index values for the 28-day mortality effect of HRG, presepsin, procalcitonin, and C-reactive protein were 0.72, 0.70, 0.63, and 0.59, respectively. HRG levels in non-survivors were consistently lower than those in survivors during the first seven days of sepsis. Repeatedly measured HRG levels were significantly associated with mortality. Furthermore, the predictive power of HRG for mortality may be superior to that of other singular biomarkers, including presepsin, procalcitonin, and C-reactive protein.


Synthesis of polystyrene-silica composite particles via one-step nanoparticle-stabilized emulsion polymerization.
Polystyrene-silica core-shell composite particles are prepared by one-step emulsion polymerization with a nonionic initiator VA-086, solely stabilized by silica nanoparticles. The silica nanoparticles are successfully incorporated as the shell, likely due to the fact that the nanoparticles are thermodynamically favorable to adsorb and remain at the liquid-liquid interfaces during the emulsion polymerization. The silica content, determined by thermogravimetric analysis, is approximately 20 wt% in the composite particles. In addition, we further explore the polymerization mechanism by studying the particle growth as a function of initiator concentration and reaction time: when the initiator/monomer ratio is increased from 0.83 to 2.5 wt%, the particle size at 24 h reaction time decreases for a fixed monomer amount, possibly due to a larger number of nuclei at the initial stage of polymerization. Further increasing the initiator/monomer ratio to 4.2 wt% does not continually decrease the particle size, which may be limited by the stabilization provided by a fixed concentration of silica nanoparticles. The surface coverage also changes with initiator concentration and reaction time although the underlying mechanism is not fully understood.


TGF-beta1-induced cell cycle arrest in renal mesangial cells involves inhibition of cyclin E-cdk 2 activation and retinoblastoma protein phosphorylation.
In glomerular disease, transforming growth factor-beta1 (TGF-beta1) has been demonstrated to exert anti-mitogenic and anti-inflammatory as well as fibrogenic effects. To better understand the TGF-beta1 action on glomerular cells at the molecular level, we investigated mechanisms of TGF-beta1-induced growth suppression in primary cultures of rat mesangial cells (MCs). TGF-beta1 (5 ng/ml) markedly inhibited proliferation of MCs incubated with PDGF, endothelin-1, bFGF, serotonin, or EGF, indicating that TGF-beta1 interferes with post-receptor signals of mitogenesis. TGF-beta1 did not affect mitogen-stimulated induction of the immediate early genes, c-fos, c-jun, and Egr-1 in MCs that occurred transiently at 30 to 120 minutes. Time-course studies revealed that TGF-beta1 inhibited DNA synthesis and MC replication when added up to six to eight hours after MC stimulation with PDGF. FACS analysis demonstrated that MCs had reached middle to late G1 phase of cell cycle progression at this timepoint. PDGF stimulation of MCs induced protein expression of the G1 phase cyclin D1 as well as the cyclin-dependent kinases cdk 4 and cdk 2. This was not significantly altered when MCs were coincubated with both, PDGF and TGF-beta1. However, TGF-beta1 prevented PDGF-elicited phosphorylation of the retinoblastoma tumor suppressor (pRb), a negative cell cycle regulator. Moreover, TGF-beta1 significantly reduced cyclin E-associated histone H1 kinase activity in the presence of PDGF. These results indicate that TGF-beta1 inhibits mitogen-stimulated MC growth by causing cell cycle arrest in late G1 phase. While TGF-beta1 does not alter the mitogen-induced expression and abundance of G1 phase cyclin D1 and cdks 4 and 2 in MCs, it inhibits cyclin E-cdk 2 activity, thus preventing mitogen-elicited phosphorylation and inactivation of pRb in G1 phase and transition to S phase.


Receptor and substrate interactions of clostridial neurotoxins.
The high potency of clostridial neurotoxins relies predominantly on their neurospecific binding and specific hydrolysis of SNARE proteins. Their multi-step mode of mechanism can be ascribed to their multi-domain three-dimensional structure. The C-terminal H(CC)-domain interacts subsequently with complex polysialo-gangliosides such as GT1b and a synaptic vesicle protein receptor via two neighbouring binding sites, resulting in highly specific uptake of the neurotoxins at synapses of cholinergic motoneurons. After its translocation the enzymatically active light chain specifically hydrolyses specific SNARE proteins, preventing SNARE complex assembly and thereby blocking exocytosis of neurotransmitter.


Direct measurement of light and heavy antibody chains using ion mobility and middle-down mass spectrometry.
The analysis of monoclonal antibodies (mAbs) by a middle-down mass spectrometry (MS) approach is a growing field that attracts the attention of many researchers and biopharmaceutical companies. Usually, liquid fractionation techniques are used to separate mAbs polypeptides chains before MS analysis. Gas-phase fractionation techniques such as high-field asymmetric waveform ion mobility spectrometry (FAIMS) can replace liquid-based separations and reduce both analysis time and cost. Here, we present a rapid FAIMS tandem MS method capable of characterizing the polypeptide sequence of mAbs light and heavy chains in an unprecedented, easy, and fast fashion. This new method uses commercially available instruments and takes ~24 min, which is 40-60% faster than regular liquid chromatography-MS/MS analysis, to acquire fragmentation data using different dissociation methods.


The prevalence of non-carious cervical lesions (NCCLs) with or without erosive etiological factors among adults of different ages in Tokyo.
To evaluate the prevalence of non-carious cervical lesions (NCCLs) on teeth with or without erosive etiological factors across a broad range of ages of Japanese adults. The study sample consisted of a total of 1108 subjects aged 15 to 89 years in Tokyo, Japan. Two examiners evaluated NCCLs and dental erosion (DE) during a full-mouth examination. Subjects were asked to complete a self-administered daily diet, habits, and health condition questionnaire. Subjects who had frequent acid consumption or gastric reflux and at least one tooth with initial enamel wear were placed in the erosion present (EP) group, and the remainder of subjects were placed in the erosion not present (EN) group. Logistic regression analyses were carried out to identify etiological factors of NCCLs associated with DE. Overall prevalence of NCCLs was 60.2%; the prevalence increased with age. There were no statistical differences in the prevalence of NCCLs between the EP and EN groups, except for the 60-69 years group. Multiple logistic regression analysis showed the frequency of consumption of carbonated soft drinks, citrus juice, and acidic fruits such as oranges; tooth brushing pressure; and bruxism were associated with the presence of NCCLs. There were no statistical differences in the prevalence of NCCLs with or without erosive etiological factors except for the 60-69 years group. NCCL distribution increased with age, and erosive risk factors caused by change in dietary habits might affect the incidence of NCCLs for elders. UMIN000041982.


Exploring parent-reported barriers to supporting their child's health behaviors: a cross-sectional study.
Parents can influence the health behaviors of their children by engaging in supportive behaviors (e.g., playing outside with their child, limiting recreational screen time). How, and the extent to which parents engage in supportive behaviors may be influenced by perceived barriers. The purpose of this study is to explore whether the frequency, and types, of barriers to providing parental support are dependent on the type of child health behavior being supported (i.e., physical activity, recreational screen time reduction, healthy eating, and sleep). Study participants were 1140 Ontario parents with at least one child under the age of 18 who completed a Computer Assisted Telephone Interview (CATI) survey about parental support behaviors. Open-ended responses about perceived barriers to parental support were coded, and aggregated to meta-categories adopted from the social-ecological model (i.e., individual child, individual parent, interpersonal, environmental). Freidman rank sum tests were used to assess differences across child behaviors. Wilcoxon rank sum tests with Bonferroni adjustments were used as a post hoc test for significant Freidman results. There were more barriers reported for supporting physical activity than for any other child behavior (ps < .01, As ≥ .53). Parents reported more parent level and environmental level barriers to supporting child physical activity versus other behaviors (ps < .001, As ≥ .55), child level barriers were more frequently reported for supporting healthy eating and sleep (ps < .001, As ≥ .57), and interpersonal barriers were more frequently reported for supporting recreational screen time reduction (ps < .001, As ≥ .52). Overall, parents reported more child and parent level barriers versus interpersonal and environmental barriers to supporting child health. Parents experience a variety of barriers to supporting their children's health behaviors. Differences in types of barriers across child health behaviors emerged; however, some frequently reported barriers (e.g., child preferences) were common across behaviors. Interventions promoting parental support should consider strategies that can accommodate parents' busy schedules, and relate to activities that children find enjoyable. Creating supportive environments that help facilitate support behaviors, while minimizing parent level barriers, may be of particular benefit. Future research should explore the impact of barriers on parental support behaviors, and effective strategies for overcoming common barriers.


Ribose-5-phosphate isomerase and ribulose-5-phosphate kinase show apparent specificity for a specific ribulose 5-phosphate species.
Ribose-5-phosphate isomerase and ribulose-5-phosphate kinase appear to show specificity for a particular ribulose 5-phosphate species. The effect of this specificity will be channeling of ribulose 5-phosphate from the isomerase to the kinase during photosynthesis.


COVID-19 indoor exposure levels: An analysis of foot traffic scenarios within an academic building.
Minimizing all aspects of COVID-19 exposure is a high priority as universities prepare to reopen. One of those aspects includes developing protocols for interior spaces such as academic buildings. This paper applies mathematical modeling to investigate different virus exposure levels due to traffic patterns within academic buildings. The assumption used are: 1) Risk of infection is a product of exposure rate and time and 2) the exposure rate decreases with distance. One-way vs. two-way pedestrian traffic scenarios within hallways were modeled and analyzed for various configurations. The underlying assumption that a small exposure to a large number of people is similar to a large exposure to a few people is the driver to minimize exposures levels in all aspects. The analysis indicates that minimizing the time spent in passing between classes is the driving factor in minimizing risk, and one-way traffic may increase the time required to pass between classes. While the case presented is limited, the modeled approaches are intended to provoke future research that can be extended and applied to larger populations to help provide decision makers with more rigorous tools to shape future policies regarding traffic flow within buildings.


