Traumatic Ventricular Septal Defect Resulting from a Motor Vehicle Collision.
This case report describes a rare case of ventricular septal defect due to non-penetrating trauma in a 43 year old male involved in a motor vehicle collision. The diagnosis was made by echocardiogram and the patient was taken immediately to the operating room for emergent surgical repair of the ventricular septal defect and survived.


Measurement of Load Redistribution Properties of Wheelchair Cushions Using a Compliant Cushion Loading Indenter.
The aim of this project was to develop and validate a compliant cushion loading indenter (CCLI) capable of evaluating wheelchair cushion performance by measuring internal pressures and deflection. The design of the CCLI consists of 3 subsystems: 1) an internal substructure with medial and lateral protuberances to mimic the load-bearing ischial tuberosities and trochanters, 2) an elastomeric shell to mimic soft tissue and 3) instrumentation to measure internal pressures at both protuberances and deflection of the elastomer at 7 locations. It is parametrically designed so can be scaled larger or smaller to represent different body sizes. To assess the repeatability and sensitivity of measurements, the model was loaded onto two wheelchair cushions, 3″ flat foam and Jay3, using two loads, 44kgf and 53kgf, representing the average upper body mass of 70kg and 83kg persons, respectively. The results showed a high precision of pressure and deflection measurement across two different cushions and loads. Under both loads, pressure measurements exhibited a standard error of < 1 mm and <3 mmHg. The standard deviations of deflection values were less than 2.5 mm (0.1 in.). The pressures and absolute deflection differed significantly across load and cushion type indicating sensitivity to change.


Monoclonal antibodies to the glycoprotein of vesicular stomatitis virus: comparative neutralizing activity.
Nineteen independently isolated hybridomas producing monoclonal antibodies to the glycoprotein of vesicular stomatitis virus were isolated and studied for their capacity to neutralize viral infectivity. By measuring competitive binding of 125I-labeled monoclonal antibodies in a radioimmunoassay. 11 different, non-cross-reacting antigenic determinants were identified on the vesicular stomatitis virus G protein. All monoclonal antibodies reacting with determinants 1, 2, 3, and 4 resulted in viral neutralization, whereas those binding to the other seven determinants did not neutralize infectivity. The mixture of two monoclonal antibodies binding to different determinants resulted in a more rapid neutralization than either antibody alone, suggesting that different antibodies can exert a synergistic effect on viral neutralization. Kinetic experiments revealed biphasic neutralization curves similar to those expected for heterologous antibody. No evidence could be obtained to relate biphasic kinetics of viral neutralization to heterogeneous populations either of antibody molecules or of virus. The possible significance of the kinetic data with monoclonal antibodies is discussed.


Lobular breast carcinoma metastatic to the vulva: a case report and literature review.
Six previous reports have documented a vulvar metastasis from breast cancer; one has noted involvement of the Bartholin's gland. A 53-year-old woman presented with an enlarging vulvar mass. Evaluation also identified a breast lesion. Surgical excision confirmed an invasive lobular breast carcinoma with a distant metastatic focus on the vulva. This is the first report in the English literature to document a vulvar metastasis from an invasive lobular carcinoma and the second to identify involvement of the Bartholin's gland. Careful gynecologic surveillance is needed in women with breast cancer.


Optical Coherence Tomography For the Detection of the Vulnerable Plaque.
Morphological characteristics of the atheromatous plaque have been associated with the development of plaque rupture and the pathogenesis of acute coronary syndromes (ACS). Plaques with a specific morphological phenotype that are at high risk of causing ACS are called vulnerable plaques, and can be identified in vivo through the use of intracoronary imaging. Optical coherence tomography (OCT) is a high-resolution intravascular imaging modality that enables detailed visualization of atheromatous plaques. Consequently, OCT is a valuable research tool for examining the role of morphological characteristics of atheromatous plaques in the progression of coronary artery disease and plaque destabilisation, which leads to the clinical manifestation of ACS. This article summarises the pathophysiological insights obtained by OCT imaging in the formation and rupture of the vulnerable plaque.


Predictive Model for Response Rate to Narrowband Ultraviolet B Phototherapy in Vitiligo: A Retrospective Cohort Study of 579 Patients.
Vitiligo is an acquired depigmenting disorder. To date, there is no predictive model for its response rate to narrowband ultraviolet B (NBUVB) phototherapy. The aim of this study was to investigate the different types of response of patients with non-segmental vitiligo undergoing NBUVB 3 times a week. Many patients who were previously considered non-responders were given the opportunity to continue the treatment. Long-term maintenance of treatment and follow-up of a cohort of 579 patients enabled different subtypes of response (very rapid, rapid, average, slow and "non-responders") to be described for the first time, and a predictive model of response to be constructed based on repigmentation rate in the first 48 sessions of NBUVB. Among those patients who did not respond during the first 48 sessions, a new subgroup of patients was found, termed "very-slow" responders, who achieved a low, but significant, level of repigmentation after 96 sessions of NBUVB.


Metallic ureteral stents in malignant ureteral obstruction: clinical factors predicting stent failure.
To provide clinical outcomes of the Resonance metallic ureteral stent in patients with malignant ureteral obstruction, as well as clinical factors predicting stent failure. Cancer patients who have received Resonance stents from July 2009 to March 2012 for ureteral obstruction were included for chart review. Stent failure was detected by clinical symptoms, image studies, and renal function tests. Survival analysis for stent duration was used to estimate patency rate and factors predicting stent failure. A total of 117 stents were inserted successfully into 94 ureteral units in 79 patients. There were no major complications. These stents underwent survival analysis and proportional hazard regression. The median duration for the stents was 5.77 months. In multivariate analysis, age (P=0.043), preoperative serum creatinine level (P=0.0174), and cancer type (P=0.0494) were significant factors associated with stent failure. Cancer treatment before and after stent insertion had no effect on stent duration. Resonance stents are effective and safe in relieving malignant ureteral obstructions. Old age and high serum creatinine level are predictors for stent failure. Stents in patients with lower gastrointestinal cancers have longer functional duration.


Identification of a novel aquaporin, AQP12, expressed in pancreatic acinar cells.
Members of the aquaporin (AQP) water channel family are widely distributed in various tissues and contribute to the water permeability of epithelial and endothelial cells. Currently 11 members of the AQP family (AQP0-10) have been reported in mammals. Here we report the identification of AQP12, which we found by performing a BLAST program search. Northern blot analysis revealed that AQP12 was specifically expressed in the pancreas. Further analysis by in situ hybridization and RT-PCR studies showed that AQP12 was selectively localized in the acinar cells of the pancreas. To analyze the cellular localization and function of AQP12, we expressed AQP12 in Xenopus oocytes and cultured mammalian cells. Immunocytochemistry revealed that AQP12 was not targeted to the plasma membrane. The selective localization of AQP12 in pancreatic acinar cells and possibly in the intracellular organelles suggests a role of AQP12 in digestive enzyme secretion such as maturation and exocytosis of secretory granules.


Pharmacogenomic biomarkers do not predict response to drotrecogin alfa in patients with severe sepsis.
To explore potential design for pharmacogenomics trials in sepsis, we investigate the interaction between pharmacogenomic biomarkers and response to drotrecogin alfa (activated) (DrotAA). This trial was designed to validate whether previously identified improved response polymorphisms (IRPs A and B) were associated with an improved response to DrotAA in severe sepsis. Patients with severe sepsis at high risk of death, who received DrotAA or not, with DNA available were included and matched to controls adjusting for age, APACHE II or SAPS II, organ dysfunction, ventilation, medical/surgical status, infection site, and propensity score (probability that a patient would have received DrotAA given their baseline characteristics). Independent genotyping and two-phase data transfer mitigated bias. The primary analysis compared the effect of DrotAA in IRP+ and IRP- groups on in-hospital 28-day mortality. Secondary endpoints included time to death in hospital; intensive care unit (ICU)-, hospital-, and ventilator-free days; and overall DrotAA treatment effect on mortality. Six hundred and ninety-two patients treated with DrotAA were successfully matched to 1935 patients not treated with DrotAA. Genotyping was successful for 639 (DrotAA) and 1684 (nonDrotAA) matched patients. The primary hypothesis of a genotype-by-treatment interaction (assessed by conditional logistic regression analysis) was not significant (P = 0.30 IRP A; P = 0.78 IRP B), and there was no significant genotype by treatment interaction for any secondary endpoint. Neither IRP A nor IRP B predicted differential response to DrotAA on in-hospital 28-day mortality. ClinicalTrials.gov registration NCT01486524.


[Sensorineural hearing loss due to neonatal hyperbilirubinemia].
In this article, the sensorineural hearing loss is presented as a possible sequelae of neonatal hyperbilirubinemia. In our program of early hipoacusia detection, 241 babies were examined from January 1996 until November 1999; 7 cases had a history of hyperbilirubinemia in the neonatal period and 2 of them were diagnosed of sensorineural hearing loss. We discuss how the bilirubin or any other associated factor might have been the cause and this could explain the selective affectation of some children.


Serum homocysteine level in newly diagnosed young patients with abnormal glucose tolerance.
Hyperhomocysteinemia is an emerging risk factor causing early-onset cardiovascular events. The objective of the study was to assess serum homocysteine levels in newly diagnosed young persons (age < 30 years) with abnormal glucose tolerance. This cross-sectional study included 40 young participants with newly diagnosed abnormal glucose tolerance (including prediabetes and diabetes mellitus) and an equal number of young persons with normal glucose tolerance (normal glucose tolerance vs prediabetes vs. diabetes mellitus-age (years): 25.0 (22.0, 28.0) vs 25.50 (21.50, 27.0) vs 28.0 (25.0, 29.0), median (interquartile range)). Glycemic status was diagnosed by American Diabetes Association, 2021 criteria. After taking clinical information, fasting blood was collected to measure homocysteine by chemiluminescent immunoassay. Homocysteine level was different across the spectrum of glycemic status (normal glucose tolerance vs. prediabetes vs. diabetes mellitus: 15.57 (13.89-20.71) vs 13.19 (11.40-18.11) vs 12.27 (9.97-14.42) µmol/L; median (interquartile range); p = 0.006). Serum homocysteine was significantly elevated in participants with normal glucose tolerance than diabetes mellitus (p = 0.006) but statistically similar in prediabetes in comparison to both normal glucose tolerance and diabetes mellitus (p = NS for both). Homocysteine level was above the normal level in 47.5% of participants with normal glucose tolerance and in 22.5% with abnormal glucose tolerance (p = 0.019). Patients under 30 years with diabetes mellitus had lower homocysteine levels than those with normal glucose tolerance.


