Identification of Early and Extra-Early Maturing Tropical Maize Inbred Lines with Multiple Disease Resistance for Enhanced Maize Production and Productivity in Sub-Saharan Africa.
Maize, a staple for millions across sub-Saharan Africa (SSA), faces major biotic constraints affecting production and safety of the crop. These include northern corn leaf blight (NCLB), southern corn leaf blight (SCLB), Curvularia leaf spot (CLS), and aflatoxin contamination by Exserohilum turcicum, Bipolaris maydis, Curvularia lunata, and Aspergillus flavus, respectively. Farmers in SSA would benefit tremendously if high-yielding maize hybrids with multiple disease resistance (MDR) were developed and commercialized. In all, 49 early-maturing (EM; 90 to 95 days to physiological maturity) and 55 extra-early-maturing (EEM, 80 to 85 days to physiological maturity) inbred lines developed by the International Institute of Tropical Agriculture were identified as resistant to NCLB in field evaluations in multiple agroecologies of Nigeria in 2017 and 2018. From each maturity group, the 30 most resistant inbreds were selected for evaluation for resistance to SCLB and CLS using a detached-leaf assay. Additionally, the inbreds were screened for resistance to kernel rot and aflatoxin contamination using a kernel screening assay. In all, 7 EM and 6 EEM maize inbreds were found to be highly resistant to the three foliar pathogens while 10 inbreds were resistant to the foliar pathogens and supported significantly less (P = 0.01) aflatoxin accumulation than other inbreds. Inbreds having MDR should be tested extensively in hybrid combinations and commercialized. Large-scale use of maize hybrids with MDR would (i) increase maize production and productivity and (ii) reduce losses caused by aflatoxin contamination. Overall, planting of EM and EEM maize hybrids with MDR would contribute to food security, reduced aflatoxin exposure, and increased incomes of maize farmers in SSA.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.


Culturing Borrelia burgdorferi from spleen and kidney tissues of wild-caught white-footed mice, Peromyscus leucopus.
Borrelia burgdorferi was isolated most frequently from tissue of spleen (n = 13) and kidney (n = 10) and less often from blood (n = 5) of wild-caught Peromyscus leucopus. Prevalence of infection tended to be highest at sites where Lyme disease was most common (e.g., 5 of 6 mice were positive in East Haddam, Connecticut). Spirochetes were not isolated in Danbury or New Hartford, areas where this malady is rare. However, in Fairfield, where the disease is also uncommon, 4 of 9 mice were infected. Larval and nymphal I. dammini, containing borreliae, parasitized P. leucopus at all sites where B. burgdorferi was cultured from mice. Borreliae were also detected in D. variabilis feeding on hosts at two of the sites. P. leucopus appears to be an excellent animal to identify focal areas of B. burgdorferi.


Successful pregnancy-preserving laparoscopic adnexectomy for complicated ovarian torsion during late pregnancy: A case report and review of the literature.
A rare disorder called ovarian torsion (OT) during pregnancy can harm both the mother and the fetus. Predisposing variables for the condition include enlarged ovaries, free mobility, and a long pedicle, despite the fact that its genesis is not entirely understood. When ovarian stimulation is used to treat infertility, the disease's incidence rises. Magnetic resonance imaging and ultrasound are examples of diagnostic imaging modalities (MRI). A 26-year-old woman with a 33-week pregnancy presented to our emergency department with acute, severe left groin pain. Laboratory evaluation was unremarkable except for leukocytosis (18.800/μL) with neutrophil shift. A radiologist used ultrasound to examine the abdomen and pelvis, and the results revealed a bulk enlargement of the left adnexa. The patient underwent a non-enhanced MRI in order to obtain a conclusive diagnosis, which revealed a massive enlargement and torsion of the left ovary with large areas of necrosis. The patient underwent a successful laparoscopic adnexectomy with preservation of the pregnancy. She delivered a healthy baby and had an uneventful follow up period. The etiology of OT is largely unknown. Any tendency to rotate the infundibulopelvic and utero-ovarian ligaments should be considered as a possible etiology. The prevalence of OT among pregnant women is underreported and determined by small limited studies. Ovarian torsion should be included in the differential diagnosis of patients with suspected acute abdomen in advanced stages of pregnancy. In addition, MRI should be used as an alternative diagnostic modality in patients with normal sonographic findings.