Investigation of the optimal culture time for warmed bovine ovarian tissues before transplantation†.
Ovarian tissue cryopreservation by vitrification is an effective technique, but there are still many unresolved issues related to the procedure. The aim of this study was to investigate the optimal culture time of postwarmed ovarian tissues and their viability before ovarian tissue transplantation. The bovine ovarian tissues were used to evaluate the effect of postwarming culture periods (0, 0.25, 0.5, 1, 2, 5, and 24 h) in the levels of residual cryoprotectant, LDH release, ROS generation, gene and protein abundance, and follicle viability and its mitochondrial membrane potential. Residual cryoprotectant concentration decreased significantly after 1 h of culture. The warmed ovarian tissues that underwent between 0 and 2 h of culture time showed similar LDH and ROS levels compared with fresh nonfrozen tissues. The anti-Mullerian hormone transcript abundance did not differ in any of the groups. No increase in the relative transcript abundance and protein level of Caspase 3 and Cleaved-Caspase 3, respectively, in the first 2 h of culture after warming. On the other hand, an increased protein level of double stranded DNA breaks (gamma-H2AX) was observed in postwarmed tissues disregarding the length of culture time, and a temporary reduction in pan-AKT was detected in postwarming tissues between 0 and 0.25 h of culture time. Prolonged culture time lowered the percentage of viable follicles in warmed tissues, but it did not seem to affect the follicular mitochondrial membrane potential. In conclusion, 1-2 h of culture time would be optimal for vitrified-warmed tissues before transplantation.


Clinical Profile and Treatment Outcome of Aluminum Phosphide Poisoning in Felege Hiwot Referral Hospital, Northwest Ethiopia: A Retrospective Study.
Aluminum phosphide (AlP) is an effective fumigant and rodenticide which is a commonly used agent for self-poisoning in parts of Ethiopia. AlP poisoning results in serious manifestations involving many vital organs and it has high mortality. Despite its high incidence and mortality, studies on AlP poisoning in Ethiopia are lacking. Our objective was to study the clinical profile and treatment outcome of AlP poisoning in Felege Hiwot Referral Hospital (FHRH), a major referral hospital in Ethiopia. It is a retrospective study conducted over all consecutive AlP poisoning cases who presented to the emergency department (ED) of the hospital from March 2018 to August 2020. A questionnaire was used to collect data from patient medical records. All data were analyzed using SPSS 25. A total of 125 patients were studied. Females were 57.6% and males were 42.4%. Age of patients ranged from 12 to 60 with mean age 28.5 years. The average number of AlP tablets taken was 1.2 (3.6 gm) and the average time of arrival to hospital after AlP ingestion was 4.8 hours. Nausea and vomiting were the commonest presenting features seen in 74.4% of the cases followed by hypotension which was seen in half of the cases. A wide range of laboratory findings and complications were also observed. Cases of AlP poisoning with hypotension were managed in the ICU with dopamine infusion, magnesium sulphate, hydrocortisone, and calcium gluconate in addition to gastric lavage and fluid administration. Those cases without hypotension were managed with gastric lavage and maintenance fluid only. Overall mortality from AlP poisoning was 31.2%. With a treatment protocol used in FHRH, mortality from AlP poisoning was 31.2%. Using this protocol in resource limited settings might give opportunities to reduce mortality from AlP poisoning.


Diffusion tensor imaging of normal-appearing cervical spinal cords in patients with multiple sclerosis: Correlations with clinical evaluation and cerebral diffusion tensor imaging changes. Preliminary experience.
Several studies have identified changes in the spinal cord DTI measurements in patients with multiple sclerosis (MS). However, correlations between changes in DTI parameters in normal appearing cervical spine and neurological findings have not been clearly established. To determine whether diffusion tensor imaging (DTI) measurements such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC) are sufficiently sensitive in detecting microstructure alterations in normal-appearing spinal cords in patients with MS and whether they reflect these patients' clinical disability. Fifteen patients diagnosed with relapsing-remitting MS (RRMS) with normal-appearing cervical spinal cords on plain MRI and 11 asymptomatic volunteers were enrolled in the study. Overall, 75 cervical spinal segments were analyzed. The regions of interest were drawn from the entire spinal cord cross-section and in the normal-appearing white matter tracts: the superior and inferior cerebellar peduncles and the posterior limbs of the internal capsules. Neurological deficit and the level of disability were evaluated using the Expanded Disability Status Scale (EDSS), the timed 25-foot walk test (T25FW) and the 9-hole peg test (9HPT) for manual dexterity. A significant difference (p < 0.05) in FA values between patients with MS and the control group was found at levels C2 (p = 0.047) and C3 (p = 0.023). No significant changes in ADC values were found. There was correlation between FA and ADC values in selected white matter tracts and at particular spinal cord levels. We also observed significant correlations between diffusion tensor imaging parameters and manual dexterity. Our preliminary results may suggest that the spinal cord's structural loss is the dominant factor in the inflammatory/demyelinating component in patients with MS. Diffusion tensor imaging changes in the spinal cord correlate with brain DTI changes. Manual functioning seems to be more affected than walking.


Test positivity - Evaluation of a new metric to assess epidemic dispersal mediated by non-symptomatic cases.
Epidemic control may be hampered when the percentage of asymptomatic cases is high. Seeking remedies for this problem, test positivity was explored between the first 60 to 90 epidemic days in six countries that reported their first COVID-19 case between February and March 2020: Argentina, Bolivia, Chile, Cuba, Mexico, and Uruguay. Test positivity (TP) is the percentage of test-positive individuals reported on a given day out of all individuals tested the same day. To generate both country-specific and multi-country information, this study was implemented in two stages. First, the epidemiologic data of the country infected last (Uruguay) were analyzed. If at least one TP-related analysis yielded a statistically significant relationship, later assessments would investigate the six countries. The Uruguayan data indicated (i) a positive correlation between daily TP and daily new cases (r = 0.75); (ii) a negative correlation between TP and the number of tests conducted per million inhabitants (TPMI, r = -0.66); and (iii) three temporal stages, which differed from one another in both TP and TPMI medians (p < 0.01) and, together, revealed a negative relationship between TPMI and TP. No significant relationship was found between TP and the number of active or recovered patients. The six countries showed a positive correlation between TP and the number of deaths/million inhabitants (DMI, r = 0.65, p < 0.01). With one exception -a country where isolation was not pursued-, all countries showed a negative correlation between TP and TPMI (r = 0.74). The temporal analysis of country-specific policies revealed four patterns, characterized by: (1) low TPMI and high DMI, (2) high TPMI and low DMI; (3) an intermediate pattern, and (4) high TPMI and high DMI. Findings support the hypothesis that test positivity may guide epidemiologic policy-making, provided that policy-related factors are considered and high-resolution geographical data are utilized.


Considerations for Pooled Testing of Employees for SARS-CoV-2.
To identify important background information on pooled tested of employees that employers workers, and health authorities should consider. This paper is a commentary based on the review by the authors of pertinent literature generally from preprints in medrixiv.org prior to August 2020. Pooled testing may be particularly useful to employers in communities with low prevalence of COVID-19. It can be used to reduce the number of tests and associated financial costs. For effective and efficient pooled testing employers should consider it as part of a broader, more comprehensive workplace COVID-19 prevention and control program. Pooled testing of asymptomatic employees can prevent transmission of SARS-CoV-2 and help assure employers and customers that employees are not infectious.


Use of smartphone application versus written titration charts for basal insulin titration in adults with type 2 diabetes and suboptimal glycaemic control (My Dose Coach): multicentre, open-label, parallel, randomised controlled trial.
The majority of people with type 2 diabetes who require insulin therapy use only basal insulin in combination with other anti-diabetic agents. We tested whether using a smartphone application to titrate insulin could improve glycaemic control in people with type 2 diabetes who use basal insulin. This was a 12-week, multicentre, open-label, parallel, randomised controlled trial conducted in 36 diabetes practices in Germany. Eligible participants had type 2 diabetes, a BMI ≥25.0 kg/m2, were on basal insulin therapy or were initiating basal insulin therapy, and had suboptimal glycaemic control (HbA1c >7.5%; 58.5 mmol/mol). Block randomisation with 1:1 allocation was performed centrally. Participants in the intervention group titrated their basal insulin dose using a smartphone application (My Dose Coach) for 12 weeks. Control group participants titrated their basal insulin dose according to a written titration chart. The primary outcome was the baseline-adjusted change in HbA1c at 12 weeks. The intention-to-treat analysis included all randomised participants. Between 13 July 2021 and 21 March 2022, 251 study participants were randomly assigned (control group: n = 123; intervention group: n = 128), and 236 completed the follow-up phase (control group: n = 119; intervention group: n = 117). Regarding the HbA1c a model-based adjusted between-group difference of -0.31% (95% CI: 0.01%-0.69%; p = 0.0388) in favour of the intervention group was observed. There were 30 adverse events reported: 16 in the control group, 14 in the intervention group. Of these, 15 adverse events were serious. No event was considered to be related to the investigational device. Study results suggest that utilizing this digital health smartphone application for basal insulin titration may have resulted in a comparatively greater reduction in HbA1c levels among individuals with type 2 diabetes, as compared to basal insulin titration guided by a written titration schedule. No negative effect on safety outcomes was observed. Sanofi-Aventis Deutschland GmbH.