Effects of high-fat and high-carbohydrate diets on metabolism and performance in cycling.
We compared the effects of high-fat and high-carbohydrate dietary conditions on metabolism and short- and ultra-endurance cycling performance. Seven cyclists (VO(2)max 72 +/- 7 mL x kg(-1) x min(-1)) underwent a 2-week adaptation to each of the following 3 diets: 14-day high carbohydrate with 70 +/- 9 percent energy (%E) carbohydrate, 16 +/- 5%E fat, and 14 +/- 2%E protein; 14-day high fat with 66 +/- 10%E fat, 20 +/- 3%E protein, and 15 +/- 4%E carbohydrate; and 11.5-day high-fat diet followed by 2.5-day carbohydrate-loading. The conditions included a pre-exercise meal of the same composition as the preceding diet. Each diet condition was preceded by a 2-week standardizing normal diet. The exercise test lasted approximately 5 hours and comprised a 15-minute trial, an incremental test to measure the peak fat-oxidation rate, and a 100-km trial. Sports bars and a 5% carbohydrate solution were ingested during the tests. The diets had no statistically significant effect on 15-minute performance, although the high-fat condition tended to reduce distance covered by -2.4% (95% confidence interval: -5.4% to +0.6%, P =.11) relative to the fat with carbo-loading condition. In the 100-km time trial, the high-fat and the fat with carbohydrate-loading conditions attenuated the decline in power output observed in the high-carbohydrate condition (P =.03 to.07), although the corresponding improvement in performance time of 3% to 4% (-2% to 10%) was not statistically significant (P =.16 to.22). Power output during the final 5 km of the time trial in the fat with carbo-loading condition was 1.3-fold (1.0 to 1.6, P =.04) greater than in the high-carbohydrate condition. Overall, for every 10%E increase in dietary fat, 100-km mean power increased by 2% (-0.0% to 4%, P =.06). Relative to the high-carbohydrate condition, the high-fat conditions resulted in the following metabolic changes consistent with greater lipolysis and fuel availability: lower plasma insulin concentration before exercise (P <.0001), and during exercise a 10% to 20% higher plasma-glucose concentration (P <.01), higher plasma glycerol (P <.05), and a 2.5-fold to 2.9-fold increase in the peak fat-oxidation rate (P <.0001). In conclusion, high-fat dietary conditioning increased fat oxidation, and although the main effects were not statistically significant, there was some evidence for enhanced ultra-endurance cycling performance relative to high-carbohydrate.


Neuroblastoma in father and son.
A growing literature supports the concept that some cases of neuroblastoma are hereditary. To this we add the first known case, to our knowledge, of neuroblastoma in a parent and child. Various factors, such as the remarkable tendency for this tumor to regress spontaneously, as well as its frequent fatal outcome, have reduced the number of observed familial cases. It is important that siblings and progeny of patients with neuroblastoma be examined to detect possible subclinical neuroblastoma.


From Energetics to Intracluster Chemistry: Valence Photoionization of Trifluoromethylsulfur Pentafluoride (CF3SF5) by Double Velocity Map Imaging.
Trifluoromethylsulfur pentafluoride (CF3SF5) was valence threshold photoionized in a double imaging photoelectron photoion coincidence spectrometer using vacuum ultraviolet synchrotron radiation. In the 12.5-16.4 eV photon energy range, CF3+, SF5+, and SF3+ cations were observed in both room temperature (RT) and molecular beam (MB) experiments. Their fractional abundances exhibited differences beyond the sample temperature. Kinetic energy analysis of the fragment ions confirmed the difference in the dissociative photoionization mechanism. In the RT experiment, the CF3+ kinetic energies were extrapolated to a 11.84 ± 0.15 eV threshold, which was used in an ion cycle to determine the enthalpy of formation of CF3SF5 as ΔfH°298K(CF3SF5) = -1593 ± 16 kJ mol-1. We also updated the enthalpy of formation of the sulfur pentafluoride radical as ΔfH°298K(SF5) = -854 ± 7 kJ mol-1 and discuss the discrepancy between the CF3 ionization energy based on the Active Thermochemical Tables and the value anchored to the CF ionization energy. A computed reaction enthalpy network optimization resulted in ΔfH°298K(CF3SF5) = -1608 ± 20 kJ mol-1. Both values for ΔfH°298K(CF3SF5) agree with previous ab initio ones in contrast to the original, experimental determination. SF3+ is formed by F-transfer processes both in the RT and MB experiments. Although the same peaks were observed in both experiments, the lower SF3+ onset energy and the more slowly rising CF3+ kinetic energy release in the MB experiment revealed clustering and intracluster F-transfer reactions upon ionization. The monomer and dimer cation potential energy surfaces were explored to rationalize the observations. In the dimer cation, the observer CF3SF5 catalyzes fluorine transfer and promotes CF4 formation, which ultimately leads to the SF3+ fragment ion.


Comprehensive analysis identifies novel targets of gemcitabine to improve chemotherapy treatment strategies for colorectal cancer.
Gemcitabine (GEM) is a second-line anticancer drug of choice for some colorectal cancer (CRC) patients, and GEM inability to be commonly available in the clinic due to the lack of clarity of the exact action targets. The half maximal inhibitory concentration (IC50) of GEM treatment for 42 CRC cell lines were accessed from the Genomics of Drug sensitivity in Cancer (GDSC) database. High-throughput sequencing data of CRC patients were captured in The Cancer Genome Atlas (TCGA) and Weighted correlation network analysis (WGCNA) was conducted. Pearson correlations were derived for GEM potency-related genes. Differential analysis was conducted in the TCGA cohort to obtain CRC development-related genes (CDRGs), and univariate COX model analysis was performed on CDRGs overlapping with GEM potency-related genes to obtain CDRGs affecting CRC prognosis. Hub genes affecting GEM potency were identified by Spearman correlation. CALB2 and GPX3 were identified as potential targets for GEM treatment of CRC via prognostic analysis, which we also observed to be elevated with elevated clinical stage in CRC patients. The enhanced expression of CALB2 and GPX3 genes identified in the pathway analysis might inhibit the body metabolism as well as activate immune and inflammation related pathways. In addition, we found that CALB2 and GPX3 could also be considered as prognostic biomarkers in pan-cancer. Finally, we found that CALB2 and GPX3 were remarkably associated with the drug sensitivity of MG-132, Dasatinib, Shikonin, Midostaurin, MS-275, and Z-LNle-CHO, which were expected to be the drugs of choice for GEM combination. CALB2 and GPX3 represent prognostic biomarkers for CRC and they might be potential action targets for GEM. Our study offered innovative ideas for GEM administration strategies.


[Adenocarcinoma of the Vater's ampulla associated with Von Recklinghausen's neurofibromatosis].
Von Recklinghausen's Neurofibromatosis is an autosomal dominant disease of variable manifestations. Association with gastrointestinal and hepatobiliary tumours is well documented, most of them being benign neurofibromas. Other tumours, such as leiomyomas, sarcomas, ganglioneuromas and carcinoids are less frequent. Much rarer is the development of epithelial malignancies and an ontogenic relation is not clear. The authors reports a case of adenocarcinoma of Vater's Ampulla and duodenal neurofibromas, in a patient with Von Recklinghausen's disease, presenting obstructive jaundice.


Analysis of glycyrrhizic acid and liquiritin in liquorice root with microwave-assisted micellar extraction and pre-concentration.
The feasibility of employing a non-ionic surfactant (Triton X-100) as an alternative and effective solvent for the microwave-assisted extraction of glycyrrhizic acid and liquiritin from liquorice root has been demonstrated. When compared with commonly used solvents, 5% Triton X-100 yielded higher extraction efficiency than aqueous solutions of ethanol or methanol. Under optimal conditions, i.e. 5% Triton X-100 (v/v) and microwave-assisted extraction for 3-5 min at 100 degrees C, the percentage extraction of active ingredients reached the highest value. The pre-concentration factor for the glycyrrhizic acid and liquiritin was about 13, and the cloud-point extraction recoveries for the two ingredients were 98.4 and 96.1%, respectively. The results showed that the coupling of microwave-assisted extraction and cloud-point extraction could be employed as a new and effective approach for the rapid extraction and pre-concentration of pharmacologically active ingredients from liquorice root without disturbing the subsequent chromatographic analysis.


Golgi-Targeting Fluorescent Probe for Monitoring CO-Releasing Molecule-3 In Vitro and In Vivo.
CO-releasing molecule-3 (CORM-3), mainly metal carbonyl compounds, is widely used as experimental tools to deliver CO, a biological "gasotransmitter", in mammalian systems. CORM-3 is also proposed as a potential new antimicrobial agent, which kills bacteria effectively and rapidly in vitro and in animal models. Organelle-targeting therapy, as a highly effective therapeutic strategy with little toxic and side effects, has important research significance and development prospects. Therefore, the development of effective methods for detecting and tracking CORM-3 at the subcellular level has important implications. In this paper, an easily available Golgi-targetable fluorescent probe (Golgi-Nap-CORM-3) was proposed for CORM-3 detection. In the probe Golgi-Nap-CORM-3, the phenyl sulfonamide group was selected as the Golgi-targetable unit, naphthalimide dye was chosen as a fluorophore, and the nitro group was selected as a CORM-3-responsive unit. Golgi-Nap-CORM-3 shows a CORM-3-reponsive increase of fluorescence emission at 520 nm. Using the excellent probe, the change of CORM-3 in HeLa cells, HepG2 cells, and zebrafish is successfully monitored. This study demonstrates very important information for the study of CORM-3 in vivo systems.


[The concept of mania in Greek medical and philosophical literature].
Coverage of the concept of mania in late archaic Greek culture displays a clear difference between its use in medical and philosophical works. Medical literature uses the terms [Greek] and [Greek] to describe mania, with the condition seen largely associated with physical illness. Specific treatment for this attered psychic state is not advanced. The philosophical view sees mania as a divine folly and thus possessing positive as well as negative aspects. Plate identifies four types of mania and treatment is closely associated with the divinity seen as responsible for that particular type. The radical rationalism found in the medical literature is a counterpoint to moderation as shown by Plato with his interest on regulations of society.


Association of metal tolerance with multiple antibiotic resistance of bacteria isolated from drinking water.
Bacterial isolates from the drinking water system of an Oregon coastal community were examined to assess the association of metal tolerance with multiple antibiotic resistance. Positive correlations between tolerance to high levels of Cu2+, Pb2+, and Zn2+ and multiple antibiotic resistance were noted among bacteria from distribution waters but not among bacteria from raw waters. Tolerances to higher levels of Al3+ and Sn2+ were demonstrated more often by raw water isolates which were not typically multiple antibiotic resistant. A similar incidence of tolerance to Cd2+ was demonstrated by isolates of both water types and was not associated with multiple antibiotic resistance. These results suggest that simultaneous selection phenomena occurred in distribution water for bacteria which exhibited unique patterns of tolerance to Cu2+, Pb2+, and Zn2+ and antibiotic resistance.