Palliative ICU beds for potential organ donors: an effective use of resources based on quality-adjusted life-years gained.
To evaluate whether the admission of a palliative patient to the intensive care unit for end-of-life care and consideration of organ donation provides an equivalent net benefit in quality-adjusted life-years (QALYs) compared with the admission of a non-palliative patient for active management. Relevant publications from the period 1995-2015 were reviewed to estimate the mean QALYs gained from ICU admission of a critically ill patient and mean QALYs gained from transplantation of solid organs from an organ donor. Australian audit data were used to estimate the likelihood of a palliative patient admitted to the ICU progressing to organ donation. We calculated probabilities of each outcome and developed an algorithm to illustrate possible pathways for a patient who may progress to organ donation. A non-palliative ICU admission provides to the patient about 1.0 QALY per ICU bed-day. An ICU bed provided to a patient admitted to the ICU for palliation and consideration of organ donation results in 7.3 QALYs gained for the community per ICU bed-day. The admission of a dying patient to the ICU when organ donation may be possible is of considerable community benefit, yielding an average of over seven times the QALYs per ICU bed-day compared with the average benefit for ICU patients expected to survive. When it is possible to offer end-of-life care in the ICU, it should not be denied on the basis of concerns about lack of benefit or inappropriate use of resources.


Reorganizing nursing for the future: nursing commission recommendations and research implications.
The department of Health and Human Services Commission on Nursing, along with various nurse advisors, has developed a series of findings and recommendations relevant to the nursing shortage. This article discusses the findings and recommendations and their relevance to practice in the current climate of the nursing shortage and changing work environment, and presents implications for future organizational and clinical research.


Effect of the Trendelenburg position on the distribution of arterial air emboli in dogs.
We examined the effects of buoyancy on the distribution of arterial gas bubbles using in vitro and in vivo techniques in dogs. A simulated carotid artery preparation was used to determine the effects of bubble size and vessel angle on the velocity and direction of bubble movement in flowing blood. Because buoyancy tends to float bubbles away from dependent areas, bubble velocity would be expected to decrease as the vessel angle increased. We found that larger bubbles increased in velocity in the same direction as the blood flow at 0-, 10-, and 30-degree vessel angles and decreased when the vessel was positioned at 90 degrees. Smaller bubbles did not change velocity from 0 to 30 degrees and increased in velocity in the same direction as blood flow at 90 degrees. In 10 anesthetized dogs, we studied the effects of 0-, 10-, 15-, and 30-degree Trendelenburg's position on carotid artery distribution of gas bubbles injected into the left ventricle or ascending aorta. Regardless of the degree of the Trendelenburg position, the bubbles passed into the carotid artery simultaneously with passage into the abdominal aorta. We conclude that the forces of buoyancy do not overcome the force of arterial blood flow and that the Trendelenburg position does not prevent arterial bubbles from reaching the brain.


Epilepsy surgery can help many more adult patients with intractable seizures.
To quantify underreferral for epilepsy surgery in The Netherlands, and reveal its causes. Cross-sectional sample of medical files of epilepsy patients from eight general hospitals and two tertiary care epilepsy centers. We selected patients, not seizure free despite 3 or more anti-epileptic drugs. Medical records were judged by an expert panel whether referral should have been done according to published Dutch guidelines. The treating neurologists were confronted with the panel's judgement. In a sample of 1424 patients, 69 had been referred; another 265 were intractable and not referred; 139 of these 265 patients should have been according to the panel. In 89 of 139 patients, the neurologist gave additional arguments for not referring, mainly the physician's estimate of (low) seizure burden or the patient's psychological condition. In 66 of 89 cases, this could not convince the panel. Attitudes were similar in secondary and tertiary treatment centers. Multivariable data analysis showed independent predictors of incorrectly, versus correctly, not referred patients. Substantial underreferral exists in The Netherlands, withholding refractory patients seizure freedom. Adherence to existing guidelines, better prioritizing of surgical work-up, and unprejudiced discussion of surgical treatment with the patient, could lead to 2-2.5 times more referrals.


Conversion of the neurotoxic precursor 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine into its pyridinium metabolite by human platelet monoamine oxidase type B.
MPTP (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine) causes selective and irreversible degeneration of the substantia nigra of human and non-human primates. In the central nervous system, the oxidative metabolism of MPTP to 1-methyl-4-phenyl-pyridinium (MPP+) by monoamine oxidase type B (MAO-B) seems to be a critical feature in the neurotoxic process. We now report that [3H]MPTP is rapidly converted in vitro into [3H]MPP+ by human platelet MAO-B. The formation of [3H]MPP+ in human platelets is prevented by specific MAO-B but not by MAO-A or by 5-hydroxytryptamine uptake inhibitors.