The long-acting gonadotropin-releasing hormone analogues impaired the implantation rate.
To determine the efficacy and innocuousness of long-acting versus short-acting GnRH analogues (GnRH-a) in long protocol for in IVF-ET. Prospective randomized study. The IVF unit at an academic hospital. One hundred couples admitted for their first IVF-ET attempt. Serum concentrations of LH, E2, and P during the all cycles and duration of pituitary desensitization were assessed, as well as fertilization rate, embryo quality, and implantation and pregnancy rates. Significantly more days (10.8 +/- 1.8 versus 9.2 +/- 1.7 days) of stimulation and more ampules of hMG (47 +/- 22 versus 33 +/- 16) were necessary to obtain similar numbers of embryos of quality with the long-acting GnRH-a. Implantation and delivery rates were significantly lower with the long-acting GnRH-a (32.8% versus 21.1%; 48.9% versus 29.1%, respectively). As the long-acting GnRH-a might interfere with the luteal phase and embryo development, short-acting GnRH-a should be preferred for ovarian hyperstimulation in IVF-ET.


Calculated Plasma Volume Status Is Associated with Adverse Outcomes in Patients Undergoing Transcatheter Aortic Valve Implantation.
Calculated plasma volume status (PVS) reflects volume overload based on the deviation of the estimated plasma volume (ePV) from the ideal plasma volume (iPV). Calculated PVS is associated with prognosis in the context of heart failure. This single-center study investigated the prognostic impact of PVS in patients undergoing transcatheter aortic valve implantation (TAVI). A total of 859 TAVI patients had been prospectively enrolled in an observational study and were included in the analysis. An optimal cutoff for PVS of -5.4% was determined by receiver operating characteristic curve analysis. The primary endpoint was a composite of all-cause mortality or heart failure hospitalization within 1 year after TAVI. A total of 324 patients had a PVS < -5.4% (no congestion), while 535 patients showed a PVS ≥ -5.4% (congestion). The primary endpoint occurred more frequently in patients with a PVS ≥ -5.4% compared to patients with PVS < -5.4% (22.6% vs. 13.0%, p < 0.001). After multivariable adjustment, PVS was confirmed as a significant predictor of the primary endpoint (HR 1.53, 95% CI 1.05-2.22, p = 0.026). Elevated PVS, as a marker of subclinical congestion, is significantly associated with all-cause mortality and heart failure hospitalization within 1 year after TAVI.


Distinctive immunomodulating properties and interactivity with model membranes and cells of two homologous muramyl dipeptide derivatives differing by their lipophilicity.
We have studied and compared the immunomodulating activities of two muramyl dipeptide (MDP) derivatives: beta-heptylglycoside-MDP (C7H15MDP) and beta-hexadecylglycoside-MDP (C16H33MDP). The amphiphilic derivative C7H15MDP has been found to be a more effective stimulator of T lymphocyte proliferation and allospecific cytotoxic T cell generation in a mixed lymphocyte culture, and a more effective activator of interleukin-1 (IL-1) and tumour necrosis factor (TNF) production by murine peritoneal macrophages, in comparison with MDP and C16H33MDP used in equimolar concentrations. C7H15MDP also stimulated cytotoxicity of natural killer (NK) cells: On the contrary, its lipophilic homologue C16H33MDP did not show such activities in vitro except for its influence on IL-1 and TNF production. We have found significant differences in the interaction of these two 14C-labelled MDP derivatives with model membranes and in the uptake of these preparations by erythroleukemia K562 cells. We consider the hydrolipophilic balance of the above preparations to be the main cause of their different interactions with membranes and their uptake by cells and, as a result, their opposite immunomodulating activities in vitro.


Illustrate: Software for Biomolecular Illustration.
The small program Illustrate generates non-photorealistic images of biological molecules for use in dissemination, outreach, and education. The method has been used as part of the "Molecule of the Month," an ongoing educational column at the RCSB Protein Data Bank (http://rcsb.org). Insights from 20 years of application of the program are presented, and the program has been released both as open-source Fortran at GitHub and through an interactive web-based interface.


A statistical test for demonstrating a presynaptic site of action for a modulator of synaptic amplitude.
A statistical technique for demonstrating a presynaptic site of action for a modulator of synaptic amplitude was developed and tested. It requires that multiple measurements of peak synaptic amplitude be made under control and test conditions. The ratio of the coefficients of variation (CV) obtained under test and control conditions is calculated. A method was developed for determining the confidence interval for the CV ratio (CVR) statistic based on the null hypothesis that the synaptic modulation is purely postsynaptic. If the measured CVR falls outside the confidence interval, this implies that the modulator of synaptic amplitude is, at least in part, acting at a presynaptic site. The effectiveness of the technique and its limitations were investigated using Monte Carlo simulations. It was found to be sensitive and reliable under a variety of realistic recording conditions. The test was effective even in the presence of simulated presynaptic rundown of the synaptic response. Conventional deconvolution analysis was also applied to the Monte Carlo simulations and was found to be an inadequate indicator of the site of synaptic modulation when the discrete amplitude components were not well resolved. The CVR technique was applied to excitatory postsynaptic currents (epsc) recorded between pairs of cultured hippocampal neurones in control and test media containing 1 mM Ca2+ and 2 mM Ca2+, respectively. Test conditions increased the average synaptic amplitude, and the statistical analysis indicated that this modulation was produced by an action at a presynaptic site.


Induction of diabetes in rhesus monkeys and establishment of insulin administration strategy.
The diabetic rhesus monkey seems to be a useful model for preclinical investigations of islet transplantation and new drug treatments for type 1 diabetes mellitus (T1DM). Information is limited regarding a standard technique to induce and assess diabetes in rhesus monkeys as well as the strategy to apply insulin administration. Herein, we have established and characterized a model of diabetic rhesus macaques. Four monkeys were divided into 2 groups of 2 each: group 1, total pancreatectomy; and group 2, partial pancreatectomy (75%) with low-dose streptozotocin (STZ) administration. Pancreatic function was measured using intravenous glucose tolerance tests before the operation. Spiral computed tomography (CT) scans of the pancreas were obtained before and after pancreatectomy. Fasting blood glucose and postprandial blood glucose levels were monitored twice daily using blood samples from the fingers or toes. Various types and doses of insulin were administered twice daily. We performed regular assessments of hematological and serum biochemical parameters, insulin, and C-peptide. Both total pancreatectomy and partial pancreatectomy (75%) with STZ administration induced T1DM in rhesus monkeys; there was interindividual variation in the STZ dose. Excluding C-peptide and insulin, the hematological and serum biochemical parameters did not differ significantly from normal values postoperatively. The various insulin treatment strategies are achieved stable blood glucose (BG) levels. STZ injection after partial pancreatectomy may be a safe, reproducible method to induce T1DM. Porcine insulin administration was a safe, economical method to control BG levels in a diabetic rhesus monkey before islet transplantation.


Primary care physician responses to requests by older adults for unnecessary drugs: a qualitative study.
Unnecessary drug use can cause avoidable harm to older adults and is particularly common in primary care, but how primary care physicians (PCPs) respond to older adult requests for unnecessary drugs has not been well studied. This study is to explore PCPs' responses to requests for unnecessary drugs from older adults, and their influencing factors and potential solutions. This qualitative study was conducted through semi-structured, in-depth interviews from January 4 to September 30, 2020 using a grounded theory methodology. A purposive sample of PCPs affiliated with community healthcare centers in Zhejiang Province and Guangdong Province, China were recruited. The face-to-face interviews were audio-recorded, transcribed verbatim, and independently coded by two investigators. Themes surrounding PCPs' responses to requests for unnecessary drugs, their influencing factors and potential solutions were analysed using a constant comparative approach. Of the 23 participants involved in this study, 12 (52%) were women and the mean age was 35 years. PCPs frequently declined older adults' requests for unnecessary drugs through dissuasion, and occasionally rebuffed patients or referred them to another practitioner. PCPs may fulfill requests due to physician acquiescence, patient pressure, or inadequate supervision and support. Participants recommended four potential solutions to improve the quality of prescribing, including developing professional communication skills, enhancing pharmacist-physician collaboration, improving electronic prescription systems, and strengthening prescription management. PCPs typically deny requests by older adults for unnecessary drugs according to three main patterns, and guidance is necessary to reduce the potential for adverse consequences. Factors contributing to request fulfillment by PCPs require attention, and the potential solutions recommended by participants deserve consideration to improve the service quality of prescribing for older adults in primary care practices.


Engineering of Amphiphilic Erlotinib Analogue as Novel Nanomedicine for Non-Small Cell Lung Cancer Therapy.
Molecular targeted therapy is one of the most pivotal strategies in the treatment of non-small cell lung cancer, yet its curative effect is severely compromised by the poor aqueous solubility, low bioavailability and inadequate tumor accumulation of targeted agents. To enhance the efficacy of targeted agents, we demonstrate a novel self-assemble amphiphilic molecule based on erlotinib as an effective nanodrug for anti-cancer treatment. An amphiphilic molecule composed of hydrophobic erlotinib and hydrophilic biotin block was synthesized and characterized by nuclear magnetic resonance (NMR) as well as high-resolution mass spectrometry (HRMS). Then, nanoassemblies of the amphiphilic molecules are formulated by using nanoprecipitation method. Subsequently, the size, morphology, cell uptake, the anticancer activity and in vivo distribution of the newly constructed erlotinib nanodrug were systematically assessed by some methods, including transmission electron microscopy (TEM), dynamic light-scattering (DLS), flow cytometry, in vivo imaging system etc. We developed a novel nanoformulation of erlotinib, which possesses a high drug loading of 45%. With the features of well-defined structure and small size, the obtained nanodrug could be effectively accumulated in tumor sites and rapidly internalized by cancer cells. Finally, the erlotinib-based nanoformulation showed considerably better anticancer activity compared to free erlotinib both in vitro and in vivo. Moreover, the nanodrug displayed great tolerability. Combining the advantageous features of both nanotechnology and self-assemble, this novel erlotinib nanomedicine constitutes a promising therapeutic candidate for cancer treatment. This study also underlines the potential use of amphiphilic molecule for improving drug efficacy as well as reducing drug toxicity, which could become a general strategy for the preparation of nanodrugs of active agents.


