The Effects of Lactobacillus farciminis and Lactobacillus rhamnosus on Growth, Blood Biochemical, and Meat Quality Indicators of Specific Pathogen-Free Broiler Chickens.
The aim of our study was to evaluate the effects of Lactobacillus farciminis and Lactobacillus rhamnosus on live weight gain, feed consumption indicators, and some metabolic blood biochemical and meat quality indicators of specific pathogen-free Ross 308 broiler chickens. We carried out the study in three trials and included a total of 780 unsexed Ross 308 chickens, which we randomly divided into two groups: the control group (Con, n = 390, basal diet) and the probiotic group (ProL, n = 390, basal diet + a powder consisting of L. farciminis and L. rhamnosus 4 g/10 kg of feed). We raised broilers until day 35. We determined the amount of feed consumed, the average daily weight gain, the feed conversion ratio, the average daily feed intake, and the cumulative feed intake once a week. We collected blood samples from 45 broilers from each group at the end of the study. In addition, we slaughtered 30 broilers from each group by cervical dislocation to obtain a breast muscle sample (without skin) to determine meat quality in these chickens (cholesterol and unsaturated, omega-3, omega-6, omega-9, and saturated fatty acids). Feeding a probiotic mixture containing L. farciminis and L. rhamnosus did not significantly affect the growth and feed intake indicators. Feeding these probiotics significantly lowered the blood serum cholesterol levels but did not provide the expected reduction in meat cholesterol levels. However, feeding a probiotic mixture increased the levels of polyunsaturated fatty acids (omega-3 and omega-6 fatty acids) in the breast meat and decreased saturated fatty acids. To better explain the effect of the combination of lactic acid bacteria (L. farciminis and L. rhamnosus) on the growth and development of broiler chickens in our study, histological and immunohistochemical examinations should be performed.


Influence of Different Dentin Substrate (Caries-Affected, Caries-Infected, Sound) on Long-Term μTBS.
The aim of this study was to evaluate the μTBS in different dentin substrates and water-storage periods. Twenty-four dentin blocks obtained from sound third molars were randomly divided into 3 groups: Sound dentin (Sd), Caries-affected dentin (Ca) and Caries-infected dentin (Ci). Dentin blocks from Ca and Ci groups were subjected to artificial caries development (S. mutans biofilm). The softest carious tissue was removed using spherical drills under visual inspection with Caries Detector solution (Ca group). It was considered as Ci (softer and deeply red stained dentin) and Ca (harder and slightly red stained dentin). The Adper Single Bond 2 adhesive system was applied and Z350 composite blocks were built in all groups. Teeth were stored in deionized water for 24 h at 37 ºC and sectioned into beams (1.0 mm2 section area). The beams from each tooth were randomly divided into three storages periods: 24 h, 6 months or 1 year. Specimens were submitted to µTBS using EZ test machine at a crosshead speed of 1.0 mm/min. Failure mode was examined by SEM. Data from µTBS were submitted to split plot two-way ANOVA and Tukey's HSD tests (a=0.05). The µTBS (MPa) of Sd (41.2) was significantly higher than Ca (32.4) and Ci (27.2), regardless of storage. Ca and Ci after 6 months and 1 year, presented similar µTBS. Mixed and adhesive failures predominated in all groups. The highest µTBS values (48.1±9.1) were found for Sd at 24 h storage. Storage of specimens decreased the µTBS values for all conditions.


The role of visceral and subcutaneous adipose tissue measurements and their ratio by magnetic resonance imaging in subjects with prediabetes, diabetes and healthy controls from a general population without cardiovascular disease.
To study the relationship of area- and volumetric-based visceral and subcutaneous adipose tissue (VAT and SAT) by MRI and their ratio in subjects with impaired glucose metabolism from the general population. Subjects from a population-based cohort with established prediabetes, diabetes and healthy controls without prior cardiovascular diseases underwent 3 T MRI. VAT and SAT were assessed as total volume and area on a single slice, and their ratio (VAT/SAT) was calculated. Clinical covariates and cardiovascular risk factors, such as hypertension and glycemic state were assessed in standardized fashion. Univariate and adjusted analyses were conducted. Among 384 subjects (age: 56.2 ± 9.2 years, 58.1% male) with complete MRI data available, volumetric and single-slice VAT, SAT and VAT/SAT ratio were strongly correlated (all >r = 0.89). Similarly, VAT/SATvolume ratio was strongly correlated with VATvolume but not with SAT (r = 0.72 and r = -0.21, respectively). Significant higher levels of VAT, SAT and VAT/SAT ratio were found in subjects with impaired glucose metabolism (all p ≤ 0.01). After adjustment for potential cardiovascular confounders, VATvolume and VAT/SATvolume ratio remained significantly higher in subjects with impaired glucose metabolism (VATvolume = 6.9 ± 2.5 l and 3.4 ± 2.3 l; VAT/SATvolume ratio = 0.82 ± 0.34 l and 0.49 ± 0.29 l in patients with diabetes and controls, respectively, all p < 0.02), whereas the association for SATvolume attenuated. Additionally, there was a decreasing effect of glycemic status on VAT/SATvolume ratio with increasing body mass index and waist circumference (p < 0.05). VATvolume and VAT/SATvolume ratio are associated with impaired glucose metabolism, independent of cardiovascular risk factors or MRI-based quantification technique, with a decreasing effect of VAT/SATvolume ratio in obese subjects. Advances in knowledge: Quantification of VATvolume and VAT/SATvolume ratio by MRI represents a reproducable biomarker associated with cardiometabolic risk factors in subjects with impaired glucose metabolism, while the association of VAT/SATvolume ratio with glycemic state is attenuated in obese subjects.


Induction of millimolar amounts of 5-phosphoribosyl-1-pyrophosphate in human erythrocytes by incubation in inosine-pyruvate-phosphate medium. A 31P-NMR study.
Incubation of human erythrocytes in inosine (10 mM), pyruvate (10 mM), phosphate (50 mM) and NaCl (75 mM) (IPP-medium)1 at pH 6.6 leads to a ca. 1000 fold increase in the concentration of 5-phosphoribosyl-1-pyrophosphate (PRPP) as identified and measured by 31P-NMR spectroscopy. PRPP accumulation is pH-dependent with a maximum at extracellular pH 6.60 and the maximum value of 1.3-1.6 mmol/l RBC is reached within one hour at 37 degrees C. PRPP accumulated despite high concentrations of 2,3-diphosphoglycerate (2,3-DPG), an inhibitor of PRPP-synthetase. The concentration of PRPP attained correlated with the intracellular concentration of inorganic phosphate (P1). Substitution of either adenosine or adenosine plus inosine for inosine in the medium (APP or A+IPP media) did not lead to NMR detectable accumulation of PRPP, despite the same high concentrations of intracellular P1. The lack of accumulation of PRPP in adenosine containing media may be related to the higher concentrations of nucleoside diphosphates induced in these media. These results show that neither 2,3-DPG nor PRPP itself inhibit the synthesis of PRPP in the human erythrocyte under these circumstances.


Treatment of diabetic kidney disease: current and future targets.
Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease in Korea and worldwide, and is a risk factor for the development of cardiovascular complications. The conventional treatments for DKD are control of blood glucose and blood pressure levels by inhibiting the renin-angiotensin system. However, the prevalence of DKD continues to increase and additional therapies are required to prevent or ameliorate the condition. Many drugs have been, or are being, developed to target the molecular mechanisms in play in DKD. This review focuses on DVD treatment, considering current and emerging therapeutic targets and the clinical trial-based evidence.


Considering suffocatory abuse and Munchausen by proxy in the evaluation of children experiencing apparent life-threatening events and sudden infant death syndrome.
This study describes 138 young children admitted to the hospital over a 23 year period for recurrent apparent life threatening events (ALTEs), unexplained deaths, or with Sudden Infant Death Syndrome (SIDS)-related diagnoses. In examining the potential for suffocatory abuse in living children, we utilized characteristics in the literature that distinguish SIDS or ALTEs due to natural disease states from abuse. Findings demonstrate a co-occurrence of risk factors that raise suspicions of suffocatory abuse or Munchausen by Proxy. Of the 35 children who died, SIDS was the presumed clinical diagnosis at the time of death in 71 % of the cases. Comprehensive chart review and autopsy findings revealed a non-SIDS diagnosis in 54% and confirmed or suspicious child abuse in 37% of these deaths. Reports to Child Protective Services were made in 6% of cases. Recommendations for assessment of children including attention to risk indicators, involvement of child protection teams, mandatory autopsies, and eath scene investigations are offered.


An Endophytic Bacterial Strain Isolated from Eucommia ulmoides Inhibits Southern Corn Leaf Blight.
Bacillus subtilis DZSY21 isolated from the leaves of Eucommia ulmoides oliv. was labeled by antibiotic marker and found to effectively colonize the leaves of maize plant. Agar diffusion assays and biocontrol effect experiments showed that strain DZSY21 and its lipopeptides had antagonistic activity against Bipolaris maydis, as well as high biocontrol effects on southern corn leaf blight caused by B. maydis. Using MALDI-TOF-MS analysis, we detected the presence of antimicrobial surfactin A, surfactin B, and fengycin in the strain DZSY21. Signaling pathways mediated by DZSY21 were analyzed by testing the expression of key plant genes involved in regulation of salicylic acid (SA) or JA/ET pathways, the defense-related genes PR1 and LOX were concurrently expressed in the leaves of DZSY21-treated plants; this corresponded to slight increase in the expression level of PDF1.2 and decreases in ERF gene transcription levels. The results indicated an induced systemic response that is dependent on the SA and jasmonic acid (JA) pathways. Thus, we hypothesized that the strain DZSY21 inhibits B. maydis by producing antifungal lipopeptides and activating an induced systemic response through SA- and JA-dependent signaling pathways. This work describes a mechanism behind reduced disease severity in plants inoculated with the endophytic bacteria DZSY21.


Beyond the PSA test: How to better stratify a patient's risk of prostate cancer.
The primary method of screening for and detecting prostate cancer is the prostate-specific antigen (PSA) test. Although this test is very prostate-specific, it is not cancer-specific; conditions other than prostate cancer can cause an elevated PSA. Many efforts have been made to discover more specific tests and methods beyond the PSA. This article describes several literature-supported tests and methods to better stratify a man's risk of having prostate cancer.


Osseous choristoma of submental region: A rare occurrence.
Osseous choristoma is a rare, benign lesion of the oral cavity. This report presents a case of osseous choristoma in the submental region of a 30-year-old female subject. Her chief complaint was a painless swelling in the submental region. Panoramic radiography showed a well-defined, round, radiopaque lesion near the inferior border of the left mental region. The lesion was diagnosed as an osseous choristoma based on the histopathological examination of the surgical specimen. This paper is an attempt to bring forward a unique occurrence of osseous choristoma, which would further help the medical fraternity in improvising their knowledge, diagnosis, and treatment of this entity.