Improving the technical efficiency of public health centers in Cambodia: a two-stage data envelopment analysis.
Cambodia is undergoing a series of reforms with the objective of reaching universal health coverage. Information on the causes of inefficiencies in health facilities could pave the way for a better utilization of limited resources available to ensure the best possible health care for the population. The purpose of this study is to evaluate the technical efficiency of health centers and the determinants for inefficiencies. This cross-sectional study used secondary data from a costing study on 43 health centers in six Cambodian provinces (2016-2017). Firstly, the Data Envelopment Analysis method with output-orientation was applied to calculate efficiency scores by selecting multiple input and output variables. Secondly, a tobit regression was performed to analyze potential explanatory variables that could influence the inefficiency of health centers. Study findings showed that 18 (43%) health centers were operating inefficiently with reference to the variable returns to scale efficiency frontier and had a mean pure technical efficiency score of 0.87. Overall, 22 (51%) revealed deficits in producing outputs at an optimal scale size. Distance to the next referral hospital, size and quality performance of the health centers were significantly correlated with health center inefficiencies. Differences in efficiency exist among health centers in Cambodia. Inefficient health centers can improve their technical efficiency by increasing the utilization and quality of health services, even if it involves higher costs. Technical efficiency should be continuously monitored to observe changes in health center performance over time.


A Meta-Analysis of Semantic Memory in Mild Cognitive Impairment.
Accumulating evidence over the past decade suggests that semantic deficits represent a consistent feature of Mild Cognitive Impairment (MCI). A meta-analysis was performed to examine if semantic deficits are consistently found in patients with MCI. Studies meeting all inclusion criteria were selected for the current meta-analysis. An effect size and a weight were calculated for each study. A random effect model was performed to assess the overall difference in semantic performances between MCI patients and healthy subjects. 22 studies (476 healthy participants, 476 MCI patients, mean Mini Mental Status Examination of the MCI patients: 27.05 ± 0.58) were included in the meta-analysis. Results indicate that MCI patients systematically performed significantly worse than healthy matched controls in terms of overall semantic performance (mean effect size of 1.02; 95% CI [0.80; 1.24]). Semantic deficits are a key feature of MCI. Semantic tests should be incorporated in routine clinical assessments.


ERAP140, a conserved tissue-specific nuclear receptor coactivator.
We report here the identification and characterization of a novel nuclear receptor coactivator, ERAP140. ERAP140 was isolated in a screen for ER alpha-interacting proteins using the ER alpha ligand binding domain as a probe. The ERAP140 protein shares no sequence and has little structural homology with other nuclear receptor cofactors. However, homologues of ERAP140 have been identified in mouse, Drosophila, and Caenorhabditis elegans. The expression of ERAP140 is cell and tissue type specific and is most abundant in the brain, where its expression is restricted to neurons. In addition to interacting with ER alpha, ERAP140 also binds ER beta, TR beta, PPAR gamma, and RAR alpha. ERAP140 interacts with ER alpha via a noncanonical interaction motif. The ER alpha-ERAP140 association can be competed by coactivator NR boxes, indicating ERAP140 binds ER alpha on a surface similar to that of other coactivators. ERAP140 can enhance the transcriptional activities of nuclear receptors with which it interacts. In vivo, ERAP140 is recruited by estrogen-bound ER alpha to the promoter region of endogenous ER alpha target genes. Furthermore, the E(2)-induced recruitment of ERAP140 to the promoter follows a cyclic pattern similar to that of other coactivators. Our results suggest that ERAP140 represents a distinct class of nuclear receptor coactivators that mediates receptor signaling in specific target tissues.


Efficacy and safety of traditional Chinese medicine for the treatment of influenza A (H1N1): A meta-analysis.
In March 2009, the first reported case infected with influenza A (H1N1) virus was identified in Mexico. The World Health Organization officially declared the outbreak to be a pandemic on June 11, 2009. The objective of this study was to evaluate the efficacy and safety of traditional Chinese medicine (TCM) in the treatment of influenza A (H1N1) infection. We electronically and manually searched electronic databases, reference lists, and conference compilations to identify randomized clinical trials that compared the treatment of influenza A (H1N1) using TCM with a control group receiving oseltamivir or antivirus therapy. The Jadad score was used to assess trial quality. Duration of viral shedding, time to defervescence, and effective rate were taken as outcome measurements; additionally, heterogeneity analysis and meta-analysis were performed. A total of 30 studies were included in our investigation, and these studies together included 3444 cases. Based on the Jadad score, each of these studies were divided as follows: high-quality studies (n = 3), medium-quality studies (n = 2), and low quality studies (n = 25). A meta analysis was performed, which indicated that the time to defervescence between the TCM treatment group and the control group was statistically significant, the duration of viral [Influenza A (H1N1)] shedding in the integrated Chinese and Western medicine subgroups was statistically significant, but it was not statistically significant between the two groups, the effective rate between the two groups was not statistically significant. A total of 18 studies described adverse drug reactions. The results of our study indicated that the mean time to defervescence in the TCM treatment group was less than noted in the control group, and that the duration of viral [Influenza A (H1N1)] shedding in the integrated Chinese and Western medicine subgroups was less than that noted in the control group. However, the available evidence does not consider the fact that the difference in duration of viral shedding and effective rate between the two groups was statistically similar. No obvious adverse events were reported in the included studies.