The FOXO signaling axis displays conjoined functions in redox homeostasis and stemness.
Previous views of reactive oxygen species (ROS) depicted them as harmful byproducts of metabolism as uncontrolled levels of ROS can lead to DNA damage and cell death. However, recent studies have shed light into the key role of ROS in the self-renewal or differentiation of the stem cell. The interplay between ROS levels, metabolism, and the downstream redox signaling pathways influence stem cell fate. In this review we will define ROS, explain how they are generated, and how ROS signaling can influence transcription factors, first and foremost forkhead box-O transcription factors, that shape not only the cellular redox state, but also stem cell fate. Now that studies have illustrated the importance of redox homeostasis and the role of redox signaling, understanding the mechanisms behind this interplay will further shed light into stem cell biology.


Plastination of larger and massive specimens-With Silicone.
In 1977, plastination was unveiled, which replaced tissue fluid with a curable polymer. Today preservation via plastination of various animal and plant tissues, organs, and whole bodies is an extremely useful technique to display such and help educate vast arrays of both allied science students and the lay public across the planet. The diversity of applications of plastination techniques seems to be without limits. In fact, the only real limitation to plastination is one's imagination! The size of plastinates during the early years of plastination was comparatively small and dictated primarily by the size of the available plastination kettle/chamber, 35 L Heidelberg plastination kettle (49 cm H × 34.5 cm diam.). In the 1990s larger chambers were designed and slowly became available:150-210 cm (long) × 65-80 cm (wide) and 83-92 cm (high). Today a few large vacuum chambers are in service which will accommodate whole bodies of man and domestic or exotic animals. Today, at least two gigantic chambers are available to impregnate massive specimens. These are 3.5 m × 2 m × 1.5 m (Dalian) and 4 m × 3 m × 2.2 m (Guben). Also, the need for larger quantities of acetone and impregnation mix, not to mention the great increase in specimen preparation time, makes this a major investment. The "cold temperature process" is used to impregnate these massive creations. The room temperature technique could be used. The same four plastination steps are necessary for larger and massive specimens. Besides their tremendous size, the slippery silicone polymer is a reckoning force.


Sotrovimab Use in Young Pediatric Patients at High Risk of Progression to Severe COVID-19 Disease.
This retrospective analysis describes the administration of sotrovimab in 32 children (22 aged 12-16 years old; 10 aged 1-11 years old) who were at high risk of deterioration to severe COVID-19 disease. We provide dosing suggestions and demonstrate the feasibility of sotrovimab use in the younger pediatric population (<12 years old and <40 kg).


The CC-genotype of the cyclooxygenase-2 gene associates with decreased risk of nasopharyngeal carcinoma in a Tunisian population.
The cyclooxygenase-2 (cox-2) pathway is now recognized to be important in human cancer development and progression. The gene for cox-2 carries a common single nucleotide polymorphism, T8473C, located within a potential functional region in the 3'-UTR of cox-2 gene was identified. We have investigated the frequencies of cox-2 genotypes in Tunisian population to determine whether that polymorphism was associated with the risk of nasopharyngeal carcinoma (NPC) in Tunisian population. One hundred and eighty-nine NPC patients were compared to 237 healthy controls. The cox-2 T8473C polymorphism was significantly associated with NPC (P=0.031). The CC-genotype and C allele were more frequent in control compared to patients group [CC: OR=0.37; P=0.013; 95% CI: 0.17-0.81; C: OR=0.72; P=0.032; 95% CI: 0.53-0.97]. Multivariate logistic regression analyses revealed that the CC-genotype was associated with a significantly decreased risk of NPC (P=0.013). Tumor sizes, histologic grade, presence of primary lymph node metastases, age or sex were not associated with cox-2 genotypes. We conclude that the CC-genotype and C allele of cox-2 T8473C gene polymorphism are associated with decreased risk of nasopharyngeal carcinoma in a Tunisian population.


Distribution of genetic alterations in high-risk early-stage cervical cancer patients treated with postoperative radiation therapy.
Somatic genetic alteration analysis was performed for post-hysterectomy high-risk early-stage uterine cervical cancer patients who underwent post-operative radiation therapy. Post-operative radiation therapy was performed for patients with pathological features of pelvic lymph node metastasis, parametrium invasion, or positive vaginal margin, which corresponded to the post-operative high-risk category. DNA was extracted from paraffin-embedded surgical specimens, and 50 somatic hotspot genetic alternations were detected using Ion AmpliSeq Cancer Hotspot Panel. The existence of actionable mutation was assessed based on OncoKB evidence level > 3A. Between January 2008 and November 2019, 89 patients who underwent abdominal radical hysterectomy followed by post-operative radiation therapy were identified. The follow-up period for living patients was 82.3 months (range 9.3-153.9), and the 5-year relapse-free survival and overall survival rates were 72.6% and 85.9%, respectively. The most frequently detected somatic mutation was PIK3CA (26 [29.2%] patients); however, no prognostic somatic genetic alterations were identified. Actionable mutations were detected in 30 (33.7%) patients. Actionable mutations were detected in approximately one-third of patients, suggesting that precision medicine can be offered to patients with post-operative high-risk uterine cervical cancer in the near future.


Small cell carcinoma of the lung. A progress report of 15 years' experience.
To assess the results of therapeutic advances in the treatment of small cell carcinoma of the lung (SCCL) achieved during the past 15-year period at a single large institution, 508 patients treated between 1968 and 1982 were divided into two groups: 157 patients (66 in the category of limited-stage disease and 91 in the extensive-stage disease category) treated with low-dose small-volume radiotherapy (RT) (time dose fractionation [TDF] 49-66) and with cyclophosphamide alone or a COPP program during the first period of 7 years (1968-1974); 351 patients (180 in limited and 171 in extensive stage) treated with multidrug chemotherapy (CT) and high-dose large-volume RT (TDF 73-89) during the second period of 8 years (1975-1982). For patients with limited-stage cancer, 5-year actuarial survivals were 3% versus 7% for the periods 1968-1974 versus 1975-1982, respectively, P less than 0.01. For patients with extensive-stage cancer, the median survival time (MST) and 2-year actuarial survivals were 5 months and 2% versus 7 months and 4% for the periods 1968-1974 versus 1975-1982, respectively. To evaluate the outcome of a contemporary approach, i.e., CT alone, with RT reserved for locoregional failure, 180 patients with limited-stage cancer who were treated (1975-1982) were further analyzed for MST, 2- and 5-year actuarial survival figures, and local-tumor control rates according to the therapeutic approaches employed: CT + RT (112); CT alone (36); RT alone (17); and surgery (S) +/- CT +/- RT (15). Although the 36 patients in CT alone seems a small number, 17 of the 36 patients were enrolled in this approach in 1981-1982, reflecting a shift of emphasis from RT to CT. The MST and 2-year actuarial survival figures were 11 months and 0% versus 13 months and 21% for CT alone versus CT + RT respectively, P less than 0.05. CT + RT achieved a 5-year cure rate of 8%. S +/- CT +/- RT or RT alone also achieved 5-year cure rates of 8% and 10.5%, respectively, in selected subsets of patients. Local relapse rates were 80% (29/36) versus 25% (28/112) for CT alone versus CT + RT. These data emphasize the importance of thoracic RT given at the early phase of treatment to improve long-term survival for patients with limited-stage SCCL.


Ethanol increases single unit activity in the inferior olivary nucleus.
Single unit recording of rat inferior olivary nucleus neurons reveals significantly elevated discharge after acute intraperitoneal injection of 2 g/kg ethanol. This effect is consistent across 3 different methods of anesthesia and immobilization: local Xylocaine plus intraperitoneal D-tubocurare, intraperitoneal chloral hydrate and halothane vapor. In contrast, under urethane anesthesia acute ethanol produces significant depression of olivary discharge. Since this effect is opposite to that found under the other anesthetic conditions (including topical Xylocaine only), urethane anesthesia may compromise generalizations of electrophysiologic studies of ethanol. Neurons of the inferior olivary nucleus excite cerebellar Purkinje cells through a powerful afferent circuit; our data therefore suggest that ethanol-induced increases in cerebellar Purkinje cell complex (climbing fiber burst) spikes, obtained in our previous studies, are secondary to olivary activation.


Lowering the Toxicity of Cd to Theobroma cacao Using Soil Amendments Based on Commercial Charcoal and Lime.
Carbonaceous and calcareous materials are commonly used as amendments to decrease the Cd mobility in contaminated soils. This study evaluated the effect of amendments applied to cocoa seedlings in the greenhouse, considering the mobilization of soil cadmium toward the seedlings as the main response. The experimental conditions considered soil artificially contaminated with Cd at a concentration of 50 mg Cd kg-1 and applications of amendments in different treatments with the presence of charcoal dust and calcium carbonate. The charcoal was characterized by microscopy and by adsorption tests, and it proved to be a material with macropores, with a maximum capacity of 8.06 mg Cd g-1 and favorable kinetic behavior according to the adjustment of the data obtained to the pseudo-second-order model. The results also showed that the application of liming decreased the mobility of Cd toward the seedlings, with the liming combined with charcoal leading to the absence of Cd in the cocoa seedlings, considering a residual concentration of Cd in the soil of 35 mg Cd kg-1. The results, although limited to a small scale, demonstrated the possibility of applying low-cost and easy-to-handle amendments for the control of Cd in cocoa plantations.