Clinical value of components of the plasminogen activation system in ovarian cyst fluid.
The aim of this study was to analyze the concentrations of different components of the plasminogen activation system in cyst fluid from malignant, borderline and benign ovarian tumors and to compare these results with clinicopathological characteristics (FIGO staging, histological grading, residual tumor, ascites, tumor recurrence and disease-free survival). One hundred and seven cyst fluid samples were enrolled from 25 malignant, 12 borderline and 70 benign ovarian tumors. Determination of uPA, tPA, PAI-1, PAI-2, uPA:PAI-1 complex and tPA:PAI-1 complex was performed by specific double determinant ELISAs based on the concept described previously by Grebenschikov et al. With these ELISAs both complexes of the activators (uPA, tPA) with their inhibitor (PAI-1) can be measured as a separate component. Significant differences were found in median cyst fluid concentrations of uPA, PAI-1, uPA:PAI-1 and tPA:PAI-1 from malignant, borderline and benign ovarian tumors, with the highest levels in malignant ovarian tumors. Cystic endometriosis seems to be a special entity within the benign subclass. To achieve better discrimination between malignant and benign cases we introduced a new malignancy index: ([uPA:PAI-1]+[tPA:PAI-1])x [PAI-1]. The area under a Receiver Operating Characteristic (ROC) curve amounted to 0.80. Significantly higher concentrations were found in FIGO stages II-III-IV compared with stage I for uPA (p<0.05), tPA (p<0.05), uPA:PAI-1 (p<0.01) and tPA:PAI-1 (p<0.05). Concentrations of plasminogen activation system markers in cyst fluid from ovarian tumors are related to histological subtype. The most significant components are uPA, PAI-1 and the complexes uPA:PAI-1, tPA:PAI-1. The prognostic value of the components seems to be limited but might be important in detecting high-risk borderline or low stage patients.


Micelle formulation of hexadecyloxypropyl-cidofovir (HDP-CDV) as an intravitreal long-lasting delivery system.
There still is an unmet need for a safe and sustained intravitreal drug delivery system. In this study we are proposing and characterizing a micelle based, clear-media intravitreal drug delivery system using the lipid derivatized nucleoside analog, hexadecyloxypropyl-cidofovir (HDP-CDV, CMX 001). HDP-CDV forms micelles in water and in vitreous supernatant with the critical micelle concentration of 19 μg/mL and 9 μg/mL, respectively at 37 °C. The formed micelles had the average size of 274.7 nm and the Zeta potential of -47.1 mV. Drug release study in the excised rabbit vitreous showed a sustained release profile with a half-life of 2.7 days. The micelle formulation of HDP-CDV demonstrated a good safety profile in two animal species (rabbit and guinea pig) following intravitreal injection. The sustained efficacy was tested in a pretreatment study design and the drug potency was tested in an ongoing herpes simplex virus (HSV-1) retinitis model. The pretreatment studies using single intravitreal injection and later HSV-1 infection revealed at least 9 weeks of vitreous presence and therapeutic level of HDP-CDV, with 71% eyes protection from infection. The treatment study demonstrated that intravitreal administration halted active HSV-1 retinitis in 80% of the infected eyes while cidofovir (CDV) treatment failed to suppress active HSV-1 retinitis. In summary, lipid derivatized nucleoside analogs can be formulated as a micelle intravitreal injection and provides a sustained drug release in vitreous for chronic retinal diseases.


Thoracic aortic plaque enhances hypercoagulability in patients with nonrheumatic atrial fibrillation.
Patients with atrial fibrillation (AF) are at risk for thromboembolism, and coexistent cardiovascular diseases could affect their prothrombotic profiles. The relationship between plasma hemostatic markers and aortic atherosclerosis was determined in patients with AF or in sinus rhythm (SR). Sixty patients with nonrheumatic AF and 46 patients in SR who underwent transesophageal echocardiography and did not receive anticoagulant therapy constituted the study group. Markers for platelet activity (platelet factor 4 and beta-thromboglobulin), thrombotic status (thrombin-antithrombin III complex and prothrombin fragment 1+2 (F1+2)) and fibrinolytic status (plasmin-alpha2-plasmin inhibitor complex (PIC) and D-dimer) were determined. Levels of F1+2, PIC and D-dimer were higher in AF patients with severe atheroma than in those without severe atheroma (p<0.05). In patients in SR, hemostatic markers were not significantly increased even if they had severe aortic atherosclerosis. AF (Odds ratio (OR) 4.06, p=0.04) and age>or=75 years (OR 3.98, p=0.02) were independently predictive of elevated D-dimer levels and severe atheroma was predictive of elevated F1+2 levels (OR 5.52, p=0.04). Elderly patients with AF and severe aortic atherosclerosis might be in a prothrombotic state, and could benefit from intensive antithrombotic therapy.


Methylation of avpr1a in the cortex of wild prairie voles: effects of CpG position and polymorphism.
DNA methylation can cause stable changes in neuronal gene expression, but we know little about its role in individual differences in the wild. In this study, we focus on the vasopressin 1a receptor (avpr1a), a gene extensively implicated in vertebrate social behaviour, and explore natural variation in DNA methylation, genetic polymorphism and neuronal gene expression among 30 wild prairie voles (Microtus ochrogaster). Examination of CpG density across 8 kb of the locus revealed two distinct CpG islands overlapping promoter and first exon, characterized by few CpG polymorphisms. We used a targeted bisulfite sequencing approach to measure DNA methylation across approximately 3 kb of avpr1a in the retrosplenial cortex, a brain region implicated in male space use and sexual fidelity. We find dramatic variation in methylation across the avrp1a locus, with pronounced diversity near the exon-intron boundary and in a genetically variable putative enhancer within the intron. Among our wild voles, differences in cortical avpr1a expression correlate with DNA methylation in this putative enhancer, but not with the methylation status of the promoter. We also find an unusually high number of polymorphic CpG sites (polyCpGs) in this focal enhancer. One polyCpG within this enhancer (polyCpG 2170) may drive variation in expression either by disrupting transcription factor binding motifs or by changing local DNA methylation and chromatin silencing. Our results contradict some assumptions made within behavioural epigenetics, but are remarkably concordant with genome-wide studies of gene regulation.


Retraction Note: Combined effect of Schroth method and Gensingen brace on Cobb's angle and pulmonary functions in adolescent idiopathic scoliosis: a prospective, single blinded randomized controlled trial.
The article "Combined effect of Schroth method and Gensingen brace on Cobb's angle and pulmonary functions in adolescent idiopathic scoliosis: a prospective, single blinded randomized controlled trial", by S.A. Moawd, G. Nambi, A.E. El-Bagalaty, S.M. Hassan, S.E.B. Elsayed, F.M. Aboelmagd, N.A. Alhwoaimel, H.A. Abdeen, published in Eur Rev Med Pharmacol Sci 2023; 27 (2): 601-610-DOI: 10.26355/eurrev_202301_31061-PMID: 36734703 has been retracted by the Editor in Chief for the following reasons: After publication, concerns were raised about the use of copyright and trademark protected terms "Gensingen Brace" and "the Schroth Method" by the authors of the paper without permission for referring to results of a study with treatment of patients with a "Gensingen Brace". The owner of the copyright expressly denies the use of his trademark for scientific statements that are neither authorized by him nor correspond to the product's characteristics and qualities of his well-known products sold under the trademark. After being informed about the copyright and trademark issue, the corresponding author has been acknowledged and affirmed that the authors were not aware of the possible copyright and trademark infringement at the time of submission. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/31061.


Treatment of inferior vena cava obstruction producing Budd-Chiari syndrome.
We treated a patient who had an inferior vena cava (IVC) obstruction associated with Budd-Chiari syndrome. All of the right, middle, and left hepatic veins were completely obstructed. The IVC was obstructed by a membranous substance and thrombus at the hepatic portion and was completely occluded by a fibrous septum at the site of a suprahepatic coarctation. A cavotomy was performed transversely at the suprahepatic level and then longitudinally to the level just above the renal veins, and the obstructing tissue was removed. An additional vertical incision was made in the IVC over the coarctation, and an autologous pericardial patch was sutured in place to widen the IVC. The patient was discharged with the patency of the IVC restored.


The citrate cleavage pathway and lipogenesis in rat adipose tissue: replenishment of oxaloacetate.
Fatty acid synthesis via the citrate cleavage pathway requires the continual replenishment of oxaloacetate within the mitochondria, probably by carboxylation of pyruvate. Malic enzyme, although present in adipose tissue, is completely localized in the cytoplasm and has insufficient activity to support lipogenesis. Pyruvate carboxylase was found to be active in both the mitochondria and cytoplasm of epididymal adipose tissue cells; it was dependent on both ATP and biotin. Alteractions in dietary conditions induced no significant changes in mitochondrial pyruvate carboxylase activity, but the soluble activity was depressed in fat-fed animals. The possible importance of the soluble activity in lipogenesis lies in its participation in a soluble malate transhydrogenation cycle with NAD malate dehydrogenase and malic enzyme, whereby a continual supply of NADPH is produced. Consequently, the pyruvate carboxylase in adipose tissue both generates mitochondrial oxaloacetate for the citrate cleavage pathway and supplies soluble NADPH for the conversion of acetyl-CoA to fatty acid.


A systematic review of the economic evaluations of non-calcium-containing phosphate binders, sevelamer and Lanthanum, in end-stage renal disease patients with hyperphosphatemia.
End-stage renal disease is associated with significant comorbidity and mortality. Among its implications, hyperphosphatemia constitutes a consistent and independent risk factor. The use of benchmark treatment, low-cost calcium-based binders declined due to a potential calcification effect on coronary arteries. Given the increasing prevalence of end-stage renal disease and the high cost of hyperphosphatemia's new primary modality, the non-calcium based phosphate binders, we set-off to systematically assess the economic evaluations of non-calcium containing phosphate binders, sevelamer and lanthanum. The study was performed based on a systematic review of the economic evaluations of sevelamer and lanthanum. The cost-effectiveness profile of the two non-calcium-containing Phosphate Binders compared to calcium-based phosphate binders depends on several factors such as future dialysis costs, utility values, age, survival, and phosphorus levels. The comparison between the two agents is rather inconclusive; nevertheless, current review suggests that non-calcium-based phosphate binders may yield a positive cost-effectiveness ratio in patients with inadequate phosphorus management and patient with longer life-expectancy. It is crucial that the literature is endowed with more data, specifically on survival, future dialysis costs, and calcification.