The c-ets proto-oncogenes encode transcription factors that cooperate with c-Fos and c-Jun for transcriptional activation.
Cell transformation by oncogenes leads to changes in gene expression. A key event in this process seems to be activation of the transcription factors AP-1 and PEA 3. Their synergistic activities are required for efficient activation of transcription from different promoters by many different oncogenes, serum growth factors and the tumour promoter TPA. We show here that the products of the ets-1 and -2 proto-oncogenes, whose biological function was previously unknown, are transcription factors that activate transcription through the PEA 3 motif. The p68c-ets-1 protein specifically binds to DNA and contains a transcriptional activation domain. The ets-like gene family therefore seems to encode a new family of transcription factors, apparently unrelated to other transcription factors. The p68c-ets-1 protein cooperates with c-Fos and c-Jun (components of AP-1) for activation of transcription from the oncogene-responsive domain of the polyoma enhancer, indicating that combined activity of all three oncoproteins could be involved in the response of cells to growth stimuli.


Relationship of Sonographer Credentialing to Intersocietal Accreditation Commission Echocardiography Case Study Image Quality.
Cardiac sonographer credentialing may guarantee baseline content knowledge but does not directly evaluate clinical scanning skills. The aim of this study was to determine the relationship of sonographer credentialing status to clinical competence, as defined by image quality of case studies submitted for Intersocietal Accreditation Commission (IAC) adult transthoracic echocardiography laboratory accreditation. In this study, data were retrieved retrospectively from the IAC Echocardiography application database for all adult echocardiography laboratories applying online from August 10, 2011, to December 12, 2013. Aortic stenosis (AS) and left ventricular (LV) regional dysfunction case studies were analyzed separately. Sonographers submitting case studies were coded as credentialed or noncredentialed. An image quality score (IQS) was calculated for each case study, reflecting review scores for examination components directly related to image quality and acquisition. The group of sonographers was divided into quartiles on the basis of annual procedure volume; mean case study IQS was compared between credentialed and noncredentialed sonographers. For all four quartiles of the LV cases and the lowest three volume quartiles of the AS cases, mean IQS was significantly higher for credentialed than noncredentialed sonographers. Mean IQS in the highest volume quartile for AS studies was not significantly different by credential status. In the setting of IAC Echocardiography accreditation, credentialed sonographers achieved higher mean IQSs than noncredentialed sonographers in seven of eight comparisons. However, further research will be required to expand the scope of this inference beyond AS and LV regional dysfunction cases submitted for IAC adult transthoracic echocardiography laboratory accreditation.


Secondary causes of elevated hemoglobin in patients undergoing molecular testing for suspected polycythemia vera in southwestern Ontario: a chart review.
Molecular testing for JAK2 mutations is part of the standard diagnostic workup for patients with suspected polycythemia vera. We sought to characterize evolving practice patterns in the investigation of erythrocytosis and the prevalence of secondary causes, including use of medications such as sodium-glucose cotransporter-2 (SGLT2) inhibitors, among patients who underwent molecular testing. We reviewed charts of all consecutive patients investigated for erythrocytosis (hemoglobin > 160 g/L for women, > 165 g/L for men) with JAK2 testing between 2015 and 2021 at London Health Sciences Centre, a tertiary referral centre in Ontario, Canada, to assess changes in rates of JAK2 mutation positivity, average hemoglobin levels and the prevalence of secondary causes of erythrocytosis. A total of 891 patients with erythrocytosis underwent JAK2 mutation testing with an increase in number of tests (particularly from 2017 to 2018), a decrease in the rate of JAK2 positivity and similar average hemoglobin levels over the study period. We observed a high proportion of patients with secondary causes of erythrocytosis, ranging from 59% to 74% over the study period, including medications associated with erythrocytosis, namely testosterone (6%-11%) and SGLT2 inhibitors (2%-19%). Stopping SGLT2 inhibitors was associated with a significant decrease in hemoglobin levels (mean -14.7 g/L, 95% confidence interval -18.9 to -10.5 g/L) compared with continuation. Use of SGLT2 inhibitors may be a common and underrecognized secondary cause of elevated hemoglobin levels in patients investigated for erythrocytosis. Our findings underscore the importance of a detailed medical history to support judicious use of molecular testing, in adherence with the current guideline on the investigation of erythrocytosis.