Apoptosis of hemocytes is associated with the infection process of white spot syndrome virus in Litopenaeus vannamei.
Previous studies have demonstrated that white spot syndrome virus (WSSV) could induce hemocytes apoptosis in shrimps, however the inter-relationship between apoptotic process and the WSSV infection status is still currently underexplored. In the present work, the apoptosis and the viral proliferation in hemocytes of Litopenaeus vannamei were simultaneously investigated post WSSV infection by two-color immunofluorescence flow cytometry and real-time quantitative PCR. The apoptotic hemocytes of WSSV-infected shrimp was significantly increased at 12 h post infection (hpi), whereas underwent a slight decline at 24 hpi subsequently. Since 24 hpi, the apoptotic rate of hemocytes in the WSSV-infected shrimp exhibited a rapid and significant increase, and reached the peak level at 48 hpi with the ratio of 18.1 ± 2.0%. Meanwhile, the percentage of WSSV-infected hemocytes and WSSV copies in hemocytes significantly increased at 24 hpi and maintained at a high level afterwards. With the rapid increase of hemocytes apoptosis, hemocyte density in hemolymph decreased dramatically to less than 20% of the mean value of control. Co-localization assay showed that the apoptotic WSSV-infected hemocytes occupied the dominant proportion of total apoptotic hemocytes, which reached the peak at 48 hpi with 12.6 ± 1.5%. The expression profiles of seven pro-apoptotic genes and two apoptosis-inhibiting genes showed significant differential responses at different stages of WSSV infection, reflecting the interplay between the virus and the host immune response. Our results demonstrated that the apoptotic response of shrimp hemocytes could be significantly influenced by the WSSV infection process, which might provide an insight into deeper relationships between viral infection and apoptosis.


Experimental immune pancreatitis in the mouse by rabbit immune sera directed against purified enzymes of the exocrine pancreas.
An experimental xenogeneic immune pancreatitis was induced in AB-mice by repeated intraperitoneal injections of rabbit immune sera directed against purified pancreatic enzymes (alpha-amylase, lipase, trypsin) for 3 hours up to 8 days. Histologically, the immune pancreatitis is characterized by three different findings: 1. Multiple acinar cell necroses on the 2nd, 3rd and 5th day of immune serum application. 2. A dedifferentiating acinar cell atrophy with development of pseudocanalicular acini on the 5th and 9th day. 3. An increasing interstitial histiolymphoplasmocytic pancreatitis on the 5th and 9th experimental day. Ultrastructurally, the acinar cell necroses proved as the final stage of a step-by-step developing acute lethal cell damage. The dedifferentiating acinar cell atrophy corresponds to a chronic sublethal cell injury with alteration of different cytoplasmic components. The interstitial pancreatitis in immune serum treatment is characterized by differently activated histiocytes and lymphocytes as well as by mature plasma cells. Because of immune histological findings (peri- and intraacinar deposition of rabbit globulin, specific fixation of guinea-pig complement, and appearance of mouse globulin in the mouse exocrine pancreas) and control experiments with rabbit and mouse normal serum as well as with physiological saline, the pathogenesis of the induced xenogeneic immune pancreatitis is regarded as a twophase process: 1. The acinar cell necroses are mainly due to a cytotoxic immune reaction (possibly in combination with an immune complex reaction) caused by specific anti-pancreatic enzyme antibodies of the applied immune sera. The dedifferentiating acinar cell atrophy may be the result of a specific action of the anti-enzyme antibodies against the corresponding pancreatic enzymes in the apical secretion granules of the pancreatic acinar cells. 2. The interstitial histiolymphoplasmocytic pancreatitis is mainly the morphologic substrate of an extravascularly (intraperitoneally) induced serum sickness reaction (immune complex reaction) due to the foreign proteins applied with the xenogeneic immune sera.


Microarray expression profiling and functional characterization of AtTPS genes: duplicated Arabidopsis thaliana sesquiterpene synthase genes At4g13280 and At4g13300 encode root-specific and wound-inducible (Z)-gamma-bisabolene synthases.
The Arabidopsis thaliana genome contains at least 32 terpenoid synthase (AtTPS) genes [Aubourg et al., Mol. Genet. Genom. 267 (2002) 730] a few of which have recently been characterized. Based on hierarchical cluster analysis of AtTPS gene expression, measured by microarray profiling and validated with published expression data, we identified two groups of predominantly root expressed AtTPS genes containing five members with previously unknown biochemical functions (At4g13280, At4g13300, At5g48110, At1g33750, and At3g29410). Among the root expressed AtTPS genes, a pair of tandem-organized genes, At4g13280 (AtTPS12) and At4g13300 (AtTPS13), shares 91% predicted amino acid identity indicating recent gene duplication. Bacterial expression of cDNAs and enzyme assays showed that both At4g13280 and At4g13300 encode sesquiterpene synthases catalyzing the conversion of farnesyl diphosphate to (Z)-gamma-bisabolene and the additional minor products E-nerolidol and alpha-bisabolol. Expression of beta-glucuronidase (GUS) reporter gene fused to upstream genomic regions of At4g13280 or At4g13300 showed constitutive promoter activities in the cortex and sub-epidermal layers of Arabidopsis roots. In addition, highly localized promoter activities were found in leaf hydathodes and flower stigmata. Mechanical wounding of Arabidopsis leaves induced local expression of At4g13280 and At4g13300. The functional characterization of At4g13280 gene product AtTPS12 and At4g13230 gene product AtTPS13 as (Z)-gamma-bisabolene synthases, together with the recent characterization of two flower-specific AtTPS [At5g23960 and At5g44630; Tholl et al., Plant J. 42 (2005) 757], concludes the biochemical functional annotation of all four predicted Arabidopsis sesquiterpene synthase genes. Our data suggest biological functions for At4g13280 and At4g13300 in the rhizosphere with additional roles in aerial plant tissues.


Are you better off than you were 4 years ago? Measuring the impact of the ABS flexible endoscopy curriculum.
In 2014, the ABS introduced the Flexible Endoscopy Curriculum (FEC). The FEC did not alter the minimum defined category case volumes for endoscopy; however, it did introduce specific cognitive and technical milestones for endoscopy training. It also mandated that residents pass the Fundamentals of Endoscopic Skills (FES) exam to qualify for board certification. Although significant research has been published regarding residents' success on the FES exam, very little is known regarding how the FEC has changed the way general surgery programs train their residents in surgical endoscopy. The aim of this study was to quantify changes in flexible endoscopy education at a large academic program in the 4 years since the FEC was published. We classified the impact of FEC into four categories: (a) case volume or distribution, (b) clinical rotations, (c) required didactics or simulation exercises, and (d) FES pass rates. For category (a), we reviewed current and historical case logs for all categorical residents from 2013 to 2018. Mann-Whitney U tests were used to compare endoscopy volumes for each PGY level in 2013-2014 to the respective PGY level in 2017-2018 with p < 0.05 considered significant. For categories (b)-(d), we gathered historical records from the residency coordinator and endoscopy rotation director. Complete data were available for 57 residents in the 2013-2014 academic year and 56 residents in the 2017-2018 academic year. Median total endoscopies performed by PGY2, PGY3, and PGY5 residents all significantly increased during the FEC rollout. Our program's focus on endoscopy also expanded with absolute increases in endoscopy rotations, didactics, and simulation exercises. These changes translated into significantly increased pass rates on the FES exam from 40 to 100%. Implementation of the FEC at a large academic program led to measurable improvements in clinical experience, program structure, educational programing, and performance on high-stakes assessments.


Development and Implementation of APRN Competency Validation Tools in Four Nurse-Led Clinics in Rural East Tennessee.
Graduate nursing academic faculty rely heavily on clinical preceptors for mentorship and clinical practicum experiences for BSN-DNP degree-seeking family nurse practitioner (FNP) students. Thus, it is important that preceptors have documented clinical competencies to assure the delivery of quality, evidence-based practice that meets regulatory requirements prior to precepting students. The objectives of this quality improvement project were to develop and implement APRN competency validation tools (CVTs) in nurse-led clinic settings. Rapid Cycle Quality Improvement (RCQI) strategies were used to develop and implement APRN CVTs. Three APRN CVTs were successfully developed, tested, refined, and implemented in four nurse-led clinics in rural east Tennessee. With one exception, the APRN preceptors had documentation of clinical competency prior to approval as a SPADES preceptor. Graduate academic faculty, preceptors, and students reported satisfaction with the SPADES project. CVTs are feasible tools for documentation of validated clinical APRN preceptors' competency in nurse-led clinics. The CVTs and the medical record review checklist are available upon request from the primary author. Use of APRN CVTs provides documentation that the preceptor uses evidence-based practice in the clinic setting prior to precepting students.


Correlation of supine MRI and standing radiographs for cervical sagittal balance in myelopathy patients: a cross-sectional study.
Cervical sagittal alignment is correlated with myelopathy severity and used by spinal surgeons for surgical planification. Magnetic resonance imaging (MRI) is the gold standard for the evaluation of cervical myelopathy but may not be for the assessment of cervical sagittal balance compared to X-rays. The objective of this study was to assess the correlation of cervical alignment between supine MRI and standing radiographs in patients with cervical spondylotic myelopathy (CSM). Cobb, Jackson and Harrison methods were used to measure cervical sagittal alignment on supine MRI and standing radiographs of CSM adults. Cervical alignment was divided based on Cobb angle values on lordotic (> 4°), kyphotic (< - 4°) and rectitude (- 4° to 4°). Correlations between radiographic and MRI measurements were determined. Intra- and interobserver reliability were assessed and MRI and X-Ray-measured angles were compared. One hundred and thirty patients with CSM were reviewed. Correlations of cervical lordosis measures between radiographs and MRI were strong using the Cobb (0.65) and Jackson (0.63) methods, and moderate using the Harrison (0.37) method. Mean cervical lordosis angle was significantly lower on supine MRI compared to standing radiographs for all methods (Cobb 11.6 Rx vs. 9.2 MRI, Jackson 14.6 vs. 11.6, Harrison 23.5 vs. 19.9). Eighteen patients (15.4%) without lordosis on supine MRI presented lordosis on standing radiographs. A substantial proportion of patients has sagittal alignment discrepancies between supine MRI and standing radiographs. Therefore, standing radiographs of the cervical spine should always be included in surgical planning of CSM patients.