"The effectiveness of rapid antigen test-based for SARS-CoV-2 detection in nursing homes in Valencia, Spain".
The usefulness of the PANBIO ™ COVID-19 Ag rapid test for SARS-CoV-2 infection detection has not been widely studied, especially in specific population groups such as the elderly who are institutionalized. Rapid diagnostic tests have the potential to benefit testing strategies, as they have short turnaround times, they are cheap, simple to perform and can be used in decentralized testing. The objective of this study is to show the performance of the PANBIO™ COVID-19 Ag Rapid test device conducted at geriatric institutions and to compare results to those obtained from RT-PCR. A total of 448 individuals were enrolled in the study, including both residents and employees. Nasopharyngeal swabs were collected for both PANBIO™ COVID-19 Ag Rapid test and RT-PCR testing. All the samples were analyzed by specialized microbiologists. A total of 117 out of 448 individuals (26%) tested positive by RT-PCR, of whom 99 (85%) returned positive Antigen test results. There were 18 Antigen negative cases with positive RT-PCR results. Accordingly, concordance between RT-PCR and Antigen test results was acceptable (K index, 0.89; 95% IC 0.8455-0.9345). Overall sensitivity and specificity of Antigen test was 85% and 100%, respectively. When defining RT-PCR CT positivity on a cut-off value of 35, LFA sensitivity was 90%. In case a cut-off value of 30 was used, LFA would increase up to 99%. In this real-life evaluation of the PANBIO™ COVID-Ag rapid test, the assay reliably identified SARS-CoV-2 infected individuals with low CT-values by RT-PCR. False negative results were observed only at high CT-values, meaning low viral loads in nasopharyngeal samples.


Histographic DNA pattern as an aid for diagnosis and therapy of minimal invasive endometrial cancer.
The atypical adenomatous hyperplasia of the endometrium may be considered as carcinoma in situ. The histologic diagnosis from curettings of passages to minimal invasive or occult carcinomas of the corpus uteri may be difficult. Also the determination of DNA in the cell nuclei and its histographic evaluation do not permit to differentiate between atypical hyperplasias and invasive adenocarcinomas. Only the early or minimal invasive carcinoma shows a higher rate of proliferation, assuming a stepwise development of carcinoma in which phases of activity and retirement are changing. In these cases the DNA photometry may support the histologic diagnosis of invasive growth and facilitate the choice of therapy.


Frontal lobe hypoperfusion and depressive symptoms in Alzheimer disease.
Depressive symptoms of varying severity are prevalent in up to 63% of Alzheimer disease (AD) patients and often result in greater cognitive decline and increased caregiver burden. The current study aimed to determine the neural correlates of depressive symptoms in a sample of AD patients. Using the Cornell Scale for Depression in Dementia, we assessed 56 patients who met criteria for probable AD. Data obtained from Technetium-99m ethyl cysteinate dimer single photon emission computed tomography (SPECT) were analyzed with the use of a magnetic resonance imaging-derived region of interest (ROI) anatomic template before and after atrophy correction and statistical parametric mapping (SPM). The following 4 frontal ROIs were investigated bilaterally: middle frontal gyrus (Brodmann's area [BA] 46), orbitofrontal cortex (BA 11), superior prefrontal (BA 8/9) and anterior cingulate (BA 24/25/32/33). Depressive symptoms were present in 27 of the AD patients (48%). Patients with depressive symptoms showed less perfusion in the right superior and bilateral middle frontal gyri (p < 0.005), left superior frontal (p < 0.05) and anterior cingulate gyri (p < 0.005) before atrophy correction. SPM analyses revealed significantly lower perfusion in bilateral dorsolateral and superior prefrontal cortex of patients with depressive symptoms (right, p < 0.005; left, p < 0.05). SPECT ROI analyses with atrophy correction revealed trends similar to data without atrophy correction but did not reach statistical significance. In this study, depressive symptoms in AD patients were associated with relative hypoperfusion in the prefrontal cortex when they were compared with AD patients without depressive symptoms. These findings are consistent with previous reports in studies of primary depression suggesting that these regions are involved in affect and emotional regulation.


The effect of fluid shear and co-adsorbed proteins on the stability of immobilized fibrinogen and subsequent platelet interactions.
The conformation adopted by the plasma protein fibrinogen upon its adsorption onto synthetic surfaces has been implicated to play an important role in determining the blood compatibility of biomaterials. It has recently been shown that adsorbed fibrinogen undergoes biologically significant conformational changes with increasing residence time on the surface of selected biomaterials. The purpose of this study was to examine the effects of co-adsorbed proteins and shear forces on such time-dependent functional changes in fibrinogen adsorbed onto polyethylene (PE), polytetrafluoroethylene (PTFE), and silicone rubber (SR). Fibrinogen was adsorbed onto these materials for 1 min and then allowed to 'reside' on these surfaces for up to 2 h prior to assessing its biological activity. Changes in fibrinogen reactivity were determined by measuring the adhesion of 51Cr-labeled platelets and the ability of blood plasma to displace previously adsorbed fibrinogen. The magnitude of platelet adhesion to substrates adsorbed with pure fibrinogen increased in the presence of shear, compared with static conditions; at the lowest shear rate of 200 s(-1), samples exhibited a 20-fold increase in adhered platelet levels. In contrast, at a higher shear rate of 1000 s(-1), the three polymers supported minimal levels of platelet attachment. Surfaces pre-adsorbed with 10% plasma did not promote a significant increase in the number of adherent platelets with increasing shear when compared with the pure fibrinogen-coated substrates. The presence of shear also significantly altered the materials' ability to retain fibrinogen. Under static conditions, the amount of fibrinogen retained following incubation in blood plasma increased on all materials with increasing fibrinogen residence time. However, the materials varied distinctly in their ability to retain adsorbed fibrinogen with increasing fibrinogen residence time, shear rate, and nature of the co-adsorbed proteins. Thus, the results from this study indicate that fluid shear, residence time of the adsorbed protein, nature of the co-adsorbed proteins, and surface chemistry of the material all play important roles in influencing platelet-surface interactions and that they act in a complex manner to influence the biocompatibility of a material.


Neck and back pain in bicycling.
Neck and back pain are among the most common overuse injuries in cyclists. Bicycle fit, improper equipment, training errors, and individual anatomic factors are important evaluation considerations. By learning how to recognize and treat contributing factors, as well as learning a few simple bike-fitting techniques, physicians can treat and prevent many common problems of this popular activity.


A margin-negative R0 resection accomplished with minimal postoperative complications is the surgeon's contribution to long-term survival in pancreatic cancer.
Pancreatic cancer has a poor prognosis with complete surgical resection being the only therapy to offer a realistic chance for long-term survival. The aim of this study is to identify surgery-related variables that influence long-term survival. Between 1990 and 2002, 226 consecutive patients (mean age of 64+/-11 years) had resection for pancreatic adenocarcinoma. Prognostic variables in these patients were analyzed using univariate and multivariate analysis. Two hundred four patients (90%) had pancreaticoduodenectomy, 13 patients (6%) had distal pancreatectomy, and 9 patients (4%) had a TP. Stage I disease was present in 50 (22%), stage II disease in 170 (75%), and stage III disease in 6 (3%). R0 resections were achieved in 70%. Operative morbidity was 36% and 30-day mortality was 6%. Actual 1-year, 3-year, and 5-year survival rates were 49% (n=111), 14% (n=31), and 4% (n=9). Using multivariate analysis: tumor size, tumor differentiation, obtaining an R0 resection, and lack of postoperative complications were variables associated with long-term survival. Long-term survival in patients with pancreatic cancer after resection remains poor. Achieving a margin negative resection (R0) with no postoperative complications are prognostic variables that can be affected by the surgeon.


Sperm cryopreservation of transgender individuals: trends and findings in the past decade.
Awareness and acceptance of transgenderism have increased in the last two decades. There is limited literature regarding the incidence and semen characteristics of transwomen banking spermatozoa. We sought to assess the incidence of sperm cryopreservation of transgender individuals compared with the cisgender population in the last 10 years. Semen parameters were also compared between the two groups. We performed a retrospective analysis of sperm cryopreservation performed at a single center from 2006 through 2016. Using available data on indications for banking and prior hormonal therapy status, we isolated healthy transgender and cisgender cohorts for semen parameter comparison. Linear regression was used to compare the incidence trends. Semen parameters were compared using the generalized estimating equations method. The rates of semen parameter abnormality of each group were compared using chi-square test. Semen parameter abnormalities were defined using WHO 2010 reference values. We analyzed 194 transgender samples and 2327 cisgender samples for a total of 84 unique transgender sperm bankers and 1398 unique cisgender sperm bankers. The number of transgender sperm bankers increased relative to cisgender sperm bankers from 2006 to 2016. Following exclusion of cisgender sperm bankers with health issues that might impact semen quality and transgender sperm bankers with known prior hormonal therapy, we compared the semen parameters of 141 healthy cisgender sperm bankers and 78 healthy transgender sperm bankers. The transgender sperm bankers demonstrated lower sperm concentration, total motile sperm count, and post-thaw sperm parameters. The transgender sperm bankers also demonstrated a higher incidence of oligozoospermia. This is the largest report to date on the incidence of transgender sperm cryopreservation and comparison of semen characteristics with cisgender sperm bankers. The data reveal an increased incidence of transgender sperm banking as well as poorer semen parameters of transgender individuals compared with cisgender controls.


Anthranilamide-based 2-phenylcyclopropane-1-carboxamides, 1,1'-biphenyl-4-carboxamides and 1,1'-biphenyl-2-carboxamides: Synthesis biological evaluation and mechanism of action.
Several anthranilamide-based 2-phenylcyclopropane-1-carboxamides 13a-f, 1,1'-biphenyl-4-carboxamides 14a-f and 1,1'-biphenyl-2-carboxamides 17a-f were obtained by a multistep procedure starting from the (1S,2S)-2-phenylcyclopropane-1-carbonyl chloride 11, the 1,1'-biphenyl-4-carbonyl chloride 12 or the 1,1'-biphenyl-2-carbonyl chloride 16 with the appropriate anthranilamide derivative 10a-f. Derivatives 13a-f, 14a-f and 17a-f showed antiproliferative activity against human leukemia K562 cells. Among these derivatives 13b, 14b and 17b exerted a particular cytotoxic effect on tumor cells. Derivative 17b showed a better antitumoral effect on K562 cells than 13b and 14b. Analyses performed to explore 17b mode of action revealed that it induced an arrest in G2/M phase of cell cycle which was consequent to DNA lesions as demonstrated by the increase in phospho-ATM and γH2AX, two known markers of DNA repair response system. The effect of 17b was also related to ROS generation, activation of JNK and induction of caspase-3 dependent apoptosis.