Effects of endocrine disrupting chemicals on estrogen receptor alpha and heat shock protein 60 gene expression in primary cultures of loggerhead sea turtle (Caretta caretta) erythrocytes.
The loggerhead turtle (Caretta caretta) can be considered a good indicator species for studying the ecological impact of endocrine disrupting chemicals (EDCs) on wildlife. However, the effect of these environmental pollutants on nuclear steroid hormone signaling has not yet been addressed in sea turtles mainly due to the legal constraints of their endangered status. Here we describe the use of primary erythrocyte cell cultures as in vitro models for evaluating the effects of different EDCs on the expression of estrogen receptor α (ERα). In addition, we evaluated erythrocyte toxicity caused by EDCs using Alamar Blue assay and heat shock proteins 60 (HSP60) expression. Primary cultures of erythrocytes were exposed to increasing concentrations of 4-nonylphenol (4NP), Diisodecyl phthalate (DiDP), Tri-m-cresyl phosphate (TMCP) and Tributyltin (TBT) for 48h. Alamar Blue demonstrated that exposure of erythrocytes to each contaminant for up to 48h led to a significant impairment of cellular metabolic activity at 100μM, with the exception of TBT. Moreover, our data indicate that loggerhead erythrocytes constitutively express ERα and HSP60 at the transcript level and respond to EDCs by up-regulating their expression. In this regard, ERα was up-regulated in a dose-dependent manner after 48h exposure to both 4NP and TMCP. Interestingly, the dosage-dependent effects of DiDP on ERα expression were opposite in comparison to that obtained following exposure to the other tested compounds. This work provides the first indication regarding the potential of primary erythrocytes as study models for evaluating the effects of EDCs on sea turtles.


Characterization of the denaturation of human alpha-lactalbumin in urea by molecular dynamics simulations.
Molecular dynamics (MD) simulations were used to characterize the non-cooperative denaturation of the molten globule A-state of human alpha-lactalbumin by urea. A solvent of explicit urea and water molecules was used, corresponding to a urea concentration of approximately 6M. Three simulations were performed at temperatures of 293K, 360K and 400K, with lengths of 2 ns, 8 ns and 8 ns respectively. The results of the simulations were compared with experimental data from NMR studies of human alpha-lactalbumin and related peptides. During the simulations, hydrogen bonds were formed from the protein to both urea and water molecules as intra-protein hydrogen bonds were lost. Urea was shown to compete efficiently with water as both a hydrogen bond donor and acceptor. Radial distribution functions of water and urea around hydrophobic side chain atoms showed a significant increase in urea molecules in the solvation shell as the side chains became exposed during denaturation. A considerable portion of the native-like secondary structure persisted throughout the simulations. However, in the simulations at 360K and 400K, there were substantial changes in the packing of aromatic and other hydrophobic side chains in the protein, and many native contacts were lost. The results suggest that during the non-cooperative denaturation of the molten globule, secondary structure elements are stabilized by non-specific, non-native interactions.


Determinants of Cervical Cancer Screening Among Women Aged 30-49 Years Old in Four African Countries: A Cross-Sectional Secondary Data Analysis.
Early-stage cervical cancer screening is essential for providing women with a better chance of receiving effective treatment for precancerous and cancer stages. Delay in cervical cancer screening results in late presentation and cancer metastasis. National-level cervical cancer screening in resource-limited countries was scarce and not well studied in Africa based on national data specifically in Kenya, Cameroon, Nambia, and Zimbabwe. To determine the prevalence and determinants of cervical cancer screening among eligible women in Kenya, Cameroon, Nambia, and Zimbabwe. This study analyzed demographic and health survey data from Kenya, Cameroon, Nambia, and Zimbabwe. The data were extracted and analyzed by STATA version 15 and further analysis was done. Intraclass correlation coefficient, median odds ratio, and proportional change in variance were calculated to check the appropriateness of multilevel analysis. Variables with P-value < .25 were selected for multivariable multilevel logistic regression analysis. Finally, statistical significance between dependent and independent variables was assessed by odds ratios and 95% confidence intervals. The prevalence of cervical cancer screening in 4 African countries (Nambia, Kenya, Cameroon, and Zimbabwe) was 23.4 [95%CI: 22.8-24.1]. The determinants identified in this study were women of age 41-50 years [AOR = 1.47; 95% CI 1.24, 1.73], rural residence [AOR = .67; 95% CI .55, .81], women who have their own work [AOR = 1.1; 95% CI 1.0, 1.37], smoking status [AOR = 1.89; 95% CI 1.17, 3.0], age at first birth >=35 [AOR = 5.27; 95% CI 1.29-21.52], condom use [AOR = 1.79; 95% CI 1.46,2.19], husbands having worked [AOR = 1.5; 95% CI 1.08,2.11], rich household wealth [AOR = 1.43; 95% CI 1.13,1.8], and having health insurance [AOR = 2.2; 95% CI 1.8,2.7]. The prevalence of cervical cancer screening in Kenya, Cameroon, Nambia, and Zimbabwe was low as compared to World Health Organization (WHO) recommendations. Age, residence, work status, smoking status, women's age at first birth, condom use, husbands having work, wealth status, and health insurance were the identified determinants of cervical cancer screening. Programme and policy interventions could address younger, rural residence women, poor wealth status women, women without work, and those who never use health insurance for the uptake of cervical cancer screening.


Accurate and Fast Image Denoising via Attention Guided Scaling.
Image denoising is a classical topic yet still a challenging problem, especially for reducing noise from the texture information. Feature scaling (e.g., downscale and upscale) is a widely practice in image denoising to enlarge receptive field size and save resources. However, such a common operation would lose some visual informative details. To address those problems, we propose fast and accurate image denoising via attention guided scaling (AGS). We find that the main informative feature channel and visual primitives during the scaling should keep similar. We then propose to extract the global channel-wise attention to maintain main channel information. Moreover, we propose to collect global descriptors by considering the entire spatial feature. And we then distribute the global descriptors to local positions of the scaled feature, based on their specific needs. We further introduce AGS for adversarial training, resulting in a more powerful discriminator. Extensive experiments show the effectiveness of our proposed method, where we clearly surpass all the state-of-the-art methods on most popular synthetic and real-world denoising benchmarks quantitatively and visually. We further show that our network contributes to other high-level vision applications and improves their performances significantly.


Fetal ossification centers as predictors of gestational age in normal and abnormal pregnancies.
The main fetal ossification centers appear ultrasonically as egg-shaped echo-rich areas. The calcaneal and talar ossification centers are seen at the level of the tarsus osseus, and the distal femoral epiphyseal and proximal tibial epiphyseal ossification centers are found at the level of the knee. Examination of 312 normal pregnancies between 20 and 40 weeks of gestation showed that the calcaneal ossification center was detectable for 24 weeks of gestation, the talar ossification center from 26 weeks, and the distal femoral epiphyseal and proximal tibial epiphyseal ossification centers, from 32 and 36 weeks, respectively. Corresponding figures found for 36 pregnancies showing intrauterine growth retardation (IUGR), examined between 34 and 40 weeks of gestation, were similar for the calcaneal and talar ossification centers but showed delays in the development of the epiphyseal ossification centers, which were particularly striking in cases of symmetrical IUGR. The amniotic fluid lecithin/sphingomyelin ratio was also evaluated in 51 normal pregnancies between 31 and 38 weeks of gestation and was found to be greater than or equal to 2 in every case where the distal femoral epiphyseal ossification center was greater than or equal to 6 mm in diameter. Evaluation of fetal ossification centers may be another useful means to evaluate gestational age in late pregnancy


A case of B-cell lymphoblastic lymphoma involving the uterus.
A 59-year-old postmenopausal woman presented with vaginal bleeding, lower abdominal pain, severe anaemia, leucocytosis, and an ultrasonographic finding of a large mass arising within the pelvis, most likely ovarian in origin. The patient was taken to the operating theatre with the possible diagnosis of acute haemorrhage into an ovarian cyst. At laparotomy there was a large mass at the posterior uterine wall extending retroperitoneally into the left pelvic side-wall. There was also significant paraaortic lymphadenopathy. The tumor was not resectable and biopsies were taken for pathological examination which showed a precursor B cell lymphoblastic lymphoma. Although the existence of lymphomas involving the uterus is well documented, the presentation of the lymphoma in this case was very unusual and this is the first reported case of a confirmed precursor B-cell lymphoblastic lymphoma involving the uterus.


Immigration Enforcement, Parent-Child Separations, and Intent to Remigrate by Central American Deportees.
Given the unprecedented increase in the flow of migrants from El Salvador, Guatemala, and Honduras to the United States, this article analyzes the impact of U.S. interior enforcement on parent-child separations among Central American deportees, along with its implications for deportees' intentions to remigrate to the United States. Using the EMIF sur survey data, we find that interior enforcement raises the likelihood of parent-child separations as well as the likelihood that parents forcedly separated from their young children report the intention to return to the United States, presumably without documents. By increasing parent-child separations, interior enforcement could prove counterproductive in deterring repetitive unauthorized crossings among Central American deportees.


ONYX-411, a conditionally replicative oncolytic adenovirus, induces cell death in anaplastic thyroid carcinoma cell lines and suppresses the growth of xenograft tumors in nude mice.
Anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid cancer variant, accounting for 1-2% of all cases, but 33% of deaths, and exhibiting an average life expectancy of 5 months. ATC is largely unresponsive to radioactive iodine, chemotherapy, external beam radiation or surgery, underscoring the need for new and effective therapies. We evaluated the therapeutic potential of an oncolytic adenovirus, ONYX-411, that replicates selectively in and kills cells with dysfunction of the retinoblastoma (RB) pathway. In the present study, we report that ONYX-411 is able to induce cell death in eight human anaplastic carcinoma cell lines in vitro. The cytopathic effect of the virus is specific to cells with RB dysfunction, which appears to be frequent in ATC. We confirmed the expression of the coxsackie adenovirus receptor, CAR, in all ATC cell lines, demonstrating the potentially universal application of this oncolytic viral therapy to ATC. In addition, the growth of xenograft tumors induced in athymic mice with the ARO and DRO cell lines was significantly reduced by ONYX-411 treatment. These results indicate that ONYX-411 can be a potential therapeutic agent for the treatment of ATC, rendering this class of conditionally replicating adenoviruses an attractive candidate for clinical trials.


Human urinary amylolytic enzymes in acute hepatitis.
Using paper eletrophoresis two amylolytic enzymes in human urine were demonstrated. A main peak was shown in the gamma globulin zone in normal urine and a second minor peak, in contrast to earlier findings, in the beta globulin zone. The organic source of the minor peak is probably in the liver. Urines from cases of acute hepatitis were studied in the same way and showed that the electrophoretic beta peak was raised in acute hepatitis, also pointing to a possible origin in the liver. Further studies are required to confirm this hypothesis.