Are the Developmental Features of Emerging Adulthood Associated with Willingness to Engage in Consensually Nonmonogamous Relationships?
The purpose of this study was to examine whether the developmental features of emerging adulthood were associated with willingness to engage in consensually nonmonogamous (CNM) relationships. All participants (N = 792) were English speaking emerging adults (ages 18-25) residing in the USA. About half were attending college, whereas the other half had no college experience. After controlling for a number of variables (i.e., college status, sex/gender, sexual orientation, sexual identity exploration, sexual identity commitment, and casual sex attitudes), greater perceptions of emerging adulthood as a time of identity exploration and feeling in between were negatively associated with willingness to engage in CNM relationships. Also, greater perceptions of emerging adulthood as a time of experimentation/possibilities was positively associated with willingness to engage in CNM. Although our final model explained 33.5% of the variance in willingness to engage in CNM relationships, perceptions of the developmental features of emerging adulthood accounted for just 4.2% of the variance explained. Future research on CNM relationships and relationship education for emerging adults are discussed.


Transradial percutaneous coronary intervention in acute ST elevation myocardial infarction and high-risk patients: experience in a single centre without cardiothoracic surgical backup.
Primary transradial percutaneous coronary intervention (TRI) is shown to be efficacious in stable patients with acute coronary syndrome. We aimed to evaluate the application of primary TRI for acute ST elevation myocardial infarction (STEMI), including among high-risk patients from our registry. This was a single-centre case series comprising 138 patients who underwent primary TRI for STEMI between May 2007 and June 2008. TRI was attempted with a 6-Fr guiding catheter in all patients regardless of Killip class status. Outcome measures were success rates of primary TRI, door-to-balloon time, procedure duration and volume of contrast used. All patients were followed up for major adverse cardiac events in-hospital, at 30 days and six months. A total of 138 patients had primary TRI attempted for STEMI. Four patients failed primary TRI and required a femoral approach. The remaining 134 patients underwent primary TRI. The mean patient age was 56.4 years. Most patients with acute STEMI presented in Killip class I and II (91.8 percent). Only 8.2 percent were in Killip class III or IV on admission. 50 percent of patients presented with anterior STEMI. The median door-to-balloon time for this group was 92 (interquartile range [IQR] 77-121) minutes, with a median procedure time of 39 (IQR 29-51) minutes. The success rate of primary TRI was 97.1 percent. Success rate, procedural and radiation time for TRI are comparable to those achieved via the femoral approach. Primary TRI is therefore a feasible and effective approach for acute STEMI, even in high-risk patients.


Laundry wastewater and domestic sewage pilot-scale anaerobic treatment: Microbial community resilience regarding sulfide production.
In this study, the removal of anionic surfactant Linear Alkylbenzene Sulfonate (LAS) from laundry wastewater was evaluated in co-digestion with domestic sewage, using a pilot-scale Expanded Granular Sludge Bed reactor. Surfactant influent concentration was enhanced from 5 ± 3 mg LAS L-1 (stage I) to 19 ± 10 mg LAS L-1 (stage II) and 36 ± 19 mg LAS L-1 (stage III) throughout reactor operation. Sulfide levels higher than 20 mg L-1 influenced LAS removal efficiency, which decreased from 71% to 55% and 32% in stage I, II and III, respectively. Acclimation of microbial population was verified and higher relative abundance of the genera similar to Cytophaga, Bacteroides, Syntrophus and Syntrophobacter in the early stages (adaptation and stage I) was replaced by higher relative abundance of the genera Anaerophaga, Nitrosovibrio, Sulfurovum and Desulfovibrio in the last stages (stage II and III).


Perioperative amino acid supplementation of hypocaloric glucose does not impair glucose metabolism after surgery.
We tested the hypothesis that perioperative amino acid supplementation of hypocaloric dextrose would attenuate the inhibitory effect of glucose on endogenous glucose production after surgery. Sixteen patients undergoing colorectal cancer surgery were randomly assigned to receive intravenous glucose either with or without amino acids. Nutrition was administered over 48 hours from surgical skin incision until the second postoperative day. Glucose provided 50% and amino acids 20% of the patient's measured resting energy expenditure. Glucose rate of appearance was assessed by [6,6-2H2]glucose before and after surgery. Circulating concentrations of glucose, lactate, insulin, and glucagon were also determined. Hypocaloric glucose suppressed postoperative endogenous glucose production to a similar degree in both groups. The circulating concentrations of glucose increased to the same extent, whereas there was no significant change in plasma concentrations of lactate, glucagon, and cortisol. Postoperative plasma levels of insulin were significantly higher in patients receiving amino acids (P = .009). Perioperative amino acid administration does not mitigate the inhibitory effect of glucose on glucose production or aggravate hyperglycemia after colorectal surgery.


[Corticotrope].
Gene structure, transcription and processing of pro-opiomelanocortin (POMC) are described. Some of the regulatory factors for POMC gene transcription are also discussed. POMC gene consists of three exons and two relatively large introns. The exon-1 encodes 5' untranslated region and exon-2 encodes mostly signal peptide and N-terminal peptide of POMC. Exon 3 encodes all of the biologically active peptides contained in POMC. The translation product from mRNA is glycosylated and processed by peptidases to generate ACTH, beta-LPH, gamma-LPH and beta-endorphin in the anterior pituitary. However, in the neurointermediate lobe of the pituitary, ACTH is further processed to alpha-MSH and corticotropin-like intermediate peptide and beta-endorphin is processed to acetyl-beta-endorphin.


Supplemental dietary genistein improves the laying performance and antioxidant capacity of Hy-Line brown hens during the late laying period.
The present study evaluated the effects of 3 supplemental levels of dietary genistein ingested during the late laying period (66-73 wk) of laying hens. A total of 384 Hy-Line brown hens (66 wk old) were randomly divided into 4 groups (6 replicates of 16 hens in each group), the basal diet group (CON), and groups for the basal diet supplemented with 80, 120, and 400 mg/kg of genistein, G1, G2, and G3, respectively. The results of the present study showed an increased laying rate in groups G2 and G3 (linear, P < 0.01), and decreased feed-egg ratios (linear, P < 0.05) and broken egg rate (P < 0.01) in all genistein-treated groups compared with the CON group. Moreover, the G2 group showed an increase in eggshell strength and ratio (linear, P < 0.05), whereas all genistein-treated groups saw a decrease in the L* value (linear, P < 0.01) and an increase in the a* value (linear, P < 0.05) compared with the CON group. Additionally, all genistein-treated groups had an increase in the total antioxidant capacity of plasma (linear, P < 0.05), along with reduced plasma, ovarian, and yolk malondialdehyde levels (linear, P < 0.05), compared with the CON group. The G2 group had an increase in both the superoxide dismutase activity of plasma (P < 0.01) and the total antioxidant capacity of the ovaries (linear, P < 0.05), compared with the CON group. The G3 group had an increase in both the glutathione peroxidase concentration of plasma (linear, P < 0.05) and the total antioxidant capacity of the ovaries (linear, P < 0.01), compared with the CON group. The transcript levels of nuclear factor erythroid 2-related factor 2, superoxide dismutase 1, and catalase were increased in all of the genistein-treated groups (P < 0.05) compared with the CON group, whereas heme oxygenase 1 and glutamate-cysteine ligase modifier subunit were increased only in the G2 group (P < 0.05). In conclusion, supplementation with 120 mg/kg dietary genistein had the best effect on improving the laying rate, eggshell quality, and antioxidant capacity in Hy-Line brown hens during the late laying period.


Embolic Protection Devices for Saphenous Vein Graft Percutaneous Coronary Interventions.
Saphenous vein graft (SVG) percutaneous coronary interventions (PCIs) are associated with adverse clinical events caused by distal embolization in 10% to 20% of cases. Various embolic protection devices (EPDs) have been developed to lower the risk of distal embolization during SVG PCI: distal balloon occlusive devices, distal embolic filters, and proximal balloon occlusive devices. Despite evidence for improved outcomes and cost-effectiveness, rates of national EPD use remain low, the main cause of underutilization being operator preference. With increasing familiarity of operators with EPDs, their use should continue to increase in SVG PCI and lead to better outcomes.


Sequence analysis and expression of the polyhedrin gene of Choristoneura fumiferana cytoplasmic polyhedrosis virus (CfCPV).
The segmented double-stranded RNA genome of Choristoneura fumiferana cytoplasmic polyhedrosis virus (CfCPV) was extracted, polyadenylated, reverse-transcribed into cDNA and cloned. The cDNA clones that hybridized to the smallest genomic segment (segment 10) were identified, and its nucleotide sequence was determined. Genome segment 10 of CfCPV was found to be 1171 nucleotides in length with a single open reading frame in one strand capable of coding a predicted protein of 258 residues (Mr of 29,795), consistent with an apparent Mr of 30.5 kDa determined by SDS-PAGE of purified polyhedrin. Comparison of the nucleotide and amino acid sequences of the polyhedrin gene of CfCPV with those of other CPVs and with several nuclear polyhedrosis viruses revealed no particular homology. Analysis of the hydrophilic profiles and predicted secondary structures of Bombyx mori (BmCPV), Euxoa scandens (EsCPV) and CfCPV indicated the presence of seven similar regions located at the amino terminus of the polyhedrin polypeptide of the three viruses. The expression of the cloned CfCPV polyhedrin gene in Escherichia coli demonstrated that this polyhedrin has the property of self-assembly, since the production of crystal-like occlusion with a well-defined crystalline lattice structure was observed.


Nucleosome positioning and chromatin organization.
In our cells, DNA is folded and packed with the help of many proteins into chromatin whose basic unit is a nucleosome-DNA wrapped around octamer of histone proteins. The chain of nucleosomes is further folded and arranged into many layers and has a dynamic organization. How does the complex chromatin organization emerge from interactions among DNA, histones, and non-histone proteins have been a question of great interest. Here we review recent literature that investigated how nucleosome positioning and nucleosome-mediated interactions drive chromatin organization. Unlike our earlier understanding, chromatin is organized into 3D domains of various sizes having irregularly organized nucleosomes. These domains emerge due to heterogeneous nucleosome positioning and diverse inter-nucleosome interactions that vary in space and time.