Novel cases of pediatric sudden cardiac death secondary to TRDN mutations presenting as long QT syndrome at rest and catecholaminergic polymorphic ventricular tachycardia during exercise: The TRDN arrhythmia syndrome.
TRDN mutations cause catecholaminergic polymorphic ventricular tachycardia (CPVT) but may present with abnormal electrocardiogram (ECG) findings provoking a diagnosis of long QT syndrome (LQTS). We report two novel cases of sudden cardiac death in children due to mutations of TRDN, providing further insight into this rare and aggressive inherited arrhythmia syndrome. Whole exome sequencing (WES) was performed in two unrelated children who experienced cardiac arrest during exercise and were negative for targeted testing of LQTS. WES identified a novel homozygous splice-site mutation in both patients, denoted c.22+1G>T, absent from gnomAD and suggesting a founder variant in the Iranian population. We now summarize the genetic architecture of all reported TRDN-related patients, including 27 patients from 21 families. The average age-onset was 30 months (range 1-10) for all cases. Adrenergic-mediated cardiac events were common, occurring in 23 of 27 cases (85%). LQTS was diagnosed in 10 cases (37%), CPVT in 10 (37%) cases, and in 7 cases. No phenotypic diagnosis was provided. Five cases (15%) had evidence for associated skeletal myopathy. Four missense TRDN variants (24%) were observed in diseased cases, while the remaining variants reflect putative loss-of-function (LOF) mutations. No disease phenotype was reported in 26 heterozygous carriers. In conclusion, TRDN mutations cause a rare autosomal recessive arrhythmia syndrome presenting with adrenergic-mediated arrhythmic events, but with ECG abnormalities leading to a diagnosis of LQTS in a proportion of cases. Heterozygous carriers are free of disease manifestations.


SOCS6 Promotes Mitochondrial Fission and Cardiomyocyte Apoptosis and Is Negatively Regulated by Quaking-Mediated miR-19b.
Mitochondrial dysfunction and abnormal mitochondrial fission have been implicated in the complications associated with I/R injury as cardiomyocytes are abundant in mitochondria. SOCS6 is known to participate in mitochondrial fragmentation, but its exact involvement and the pathways associated are uncertain. The expression of SOCS6 was analyzed by western blot in cardiomyocytes under a hypoxia and reoxygenation (H/R) model. A dual-luciferase reporter assay was used to confirm the direct interaction between miR-19b and the 3'-UTR of Socs6. In the present study, we found that Socs6 inhibition by RNA interference attenuated H/R-induced mitochondrial fission and apoptosis in cardiomyocytes. A luciferase assay indicated that Socs6 is a direct target of miR-19b. The overexpression of miR-19b decreased mitochondrial fission and apoptosis in vitro. Moreover, the presence of miR-19b reduced the level of SOCS6 and the injury caused by I/R in vivo. There were less apoptotic cells in the myocardium of mice injected with miR-19b. In addition, we found that the RNA-binding protein, Quaking (QK), participates in the regulation of miR-19b expression. Our results indicate that the inhibition of mitochondrial fission through downregulating Socs6 via the QK/miR-19b/Socs6 pathway attenuated the damage sustained by I/R. The QK/miR-19b/Socs6 axis plays a vital role in regulation of mitochondrial fission and cardiomyocyte apoptosis and could form the basis of future research in the development of therapies for the management of cardiac diseases.


Global prevalence and incidence of traumatic spinal cord injury.
Spinal cord injury (SCI) is a traumatic event that impacts a patient's physical, psychological, and social well-being and places substantial financial burden on health care systems. To determine the true impact of SCI, this systematic review aims to summarize literature reporting on either the incidence or prevalence of SCI. A systematic search was conducted using PubMed, MEDLINE, MEDLINE in process, EMBASE, Cochrane Controlled Trial Register, and Cochrane Database of Systematic Reviews to identify relevant literature published through June 2013. We sought studies that provided regional, provincial/state, or national data on the incidence of SCI or reported estimates of disease prevalence. The level of evidence of each study was rated using a scale that evaluated study design, methodology, sampling bias, and precision of estimates. The initial search yielded 5,874 articles, 48 of which met the inclusion criteria. Forty-four studies estimated the incidence of SCI and nine reported the prevalence, with five discussing both. Of the incidence studies, 14 provided figures at a regional, ten at a state or provincial level and 21 at a national level. The prevalence of SCI was highest in the United States of America (906 per million) and lowest in the Rhone-Alpes region, France (250 per million) and Helsinki, Finland (280 per million). With respect to states and provinces in North America, the crude annual incidence of SCI was highest in Alaska (83 per million) and Mississippi (77 per million) and lowest in Alabama (29.4 per million), despite a large percentage of violence injuries (21.2%). Annual incidences were above 50 per million in the Hualien County in Taiwan (56.1 per million), the central Portugal region (58 per million), and Olmsted County in Minnesota (54.8 per million) and were lower than 20 per million in Taipei, Taiwan (14.6 per million), the Rhone-Alpes region in France (12.7 per million), Aragon, Spain (12.1 per million), Southeast Turkey (16.9 per million), and Stockholm, Sweden (19.5 per million). The highest national incidence was 49.1 per million in New Zealand, and the lowest incidences were in Fiji (10.0 per million) and Spain (8.0 per million). The majority of studies showed a high male-to-female ratio and an age of peak incidence of younger than 30 years old. Traffic accidents were typically the most common cause of SCI, followed by falls in the elderly population. This review demonstrates that the incidence, prevalence, and causation of SCI differs between developing and developed countries and suggests that management and preventative strategies need to be tailored to regional trends. The rising aging population in westernized countries also indicates that traumatic SCI secondary to falls may become an increasing public health challenge and that incidence among the elderly may rise with increasing life expectancy.


Seroprevalence of Toxoplasma gondii among patients with schizophrenia and bipolar disorder in Upper Egypt: a comparative study with a control group.
Schizophrenia and bipolar disorder are serious neuropsychiatric disorders. Studies have found a high seroprevalence of Toxoplasma gondii in psychiatric patients. This study aimed to estimate the seroprevalence of T. gondii infection among schizophrenia and bipolar disorder patients. A case-control study was conducted in Assiut University Hospitals on 53 patients with schizophrenia, 57 patients with bipolar disorder, and 50 healthy volunteers. The psychiatric patients were recruited from the psychiatry department and the controls from their relatives. Both groups were subjected to socio-demographic assessment. Neither of them was immunodeficient nor with any other psychiatric disorders. Anti-Toxoplasma IgG antibodies were detected by indirect-ELISA to find the relationship between T. gondii infection and psychiatric disorders. Data were analysed using Chi-square test. The seropositivity rate, among patients with schizophrenia (50.9%) and patients with bipolar disorders (52.6%), was significantly higher than control group (30%) (P = 0.031 and 0.018 respectively). We found no statistically significant difference among all groups regarding environmental risk factors associated with T. gondii infection, except cat contact which was higher in schizophrenia and bipolar disorder patients (P = 0.011 and 0.007 respectively). The results of our study confirm that T. gondii infection is significantly correlated with schizophrenia and bipolar disorder and significantly associated with cat contact rather than beef consumption.


Impact of exercise on overnight glycemic control in children with type 1 diabetes mellitus.
To examine the effect of exercise on overnight hypoglycemia in children with type 1 diabetes mellitus (T1DM). At 5 clinical sites, 50 subjects with T1DM (age 11 to 17 years) were studied in a clinical research center on 2 separate days. One day included an afternoon exercise session on a treadmill. On both days, frequently sampled blood glucose levels were measured at the DirecNet central laboratory. Insulin doses were similar on both days. During exercise, plasma glucose levels fell in almost all subjects; 11 (22%) developed hypoglycemia. Mean glucose level from 10 pm to 6 am was lower on the exercise day than on the sedentary day (131 vs 154 mg/dL; P=.003). Hypoglycemia developed overnight more often on the exercise nights than on the sedentary nights (P=.009), occurring on the exercise night only in 13 (26%), on the sedentary night only in 3 (6%), on both nights in 11 (22%), and on neither night in 23 (46%). Hypoglycemia was unusual on the sedentary night if the pre-bedtime snack glucose level was>130 mg/dL. These findings indicate that overnight hypoglycemia after exercise is common in children with T1DM and support the importance of modifying diabetes management after afternoon exercise to reduce the risk of hypoglycemia.


Contribution of Ca(2+) transporters to relaxation in intact ventricular myocytes from developing rats.
The relative contributions of Ca(2+) transporters to intracellular Ca(2+) concentration ([Ca(2+)](i)) decline associated with twitch relaxation were analyzed in intact ventricular myocytes from developing and adult rats. This was accomplished by estimation of individual integrated Ca(2+) fluxes with the use of kinetic parameters calculated from [Ca(2+)](i) measurements during twitches and caffeine-evoked contractures, and from myocardial passive Ca(2+) buffering data. Our main findings were the following: 1) twitch relaxation and [Ca(2+)](i) decline were significantly slower during the first postnatal week than in adults, 2) inhibition of sarcoplasmic reticulum (SR) Ca(2+) accumulation resulted in faster [Ca(2+)](i) decline in young cells than in adult cells, 3) the contributions of the SR Ca(2+) uptake and Na(+)/Ca(2+) exchange (NCX) to twitch relaxation increased from ~75 to 92%, and decreased from 24 to 5%, respectively, from birth to adulthood, and 4) Ca(2+) transport by the sarcolemmal Ca(2+)-ATPase was apparently increased in neonates. Our data indicate that despite a marked increase in NCX contribution to cell relaxation in immature rats, the SR Ca(2+)-ATPase appears to be the predominant transporter responsible for relaxation-associated [Ca(2+)](i) decline from birth to adulthood.


Value of routine estimation of erythrocyte sedimentation rate in surgical patients.
The value of the erythrocyte sedimentation rate (ESR) as a screening test has been assessed through a retrospective analysis of 1648 surgical patients, in whom this test was not necessary for diagnosis, treatment or evaluation of risk factors. The ESR was inexplicably elevated in 42 patients (2.5%), but a marked increase was found in only very few cases, and in none had this finding been of any consequence for the admission in question. One patient had a malignant disease, which was not diagnosed during hospitalization, but the reasons for this were incorrect interpretation of relevant diagnostic procedures. We conclude that ESR can be excluded as a screening test in surgical patients, when diagnosis and therapeutic measures can be decided by history-taking and physical examination.