Isotopic (δ15 N) relationship of pregnant females and their embryos: Comparing placental and yolk-sac viviparous elasmobranchs.
Nitrogen stable isotopes ratios (δ15 N) were determined for selected tissues (muscle, liver, blood and yolk) of pregnant females and their embryos of a placental viviparous species, the Pacific sharpnose shark (Rhizoprionodon longurio), and a yolk-sac viviparous species, the speckled guitarfish (Pseudobatos glaucostigmus). The R. longurio embryo tissues were 15 N enriched compared to the same tissues in the pregnant female, using the difference in δ15 N (Δδ15 N) between embryo and adult. Mean Δδ15 N was 2.17‰ in muscle, 4.39‰ in liver and 0.80‰ in blood. For P. glaucostigmus, embryo liver tissue was significantly 15 N enriched in comparison with liver of the pregnant female (Δδ15 N mean = 1.22‰), whereas embryo muscle was 15 N depleted relative to the muscle of the pregnant female (Δδ15 N mean = -1.22‰). Both species presented a significant positive linear relationship between Δδ15 N and embryo total length (LT ). The results indicated that embryos have different Δδ15 N depending on their reproductive strategy, tissue type analysed and embryo LT .


Chemopreventive potential of fungal taxol against 7, 12-dimethylbenz[a]anthracene induced mammary gland carcinogenesis in Sprague Dawley rats.
Breast cancer is the second most prevalent cancer and foremost global public health problem. The present study was designed to appraise the chemopreventive potential of fungal taxol against 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary gland carcinogenesis in Sprague Dawley rats. After 90 days of tumor induction, fungal and authentic taxol were given intraperitoneally once in a week for four weeks. Infrared thermal imaging analysis, serum biochemical parameters such as lipid peroxidase (LPO), creatinine, enzymic and non enzymic antioxidants, liver markers tests such as alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG) and lipoproteins was analysed. In addition, histopathological observation (breast, kidney and liver), immunohistochemical analysis (p53 and Her2/neu) and western blotting experiments (bcl-2, bax and caspase-9) were performed both in control and experimental animals. In thermal imaging, decreased temperature was observed in rat treated with fungal and authentic taxol when compared to tumor induced rats. The significant decrease in LPO, creatinine, ALT, AST, TC, TG, lipoproteins and increase in enzymic, non-enzymic antioxidants were exemplified in serum of treated groups. Further histopathology, immunohistochemical and western blot analysis (bax, cas-9 and bcl-2) of apoptotic markers in breast tissues clearly showed the anti-carcinogenic property of fungal taxol. Our findings implement that fungal taxol is a potential chemo preventive agent against DMBA induced mammary gland carcinogenesis.


Neurotoxicity of intra-CSF liposomal cytarabine (DepoCyt) administered for the treatment of leptomeningeal metastases: a retrospective case series.
Treatment of leptomeningeal metastasis (LMD) remains challenging due to advanced systemic disease at presentation and limited treatment options. All patients underwent standard pre-treatment LMD evaluation including CSF assessment (cytology or flow cytometry), brain and spine MR imaging, and radioisotope CSF flow study. DepoCyt (liposomal cytarabine) was administered intraventricularly (n = 80) or intralumbar (n = 40) at 50 mg every 2 weeks × 4 and then every 4 weeks × 6 in responding patients. Dexamethasone (4 mg orally twice per day × 5 days) was co-administered with each DepoCyt treatment. Patients were seen with each DepoCyt treatment and assessed for toxicity. 120 adult patients [median age 51 years (range 33-68)] with LMD were treated with DepoCyt. DepoCyt Common Toxicity Criteria ≥ Grade 3 neurotoxicity was seen in 60 cycles (11.5 %) in 28 patients (23.3 %). Toxicity included bacterial meningitis (3.75 % of ventricular treatments: 0 % of lumbar treatments); chemical meningitis (17.5:15 %); communicating hydrocephalus (3.75:5 %); conus medullaris/cauda equina syndrome (5:5 %); decreased visual acuity (5:2.5 %); encephalopathy (5:5 %); leukoencephalopathy (7.5:2.5 %); myelopathy (2.5:2.5 %); radiculopathy (1.25:5 %); and seizures (1.25:2.5 %). Distribution of toxicity was similar regardless of route of administration (ventricular vs. lumbar). Toxicities were transient in 34 episodes (57 %) and permanent in 26 (43 %). There were no treatment-related deaths however 20 treatment-related toxicities (32.2 %) required hospitalization. In this retrospective case series, DepoCyt is generally well tolerated however a subset of patients (12.5 %) not easily identified pre-treatment, develop serious treatment-related neurological complications that may be persistent and impact quality of life.