A randomized study of neighborhood effects on low-income children's educational outcomes.
Experimental data from the Moving to Opportunity for Fair Housing Demonstration were used to examine (a) if moving from high- to low-poverty neighborhoods (via randomization) was associated with low-income minority children's achievement, grade retention, and suspensions/expulsions; (b) if moving minimized gender differences in these outcomes; and (c) potential mediators of observed program effects. Data on school-age children (mean age = 11.79 years, SD = 3.26) were obtained from standardized assessments and parent and adolescent interviews during the New York City site's 3-year follow-up evaluation (N = 588). Moving to low-poverty neighborhoods had positive effects on 11-18-year-old boys' achievement scores compared with those of their peers in high-poverty neighborhoods. These male adolescents' scores were comparable to females' scores, whereas male adolescents in high-poverty neighborhoods scored 10 points lower than female peers. Homework time and school safety partially accounted for program effects. From a policy perspective, the program benefited disadvantaged male adolescents at high risk for dropping out of school.


Estimation of genetic parameters for a new model for defining body structure scores (frame scores) in Nellore cattle.
Models for estimation of frame scores in Nellore beef cattle (FRAME_GMA) were developed, comparing them with frame scores estimated using equations proposed by the Beef Improvement Federation (FRAME_BIF, USA). Correlation among frame scores obtained by these two methodologies, along with the independent variables considered in the estimation models, were also studied. A data set with 12,728 animals, with ages between 490 and 610 days, was used. The models that best adjusted to FRAME_GMA included hip height, weight and interaction between height and weight. Estimates of heritability for FRAME_GMA and FRAME_BIF were 0.26 +/- 0.03 and 0.23 +/- 0.03, respectively, in single trait analysis, and 0.28 and 0.24, respectively, in multi-trait analysis. Phenotypic Pearson and Spearman correlation coefficients between FRAME_GMA and FRAME_BIF for males were 0.87 and 0.83, respectively, being lower than those found for females (0.92 for both coefficients). Genetic correlation between the frame scores did not differ between genders, with values of 0.92 for the Pearson coefficient and 0.91 for the Spearman coefficient. We concluded that FRAME_GMA was better adapted to this data set than FRAME_BIF. Other studies need to be made to evaluate the applicability of this proposed model to other populations of Nellore beef cattle and for other age groups.


Unique modifications with phosphocholine and phosphoethanolamine define alternate antigenic forms of Neisseria gonorrhoeae type IV pili.
Several major bacterial pathogens and related commensal species colonizing the human mucosa express phosphocholine (PC) at their cell surfaces. PC appears to impact host-microbe biology by serving as a ligand for both C-reactive protein and the receptor for platelet-activating factor. Type IV pili of Neisseria gonorrhoeae (Ng) and Neisseria meningitidis, filamentous protein structures critical to the colonization of their human hosts, are known to react variably with monoclonal antibodies recognizing a PC epitope. However, the structural basis for this reactivity has remained elusive. To address this matter, we exploited the finding that the PilE pilin subunit in Ng mutants lacking the PilV protein acquired the PC epitope independent of changes in pilin primary structure. Specifically, we show by using mass spectrometry that PilE derived from the pilV background is composed of a mixture of subunits bearing O-linked forms of either phosphoethanolamine (PE) or PC at the same residue, whereas the wild-type background carries only PE at that same site. Therefore, PilV can influence pilin structure and antigenicity by modulating the incorporation of these alternative modifications. The disaccharide covalently linked to Ng pilin was also characterized because it is present on the same peptides bearing the PE and PC modifications and, contrary to previous reports, was found to be linked by means of 2,4-diacetamido-2,4,6-trideoxyhexose. Taken together, these findings provide new insights into Ng type IV pilus structure and antigenicity and resolve long-standing issues regarding the nature of both the PC epitope and the pilin glycan.


[Rate of passage of a non-traditional diet through the digestive tract in sheep].
The rate of passage of experimental diets based on non-conventional feeds through the alimentary tract of rams was studied. The composition of diets was as follows: barley straw (D-2, D-1), conditioned beech sawdust (D-2, D-1), waste cellulose fibre (D-2, D-1), lactosylureide (D-2), peanut waste (D-2), urea (D-1), wood molasses (D-2, D-1) and mineral supplement (D-2, W-1). The control feed (K) contained straw, barley, beet molasses and mineral supplement. As a marker was used a single application (50 g) of polyethylene (PE), particle size 0.4 mm and specific weight 0.924, which formed 3.9, 3.5 and 4% of the diet dry matter. After 10 days the recovery of polyethylene amounting to 81.23% (D-2), 84.78% (D-1) and 86.6% (K) was established. The polyethylene losses occurred most probably at its administration in feed (10-12%), elapsing of polyethylene excreted after 10 days following the administration (0.5-1.5%) and by potential retention in rumen and large intestine. Maximal excretion of feces was observed during the second day after administration of the markered feed; after three days the excretion was as follows: group D-2-62%, group D-1-57% and control group 75.6%. A longer retention time in rumen at feeding D-2 and D-1 diets can be contributed to a high content of fibre in these diets. The digestibility of dry matter in diet D-2 amounted to 61.2%, i n diet D-1 to 62.3% and in control diet to 68.7%. Higher digestibility of feed is in accordance with its higher excreting. As shown by the results, the diets based on non-conventional feeds (secondary wood sources) lead to the prolongation of feed retention time in rumen and slow down the rate of passage through the alimentary tract.


A psychometric examination of the Interpersonal Sexual Objectification Scale among college men.
Whereas sexual objectification has most commonly been studied among women, recent calls by counseling psychologists have urged for an extension of objectification research to more fully include men (e.g., Heimerdinger-Edwards, Vogel, & Hammer, 2011). The present study examined the factor structure of the Interpersonal Sexual Objectification Scale (ISOS; Kozee, Tylka, Augustus-Horvath, & Denchik, 2007) with men. Specifically, analyses included exploratory factor analysis (EFA) with a sample of 287 college men and confirmatory factor analysis (CFA) with an independent sample of 221 college men. A correlated 3-factor structure was suggested by multiple criteria in EFA and was further confirmed by CFA with a bifactor model illustrating the most item variance associated with a general interpersonal sexual objectification dimension for men.


Abducens nerve paralysis: a potential presentation of sphenoid sinus cancer.
The sphenoid sinus is the paranasal sinus most commonly implicated when cranial neuropathies are present. Two patients presenting with sixth nerve paralysis secondary to sphenoid sinus involvement are presented. One patient had a primary sphenoid sinus tumor, and the other a metastasis from a bronchogenic carcinoma. Of the two patients, one carried the diagnosis of idiopathic sixth nerve paresis and had had a normal sinus x-ray film and CAT scan done previously. Even in the absence of positive radiographic findings, the high clinical suspicion of sinus malignancy must be maintained in patients manifesting abducens nerve paralysis. In these patients, the petrous apex and cavernous sinus "silent area" must be diligently evaluated. For the patient to have any chance for palliation or potential cure, the tumor must be diagnosed as soon as possible.


Phytosterol-mediated inhibition of intestinal cholesterol absorption in mice is independent of liver X receptor.
Previous studies have proposed that phytosterols activate liver X receptors (LXR) in the intestine, thereby reducing intestinal cholesterol absorption and promoting fecal cholesterol excretion. In the present study, we examined the effects of dietary phytosterol supplementation on intestinal cholesterol absorption and fecal neutral sterol excretion in LXRαβ-deficient mice, and wild-type mice treated with synthetic high-affinity LXRαβ agonists. LXRαβ deficiency led to an induction of intestinal cholesterol absorption and liver cholesterol accumulation. Phytosterol feeding resulted in an approximately 40% reduction of intestinal cholesterol absorption both in wild-type and LXRαβ-deficient mice, reduced dietary cholesterol accumulation in liver and promoted the excretion of fecal cholesterol-derived compounds. Furthermore, phytosterols produced additive inhibitory effects on cholesterol absorption in mice treated with LXRαβ agonists. Our data confirm the effect of LXR in regulating intestinal cholesterol absorption and demonstrate that the cholesterol-lowering effects of phytosterols occur in an LXR-independent manner.


Cytoprotective Effects of a Novel Nrf2 Activator, RS9, in Rhodopsin Pro347Leu Rabbits.
Rhodopsin Pro347Leu transgenic rabbits were previously generated as models of retinitis pigmentosa (RP). While the mechanism underlying the retinal deterioration in these rabbits remains unresolved, it is likely that oxidative stress is one of the factors triggering cellular loss. We have recently succeeded in obtaining a novel activator (RS9) of nuclear factor erythroid 2-related factor (Nrf2, also known as NFE2L2), which regulates antioxidant transcriptional factors. The purpose of this study was to investigate whether RS9 delays progressive retinal degeneration in the transgenic rabbits. RS9 microspheres (3 mM, 50 µL) were injected into the vitreous of rhodopsin Pro347Leu transgenic rabbits at 6 weeks, after which outer nuclear layer (ONL) thickness was measured by optical coherence tomography. Rabbits were sacrificed at 15 weeks. After intravitreal injection of RS9 microspheres, the concentration of RS9 in the vitreous was maintained at 1 nM for 2 weeks. At a concentration of 0.3 mM and 50 µL, RS9 significantly inhibited thinning of the ONL in transgenic rabbits compared to vehicle-injected transgenic rabbits. In RS9-injected transgenic rabbits, Nrf2-targeted genes had increased significantly, and levels of interleukin-6 mRNA decreased. Activation of Nrf2 signaling has potential as a novel approach for the prevention and treatment of RP, not only by driving intrinsic antioxidant enzymes, but also by inhibiting inflammatory responses. Although microspheres were employed in this study, small implants that release more compounds might be a realistic method for clinical trials.


Urrets-Zavalia Syndrome Following Cataract Surgery.
We describe a case of Urrets-Zavalia syndrome (UZS) in a healthy 56-year-old woman who underwent femtosecond-assisted phacoemulsification with intraocular lens implantation in both eyes. One month after an uneventful postoperative course in the left eye, the right eye was operated. Dilated pupil which was nonreactive to light appeared on day 21 postoperatively. This was discovered upon examination following anterior chamber inflammatory reaction which occurred 2 weeks following her surgery. Our case report emphasizes the importance and danger in developing UZS even if the reaction in the anterior chamber does not occur immediately after surgery. In addition, the importance of intraocular pressure follow-up in the period after UZS is acknowledged.