Melatonin Enhances the Photosynthesis and Antioxidant Enzyme Activities of Mung Bean under Drought and High-Temperature Stress Conditions.
Mung bean, a legume, is sensitive to abiotic stresses at different growth stages, and its yield potential is affected by drought and high-temperature stress at the sensitive stage. Melatonin is a multifunctional hormone that plays a vital role in plant stress defense mechanisms. This study aimed to evaluate the efficiency of melatonin under individual and combined drought and high-temperature stress in mung bean. An experiment was laid out with five treatments, including an exogenous application of 100 µM melatonin as a seed treatment, foliar spray, and a combination of both seed treatment and foliar spray, as well as absolute control (ambient condition) and control (stress without melatonin treatment). Stresses were imposed during the mung bean's reproductive stage (31-40 DAS) for ten days. Results revealed that drought and high-temperature stress significantly decreased chlorophyll index, Fv/Fm ratio, photosynthetic rate, stomatal conductance, and transpiration rate through increased reactive oxygen species (ROS) production. Foliar application of melatonin at 100 µM concentration enhanced the activity of antioxidant enzymes such as superoxide dismutase, catalase, and ascorbate peroxidase and the concentration of metabolites involved in osmoregulation and ion homeostasis; thereby, it improves physiological and yield-related traits in mung bean under individual and combined stress at the reproductive stage.


Cloning and targeted mutations of G alpha 7 and G alpha 8, two developmentally regulated G protein alpha-subunit genes in Dictyostelium.
GTP-binding protein (G protein)-mediated signal transduction pathways play essential roles during the aggregation and differentiation process of Dictyostelium. In addition to the five known G protein alpha-subunit genes, we recently identified three novel alpha-subunit genes, G alpha 6, G alpha 7, and G alpha 8, using the polymerase chain reaction technique. We present here a more complete analysis of G alpha 7 and G alpha 8. The cDNAs of these two genes were cloned, and their complete nucleotide sequences were determined. Sequence analyses indicate that G alpha 8 possesses some unusual features. It lacks the "TCATDT" motif, a sequence of amino acids highly conserved among G alpha subunits, and has an additional 50 amino acids at its C-terminus consisting of long stretches of asparagine. Moreover, G alpha 8 is unusually resistant to protease digestion, which may indicate a slow GTP hydrolysis rate. The possible functions of these alpha-subunits were assessed by generating mutants lacking G alpha 7 or G alpha 8 by gene targeting through homologous recombination and by overexpressing G alpha 7 or G alpha 8 protein. Overexpression of G alpha 7 resulted in abnormal morphogenesis starting at the slug stage, whereas analysis of the other strains failed to reveal any obvious growth or developmental defects under either normal or stressful conditions. The implications of these results are discussed.


[Principles of reasonable oral rehabilitation].
Dentistry today is becoming an amalgamation of medical science and precision technology. However, not all the techniques introduced in past years can be qualified as progress when the clinical results are closely examined. These results show that it is necessary to constantly reevaluate one's work in order to maintain a high standard of treatment. Every dental intervention should be planned in concurrence with the principles of prevention and cure, and executed with care and precision to avoid any progress or recurrence of the existing disease. Every oral rehabilitation should be effected following a strict sequence--establishment of good oral hygiene, precise diagnosis of the disease and careful study of the case, planning and coordination of the various interventions necessary, elimination of diseased tissue and restoration of the dentition in such a manner as to retain as much healthy tooth substance as possible and to avoid any over energetic--iatrogenic--elimination of tissue.


Rational design, synthesis, and biological evaluation of lactam-bridged gramicidin A analogues: discovery of a low-hemolytic antibacterial peptide.
A linear peptide, gramicidin A (GA), folds into a β(6.3) -helix, functions as an ion channel in the cell membrane, and exerts antibacterial activity. Herein we describe the rational design, synthesis, and biological evaluation of lactam-bridged GA analogues. The GA analogue with a 27-membered macrolactam was found to adopt a stable β(6.3) -helical conformation and exhibits higher ion-exchange activity than GA. Furthermore, this GA analogue retains the potent antibiotic activity of GA, but its hemolytic activity and toxicity toward mammalian cells are significantly lower than those of GA. This study thus dissociates the antibacterial and hemolytic/cytotoxic activities of GA, and charts a rational path forward for the development of new ion-channel-based antibiotics.


HIV disorders of the brain: pathology and pathogenesis.
Infection with HIV-1 has spread exponentially in recent years to reach alarming proportions. It is estimated than more than 33 million adults and 1.3 million children are infected worldwide. Approximately 16,000 new cases are diagnosed every day and almost 3 million people die every year from AIDS, making it the fourth leading cause of death in the world. Since the introduction of highly active anti-retroviral therapy (HAART) in the mid 1990s, the morbidity and mortality associated with HIV-1 infection has significantly decreased and AIDS has become a chronic disorder. However, neuropathological conditions associated with AIDS are still present in approximately 70 to 90% of patients and can be the result of HIV itself or of opportunistic infections. Here we briefly review the pathology and pathophysiology of AIDS-Encephalopathy, of some of the significant opportunistic infections affecting the brain in the context of AIDS, including Progressive Multifocal Leukoencephalopathy (PML) a demyelinating disease caused by the human neurotropic JC virus, Toxoplasmosis, Cryptococcosis and of primary CNS lymphoma, a brain malignancy frequently associated with HIV-1 infection, all of them considered AIDS defining conditions.


[Infective Endocarditis].
Infective endocarditis is a severe, mostly bacterial disease characterized by high mortality and morbidity. Both diagnosis and therapy are difficult, and mortality rates have not improved over decades. We review diagnostic and management problems, the disease's modern face in the era of widespread cardiac implants and valve interventions, and current diagnostic and therapeutic recommendations.


Spin-coated epoxy resin embedding technique enables facile SEM/FIB thickness determination of porous metal oxide ultra-thin films.
A facile nonsubjective method was designed to measure porous nonconductive iron oxide film thickness using a combination of a focused ion beam (FIB) and scanning electron microscopy. Iron oxide films are inherently nonconductive and porous, therefore the objective of this investigation was to optimize a methodology that would increase the conductivity of the film to facilitate high resolution imaging with a scanning electron microscopy and to preserve the porous nature of the film that could potentially be damaged by the energy of the FIB. Sputter coating the sample with a thin layer of iridium before creating the cross section with the FIB decreased sample charging and drifting, but differentiating the iron layer from the iridium coating with backscattered electron imaging was not definitive, making accurate assumptions of the delineation between the two metals difficult. Moreover, the porous nature of the film was lost due to beam damage following the FIB process. A thin layer plastication technique was therefore used to embed the porous film in epoxy resin that would provide support for the film during the FIB process. However, the thickness of the resin created using conventional thin layer plastication processing varied across the sample, making the measuring process only possible in areas where the resin layer was at its thinnest. Such variation required navigating the area for ideal milling areas, which increased the subjectivity of the process. We present a method to create uniform thin resin layers, of controlled thickness, that are ideal for quantifying the thickness of porous nonconductive films with FIB/scanning electron microscopy.


Serosurvey for antibodies against Salmonella species in free-ranging moose (Alces alces) from Norway.
An indirect ELISA was developed as a tool for surveillance of antibodies against Salmonella sp. in free-ranging moose (Alces alces) in Norway. Serum samples from 303 clinically healthy moose sampled between 1993-2000 were examined. Anti-Salmonella antibodies were detected in samples from 6 individuals (1.98%). This is the first evidence of Salmonella-seropositive free-ranging moose. Possible sources and transmission routes of Salmonella comprising environment, wildlife and man are discussed.


Impact on Faculty's Own Development When Assessing Student Performance.
Assessing learner performance is a primary focus within simulation-based education in order to prepare students with the knowledge and skills they will need going forward in their careers. In order to properly conduct these assessments of learner performance, faculty must be adequately trained on the scenario, expectations, assessment measures, and debriefing. During Operation Bushmaster, a five-day "deployment" for learners, faculty assess students as they rotate through different leadership roles. The faculty development includes online and in-person training that provides them with an understanding of the scenario; what learners know; the framework used at USU to guide curriculum, development, and assessment; how to assess learners; and how to provide feedback to learners. Research has examined the value of receiving assessment and feedback from a student perspective, but the impact of being the assessor and giving feedback has not been researched from the faculty point of view. The purpose of this study, therefore, was to examine the impact of assessing students in simulation scenarios on faculty's own development as an educator and leader. Through a phenomenological qualitative study, we explored participants' lived experiences as faculty at Operation Bushmaster. Eighteen faculty from a variety of medical specialties and military ranks volunteered to participate. Participants were interviewed in-person using a semi-structured interview. Analyses included individually reading through each transcript; then individually coding and taking notes of terms and phrases used by participants; codes were compiled and organized into categories, which became the themes of our study. The interviews demonstrated the following themes in which providers who serve as faculty of Operation Bushmaster believe they gain from the experience: (1) The experience helps to reground their own thinking; (2) acting as faculty during simulation-based education helps them remain up-to-date on necessary skills; and (3) working with students helps faculty continually develop as an educator and a leader. This work describes how even when faculty are brought in for learner assessment, they are taking away lessons and experiences that aid in their own development as an educator as well as a leader. Acting as an assessing faculty for students may allow faculty to reground their own thinking, remain up-to-date on necessary skills, and continually develop their skills as an educator and leader. These findings suggest that some faculty involved in simulation events may also gain knowledge, skills, and experiences that can help with their own development even when the focus is on learners.


Therapeutic effects of Hedyotis diffusa Willd in a COPD mouse model challenged with LPS and smoke.
Hedyotis diffusa Willd (HDW) is a constituent of several Chinese medicines used clinically to treat inflammatory diseases, including airway inflammation. The aim of the present study was to investigate whether HDW serves a protective role in suppressing chronic airway inflammation and its underlying mechanisms. A mouse model of chronic smoking was induced via exposure to cigarette smoke (CS) for 30 days, increasing the exposure time for up to 5 min per day and the administration of lipopolysaccharide (LPS). Mice were gavaged with HDW (50 or 100 mg/kg body weight), dexamethasone (1 mg/kg body weight) or normal saline (NS, 0.9%) 1 h prior to CS challenge. Compared with CS and LPS (SL)-induced mice, the levels of interleukin (IL)-1β, tumor necrosis factor-α and transforming growth factor-β in bronchoalveolar lavage fluid from HDW+SL mice were significantly decreased and IL-10 was markedly reduced. Histological examination of the lung tissues revealed that HDW treatment alleviates airway inflammation. In addition, the administration of HDW to human bronchial epithelial BEAS-2B cells suppressed the activity of the nuclear factor (NF)-κB signaling pathway. The results of the present study demonstrate that HDW has a therapeutic effect in COPD and the underlying mechanism may be attributed to inhibition of the NF-κB pathway.