Digoxin therapy and left ventricular performance in premature infants with patent ductus arteriosus.
Left ventricular systolic time intervals were assessed in 16 preterm infants with symptomatic left-to-right ductal shunts, before, during and after digoxin therapy. An intravenous loading dose of digoxin, 20 micrograms/kg, resulted in a serum digoxin concentration of 1.94 +/- 0.44 nmol/l (mean +/- 1 SD) but in no significant change in heart rate or systolic time intervals. Digoxin maintenance, 2.5 micrograms/kg/12 h, led 3-7 days later to serum concentrations of 2.57 +/- 1.06 nmol/l with an associated shortening of left ventricular ejection time (p less than 0.05) which probably reflected a reduced ductal shunt. Digoxin therapy was withdrawn after ductal closure. The terminal serum half-life was 87 +/- 17 h. Decreasing digoxin concentrations were associated with prolongation of left ventricular ejection time (p less than 0.01). Digoxin therapy did not seem to influence left ventricular systolic time intervals while ductal patency persisted. This may be attributed to limitations of the method or the left ventricle already working at its maximum.


Research progress of TIPE2 in immune-related diseases.
The tumor necrosis factor α-induced protein 8 (TNFAIP8) family, which consists of TNFAIP8 (TIPE), TNFAIP8L1 (TIPE1), TNFAIP8L2 (TIPE2) and TNFAIP8L3 (TIPE3), has recently emerged as a regulatory factor involved in immune response and tumorigenesis. Among its members, TIPE2 acts as a negative regulator of both innate and adaptive immunity, playing a crucial role in maintaining immune homeostasis by negatively regulating T cell receptor (TCR) and toll-like receptor (TLR) signal transduction. Immune homeostasis is an indispensable characteristic of the immune system, which prevents harmful inflammatory reactions and ensures the proper functioning of the body. A large number of studies have shown that abnormal TIPE2 expression exists in a variety of inflammation-related diseases such as asthma, colitis, and systemic lupus erythematosus, highlighting the importance of comprehending its function for the prevention and treatment of immune-related conditions. This review aims to provide an overview of the in vivo distribution and expression of TIPE2, its regulatory role in central and peripheral immune-related diseases, and the underlying mechanisms that govern its function in the inflammatory response. By delving into these aspects, a deeper understanding of the role and functionality of TIPE2 in inflammatory responses can be achieved.


Proteolytic signals in the primary structure of annexins.
Annexins are a superfamily of calcium-dependent membrane-associated proteins which interact with phospholipids. The primary structure of Annexins I, III, VII, VIII and XI contain a region enriched in proline, glutamate, serine and threonine (PEST sequences) towards the N-terminal end while annexins II, V and VI possess PEST regions somewhat distal to the N-terminus. These PEST sequences are believed to be the signals for rapid intracellular degradation. Annexin I is known to be cleaved by calpain near its PEST region suggesting that its PEST region might be a possible calpain recognition site. Western blot analysis of annexins V and XI in rat lung homogenates suggest that these proteins are resistant to proteolysis by calpain. Annexin V was found to be stable to intrinsic lung proteases in the presence of either Ca2+ or EGTA while annexin XI was found to be partially degraded by intrinsic lung proteases in the presence of EGTA. Eight of the 10 known mammalian annexins also contain a pentapeptide sequence that is biochemically related to the KFERQ motif which is a known signal that targets protein for lysosomal proteolysis. Our data suggest that the annexins may be regulated by limited proteolysis, most likely at their N-terminal end, while most, if not all, of them might be degraded by the lysosomal pathway.


Efficient conversion of acetate into lipids by the oleaginous yeast Cryptococcus curvatus.
Acetic acid is routinely generated during lignocelluloses degradation, syngas fermentation, dark hydrogen fermentation and other anaerobic bioprocesses. Acetate stream is commonly regarded as a by-product and detrimental to microbial cell growth. Conversion of acetate into lipids by oleaginous yeasts may be a good choice to turn the by-product into treasure. Ten well-known oleaginous yeasts were evaluated for lipid production on acetate under flask culture conditions. It was found that all of those yeasts could use acetate for microbial lipid production. In particular, Cryptococcus curvatus accumulated lipids up to 73.4 % of its dry cell mass weight. When the culture was held in a 3-L stirred-tank bioreactor, cell mass, lipid content, lipid yield and acetate consumption rate were 8.1 g/L, 49.9 %, 0.15 g/g and 0.64 g/L/h, respectively. The fatty acid compositional profiles of the acetate-derived lipids were similar to those of vegetable oil, suggesting their potential for biodiesel production. Continuous cultivation of C. curvatus was conducted under nitrogen-rich condition at a dilution rate of 0.04 h(-1), the maximal lipid content and lipid yield were 56.7 % and 0.18 g/g, respectively. The specific lipid formation rate, lipid content and lipid yield were all higher under nitrogen-rich conditions than those obtained under nitrogen-limited conditions at the same dilution rates. Effective lipid production by C. curvatus was observed on corn stover hydrolysates containing 15.9 g/L acetate. Acetate is an effective carbon source for microbial lipid production by oleaginous yeasts. Continuous cultivation of C. curvatus on acetate was promising for lipid production under both nitrogen-rich and nitrogen-limited conditions. These results provide valuable information for developing and designing more efficient acetate-into-lipids bioprocess.