Modeling Cardinality in Image Hashing.
Cardinality constraint, namely, constraining the number of nonzero outputs of models, has been widely used in structural learning. It can be used for modeling the dependencies between multidimensional labels. In hashing, the final outputs are also binary codes, which are similar to multidimensional labels. It has been validated that estimating how many 1's in a multidimensional label vector is easier than directly predicting which elements are 1 and estimating cardinality as a prior step will improve the classification performance. Hence, in this article, we incorporate cardinality constraint into the unsupervised image hashing problem. The proposed model is divided into two steps: 1) estimating the cardinalities of hashing codes and 2) then estimating which bits are 1. Unlike multidimensional labels that are known and fixed in the training phase, the hashing codes are generally learned through an iterative method and, therefore, their cardinalities are unknown and not fixed during the learning procedure. We use a neural network as a cardinality predictor and its parameters are jointly learned with the hashing code generator, which is an autoencoder in our model. The experiments demonstrate the efficiency of our proposed method.


Orbital Langerhans Cell Histiocytosis: A Case Report.
An eight-year-old boy presented with a one-month history of left eyelid swelling. The patient was diagnosed with periorbital cellulitis at another clinic and was treated with oral antibiotics. However, the swelling did not subside. On initial consultation, the patient had left upper eyelid swelling with erythema. His extraocular muscle motility was normal, and the results of blood tests were unremarkable. A computed tomographic scan demonstrated a mass in the superior orbit with destructive changes in the left frontal bone. Histopathological examinations revealed a dense infiltrate of histiocytic cells. Immunohistochemical staining of the tumors for CD1a and Langerin was positive. A pathological diagnosis of Langerhans cell histiocytosis was made. Since orbital Langerhans cell histiocytosis has a high risk for central nervous system involvement, chemotherapy was the treatment of choice for any residual lesion to prevent sequelae to the central nervous system. At the six-month follow-up, the lesion did not recur, and the patient did not experience any central nervous system sequela.


Marked microevolution of a unique Mycobacterium tuberculosis strain in 17 years of ongoing transmission in a high risk population.
The transmission and persistence of Mycobacterium tuberculosis within high risk populations is a threat to tuberculosis (TB) control. In the current study, we used whole genome sequencing (WGS) to decipher the transmission dynamics and microevolution of M. tuberculosis ON-A, an endemic strain responsible for an ongoing outbreak of TB in an urban homeless/under-housed population. Sixty-one M. tuberculosis isolates representing 57 TB cases from 1997 to 2013 were subjected to WGS. Sequencing data was integrated with available epidemiological information and analyzed to determine how the M. tuberculosis ON-A strain has evolved during almost two decades of active transmission. WGS offers higher discriminatory power than traditional genotyping techniques, dividing the M. tuberculosis ON-A strain into 6 sub-clusters, each defined by unique single nucleotide polymorphism profiles. One sub-cluster, designated ON-ANM (Natural Mutant; 26 isolates from 24 cases) was also defined by a large, 15 kb genomic deletion. WGS analysis reveals the existence of multiple transmission chains within the same population/setting. Our results help validate the utility of WGS as a powerful tool for identifying genomic changes and adaptation of M. tuberculosis.


Hard exudates segmentation based on learned initial seeds and iterative graph cut.
(Background and Objective): The occurrence of hard exudates is one of the early signs of diabetic retinopathy which is one of the leading causes of the blindness. Many patients with diabetic retinopathy lose their vision because of the late detection of the disease. Thus, this paper is to propose a novel method of hard exudates segmentation in retinal images in an automatic way. (Methods): The existing methods are based on either supervised or unsupervised learning techniques. In addition, the learned segmentation models may often cause miss-detection and/or fault-detection of hard exudates, due to the lack of rich characteristics, the intra-variations, and the similarity with other components in the retinal image. Thus, in this paper, the supervised learning based on the multilayer perceptron (MLP) is only used to identify initial seeds with high confidences to be hard exudates. Then, the segmentation is finalized by unsupervised learning based on the iterative graph cut (GC) using clusters of initial seeds. Also, in order to reduce color intra-variations of hard exudates in different retinal images, the color transfer (CT) is applied to normalize their color information, in the pre-processing step. (Results): The experiments and comparisons with the other existing methods are based on the two well-known datasets, e_ophtha EX and DIARETDB1. It can be seen that the proposed method outperforms the other existing methods in the literature, with the sensitivity in the pixel-level of 0.891 for the DIARETDB1 dataset and 0.564 for the e_ophtha EX dataset. The cross datasets validation where the training process is performed on one dataset and the testing process is performed on another dataset is also evaluated in this paper, in order to illustrate the robustness of the proposed method. (Conclusions): This newly proposed method integrates the supervised learning and unsupervised learning based techniques. It achieves the improved performance, when compared with the existing methods in the literature. The robustness of the proposed method for the scenario of cross datasets could enhance its practical usage. That is, the trained model could be more practical for unseen data in the real-world situation, especially when the capturing environments of training and testing images are not the same.


Digital Twin Technology: The Future of Predicting Neurological Complications of Pediatric Cancers and Their Treatment.
Healthcare technologies have seen a surge in utilization during the COVID 19 pandemic. Remote patient care, virtual follow-up and other forms of futurism will likely see further adaptation both as a preparational strategy for future pandemics and due to the inevitable evolution of artificial intelligence. This manuscript theorizes the healthcare applications of digital twin technology. Digital twin is a triune concept that involves a physical model, a virtual counterpart, and the interplay between the two constructs. This interface between computer science and medicine is a new frontier with broad potential applications. We propose that digital twin technology can exhaustively and methodologically analyze the associations between a physical cancer patient and a corresponding digital counterpart with the goal of isolating predictors of neurological sequalae of disease. This proposition stems from the premise that data science can complement clinical acumen to scientifically inform the diagnostics, treatment planning and prognostication of cancer care. Specifically, digital twin could predict neurological complications through its utilization in precision medicine, modelling cancer care and treatment, predictive analytics and machine learning, and in consolidating various spectra of clinician opinions.


[Development of a regimen comprehension scale].
Whether elderly patients can take prescription drugs as directed by a physician is often unclear. So elderly patients could receive adequate instruction regarding their medications, we developed a regimen comprehension scale (RCS) with simple questions regarding information on dosage and administration. This information was written on the outside of the paper bags in which the medications are usually dispensed. The subjects were 21 healthy volunteers (11 men and 10 women, averaged age 38.3 +/- 11.2 years) and 17 inpatients (9 men and 8 women, averaged age 73.4 +/- 6.8 years). Five kinds of drugs, which differed with respect to dosage and administration were used. The subjects were questioned in an interview about taking the five drugs and their regimen comprehension was assessed with the RCS (maximum score: 10 points, lowest score: 10 points. Then regimen comprehension was classified into 4 grades: normal (10), caution needed (9 or 8), training needed (7 or 6), and assistance needed (5 or less). In addition, intelligence was tested with the revised version of Hasegawa's dementia scale (HDS-R). Eight of the 21 healthy volunteers (38%) and 13 of the 17 elderly patients (76%) misunderstood some aspects of the regimens written on the paper bags. The regimen comprehension was classified as "normal", "caution needed", and "training needed" in 13, 7, and 1 of the healthy volunteers, respectively, it was classified as "normal", "caution needed", "training needed", and "assistance needed" in 4, 4, 4, and 5 elderly patients, respectively. The five elderly patients classified as "assistance needed" were suspected to have dementia because they had scores on the HDS-R of 21 or less. A significant positive correlation (r = 0.797) was noted between scores on the HDS-R and on the RCS. When treating elderly patients with chronic disease (for example, hypertension) it is important to evaluate their regimen comprehension with an index such as the RCS to determine the need for medication counseling before the start of a medication regimen.


Dose and dose-rate dependence of the frequency of HPRT deficient T lymphocytes in the spleen of the 137Cs gamma-irradiated mouse.
The frequency of hypoxanthine phosphoribosyl transferase (HPRT) deficient splenic T lymphocytes was measured in the 137Cs gamma-irradiated mouse by the T cell cloning method. Doses from 0.3 to 6 Gy were applied at the dose-rates 0.5 Gy/min, 1 Gy/day and 1 Gy/week. Mutants were determined 8-10 and 30-40 weeks after the end of exposure. Radiation-induced mutant frequency (MFi) was calculated by subtracting the age corrected spontaneous mutant frequency (MFsp) from total mutant frequency (MF) found in irradiated animals. Data were fitted to linear and linear-quadratic dose-response models. MFi depended markedly on dose, dose-rate and time after exposure. When mutants were determined 8-10 weeks after acute irradiation (0.5 Gy/min) the dose-effect curve fitted the linear-quadratic equation MFi = 6.9 x 10(-6) Gy + 1.2 x 10(-6) Gy2, whereas in low dose-rate experiments (1 Gy/day, 1 Gy/week) the dose-effect curves were linear. The slope of the linear regression was about 3 x 10(-6). When low dose-rate-irradiated animals were killed 30-40 weeks after irradiation, MFi was about one-third of that observed after 8 weeks. The dose dose-rate effectiveness factor (DDREF) for radiation mutagenicity was calculated in animals that had been exposed 8-10 weeks previously. For doses < 2 Gy the reduction in effectiveness was about 1.5 when the irradiation dose-rate was < or = 1 Gy/day. For higher doses DDREF was 3-5.


Variants of Escherichia coli giving the appearance of mixed growths in urine.
Urines from patients with symptoms of urinary tract infection yielded mixed growths of different colony types of Escherichia coli. The different colony types were found to be variants of single infecting strains caused by mutation or by phase action. It is suggested that care should be exercised in the interpretation of apparently mixed growths from urine.


Association of increased heat shock protein 70 levels in the lymphocyte with high risk of adverse pregnancy outcomes in early pregnancy: a nested case-control study.
Studies suggest that heat shock proteins (Hsps), Hsp70 in particular, may play a role in embryogenesis and reproduction. As the first trimester is the critical period of human fetal development, we tested whether there is an association between Hsp70 expression in lymphocytes and adverse pregnancy outcomes (APOs) during that period. We measured lymphocyte Hsp70 levels by immunoblot in 55 pregnant women with APOs and 110 well-matched controls selected from 778 pregnant women in a nested case-control study. Multivariate logistic regression models were used to investigate the association between lymphocyte Hsp70 levels and risk of developing APOs. Our data showed that Hsp70 levels in women with APOs, especially those younger than 29 years old, were significantly higher than controls (193 vs 135 units, P < 0.001) and that the elevated Hsp70 levels were associated with a significantly increased risk of APOs (adjusted OR = 1.014; 95% CI = 1.008-1.020, P < 0.001). Our results also showed that the sensitivity, specificity, and positive and negative predictive values were 78%, 60%, 50%, and 85%, respectively, among these pregnant women. Adjusted ORs and 95% CI for the association between a Hsp70 value > 153 IOD and APOs were statistically significant (OR = 8.78, 95% CI = 2.79-27.64, P < 0.001). These results suggest that Hsp70 may play a role in the etiology of APOs. However, the underlying mechanisms for the elevation of Hsp70 in women with APOs and whether Hsp70 can be applied as a clinical indicator of APOs warrant further investigations.