Localized adherence by enteropathogenic Escherichia coli is an inducible phenotype associated with the expression of new outer membrane proteins.
Enteropathogenic Escherichia coli grow as discrete colonies on the mucous membranes of the small intestine. A similar pattern can be demonstrated in vitro; termed localized adherence (LA), it is characterized by the presence of circumscribed clusters of bacteria attached to the surfaces of cultured epithelial cells. The LA phenotype was studied using B171, an O111:NM enteropathogenic E. coli (EPEC) strain, and HEp-2 cell monolayers. LA could be detected 30-60 min after exposure of HEp-2 cells to B171. However, bacteria transferred from infected HEp-2 cells to fresh monolayers exhibited LA within 15 min, indicating that LA is an inducible phenotype. Induction of the LA phenotype was found to be associated with de novo protein synthesis and changes in the outer membrane proteins, including the production of a new 18.5-kD polypeptide. A partial NH2-terminal amino acid sequence of this polypeptide was obtained and showed it to be identical through residue 12 to the recently described bundle-forming pilus subunit of EPEC. Expression of the 18.5-kD polypeptide required the 57-megadalton enteropathogenic E. coli adherence plasmid previously shown to be required for the LA phenotype in vitro and full virulence in vivo. This observation, the correspondence of the 18.5-kD polypeptide to an EPEC-specific pilus protein, and the temporal correlation of its expression with the development of the LA phenotype suggest that it may contribute to the EPEC colonial mode of growth.


Estimation of stroke volume changes by ultrasonic doppler.
The purpose of this study was to conduct a controlled evaluation of the continuous-wave Doppler technique for the estimation of stroke volume changes. Six anesthetized dogs were studied. Aortic blood velocity was recorded from the suprasternal notch by a special continuous-wave Doppler unit. Cardiac output was varied by fluid infusion and exsanguination, and over 300 simultaneous records of aortic blood velocity and thermodilution cardiac output were taken. Average stroke volume and average systolic velocity integral (SVI), the area under the Doppler velocity curve were calculated. The relationship of SVI to stroke volume was evaluated for each animal using linear regression. Average results were: correlation coefficient 0.95 +/- 0.04 SD; y-intercept 0.38 +/- 0.14 cm(SD); standare error of fit 0.29 +/- 0.03 cm (SD). These data show that the systolic integral of aortic blood velocity was essentially directly proportional to stroke volume, even over a six-fold range. Thus, this technique will provide an accurate non-invasive estimate of changes in stroke volume.


Neurological findings in pediatric penetrating head injury at a university teaching hospital in Durban, South Africa: a 23-year retrospective study.
OBJECTIVES Penetrating traumatic brain injuries (TBIs) can be divided into gunshot wounds or stab wounds based on the mechanisms of injury. Pediatric penetrating TBIs are of major concern as many parental and social factors may be involved in the causation. The authors describe the penetrating cranial injuries in pediatric patient subgroups at risk and presenting to the Department of Neurosurgery at the University of KwaZulu-Natal, by assessment of the Glasgow Coma Scale (GCS) score and review of the common neurological manifestations including cranial nerve abnormalities. METHODS The authors performed a retrospective chart review of children who presented with penetrating TBIs between 1985 and 2007 at a university teaching hospital. Descriptive statistical analysis with univariate and multivariate logistic regression was used to assess the variables. RESULTS Out of 223 children aged 16 years and younger with penetrating TBIs seen during the study period, stab wounds were causal in 127 (57%) of the patients, while gunshot injuries were causal in 96 (43%). Eighty-four percent of the patients were male. Apart from abnormal GCS scores, other neurological abnormalities were noted in 109 (48.9%) of the patients, the most common being cranial nerve deficits (22.4%) and hemiparesis. There was a strong correlation between left-sided stab wounds and development of seizures. The mean age of patients with neurological abnormalities was 11.72 years whereas that of patients with no neurological abnormalities was 8.96 years. CONCLUSIONS Penetrating head injuries in children are not as uncommon as previously thought. There was no correlation between the age group of the patients and the mechanism of injury, which implies that stab or gunshot injuries could occur in any of our pediatric population with the same frequency. While gunshot injuries accounted for 56% of the patient population, stab injuries still accounted for 44%. Following penetrating head injuries, neurological abnormalities tend to occur in the older subgroup of the pediatric patients. The most common neurological abnormalities were hemiparesis followed by cranial nerve deficits. Facial nerve deficits were the most commonly seen cranial nerve abnormality. Immediate convulsions were a significant feature in patients with stab injuries to the head compared to those with gunshot injuries.


Iodide Transporters in the Endometrium: A Potential Diagnostic Marker for Women with Recurrent Pregnancy Failures.
The element iodine is an essential nutrient utilized by the thyroid glands, and deficiency of this element has been linked to reproductive failures. Iodide transporters are also present in reproductive tissues and cells of embryonic origin such as the endometrium and trophoblasts, respectively. The aim of this study is to understand if levels of iodide transporters are linked to pregnancy outcomes. RNA derived from endometrial biopsies from controls or women with recurrent reproductive failures was analyzed utilizing RT-PCR and targeted RNASeq. When compared to controls, women with 2 or more reproductive failures had a significant increase (>5 fold) in mRNA levels of the iodine transporters NIS and PENDRIN, but not thyroglobulin when probed vis RT-PCR. Targeted RNASeq analysis confirmed these findings when another group of patients were analyzed. These findings suggest possible abnormal iodine metabolism and a deficiency of iodine in endometrial tissues from some of the women with reproductive failures. We hypothesize from these findings that inorganic iodide and/or iodine is required for optimal cellular function in reproductive tissues, and that iodide transporters may potentially be used as a marker for infertility or for probing potential localized iodine deficiency that may not present in a typical thyroid panel analysis.


Removal of hepatitis B surface antigen (HBsAg) from plasma fractions.
Endogenous or deliberately added hepatitis B antigen was removed and concentrated for assay from albumin, and from coagulation factor II, VII, IX, and X concentrates as model plasma fractions. The concentrates carry considerable risk of causing hepatitis in transfused patients. The amount of antigen remaining in the fraction was estimated to be less than 1/10,000 of that detectable by the Ausria II radioimmunoassay and 1/100 of that found to be infectious when highly contaminated human sera were diluted and injected in chimpanzees. Batch fractionation methods with polyethylene glycol were used. The yield of albumin was 96 per cent and of the coagulation factors about 90 per cent.


PIP-SNP: a pipeline for processing SNP data featured as linkage disequilibrium bin mapping, genotype imputing and marker synthesizing.
Genome-wide association study data analyses often face two significant challenges: (i) high dimensionality of single-nucleotide polymorphism (SNP) genotypes and (ii) imputation of missing values. SNPs are not independent due to physical linkage and natural selection. The correlation of nearby SNPs is known as linkage disequilibrium (LD), which can be used for LD conceptual SNP bin mapping, missing genotype inferencing and SNP dimension reduction. We used a stochastic process to describe the SNP signals and proposed two types of autocorrelations to measure nearby SNPs' information redundancy. Based on the calculated autocorrelation coefficients, we constructed LD bins. We adopted a k-nearest neighbors algorithm (kNN) to impute the missing genotypes. We proposed several novel methods to find the optimal synthetic marker to represent the SNP bin. We also proposed methods to evaluate the information loss or information conservation between using the original genome-wide markers and using dimension-reduced synthetic markers. Our performance assessments on the real-life SNP data from a rice recombinant inbred line (RIL) population and a rice HapMap project show that the new methods produce satisfactory results. We implemented these functional modules in C/C++ and streamlined them into a web-based pipeline named PIP-SNP (https://bioinfo.noble.org/PIP_SNP/) for processing SNP data.


[Alcohol-induced disorders of the hematopoietic system].
Alcohol has a variety of pathologic effects on hematopoiesis. It directly damages erythroid precursors, thereby contributing to macrocytosis and the anemic state of chronic alcoholics. Megaloblastic anemia in chronic alcoholism results from a combination of nutritional deficiency and the effect of ethanol as a folate antagonist. Experimental studies suggest that alcohol may disturb hepatic folate metabolism. Ethanol induces sideroblastic anemia, perhaps by direct interference with heme synthesis. Further, chronic ingestion of alcohol can lead to various types of hemolytic anemia caused by alterations in the erythrocyte membrane lipids which occur in association with alcoholic liver disease. Alcohol directly suppresses platelet formation and decreases the platelet life span. These two mechanisms contribute to thrombocytopenia which is a common complication to chronic alcoholism. Since ethanol also interferes with platelet function, prolongation of bleeding the time is common at all stages of alcoholism. Chronic ingestion of alcohol is associated with a diminished marrow granulocyte reserve and may lead to neutrocytopenia. Ethanol-induced dysfunction of granulocytes, monocyte-macrophages and T-lymphocytes undoubtedly contributes to the predisposition to infection observed in alcoholics. In contrast to alcohol-induced changes in liver, heart and central nervous system, hematopoietic disorders are reversible after alcohol withdrawal.


A Rapid Review of Sociocultural Dimensions in Nigeria's Solid Waste Management Approach.
Against the background of an arguable dearth of scholarship on the sociocultural dimensions of Nigeria's solid waste management strategies and practices, this rapid review searched for evidence in the literature. A rapid evidence review and qualitative meta-summary procedure were implemented to utilize the rigor of systematic literature review that met the timelines and limited funding available for this study. It is more appropriate to identify, extract, and synthesize a mixture of qualitative and/or quantitative empirical evidence in the literature. This rapid review found little substantive evidence of scholarly sociocultural approaches in Nigeria's solid waste management. It also discovered constant factors of inadequate and weak multidisciplinary or non-holistic approaches to driving innovation and effective social impact in Nigeria's solid waste management practices. The results were interpreted vis-à-vis the need to leverage the social sciences, particularly the range and scope of social work practice configurations and possibilities, to scientifically advance and substantially accelerate the implementation of evidence-based policy and practice in Nigeria's solid waste management system. This rapid review concluded that the negative results are due to the insufficient conceptual and theoretical bases for Nigeria's solid waste management strategies and/or practices.


Patient Activation is Inconsistently Associated with Positive Health Behaviors Among Obese Safety Net Patients.
We examine the association of patient activation and physical activity and fruit and vegetable consumption among obese safety net patients. Adult obese patients (n = 198) of three safety net clinics completed a survey assessing patient activation, physical activity, fruit and vegetable consumption, care experiences, and health status. Multivariate logistic regression models incrementally assessed the adjusted relation of patient activation and physical activity and fruit and vegetable consumption. In adjusted analyses, higher activated patients had higher odds [Odds ratio (OR) 1.58, p < 0.01] of consuming fruits and vegetables daily than less activated patients. There was no significant association between patient activation and regular physical activity. Engaging in regular physical activity appears to be difficult, even for highly activated patients. In contrast, additional fruit and vegetable consumption is a relatively easier change. Patient activation was inconsistently associated with two positive health behaviors among obese safety net patients.