Aortic valve replacement in a patient with a retrosternal gastric tube.
A 65-year-old male with a history of a total thoracic esophagectomy with a retrosternal gastric tube reconstruction required aortic valve replacement for aortic valve stenosis due to a bicuspid aortic valve. Preoperative multidetector computed tomography demonstrated that the gastric tube occupied the retrosternal space and the gastroepiploic artery was located on the left side of the gastric tube. Aortic valve replacement was performed through a median sternotomy approach. Blunt dissection on the anterior and right side of the gastric tube was performed without injury, and we could then perform cardiac surgery with the standard surgical view.


Patient-reported health minimum 8 years after operatively treated displaced sacral fractures: a prospective cohort study.
To assess long-term patient-reported health (PRH) after displaced sacral fractures, its association with clinical outcomes, and changes over time. Prospective, longitudinal single-cohort study. Level I trauma center. From 1996 to 2001, 31 consecutive patients with operatively treated displaced sacral fractures participated in a 1-year follow-up. Twenty-eight of them were available for the present long-term follow-up of mean 10.7 years (range, 8.1-13.4) postinjury. Surgical treatment with open or closed reduction and internal fixation. PRH was the main outcome, determined by the Short Form-36 (SF-36). Data were also collected on pain (using a visual analog scale), bladder function, neurologic deficits in the lower extremities, bowel function, sexual function, activities of daily living, and employment status. SF-36 scores from the present study were compared with norm-based scores for the Norwegian general population and 1-year scores. At the present follow-up, mean 10.7 years (range, 8.1-13.4) postinjury, SF-36 scores were significantly lower than norm-based scores for all domains except mental health. No significant changes were observed between 1-year scores and scores from the present study. Pain correlated significantly with poor scores in the domains physical functioning (P = 0.05), role physical (P = 0.01), bodily pain (P = 0.003), general health (P = 0.007), and role emotional (P = 0.006). Sexual dysfunction correlated with poor social functioning (P = 0.013) and poor role emotional (P = 0.04); and bowel dysfunction with bodily pain (P = 0.02) and poor role emotional (P = 0.03). No correlations were found between SF-36 scores and bladder dysfunction or neurologic deficits. Patients with displaced sacral fractures reported poor PRH, mean 10.7 years after the initial injury, with no significant improvement compared with 1-year follow-up. A significant association was found between pain and PRH. Therapeutic level IV. description of levels of evidence.


High suicide rates during psychiatric inpatient stay and shortly after discharge.
Over recent decades, intense efforts to address suicides in psychiatric admitted people have been initiated. The aim was to calculate suicide rates, rate ratios, population attributable risks (PAR) and trends among people admitted to or recently discharged from psychiatric wards. Using a cohort design, we obtained nationwide register data on 6 292 932 individuals aged 15+ living in Denmark during 1995-2016. Of these, 178 703 (5.73%) males and 201 033 females (6.33%) had been admitted to psychiatric hospital. Incidence rate ratios (IRR) were obtained using Poisson regression analyses while adjusting for age and calendar period. Trends were assessed using joinpoint analyses. In total, 15 075 persons died by suicide, of which 6174 had been psychiatrically admitted. Among males, the suicide rate during the first week of admission and after discharge was 3409 and 3148 per 100 000 person-years, respectively. The corresponding values for females were 1267 and 1631. Generally, estimated suicide rates were highest in those with affective or anxiety stress disorders. During first week of hospitalization, the IRR was 237 for males and of 322 for females when compared with those never hospitalized. In first week after discharge, the IRR was 225 and 425 for males and females, respectively. PAR estimates indicated 6% of male suicides and 13% of female suicides attributes to first week of admission and discharge. The inpatient suicide rate decreased annually 2.5% until 2009 followed by a 7.5% annual percentage increase. The suicide rate after discharge decreased steadily annually over the study period. Despite finding declining post-discharge suicide rates, the period surrounding a psychiatric admission was still associated with extremely high suicide rates.


Pseudo endophthalmitis following intravitreal triamcinolone acetonide for cystoid macular edema in a post-vitrectomised eye.
Post-operative endophthalmitis is a vision threatening complication following intraocular surgery requiring prompt treatment. Clinical picture mimicking infectious endophthalmitis can rarely be produced following intravitreal triamcinolone acetonide injection. A 65-year-old male with previous history of pars plana vitrectomy and lens removal was diagnosed with post-operative cystoid macular edema in his right eye. He received intravitreal triamcinolone acetonide injection in his right eye. Two days following the injection he complained of further reduction in vision and presented with a clinical picture resembling infectious endophthalmitis. Nil active intervention was done. There was significant improvement in vision one week following the injection. Ophthalmologists should be aware of this clinical scenario so that excessive and unwarranted treatment can be avoided.


Buckling Instabilities and Complex Trajectories in a Simple Model of Uniflagellar Bacteria.
Observations of uniflagellar bacteria show that buckling instabilities of the hook protein connecting the cell body and flagellum play a role in locomotion. To understand this phenomenon, we develop models at varying levels of description with a particular focus on the parameter dependence of the buckling instability. A key dimensionless group called the flexibility number measures the hook flexibility relative to the thrust exerted by the flagellum; this parameter and the geometric parameters of the cell determine the stability of straight swimming. Two very simple models amenable to analytical treatment are developed to examine buckling in stationary (pinned) and moving swimmers. We then consider a more detailed model incorporating a helical flagellum and the rotational degrees of freedom of the cell body and flagellum, and we use numerical simulations to map out the parameter dependence of the buckling instability. In all models, a bifurcation occurs as the flexibility number increases, separating equilibrium configurations into straight or bent, and for the full model, separating trajectories into straight or helical. More specifically for the latter, the critical flexibility marks the transition from periodicity to quasi-periodicity in the behavior of variables determining configuration. We also find that for a given body geometry, there is a specific flagellar geometry that minimizes the critical flexibility number at which buckling occurs. These results highlight the role of flexibility in the biology of real organisms and the engineering of artificial microswimmers.


Increasing treatment-seeking intentions of US veterans in the Covid-19 era: A randomized controlled trial.
Veterans have higher rates of anxiety, depression, and posttraumatic stress disorder (PTSD), and may be vulnerable to mental health consequences of the Covid-19 pandemic. More than half of veterans who meet mental illness criteria do not seek help. This study screened for clinical symptoms and evaluated the efficacy of a brief, online social-contact-based video intervention in increasing treatment-seeking intentions among veterans. We hypothesized that the video-based intervention would increase treatment-seeking intentions more than written vignette and control conditions. One hundred seventy-two veterans were randomized to either a (a) brief video-based intervention; (b) written vignette intervention, or (c) nonintervention control group. In the 3-min video, a veteran previously diagnosed with PTSD described his symptom reactivation by Covid-19, his barriers to care, and how therapy helped him to cope. Assessments were conducted at baseline, postintervention, and at 14- and 30-day follow-ups. A total of 91 (53%) veterans reported high levels of clinical symptoms, especially those self-reporting Covid-19 exposure. The brief video-based intervention yielded greater increase in treatment-seeking intentions among veterans. Within the video group, women showed an increase in treatment-seeking intentions from baseline to postintervention only, whereas men showed a more sustained effect, from baseline to Day 14. Surveyed veterans reported high symptoms levels. A brief video intervention increased treatment-seeking intention, likely through identification and emotional engagement with the video protagonist. This easily disseminable video-based intervention has the potential to increase likelihood of seeking care. Future research should examine longer term sustainability and changes in help-seeking behavior.


Herpes simplex virus type 2 among Mexican high school adolescents: prevalence and association with community characteristics.
We undertook this study to estimate the prevalence and correlates of herpes simplex virus type 2 (HSV-2) among Mexican adolescents in high school. This was a cross-sectional analysis using data that had been collected to evaluate a school-based HIV prevention intervention. As part of the final round of evaluation, capillary blood samples were taken from volunteers to test for antibodies to HSV-2. The effect of each school's seroprevalence on the probability of an individual being seropositive was estimated, and the results were grouped by town to evaluate the association between characteristics of the locality and student HSV-2 seroprevalence. Dried blood spots were collected for 80% of the 1607 participants in the survey who reported that they were sexually active. Of these samples, 21% tested positive for HSV-2 antibodies, with no significant difference in prevalence between men and women. Seroprevalence among schools ranged from 0 to 57%. The number of sex workers registered in the locality was the most important covariate of seroprevalence, with each additional female sex worker (FSW) per 1000 women between 18 and 45 years of age in the town associated with an increase of 1% in the seroprevalence of HSV-2. Characteristics of adolescents' micro-environments that influence their pool of potential sexual partners and the likelihood that these partners are HSV-2 positive may be more important predictors of the risk of STI infection than self-reported condom use.


Allergies of the dental pulp.
A review of publications relating to the allergies of the dental pulp is presented. The pulp--especially when inflamed--contains antigens, lymphocytes, plasmocytes, IgG, IgM, IgA, and IgE antibodies, mast cells, histamine, and possibly C3. However, no antibody-mediated allergy (hypersensitivity) of the pulp has yet been demonstrated. On the other hand, two types of cell-mediated allergy--the graft-rejection reaction and contact hypersensitivity--have been reported, as well as autoimmunity.