An analysis and prediction of nucleosome positioning based on information content.
Nucleosome positioning plays a key role in the regulation of many biological processes. In this study, the statistical difference of information content was investigated in nucleosome and linker DNA regions across eukaryotic organisms. By analyzing the information redundancy, D k , in Saccharomyces cerevisiae, Drosophila melanogaster, and Caenorhabditis elegans genomes, the short-range dominance of nucleotide correlation in nucleosome and linker DNA regions was confirmed. Significant difference of the D k value between the nucleosome and linker DNA regions was also found. The underlying reason for many successful oligonucleotide-based predictions of nucleosome positioning in eukaryotic model organisms may be attributed to the short-range dominance of nucleotide correlation in the nucleosome and linker DNA regions. When applying power spectrum analysis to the nucleosome and linker DNA regions, some obvious differences in sequence periodic signals were observed. The parameter F k was introduced to describe particular base correlation. Furthermore, the support vector machine combining F k was used to classify nucleosome and linker DNA regions in Homo sapiens, Oryzias latipes, C. elegans, Candida albicans, and S. cerevisiae. Independent test demonstrated that a good performance can be achieved by using this algorithm. This result further revealed that base correlation information has an important role in nucleosome positioning.


Premature induction of hypertrophy during in vitro chondrogenesis of human mesenchymal stem cells correlates with calcification and vascular invasion after ectopic transplantation in SCID mice.
Functional suitability and phenotypic stability of ectopic transplants are crucial factors in the clinical application of mesenchymal stem cells (MSCs) for articular cartilage repair, and might require a stringent control of chondrogenic differentiation. This study evaluated whether human bone marrow-derived MSCs adopt natural differentiation stages during induction of chondrogenesis in vitro, and whether they can form ectopic stable cartilage that is resistant to vascular invasion and calcification in vivo. During in vitro chondrogenesis of MSCs, the expression of 44 cartilage-, stem cell-, and bone-related genes and the deposition of aggrecan and types II and X collagen were determined. Similarly treated, expanded articular chondrocytes served as controls. MSC pellets were allowed to differentiate in chondrogenic medium for 3-7 weeks, after which the chondrocytes were implanted subcutaneously into SCID mice; after 4 weeks in vivo, samples were evaluated by histology. The 3-stage chondrogenic differentiation cascade initiated in MSCs was primarily characterized by sequential up-regulation of common cartilage genes. Premature induction of hypertrophy-related molecules (type X collagen and matrix metalloproteinase 13) occurred before production of type II collagen and was followed by up-regulation of alkaline phosphatase activity. In contrast, hypertrophy-associated genes were not induced in chondrocyte controls. Whereas control chondrocyte pellets resisted calcification and vascular invasion in vivo, most MSC pellets mineralized, in spite of persisting proteoglycan and type II collagen content. An unnatural pathway of differentiation to chondrocyte-like cells was induced in MSCs by common in vitro protocols. MSC pellets transplanted to ectopic sites in SCID mice underwent alterations related to endochondral ossification rather than adopting a stable chondrogenic phenotype. Further studies are needed to evaluate whether a more stringent control of MSC differentiation to chondrocytes can be achieved during cartilage repair in a natural joint environment.


Retinyl ester homeostasis in the adipose differentiation-related protein-deficient retina.
The retinal pigmented epithelium (RPE) plays an essential role in vision, including storing and converting retinyl esters of the visual chromophore, 11-cis-retinal. Retinyl ester storage structures (RESTs), specialized lipid droplets within the RPE, take up retinyl esters synthesized in the endoplasmic reticulum. Here we report studies of mice lacking exons 2 and 3 of the gene encoding adipose differentiation-related protein (Adfp), a structural component of RESTs. We found that dark adaptation was slower in Adfp(Delta2-3/Delta2-3) than in Adfp+/+ mice and that Adfp(Delta2-3/Delta2-3) mice had consistently delayed clearances of all-trans-retinal and all-trans-retinol from rod photoreceptor cells. Two-photon microscopy revealed aberrant trafficking of all-trans-retinyl esters in the RPE of Adfp(Delta2-3/Delta2-3) mice, a problem caused by abnormal maintenance of RESTs in the dark-adapted state. Retinyl ester accumulation was also reduced in Adfp(Delta2-3/Delta2-3) as compared with Adfp+/+ mice. These observations suggest that Adfp plays a unique role in vision by maintaining proper storage and trafficking of retinoids within the eye.


Ultrasound-guided anatomical evaluation of right internal jugular vein in children aged 0-2 years: A prospective observational study.
The right internal jugular vein is commonly preferred for central venous cannulation, and ultrasonographic assessment and guidance is the recommended technique for this procedure. Despite the safety and reliability of this technique, it requires specific training and experience as well as thorough knowledge of anatomy. The position of the right internal jugular vein with respect to carotid artery and its transverse diameter free from overlap with the carotid artery were evaluated using ultrasound in patients aged 0-2 years. This single-center, prospective, observational study included patients aged 0-2 years who underwent elective surgery between July 2018 and July 2019. The diameters and anatomical position were evaluated using ultrasound. All parameters were compared between groups classified according to postmenstrual ages. The correlations of these parameters with weight and postmenstrual ages were analyzed. A total of 156 patients were included. The diameters (P < .001) and depth (P = .012) were smaller in patients with postmenstrual age <45 weeks. The anteroposterior diameter was significantly correlated with weight in patients with postmenstrual age <45 weeks, but not in older patients. Right internal jugular vein was lateral and anterolateral with respect to carotid artery in 51.3% and 42.9% of patients, respectively, and >80% of the transverse diameter was free from overlap with the carotid artery. Our results support the current data for the high anatomical variability of the right internal jugular vein, highlighting the recommendation of the Rapid Central Vein Assessment (RaCeVA) protocol prior to and ultrasound guidance during catheterization of central veins.


Early versus late tracheostomy: a systematic review and meta-analysis.
To investigate whether early tracheostomy leads to improved outcomes compared with late tracheostomy. Ovid MEDLINE (including PubMed), Embase, and the Cochrane Central Register of Controlled Trials. A systematic search was performed of the above-mentioned databases according to PRISMA guidelines. Data were collected on the following outcomes of interest: hospital mortality, intensive care unit length of stay, length of mechanical ventilation, incidence of pneumonia, laryngotracheal injury, and sedation use. Analysis was performed using the RevMan 5 software (Cochrane Collaboration, Oxford, England). Eleven studies were included for analysis. There was a significant decrease in the intensive care unit length of stay in the early tracheostomy group (weighted mean difference, -9.13 days; 95% confidence interval [CI], -17.55 to -0.70; P = .03). There was no significant difference in hospital mortality (relative risk, 0.84; 95% CI, 0.67 to 1.04; P = .11). A pooled analysis was not performed for the incidence of pneumonia or length of mechanical ventilation, secondary to considerable heterogeneity among the studies. None of the studies reporting laryngotracheal outcomes found a significant difference between the early and late tracheostomy groups, whereas all 3 studies reporting sedation use found a significant decrease in the early tracheostomy group. Early tracheostomy performed within 7 days of intubation was associated with a decrease in intensive care unit length of stay. No difference was found in hospital mortality. Insufficient data currently exist to make conclusions about the effect of early tracheostomy on the incidence of pneumonia, length of mechanical ventilation, laryngotracheal injury, or sedation use.


Effect of calcium supplementation on bone mass in patients operated on for hyperparathyroidism.
Photon absorptiometry was used to measure bone mass in the lumbar vertebrae, proximal femur, mid-radius and distal radius in eight pairs of closely matched female patients with primary hyperparathyroidism before, and 1, 3 and 6 months after operation. One of each pair was randomised to receive 3 g of oral calcium supplementation/day for three months postoperatively, and the other to serve as a control. After successful operations on the parathyroids, the bone mass in the lumbar vertebrae, proximal femur, and distal radius increased by roughly 7% during the first six months in both the treated and the control patients. This study shows that oral calcium supplementation after operation for hyperparathyroidism does not result in any additional increase in bone mass beyond the effect that is caused by the operation.


The Longitudinal Association of Being Bullied and Gender with Suicide Ideations, Self-Harm, and Suicide Attempts from Adolescence to Young Adulthood: A Cohort Study.
Longitudinal associations between being bullied during adolescence and suicide ideations, self-harm, and suicide attempts into young adulthood were examined. A large representative sample was examined in 1998 (N = 2,464, MA 13.7), 1999/2000, and 2012 to reassess the outcome measures. At all ages, bullied participants showed more suicide ideation, self-harm, and suicide attempts, regardless of gender. Bullied females showed a decrease in suicide ideation from adolescence to adulthood, while bullied males showed an increase in suicide attempts in the same time period. Being bullied in adolescence strongly predicts suicidal behavior and self-harm. Preventive efforts might reduce the risk of later suicidality.


Sebaceoma of the auricle.
To report a case of sebaceoma of the auricle, and to discuss the differential diagnosis, histopathological features, surgical management and genetic associations of this entity. Case report and review of the medical literature. A 79-year-old man presented with a slowly growing lesion of his auricle. Excision of the mass and histopathological review revealed a benign, basaloid, adnexal neoplasm consistent with sebaceoma. Due to its association with Muir-Torre syndrome and increased risk of visceral malignancy, the patient was followed closely for signs of malignancy. At 36 months post-excision, there were no signs of recurrence; thereafter, the patient continued to receive routine cancer surveillance follow up. Sebaceoma is a rarely encountered, benign, adnexal neoplasm which can occur in the head and neck. The treatment is surgical excision, and recurrence is rare. Sebaceoma can occur as part of Muir-Torre syndrome, and in these patients there is an increased risk of other sebaceous lesions and visceral malignancy; thus, genetic testing and surveillance should be strongly considered.


A sensitive assay method for the measurement of S-adenosylmethionine in tissue.
An assay method has been developed for the measurement of tissue levels of S-adenosylmethionine based upon the ability of this compound to activate tripolyphosphatase associated with S-adenosylmethionine synthetase beta prepared from rat liver. The method has been used to measure S-adenosylmethionine levels in rat liver after feeding rats on various concentrations of methionine in the diet. The results obtained by this method agree well with those measured by the spectrophotometric method. The limit of sensitivity of the assay was about 0.1 nmol of S-adenosylmethionine in an incubation volume of 0.1 ml (10(-6) M).