Association of methylenetetrahydrofolate reductase gene 677C>T polymorphism with hypertension in older women in a population of Buenos Aires City.
We examined the relationship between the 677C >T polymorphism in the MTHFR gene and tHcy in normotensive (NT) and hypertensive (HT) subjects and the influence of sex and age in a cross-sectional study. Smoking habits, history of vascular disease, diabetes, and tHcy were significantly associated with T allele as hypertension risk factors. The T allele was significantly related with higher tHcy in (i) men versus women (P < .01), (ii) men and women older than 47 years versus the younger ones (P < .05 and P < .001, respectively), (iii) HT women versus NT women (P < .01), and (iv) older HT women versus older NT women (P < .01). We found an association between the 677C>T MTHFR polymorphism and tHcy with hypertension that in women is manifested with age.


Mouse spermatozoa contain a nuclease that is activated by pretreatment with EGTA and subsequent calcium incubation.
We demonstrated that mouse spermatozoa cleave their DNA into approximately 50 kb loop-sized fragments with topoisomerase IIB when treated with MnCl(2) and CaCl(2) in a process we term sperm chromatin fragmentation (SCF). SCF can be reversed by EDTA. A nuclease then further degrades the DNA in a process we term sperm DNA degradation (SDD). MnCl(2) alone could elicit this activity, but CaCl(2) had no effect. Here, we demonstrate the existence of a nuclease in the vas deferens that can be activated by ethylene glycol tetraacetic acid (EGTA) to digest the sperm DNA by SDD. Spermatozoa were extracted with salt and dithiothreitol to remove protamines and then incubated with EGTA. Next, the EGTA was removed and divalent cations were added. We found that Mn(2+), Ca(2+), or Zn(2+) could each activate SDD in spermatozoa but Mg(2+) could not. When the reaction was slowed by incubation on ice, EGTA pretreatment followed by incubation in Ca(2+) elicited the reversible fragmentation of sperm DNA evident in SCF. When the reactions were then incubated at 37 degrees C they progressed to the more complete degradation of DNA by SDD. EDTA could also be used to activate the nuclease, but required a higher concentration than EGTA. This EGTA-activatable nuclease activity was found in each fraction of the vas deferens plasma: in the spermatozoa, in the surrounding fluid, and in the insoluble components in the fluid. These results suggest that this sperm nuclease is regulated by a mechanism that is sensitive to EGTA, possibly by removing inhibition of a calcium binding protein.


Synthesis of a cross-bridged cyclam derivative for peptide conjugation and 64Cu radiolabeling.
The increased use of copper radioisotopes in radiopharmaceutical applications has created a need for bifunctional chelators (BFCs) that form stable radiocopper complexes and allow covalent attachment to biological molecules. Previous studies have established that 4,11-bis-(carbo- tert-butoxymethyl)-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (H 2CB-TE2A), a member of the ethylene "cross-bridged" cyclam (CB-cyclam) class of bicyclic tetraaza macrocycles, forms highly kinetically stable complexes with Cu(II) and is less susceptible to in vivo transchelation than its nonbridged analogue, 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA). Herein, we report a convenient synthesis of a novel cross-bridged BFC that is structurally analogous to CB-TE2A in that it possesses two coordinating acetate arms, but in addition possesses a third orthogonally protected arm for conjugation to peptides and other targeting agents. Application of this strategy to cross-bridged chelators may also enable the development of even further improved agents for (64)Cu-mediated diagnostic positron emission tomography (PET) imaging as well as for targeted radiotherapeutic applications.


Rapamycin promotes the anticancer action of dihydroartemisinin in breast cancer MDA-MB-231 cells by regulating expression of Atg7 and DAPK.
There is limited knowledge regarding the influence of autophagy on the anticancer effect of dihydroartemisinin (DHA). The present study aimed to investigate this influence within human breast cancer cells. Changes in cell viability, cell cycle distribution, apoptosis and associated genes were analyzed in MDA-MB-231 cells subjected to DHA following alteration in autophagy levels; the autophagy level was decreased following autophagy-related 7 (Atg7) knockdown or increased using rapamycin. The data indicated that rapamycin had the ability to notably enhance the anticancer effect of DHA on MDA-MB-231 cells. Autophagy induction may be key in mediating the anticancer effects of DHA, and rapamycin may regulate the death-associated protein kinase via the alteration of Atg7 expression, which would influence cell apoptosis. The present study presented a novel insight into enhancing the effectiveness of future treatment regimens for breast cancer using DHA.


Prenatal exposure to morphine impairs attention and impulsivity in adult rats.
An alarming number of neonates born with prenatal exposure to morphine has resulted from the opioid epidemic; however, the long-term effects of prenatal opioid exposure on offspring behavior remain relatively unknown. In this study, we evaluated whether prenatal exposure to the mu opioid receptor agonist, morphine, has enduring effects on cognitive functions in adult life. On embryonic days 11-18 (E11-E18), female pregnant rats were injected subcutaneously with either morphine or saline twice daily. Adult male offspring that was prenatally exposed to saline or morphine was trained in the 5-choice serial reaction time test (5-CSRTT) to test their cognitive abilities under baseline conditions. Next, these rats were treated with saline (1 ml/kg), naloxone (1 mg/kg), and acute morphine (1, 3, 5 mg/kg), subcutaneously, once daily and following drug challenges rats were tested in the 5-CSRTT. Meanwhile, behavioral performance on training days between opioid drug challenges were analyzed to monitor possible drug-induced shifts in baseline performance. As a final experiment in order to investigate subchronic exposure to morphine, rats were injected with 5 mg/kg morphine for 5 days and then naloxone in the last day of the experiment (day 6). Firstly, during acquisition of a stable baseline in the training phase, rats prenatally exposed to morphine showed delayed learning of the task demands. Furthermore, under baseline responding the rats prenatally exposed to morphine showed declined inhibitory control demonstrated by increased impulsive and compulsive-like responding compared to rats prenatally exposed to saline. Moreover, acute and subchronic morphine challenges in the rats prenatally exposed to morphine caused a deficit in visuospatial attention in comparison with saline treatment as well as the rats prenatally exposed to saline. These effects were abolished by naloxone. The current findings indicate a direct causal effect of prenatal morphine exposure on inhibitory control and task learning later in life, as well as deficits in attention following morphine exposure in adulthood.


Transmission electron microscope observation of interface structures of graphene on 6H-SiC.
High-resolution transmission electron microscopic cross-sectional observations of graphene-on-SiC(0001) were carried out to directly observe the interface structure. A first principles calculation allowed us to understand the interface structures and their electronic states. Our observations revealed a metastable transitional interface structure formed by decomposition of a single SiC bilayer as well as complete honeycomb graphene formed by the decomposition of three SiC bilayers. The calculations further showed that the differences in the interface structures should strongly influence the electronic states, producing either metallic or semiconducting behavior. These results may help to resolve the controversy over the electronic states of graphene-on-SiC, and promote more accurate band-gap engineering via surface decomposition.


Early left ventricular function recovery after trap-door coronary transfer repair of ALCAPA in an adult patient.
Anomalous origin of the left coronary from the pulmonary artery (ALCAPA) is a rare congenital malformation, which may result in myocardial infarction, congestive heart failure, and sudden death if left untreated. Despite frequently advanced pathologic changes, there seems to be significant potential for the recovery of myocardial function in individuals with left ventricular dysfunction after the establishment of physiologic coronary circulation, particularly in the pediatric population. Reports of ALCAPA repair in adulthood are scarce and little information exists regarding the response of the left ventricle to revascularization in this age group. In this report, repair of ALCAPA in a significantly symptomatic adult patient with ventricular dysfunction is described, leading to an early recovery of left ventricular function.


Evaluating lanreotide as maintenance therapy after first-line treatment in patients with non-resectable duodeno-pancreatic neuroendocrine tumours.
Patients with metastatic or locally advanced, non-resectable, grade 1 or 2 well-differentiated duodeno-pancreatic (WDDP) NETs are treated following European guidelines. Patients (Pts) with aggressive disease, i.e. progressive and/or symptomatic metastases and/or with significant hepatic invasion (>30-50%), and/or bone metastases, anti-tumour therapy should receive systemic combination of chemotherapy once disease control is obtained. The aim is to stop chemotherapy until progression. REMINET is an academic randomized, double-blind, placebo-controlled, phase II/III study designed to evaluate lanreotide (LAN) as maintenance treatment after L1 chemotherapy in G1-G2 WDDP NET. Main eligibility criteria: adults pts with a metastatic (synchronous or metachronous) or locally advanced, non-resectable, grade 1 or 2 WDDP NETs and documented control disease after L1 therapy at least 4 weeks prior to randomization. 222 patients will be randomly assigned in a 1:1 ratio to receive 120mg LAN or placebo, every 28 days, until disease progression or unacceptable toxicity. The aim of the phase II part is to demonstrate a 6-months PFS >45% in LAN arm. Secondary endpoints are PFS according to central review, overall survival, safety and quality of life. A bio-bank of frozen blood will be constituted. The study is currently open in France, Germany, Belgium, United Kingdom and Ireland. A total of 25 patients are randomized (NCT02288377).


Utility of Optical Coherence Tomography for Guiding Laser Therapy Among Patients With Recurrent Respiratory Papillomatosis.
Recurrent respiratory papillomatosis (RRP) is a viral-induced disease caused by human papillomavirus and the second leading cause of dysphonia in children; however, neither a cure nor a definitive surgical treatment is currently available for RRP. Although laser therapy is often used in the treatment of RRP, the lack of real-time laser-tissue interaction feedback undermines the ability of physicians to provide treatments with low morbidity. Therefore, an intraoperative tool to monitor and control laser treatment depth is needed. To investigate the potential of combining optical coherence tomography (OCT) with laser therapy for patient-tailored laryngeal RRP treatments. This in vivo study was performed at the Massachusetts Eye and Ear Infirmary from February 1, 2017, to September 1, 2017. Three-dimensional OCT images were acquired before, during, and after photoangiolytic laser therapy in 10 pediatric patients with a history of papilloma growth who presented with lesions and hoarseness. Whether intraoperative OCT monitoring of changes in optical scattering and absorption provides quantitative information to control thermal damage in tissue. Among the 10 pediatric patients (age range, 4-11 years; 6 male) included in the study, high-resolution OCT images revealed epithelial hyperplasia with clear RRP lesion margins. Images acquired during therapy indicated coagulation deep in tissue, and posttherapy images showed the ability to quantify the amount of tissue ablated by the photoangiolytic laser. Concurrent use of OCT imaging and laser therapy may improve postoperative outcomes for patients with RRP by delivering an optimal, patient-tailored treatment. Additional studies investigating the correlation between optical properties with vocal outcomes are required.