A naturally occurring conditional albino mutant in rice caused by defects in the plastid-localized OsABCI8 transporter.
A wide range of molecules are transported across membranes by the ATP binding cassette (ABC) transporters. Plants possess a collection of ABC proteins bearing similarities to the components of prokaryotic multi subunit ABC transporters, designed as ABC group I. However the functions of most of them are not well understood. Here, we characterized a naturally occurring rice mutant that exhibited albino phenotype under continuous rainy days in the field, but gradually recovered to normal green after the rainy season. Molecular and genetic analyses revealed that the phenotypes were caused by a mutation in the OsABCI8 that encoded a member of the ABCI family. Subcellular localization demonstrated that OsABCI8 is a chloroplast ABC transporter. Expression of OsABCI8 is significantly enhanced in rainy days compared to sunny days. Besides defects in chloroplast development and chlorophyll biosynthesis, the mutant phenotype is accompanied by a higher accumulation of iron, suggesting that OsABCI8 is involved in iron transportation and/or homeostasis in rice. Our results demonstrate that OsABCI8 represents a conserved ABCI protein involved in transition metals transportation and/or homeostasis and suggest an important role of the plastid-localized OsABCI8 for chloroplast development.


Clinical Significance of the Duality of Wnt/β-Catenin Signaling in Human Hepatocellular Carcinoma.
Combination therapy with immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor inhibitors has been approved as a first-line treatment for unresectable hepatocellular carcinoma (HCC), indicating a critical role of ICIs in the treatment of HCC. However, 20% of patients do not respond effectively to ICIs; mutations in the activation of the Wnt/β-catenin pathway are known to contribute to primary resistance to ICIs. From this point of view, non-invasive detection of Wnt/β-catenin activation should be informative for the management of advanced HCC. Wnt/β-catenin mutations in HCC have a dual aspect, which results in two distinct tumor phenotypes. HCC with minimal vascular invasion, metastasis, and good prognosis is named the "Jekyll phenotype", while the poorly differentiated HCC subset with frequent vascular invasion and metastasis, cancer stem cell features, and high serum Alpha fetoprotein levels, is named the "Hyde phenotype". To differentiate these two HCC phenotypes, a combination of the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging and fluoro-2-deoxy-D-glucose-PET/CT may be useful. The former is applicable for the detection of the Jekyll phenotype, as nodules present higher enhancement on the hepatobiliary phase, while the latter is likely to be informative for the detection of the Hyde phenotype by showing an increased glucose uptake.


Effect of donor embryo cell number and cell size on the efficiency of bovine embryo cloning.
To establish reliable criteria for the evaluation of nuclear donor embryos, we studied the effect of cell number and cell size of in vitro produced day 6 donor morulae on the rate of blastocyst formation following nuclear transfer to in vitro matured oocytes. In experiment 1, donor embryos were divided into three groups with low (25-34), intermediate (40-55), and high (60-81) blastomere numbers. Transfer of nuclei from day 6 morulae with intermediate and high cell numbers resulted in a significantly higher blastocyst rate (31% and 32%, respectively) than use of nuclei from day 6 morulae with low cell numbers (17%) or nuclei from day 7 morulae with 50-83 blastomeres (19%). This suggests that blastomeres from the developmentally advanced day 6 morulae are more viable than blastomeres from retarded embryos. In experiment 2, we evaluated the effect of blastomere size in day 6 donor morulae with intermediate (40-55) or high (60-81) cell numbers on the efficiency of nuclear transfer. In both classes of embryos, small blastomeres were better nuclear donors than large blastomeres. The rates of development to the blastocyst stage were 28% versus 15% (40-55 cells) and 41% versus 25% (60-81 cells), suggesting that small blastomeres include a higher proportion of totipotent cells than the polarized large blastomeres. Our results demonstrate that blastomere number and size markedly affect the efficiency of nuclear transfer and therefore are useful criteria for evaluating nuclear donor embryos. These parameters are easy to determine and may therefore be helpful to improve the efficiency of cattle cloning.


Enhancement of photocatalytic and biological activities of chitosan/activated carbon incorporated with TiO2 nanoparticles.
Novel and sustainable chitosan (CS)/activated charcoal (AC) composites were prepared by cross-linking with epichlorohydrin (ECH) to form a porous structure. Different titanium dioxide nanoparticle (TiO2 NPs) concentrations (0, 0.2, 0.4, and 0.8% w/w) were added to enhance the photocatalytic, antibacterial, larvicidal, and pupicidal activities' efficiency toward Rose Bengal (RB) dye and the Culex pipiens. The composites were characterized by FT-IR, XRD, XPS, BET and SEM. The SEM images revealed the porous structure of CS/AC and TiO2 nanoparticles were uniformly distributed in the CS/AC matrix. The degradation of RB dye was used to test the photocatalytic behavior of the composites. Supporting TiO2 on a CS/AC matrix resulted in a significant increase in photocatalytic performance. The antibacterial activities supported by CS/AC/TiO2 NPs were evaluated by bacterial growth inhibition against B. subtilis, S. aureus, E. coli, and P. aeruginosa. The results showed that CS/AC/TiO2 NPs composite has an inhibitory effect and therefore considered antibacterial agents. CS/AC/0.4%TiO2 NPs showed maximum efficacy against larvicidal activity and pupicidal of mosquito vector which recorded 99.00 ± 1.14, 95.00 ± 1.43, and 92.20 ± 2.64 for the first, second, and third larval instars and 66.00 ± 2.39 for pupal mortality, while the repellent activity reported high protection at 82.95 ± 2.99 with 3.24 mg/cm2 dose compared to control DEET.


Growth of breast cancer recurrences assessed by consecutive MRI.
Women with a personal history of breast cancer have a high risk of developing an ipsi- or contralateral recurrence. We aimed to compare the growth rate of primary breast cancer and recurrences in women who had undergone prior breast magnetic resonance imaging (MRI). Three hundred and sixty-two women were diagnosed with breast cancer and had undergone breast MRI at the time of diagnosis in our institution (2005 - 2009). Among them, 37 had at least one prior breast MRI with the lesion being visible but not diagnosed as cancer. A linear regression of tumour volume measured on MRI scans and time data was performed using a generalized logistic model to calculate growth rates. The primary objective was to compare the tumour growth rate of patients with either primary breast cancer (no history of breast cancer) or ipsi- or contralateral recurrences of breast cancer. Twenty women had no history of breast cancer and 17 patients were diagnosed as recurrences (7 and 10 were ipsi- and contralateral, respectively). The tumour growth rate was higher in contralateral recurrences than in ipsilateral recurrences (growth rate [10(-3) days(-1)] 3.56 vs 1.38, p < .001) or primary cancer (3.56 vs 2.09, p = 0.01). Differences in tumour growth were not significant for other patient-, tumour- or treatment-related characteristics. These findings suggest that contralateral breast cancer presents accelerated growth compared to ipsilateral recurrences or primary breast events.


Spinal subdural haematoma mimicking tethered cord after posterior fossa open surgery.
We report the MRI findings in a girl aged 3 years and 10 months who developed a spinal subdural haematoma after posterior fossa open surgery for cerebellar malignant rhabdoid tumour. Emergency surgery was performed immediately because of increased intracranial pressure. Control MRI 48 h after surgery showed a spinal subdural haematoma without clinical signs of paresis or bladder dysfunction. Spinal subdural haematoma is rare, and only few cases have been reported, especially in children. This report suggests that "silent" (without clinical symptoms) postoperative spinal acute subdural haemorrhage can occur after posterior fossa surgery.


Further support for the pain stages of change model: suggestions for improved measurement.
Recent efforts to operationalize persons' readiness to adopt a self-management approach to chronic pain have met with promising, but somewhat limited, results. The current study describes the development and psychometric evaluation of a German version of Pain Stages of Change Questionnaire (PSOCQ). A new item pool was developed to attempt to improve in particular the discriminant validity of the scales and in order to obtain a shortened measure. The items were administered to 494 chronic pain patients who were split into two independent samples. Item- and factor-analysis performed on data from one half of the sample resulted in four scales: precontemplation, preparation, action, and maintenance. The scales of the new measure, called the "Freiburg Questionnaire-Stages of Chronic Pain Management (FQ-STAPM)", showed good indices of reliability, homogeneity, and discriminant validity. Both the concurrent and divergent validity indices and the relationships between scale scores and pain related variables proved to be consistent with the transtheoretical model. Confirmatory factor analysis using LISREL performed on the second half of the sample supported the goodness-of-fit of the structure model. Implications of these findings for future research exploring the relevance of the pain stages of change model are discussed.


Complete brachial plexus palsy following shoulder dislocation due to sneeze: a case report.
Traumatic shoulder dislocation is a frequent condition presenting to the emergency department. Due to the anatomy of the shoulder, associated neurovascular damage is not uncommon. Although clinical intuition may suggest that a higher-energy mechanism is required to produce neurovascular sequelae, the existing literature does not support this supposition. A 55-year-old woman presented to the emergency department with a complete brachial plexus palsy from an acute anterior shoulder dislocation following a violent sneeze. The shoulder was reduced without difficulty in the emergency department within 90 min of dislocation, and the patient was discharged. Her neurologic deficits gradually improved through a program of supervised therapy and orthopedic care. Follow-up at 1 year revealed marked improvement of motor and sensory function of the affected extremity with mild residual weakness and paresthesias in the affected hand. Neurovascular injuries in the setting of shoulder dislocation may be present despite low-energy injury mechanisms.


TAK1 inhibition for treatment of cerebral ischemia.
TGFβ-activated kinase 1 (TAK1), a MAP3 kinase, is involved in at least five signaling cascades that modulate ischemic brain damage. Inhibition of TAK1 may therefore be an efficient way to interfere with multiple mechanisms in ischemic stroke. Indeed, a recent publication in Experimental Neurology confirmed that TAK1 inhibition by 5Z-7-oxozeaenol is neuroprotective. The beneficial effect of 5Z-7-oxozeaenol was associated with a reduced activation of Jun kinase that leads to inflammation and apoptosis. Recently, other TAK1 inhibitors were developed suggesting that TAK1 may prove as an efficient therapeutic target for neurodegenerative diseases if safety issues are not limiting.