A randomized, crossover, head-to-head comparison of eicosapentaenoic acid and docosahexaenoic acid supplementation to reduce inflammation markers in men and women: the Comparing EPA to DHA (ComparED) Study.
To date, most studies on the anti-inflammatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in humans have used a mixture of the 2 fatty acids in various forms and proportions. We compared the effects of EPA supplementation with those of DHA supplementation (re-esterified triacylglycerol; 90% pure) on inflammation markers (primary outcome) and blood lipids (secondary outcome) in men and women at risk of cardiovascular disease. In a double-blind, randomized, crossover, controlled study, healthy men (n = 48) and women (n = 106) with abdominal obesity and low-grade systemic inflammation consumed 3 g/d of the following supplements for periods of 10 wk: 1) EPA (2.7 g/d), 2) DHA (2.7 g/d), and 3) corn oil as a control with each supplementation separated by a 9-wk washout period. Primary analyses assessed the difference in cardiometabolic outcomes between EPA and DHA. Supplementation with DHA compared with supplementation with EPA led to a greater reduction in interleukin-18 (IL-18) (-7.0% ± 2.8% compared with -0.5% ± 3.0%, respectively; P = 0.01) and a greater increase in adiponectin (3.1% ± 1.6% compared with -1.2% ± 1.7%, respectively; P < 0.001). Between DHA and EPA, changes in CRP (-7.9% ± 5.0% compared with -1.8% ± 6.5%, respectively; P = 0.25), IL-6 (-12.0% ± 7.0% compared with -13.4% ± 7.0%, respectively; P = 0.86), and tumor necrosis factor-α (-14.8% ± 5.1% compared with -7.6% ± 10.2%, respectively; P = 0.63) were NS. DHA compared with EPA led to more pronounced reductions in triglycerides (-13.3% ± 2.3% compared with -11.9% ± 2.2%, respectively; P = 0.005) and the cholesterol:HDL-cholesterol ratio (-2.5% ± 1.3% compared with 0.3% ± 1.1%, respectively; P = 0.006) and greater increases in HDL cholesterol (7.6% ± 1.4% compared with -0.7% ± 1.1%, respectively; P < 0.0001) and LDL cholesterol (6.9% ± 1.8% compared with 2.2% ± 1.6%, respectively; P = 0.04). The increase in LDL-cholesterol concentrations for DHA compared with EPA was significant in men but not in women (P-treatment × sex interaction = 0.046). DHA is more effective than EPA in modulating specific markers of inflammation as well as blood lipids. Additional studies are needed to determine the effect of a long-term DHA supplementation per se on cardiovascular disease risk. This trial was registered at clinicaltrials.gov as NCT01810003.


Nomograms as predictive models.
Nomograms are valuable tools for estimating the likelihood of cancer being diagnosed, the pathologic features of a localized cancer, and the prognosis of a patient after treatment. Although the available nomograms are reasonably accurate, better predictive factors including additional clinical factors and new molecular analyses are needed to improve the accuracy or predictions. Nomogram performance will also be enhanced with larger datasets of patients and longer follow-up. We review the concepts of risk stratification and the development and use of nomograms as predictive tools.


Malignant anal sac melanoma in dogs: eleven cases (2000 to 2015).
To report the signalment, clinical presentation, treatments pursued and outcomes of dogs with malignant anal sac melanoma. Medical records from five institutions from January 2000 through December 2015 were reviewed and dogs with cytologically- or histologically-confirmed malignant anal sac melanoma were identified. Signalment, clinical signs, staging, cytology, histopathologic analysis, surgical and non-surgical treatments were extracted from the medical records. The referring veterinarians and owners were contacted for follow-up data. Eleven dogs were included and survival data was available for all. The most common clinical signs were bloody anal sac discharge and perianal licking. Initial treatments pursued included surgery (n=8), chemotherapy (n=1), and palliative treatment with pain medications and stool softeners (n=2). In an adjuvant setting, melanoma vaccine was pursued following surgery in three dogs and chemotherapy in one dog. Regardless of treatment, progression-free survival (mean 92 · 5 days) and overall survival times (median 107 days) were short. Dogs in this case series had a guarded to poor prognosis regardless of treatment. Ten of 11 dogs were euthanased due to local or distant disease progression. Only 1 of 11 dogs was alive one year after diagnosis. An understanding of tumour behaviour in this location could lead to improved survival times with earlier diagnosis and treatment.


[Clinicopathological significance of the expression of carbonic anhydrase I and II in human pancreatic cancer].
To explore the clinicopathological significance of the expression of carbonic anhydrase I (CAI) and carbonic anhydrase II (CAII) protein and mRNA levels in pancreatic ductal adenocarcinoma (PDAC). The expression of CAI and CAII protein in 57 pairs of paraffin-embedded PDAC specimens and adjacent non-cancerous pancreatic tissues were detected by immunohistochemistry. The relationship between the protein expression and clinicopathological characters was analyzed. Western blot and quantitative real-time polymerase chain reaction (QRT-PCR) were used to examine the expression of CAI and CAII protein and mRNA levels in 16 paired fresh PDAC specimens, adjacent non-cancerous pancreatic tissues and 3 different differentiated pancreatic cancer cells (PANC-1, BxPC-3 & SW1990). The expression of CAI protein was higher in PDAC compared with that in paired non-cancerous pancreatic tissues (t = 2.395, P = 0.020), whereas, CAII expression was significantly lower in PDAC than that in paired non-cancerous pancreatic tissues (t = 4.296, P = 0.000). The expression of CAI and CAII protein had a positive correlation with tumor differentiation (χ(2) = 7.557, P = 0.023; χ(2) = 7.822, P = 0.020) and CAI showed a direct negative correlation with vascular invasion (χ(2) = 6.349, P = 0.012). Univariate and multivariate analysis with clinicopathological characters revealed that the CAII expression was an independent prognostic indicator for PDAC patients (P = 0.017; P = 0.011 respectively). No significant difference of CAI mRNA and protein expression existed between PDAC and adjacent normal pancreatic tissues (t = 1.619, P = 0.126; t = 1.352, P = 0.197) as detected by Western blot and QRT-PCR, but the expression of CAII mRNA and protein levels was much lower in PDAC than that in paired non-cancerous pancreatic tissues, respectively (t = 3.360, P = 0.004; t = 2.934, P = 0.010). Moreover, the mRNA and protein expression of CAI and CAII gradually increased with the better differentiation degree of pancreatic cancer cells. CAI is up-regulated and CAII down-regulated in PDAC. Both of them are correlated with tumor differentiation. CAII expression is an independent prognostic indicator for PDAC patients.


In vivo identification of the mitogen-activated protein kinase cascade as a central pathogenic pathway in experimental mesangioproliferative glomerulonephritis.
Evidence was recently provided for the activation of extracellular signal-regulated kinase (ERK), the best characterized mitogen-activated protein kinase, as an intracellular convergence point for mitogenic stimuli in animal models of glomerulonephritis (GN). In this study, in vivo ERK activity was blocked, with a pharmacologic inhibitor (U0126) of the ERK-activating kinase, in rats with mesangioproliferative GN. After injection of the monoclonal anti-Thy1.1 antibody (OX-7), the rats were treated (days 3 to 6) with low (10 mg/kg body wt) or high (100 mg/kg body wt) doses of U0126 administered intraperitoneally twice daily. On day 6 after induction of the disease, whole cortical tissue and isolated glomeruli were examined by using kinase activity assays, Western blot analyses, and immunohistochemical assays. Treatment with U0126 significantly reduced glomerular stimulation of ERK in anti-Thy1 GN. In the high dose-treated group, this downregulation was accompanied by a reduction in the number of glomerular mitotic figures, back to healthy control levels, and significant decreases in the numbers of total (P < 0.05) and 5-bromo-2'-deoxyuridine-positive (P < 0.05) glomerular cells. Immunohistochemical double-staining of renal sections demonstrated that mesangial cells were the major glomerular targets of U0126 in anti-Thy1 GN. These observations point to ERK as a putative intracellular mediator of the proliferative response in GN and suggest that pharmacologic treatments that interfere with the activation of ERK may be of potential therapeutic interest.


Survey of Antibiotic-producing Bacteria Associated with the Epidermal Mucus Layers of Rays and Skates.
Elasmobranchs represent a distinct group of cartilaginous fishes that harbor a remarkable ability to heal wounds rapidly and without infection. To date very little work has addressed this phenomenon although it is suggested that antibiotic capabilities associated with epidermal surfaces may be a factor. The study of benefits derived from mutualistic interactions between unicellular and multicellular organisms is a rapidly growing area of research. Here we survey and identify bacterial associates of three ray and one skate species in order to assess the potential for antibiotic production from elasmobranch associated bacteria as a novel source for new antibiotics.


Open Gastrostomy by Mini-Laparotomy: Our Method.
When percutaneous endoscopic gastrostomy (PEG) is not feasible owing to anatomical obstacles, laparotomic or laparoscopic gastrostomy (LAG) is an alternative. At our institution, LAG has been the first choice for patients who are unable to undergo PEG; however, we have introduced a small open gastrostomy through a 2-cm-long transverse incision since 2020. By December 2022, 12 patients had undergone this procedure without complications. In one case where the stomach was located cephalad to the rib arch and the patient had a round dorsum, the incision wound was extended, and a lengthy operation was required. We believe that our small-incision gastrostomy is a useful option in addition to LAG for cases in which PEG is difficult to perform. Further studies are required to determine the indications for this procedure.


Comparison of CT ventilation imaging and hyperpolarised gas MRI: effects of breathing manoeuvre.
Image registration of lung CT images acquired at different inflation levels has been proposed as a surrogate method to map lung 'ventilation'. Prior to clinical use, it is important to understand how this technique compares with direct ventilation imaging modalities such as hyperpolarised gas MRI. However, variations in lung inflation level have been shown to affect regional ventilation distributions. Therefore, the aim of this study was to evaluate the impact of lung inflation levels when comparing CT ventilation imaging to ventilation from 3He-MRI. Seven asthma patients underwent breath-hold CT at total lung capacity (TLC) and functional residual capacity (FRC). 3He-MRI and a same-breath 1H-MRI were acquired at FRC+1L and TLC. Percentage ventilated volumes (%VVs) were calculated for FRC+1L and TLC 3He-MRI. TLC-CT and registered FRC-CT were used to compute a surrogate ventilation map from voxel-wise intensity differences in Hounsfield unit values, which was thresholded at the 10th and 20th percentiles. For direct comparison of CT and 3He-MRI ventilation, FRC+1L and TLC 3He-MRI were registered to TLC-CT indirectly via the corresponding same-breath 1H-MRI data. For 3He-MRI and CT ventilation comparison, Dice similarity coefficients (DSCs) between the binary segmentations were computed. The median (range) of %VVs for FRC+1L and TLC 3He-MRI were 90.5 (54.9-93.6) and 91.8 (67.8-96.2), respectively (p = 0.018). For MRI versus CT ventilation comparison, statistically significant improvements in DSCs were observed for TLC 3He MRI when compared with FRC+1L, with median (range) values of 0.93 (0.86-0.93) and 0.86 (0.68-0.92), respectively (p = 0.017), for the 10-100th percentile and 0.87 (0.83-0.88) and 0.81 (0.66-0.87), respectively (p = 0.027), for the 20-100th percentile. Correlation of CT ventilation imaging and hyperpolarised gas MRI is sensitive to lung inflation level. For ventilation maps derived from CT acquired at FRC and TLC, a higher correlation with gas ventilation MRI can be achieved if the MRI is acquired at TLC.