Stimulation of various functions in murine peritoneal macrophages by glucans produced by glucosyltransferases from Streptococcus mutans.
The glucan that was produced by glucosyltransferases (GTFs) from Streptococcus mutans was examined for its stimulating functions toward murine peritoneal macrophages. Soluble glucan was obtained by the reaction with cell-free crude GTFs and sucrose, followed by ethanol precipitation, dispersion in water and re-precipitation by ethanol. Soluble glucan, those average molecular weight was about 3 x 10(5), was composed of mixture of alpha-1,6 and alpha-1,3 linkages in a 3:1 ratio. When 30 and 60 microg/ml of the glucan was incubated with peritoneal macrophages, the lysosomal phosphatase activity was increased in a dose-dependent manner, indicating that soluble glucan may activate macrophages. To examine its effects on the various functions of macrophages, soluble glucan was orally administered daily at a level of 100 mg/kg of body weight to C57BL/6 mice. Significant stimulation of the production of H2O2 by the macrophages was observed without any increase in NO production. The production of tumor necrosis factor-alpha (TNF-alpha) by the macrophages was also stimulated from 538.73-555.06 pg/ml to 585.73-596.40 pg/ml during 15 days of oral administration of soluble glucan. The cytotoxicity of peritoneal macrophages against B16 tumor cells was significantly enhanced by 25-38% during 15 days of oral administration. These results may indicate that soluble glucan stimulates the immune functions of macrophages.


Effectiveness of the available early therapies in reducing severe COVID-19 in non-hospitalized patients with solid tumors on active treatment.
Emergency use authorization of drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by regulatory authorities has provided new options to treat high-risk outpatients with mild-to-moderate Coronavirus disease 2019 (COVID-19). We conducted an ambispective cohort study of patients with solid tumors on active treatment to examine the effectiveness of these drugs in preventing the progression to severe COVID-19. Sixty-nine patients with solid tumors (43 women, 26 men; median age 61, range 26-80) reported a laboratory-confirmed diagnosis of SARS-CoV-2 infection. Forty-nine patients received early therapy. Only one patient (14.5%) required hospitalization for COVID-19. As for safety, two patients (5.9%) reported nausea during nirmatrelvir/ritonavir. The majority of treated patients showed a reduced time to negative sample (73 vs. 18%, p = 0.0011) and shorter symptoms' duration (94 vs. 27%; p < 0.0001) compared to the patients not treated with the early COVID-19 therapies. Our data suggest that early therapies may reduce the morbidity of COVID-19 in patients with solid tumors.


Preliminary experience of autologous free myocutaneous flap combined with free dermal graft in the treatment of refractory empyema with bronchopleural fistula.
To explore the effects of autologous free dermal graft combined with free myocutaneous flap on bronchopleural fistula (BPF) with empyema, we summarized and analyzed two cases. Two patients with refractory empyema and BPF were treated with autologous free dermal graft combined with free myocutaneous flap. The treatment included debridement of empyema, rib resection drainage, repair of bronchopleural fistula, and free vastus lateralis myocutaneous flap transplantation to eliminate the empyema. After the free dermal graft was harvested from the healthy skin around the incision, it was inserted into the fistula and sutured with the surrounding pleural tissue. The keys to the operation lies in the anastomosis of the lateral circumflex femoral artery (LCFA), vein and nerve that supply the vastus lateralis muscle flap to the thoracodorsal vessels and nerves. After surgery, the empyema, air leakage, and the survival of the myocutaneous flap were observed. There was no disease recurrence after follow-up for seven and six months, respectively. Re-examination of the chest computed tomography (CT) or magnetic resonance imaging (MRI) indicated that the abscess cavity had disappeared. No necrosis of the myocutaneous flap was observed after surgery. The application of autologous free dermal graft combined with free vastus lateralis myocutaneous flap transplantation is effective in the treatment of patients with bronchopleural fistula with refractory chronic empyema, and the clinical effect is satisfactory.