[Cleavage activity of ribozymes on a target RNA of tobacco mosaic virus in E. coli].
A target cDNA fragment from TMV RNA was inserted to a reporter gene CAT immediately to the 3' end of the translation initiation codon ATG resulting in the formation of a chimeric CAT gene in an in vivo transcription and expression vector. The in vivo activities of various ribozymes on the target sequence were observed by determining the changes of the CAT activities of the chimeric CAT gene expressed in E. coli. The CAT activity was reduced by up to 30% when a specific ribozyme RZ1, RZ1A or RZ1B was transcribed, no change in CAT activity was observed when a non-specific ribozyme RZ3 was expressed. The protein electrophoresis and primer extension experiments indicated that this reduction in CAT activity was due to the specific cleavage of the ribozymes to the chimeric CAT mRNA at the target region hence the decrease in CAT protein synthesis.


Dietary digestible lysine requirements of male and female broilers from forty-nine to sixty-three days of age.
Experiments were conducted to evaluate digestible (dig) Lys requirements of male and female broiler chickens from 49 to 63 d of age. A dose-response diet consisting of corn, soybean meal, and corn gluten meal was formulated to be adequate in dig amino acid concentrations with the exception of Lys. L-Lysine . HCl was added to the dose-response diet to create 7 experimental diets. Concentrations of dig Lys of experimental diets ranged from 0.50 to 1.04% in increments of 0.09%. Variables measured consisted of standardized dietary Lys digestibility, feed intake, dig Lys intake, BW gain, feed conversion, mortality, abdominal fat weight and percentage, carcass weight and yield, and total breast meat weight and yield. In experiment 1, dig Lys of the dose-response diet was determined as 0.51% with cecectomized roosters. In experiment 2, dig Lys requirements of male broilers for BW gain, feed conversion, breast meat weight, and breast meat yield were 0.86, 0.88, 0.90, and 0.90%, respectively, based on 95% of the responses. From 49 to 63 d of age, male broilers optimized growth and meat yield measurements with approximately 3.0 g of dig Lys intake. In experiment 3, dig Lys requirements of female broilers were estimated as 0.79 and 0.83%, respectively, for BW gain and feed conversion. Digestible Lys intake necessary to optimize growth performance was 2.8 g/bird during 49 to 63 d of age. These results indicate that dig Lys requirements for male broilers were 0.87 and 0.90% of the diet, respectively, for growth performance and breast meat yield. Conversely, the dig dietary Lys requirement for females was 0.81% based only on growth performance.


Butterfly cartilage graft inlay tympanoplasty for large perforations.
Butterfly graft inlay tympanoplasty is a well-established technique for the repair of small perforations. However, the efficacy of the technique for medium and large tympanic membrane perforations remains unknown. Retrospective case series. Postauricular tympanoplasty and tympanomastoidectomy using a large butterfly cartilage inlay graft (>4 mm diameter to total drum replacement) were analyzed in 90 pediatric patients (99 ears). Patient ages ranged from 2 to 20 years; mean follow-up duration was 27.6 months. Successful closure occurred in 92% of the ears. No graft lateralized nor displaced into the middle ear. No retraction pocket occurred during the follow-up period. In 62 cases, intact canal wall or canal wall window tympanomastoidectomy was performed; Fifty-one (82.2%) of the patients having mastoidectomy procedures had chronic otitis media with cholesteatoma. The mean preoperative to postoperative four-tone air-bone gap improved from 23 to 21 dB; the number of patients with 0 to 10 dB hearing results increased from 16 ears preoperatively to 32 ears postoperatively. Postoperative suboptimal results included eight patients with postoperative perforations in the residual tympanic membrane adjacent to an intact cartilage graft; two of these patients were the only individuals who exhibited otorrhea. Cartilage butterfly graft inlay tympanoplasty is effective in the vast majority of patients with moderate to large perforations. The closure rate exceeded 90% with no graft displacement, postoperative adverse events were respectably low, and hearing results improved or remained stable despite the need for concurrent mastoidectomy in the majority of patients.


Risk Stratification of Advanced Fibrosis in HIV Patients With Hepatic Steatosis Using the NAFLD Fibrosis and BARD Scores.
Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent in people with HIV (PWH), yet the risk factors for disease progression are poorly understood, due to inadequate surveillance. We employed non-invasive methods to estimate the prevalence and associated factors of advanced NAFLD in PWH. We conducted a retrospective study of PWH enrolled in our clinic from 2005 to 2022. We employed imaging (ultrasound, computer tomography, magnetic resonance imaging, and transient elastography) or biopsy reports to identify cases of hepatic steatosis. We excluded patients with harmful alcohol use, hepatitis B or C infection, and other specified etiologies. We used the NAFLD Fibrosis Score (NFS), BARD Score, AST to Platelet Index (APRI), and Fibrosis-4 (FIB-4) Score to stratify fibrosis. We used logistic regression to identify predictors of advanced fibrosis. Among 3959 PWH in care, 1201 had available imaging or liver biopsies. After exclusions, 114 of the remaining 783 had evidence of hepatic steatosis (prevalence 14.6%). The majority were male (71.1%), with mean age 46.1 years, and mean body mass index (BMI) 31.4 ± 8.1 kg/m2. About 24% had lean NAFLD (BMI < 25 kg/m2). Based on the NFS, 27.2% had advanced fibrosis, which was corroborated by estimates from the other scores. In adjusted regression analysis, advanced fibrosis was associated with BMI > 35 kg/m2 (4.43, 1.27-15.48), thrombocytopenia (4.85, 1.27-18.62) and hypoalbuminemia (9.01, 2.39-33.91). We found a NAFLD prevalence of 14.6%, with 27.2% of cases having advanced fibrosis. Our study provides practical insights into the surveillance of NAFLD in PWH.


The helium paradoxes.
The ratio 3He/4He (R) plays a central role in models of mantle evolution that propose an undegassed lower mantle, rich in the primordial isotope 3He. A large primordial volatile-rich reservoir, a feature of recent models, is inconsistent with high-temperature accretion and with estimates of crustal and bulk Earth chemistry. High R can alternatively reflect high integrated 3He/(U+Th) ratios or low 4He abundances, as expected in refractory portions of the upper mantle. I show that high R materials are gas-poor and are deficient in radiogenic 4He compared with midocean ridge basalts. The seemingly primitive (i.e., high R) signatures in "hotspot" magmas may be secondary, derived from CO2-rich gases, or residual peridotite, a result of differential partitioning of U and He into magmas. A shallow and low 3He source explains the spatial variability and the temporal trends of R in ocean islands and is consistent with a volatile-poor planet. A shallow origin for the "primitive" He signature in ocean island basalts, such as at Loihi, reconciles the paradoxical juxtaposition of crustal, seawater, and atmospheric signatures with inferred "primitive" characteristics. High 238U/204Pb components in ocean island basalts are generally attributed to recycled altered oceanic crust. The low 238U/3He component may be in the associated depleted refractory mantle. High 3He/4He ratios are due to low 4He, not excess 3He, and do not imply or require a deep or primordial or undegassed reservoir. 40Ar in the atmosphere also argues against such models.


Mutation-specific hemostatic variability in mice expressing common type 2B von Willebrand disease substitutions.
Type 2B von Willebrand disease (2B VWD) results from von Willebrand factor (VWF) A1 mutations that enhance VWF-GPIbalpha binding. These "gain of function" mutations lead to an increased affinity of the mutant VWF for platelets and the binding of mutant high-molecular-weight VWF multimers to platelets in vivo, resulting in an increase in clearance of both platelets and VWF. Three common 2B VWD mutations (R1306W, V1316M, and R1341Q) were independently introduced into the mouse Vwf cDNA sequence and the expression vectors delivered to 8- to 10-week-old C57Bl6 VWF(-/-) mice, using hydrodynamic injection. The resultant phenotype was examined, and a ferric chloride-induced injury model was used to examine the thrombogenic effect of the 2B VWD variants in mice. Reconstitution of only the plasma component of VWF resulted in the generation of the 2B VWD phenotype in mice. Variable thrombocytopenia was observed in mice expressing 2B VWF, mimicking the severity seen in 2B VWD patients: mice expressing the V1316M mutation showed the most severe thrombocytopenia. Ferric chloride-induced injury to cremaster arterioles showed a marked reduction in thrombus development and platelet adhesion in the presence of circulating 2B VWF. These defects were only partially rescued by normal platelet transfusions, thus emphasizing the key role of the abnormal plasma VWF environment in 2B VWD.


Loss of Omi mitochondrial protease activity causes the neuromuscular disorder of mnd2 mutant mice.
The mouse mutant mnd2 (motor neuron degeneration 2) exhibits muscle wasting, neurodegeneration, involution of the spleen and thymus, and death by 40 days of age. Degeneration of striatal neurons, with astrogliosis and microglia activation, begins at around 3 weeks of age, and other neurons are affected at later stages. Here we have identified the mnd2 mutation as the missense mutation Ser276Cys in the protease domain of the nuclear-encoded mitochondrial serine protease Omi (also known as HtrA2 or Prss25). Protease activity of Omi is greatly reduced in tissues of mnd2 mice but is restored in mice rescued by a bacterial artificial chromosome transgene containing the wild-type Omi gene. Deletion of the PDZ domain partially restores protease activity to the inactive recombinant Omi protein carrying the Ser276Cys mutation, suggesting that the mutation impairs substrate access or binding to the active site pocket. Loss of Omi protease activity increases the susceptibility of mitochondria to induction of the permeability transition, and increases the sensitivity of mouse embryonic fibroblasts to stress-induced cell death. The neurodegeneration and juvenile lethality in mnd2 mice result from this defect in mitochondrial Omi protease.


Syringaresinol protects against hypoxia/reoxygenation-induced cardiomyocytes injury and death by destabilization of HIF-1α in a FOXO3-dependent mechanism.
Hypoxia-inducible factor 1 (HIF-1) is a master regulator of hypoxic response and has been a prime therapeutic target for ischemia/reperfusion (I/R)-derived myocardial dysfunction and tissue damage. There is also increasing evidence that HIF-1 plays a central role in regulating aging, both through interactions with key longevity factors including Sirtuins and mTOR, as well as by directly promoting longevity in Caenorhabditis elegans.We investigated a novel function and the underlying mechanism of syringaresinol, a lignan compound, in modulation of HIF-1 and protection against cellular damage and death in a cardiomyocyte model of I/R injury. Syringaresinol caused destabilization of HIF-1α following H/R and then protected against hypoxia/reoxygenation (H/R)-induced cellular damage, apoptosis, and mitochondrial dysfunction in a dose-dependent manner. Knock-down of FOXO3 by specific siRNAs completely abolished the ability of syringaresinol to inhibit HIF-1 stabilization and apoptosis caused by H/R. Syringaresinol stimulated the nuclear localization and activity of FOXO3 leading to increased expression of antioxidant genes and decreased levels of reactive oxygen species (ROS) following H/R. Our results provide a new mechanistic insight into a functional role of syringaresinol against H/R-induced cardiomyocyte injury and death. The degradation of HIF-1α through activation of FOXO3 is a potential therapeutic strategy for ischemia-related diseases.