[2016 Update in general internal medicine : Good intentions, possible bad outcomes].
Ideally, our clinical practices and decisions should be based on evidence derived from randomized clinical trials. Yet, we often have to determine the potential side effects (including interactions) of drugs that we prescribed using other level of evidence; clinical trials being obviously not appropriate for such situations. Results from observational studies published in 2016 should be of interest to primary care physicians. In this review, we present six of them. Once the limitations of these non-interventional studies acknowledged, primary care physicians should consider these results and be particularly attentive when prescribing these drugs.


Genome-wide interaction study reveals epistatic interactions for beef lipid-related traits in Nellore cattle.
Gene-gene interactions cause hidden genetic variation in natural populations and could be responsible for the lack of replication that is typically observed in complex traits studies. This study aimed to identify gene-gene interactions using the empirical Hilbert-Schmidt Independence Criterion method to test for epistasis in beef fatty acid profile traits of Nellore cattle. The dataset contained records from 963 bulls, genotyped using a 777 962k SNP chip. Meat samples of Longissimus muscle, were taken to measure fatty acid composition, which was quantified by gas chromatography. We chose to work with the sums of saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA), omega-3 (OM3), omega-6 (OM6), SFA:PUFA and OM3:OM6 fatty acid ratios. The SNPs in the interactions where P < 10 - 8 were mapped individually and used to search for candidate genes. Totals of 602, 3, 13, 23, 13, 215 and 169 candidate genes for SFAs, MUFAs, PUFAs, OM3s, OM6s and SFA:PUFA and OM3:OM6 ratios were identified respectively. The candidate genes found were associated with cholesterol, lipid regulation, low-density lipoprotein receptors, feed efficiency and inflammatory response. Enrichment analysis revealed 57 significant GO and 18 KEGG terms ( P < 0.05), most of them related to meat quality and complementary terms. Our results showed substantial genetic interactions associated with lipid profile, meat quality, carcass and feed efficiency traits for the first time in Nellore cattle. The knowledge of these SNP-SNP interactions could improve understanding of the genetic and physiological mechanisms that contribute to lipid-related traits and improve human health by the selection of healthier meat products.


Long term regulation of glycogen metabolizing enzymes by insulin in H4 hepatoma cells.
Insulin alone at concentrations of less than 1 to 5 uU/ml increased the enzyme activities of glycogen synthase, synthase phosphatase, phosphorylase, and phosphorylase phosphatase in hepatoma H4 cells in culture in the presence and absence of serum. Increase in total and active forms of glycogen synthase and phosphorylase were observed. Cycloheximide blocked the action of insulin on glycogen synthase, glycogen synthase phosphatase and phosphorylase phosphatase. The enzymes with the exception of glycogen synthase phosphatase were expressed with greater hormonal sensitivity in the absence as compared to the presence of serum in terms of hormone concentration required and or time of onset. These results demonstrate that these glycogen metabolizing enzymes are under long term control by insulin, with glycogen synthase being the most sensitive of the enzymes studied to the action of the hormone.


MIA: non-targeted mass isotopolome analysis.
MIA detects and visualizes isotopic enrichment in gas chromatography electron ionization mass spectrometry (GC-EI-MS) datasets in a non-targeted manner. It provides an easy-to-use graphical user interface that allows for visual mass isotopomer distribution analysis across multiple datasets. MIA helps to reveal changes in metabolic fluxes, visualizes metabolic proximity of isotopically enriched compounds and shows the fate of the applied stable isotope labeled tracer. Linux and Windows binaries, documentation, and sample data are freely available for download at http://massisotopolomeanalyzer.lu MIA is a stand-alone application implemented in C ++ and based on Qt5, NTFD and the MetaboliteDetector framework. email@example.com.


Cyclooxygenase (COX)-2 inhibitor celecoxib abrogates activation of cigarette smoke-induced nuclear factor (NF)-kappaB by suppressing activation of IkappaBalpha kinase in human non-small cell lung carcinoma: correlation with suppression of cyclin D1, COX-2, and matrix metalloproteinase-9.
Cigarette smoke (CS) has been linked to cardiovascular, pulmonary, and malignant diseases. CS-associated malignancies including cancers of the larynx, oral cavity, and pharynx, esophagus, pancreas, kidney, bladder, and lung; all are known to overexpress the nuclear factor-kappaB (NF-kappaB)-regulated gene products cyclin D1, cyclooxygenase (COX)-2, and matrix metalloprotease-9. Whether the COX-2 inhibitor, celecoxib, approved for the treatment of colon carcinogenesis and rheumatoid arthritis, affects CS-induced NF-kappaB activation is not known, although the role of NF-kappaB in regulation of apoptosis, angiogenesis, carcinogenesis, and inflammation is established. In our study, in which we examined DNA binding of NF-kappaB in human lung adenocarcinoma H1299 cells, we found that cigarette smoke condensate (CSC)-induced NF-kappaB activation was persistent up to 24 h, and celecoxib suppressed CSC-induced NF-kappaB activation. Celecoxib was effective even when administered 12 h after CSC treatment. This effect, however, was not cell type-specific. The activation of inhibitory subunit of NF-kappaB kinase (IkappaB), as examined by immunocomplex kinase assay, IkappaB phosphorylation, and IkappaB degradation was also inhibited. Celecoxib also abrogated CSC-induced p65 phosphorylation and nuclear translocation and NF-kappaB-dependent reporter gene expression. CSC-induced NF-kappaB reporter activity induced by NF-kappaB inducing kinase and IkappaB alpha kinase but not that activated by p65 was also blocked by celecoxib. CSC induced the expression of NF-kappaB-regulated proteins, COX-2, cyclin D1, and matrix metalloproteinase-9, and celecoxib abolished the induction of all three. The COX-2 promoter that is regulated by NF-kappaB was activated by CSC, and celecoxib suppressed its activation. Overall, our results suggest that chemopreventive effects of celecoxib may in part be mediated through suppression of NF-kappaB and NF-kappaB-regulated gene expression, which may contribute to its ability to suppress inflammation, proliferation, and angiogenesis.


Effects of increased flooding on riparian vegetation: Field experiments simulating climate change along five European lowland streams.
In many parts of the world, the magnitude and frequency of cold-season precipitation are expected to increase in the near future. This will result in an increased magnitude and duration of winter and spring flooding by rain-fed streams and rivers. Such climate-driven increases in flooding are likely to affect riparian plant communities, but future vegetation changes are hard to predict due to current lack of data. To fill this knowledge gap, we experimentally modified the hydrology of five streams across three countries in north-western Europe during late winter/early spring over a period of 3 years. We assessed the responses in riparian plant species richness, biomass, plant-available nitrogen and phosphorus and seed deposition to increased flooding depth (+18 cm on average at the lowest positions along the riparian gradient) and prolonged flooding duration (6 weeks on average). After 3 years of increased flooding, there was an overall decline in riparian species richness, while riparian plant biomass increased. Extractable soil nitrogen and phosphorus also increased and are likely to have contributed to the increased biomass. Increased flooding resulted in the arrival of more seeds of additional species to the riparian zone, thereby potentially facilitating the shifts in riparian plant species composition we observed. The results of our concerted experimental effort demonstrate that changes in stream riparian plant communities can occur rapidly following increased winter flooding, leading to strong reductions in plant species diversity.


Expression of messenger ribonucleic acid (mRNA) encoding 3beta-hydroxysteroid dehydrogenase delta4,delta5 isomerase (3beta-HSD) during recruitment and selection of bovine ovarian follicles: identification of dominant follicles by expression of 3beta-HSD mRNA within the granulosa cell layer.
The objective of the present study was to examine changes in expression of mRNA encoding 3beta-hydroxysteroid dehydrogenase delta4,delta5 isomerase (3beta-HSD) during recruitment and selection of bovine ovarian follicles. Dairy heifers (4-5/time period) were ovariectomized at 12, 24, 36, 48, 60, 72, 84, or 96 h after initiation of the first follicular wave (Time 0) following estrus. Expression of 3beta-HSD mRNA was localized by in situ hybridization and quantified by image analysis. Expression of 3beta-HSD mRNA was first detected in theca interna cells of preantral follicles with a well-developed theca layer and in granulosa cells of follicles > or = 8 mm in diameter. Regardless of stage of follicular wave, expression of 3beta-HSD mRNA in granulosa cells of follicles > or = 8 mm was correlated with follicular size (r = 0.665; p < 0.01). The 36-h time period appeared to be a transition period for selection since dominant follicles were detected by size and expression of 3beta-HSD mRNA in some cows but not in others. By 48 h after wave initiation, dominant follicles could be identified by both size and expression of 3beta-HSD mRNA. Expression of mRNA for 3beta-HSD in theca cells was higher (p < 0.05) at 24 h than at 12 h and remained elevated thereafter through 96 h. In contrast to theca cells, expression of mRNA for 3beta-HSD was undetectable within granulosa cells at 12 and 24 h. At 36 h, 3beta-HSD mRNA was expressed in granulosa cells of healthy follicles > or = 8 mm, and expression was higher (p < 0.05) at 48 h compared with 36 h. Expression of 3beta-HSD mRNA levels increased further in granulosa cells (p < 0.05) at 84 and 96 h compared to 48 h. Upon detection of mRNA for 3beta-HSD in granulosa cells, high levels of expression were always found in one (dominant) follicle/cow with the exception of two cows at 36 and 84 h that expressed 3beta-HSD mRNA in two large healthy follicles. Expression of 3beta-HSD mRNA was also detectable in granulosa cells of a few large atretic follicles in which remnant granulosa cells appeared to be luteinized. Healthy follicles expressed higher (p < 0.05) levels of 3beta-HSD mRNA in both theca and granulosa cells than did atretic follicles. Expression of 3beta-HSD mRNA in theca cells was higher (p < 0.01) in dominant follicles than in other subordinate healthy follicles. These results indicate that only selected dominant follicles express 3beta-HSD mRNA within granulosa cells, and expression increased in both thecal and granulosa cells during the follicular wave. Therefore, expression of 3beta-HSD mRNA within granulosa cells may be associated with the mechanism of selection of the dominant follicle during a follicular wave and may be required for maximum steroid production during follicular dominance.