Hypnotherapeutic management of alopecia areata.
Only limited data exist on the role of psychotherapy in alopecia areata (AA). We sought to document the influence of hypnotherapy on psychologic well-being and clinical outcome in AA. Hypnosis was used in 28 patients with extensive AA who were refractory to previous conventional treatments. It was added as a complementary treatment or used as the only treatment. In all, 21 patients, 9 with alopecia totalis or alopecia universalis and 12 with extensive AA, were analyzed during a 5-year period. After treatment, all patients had a significantly lower score for anxiety and depression. Scalp hair growth of 75% to 100% was seen in 12 patients after 3 to 8 sessions of hypnotherapy. Total growth occurred in 9 of these 12 patients, including 4 patients with alopecia universalis and 2 with ophiasis. In 5 patients, a significant relapse occurred. This is a preliminary study with a limited number of patients. A larger randomized study is necessary. Hypnotherapy may enhance the mental well-being of patients with AA and it may improve clinical outcome.


In vivo association of immunophenotyped macrophages expressing CD163 with PDGF-B in gingival overgrowth-induced by three different categories of medications.
This study was carried out to identify and outline the degree of relationship between immunophenotyped macrophages expressing CD163 and PDGF-B in cyclosporine-A, phenytoin, and nifedipine-induced gingival overgrowth. Eighty adult male albino rats were selected and divided into four equal groups. Group I received no treatment. Rats of groups II, III, and IV were administered cyclosporine-A, phenytoin, and nifedipine, respectively. Routine tissue processing was carried out for staining with CD163 and PDGF-B. The results of this study were analyzed statistically. Group I exhibited score 0 gingival overgrowth while group II yielded score 3 with blunt and bulbous gingival crests. Rats of group III showed score 2 with knife edge and group IV revealed less pronounced gingival overgrowth and mostly the gingival crest was knife edge. Group II had the highest mean value for CD163 while group I showed the lowest value. In addition, group II had the highest mean value for PDGF-B while group I showed the lowest value. Statistically, there was an overall significant difference between the studied groups as well as between each two groups. Strong association exists between immunophenotyped macrophages expressing CD163 and PDGF-B in GO induced by these medications. In addition, CD163 and PDGF-B upregulated in cyclosporine-A-induced GO compared to phenytoin and nifedipine medications.


A polyphosphoester conjugate of melphalan as antitumoral agent.
The low molecular weight of many chemotherapeutics causes their untargeted distribution in the body and fast renal clearance, which leads to a loss of therapeutic activity and to unspecific toxic side effects. Therefore, there is a growing interest in conjugating anticancer drugs to water soluble polymers and thus, take advantage of the 'enhanced permeability and retention' (EPR) effect in tumors. In this study, water soluble polyphosphoesters were used as polymer carriers of melphalan hydrochloride (hydrochloride of p-bis(2-chloroethyl)amino-L-phenylalanine), which is a multifunctional alkylating agent. Melphalan was chemically immobilized by covalent bonding to poly(oxyethylene H-phosphonate) under Atherton-Todd reaction conditions. Novel polymer-melphalan complexes with ionic and hydrogen bonds were designed as controls, basing on two other biodegradable polyphosphoesters: poly(hydroxyoxyethylene phosphate) and poly(methyloxyethylene phosphate). The structure of the formed products was elucidated by (1)H, (13)C, (31)P NMR and FT-IR spectroscopy. The cytotoxic effect of the melphalan formulations was evaluated on different tumor cell lines. The novel polymer formulations showed a concentration dependent antitumoral activity, comparable to the effect of unmodified melphalan. The polymer-melphalan conjugate was also evaluated in vivo in the human hepatocellular carcinoma HuH7 xenograft mouse model. It improved the therapeutic efficacy of pure melphalan without causing side effects.


Profile of expression of certain markers of apoptosis in chronic hepatitis C and hepatitis B patients in an Egyptian population.
Increased peripheral blood mononuclear cell (PBMC) apoptosis during viral hepatitis has been suggested to cause impaired regulation of the immune response and maintenance of the infection. The purpose of this work was to study the expression of some apoptotic markers in chronic hepatitis B (CHB) and C (CHC) infections in order to understand the underlying mechanisms of immune failure and viral persistence. This study aims to evaluate the level of PBMC apoptosis and the expression of the apoptosis-related proteins Fas and Bcl-2 in CHB and CHC patients. This case control study was carried out on 38 cases (group I: 20 chronic HCV patients; group II: 18 chronic HBV patients) attending the Tropical Medicine Clinic, Mansoura University Hospital, in addition to 10 healthy controls. Morphological assessment of apoptosis of cultured PBMCs was done. The level of Fas and Bcl-2 expression by PBMCs was detected using flow cytometry. An increased level of apoptosis correlated with increased Fas expression, but no increase in Bcl-2 expression was found on the surface of PBMCs in CHC and CHB patients compared to controls. No significant difference in the level of apoptosis, Fas, or Bcl2 expression between CHC and CHB patients was detected. Modulation of apoptosis, particularly by manipulation of Fas receptor activation, may be of therapeutic benefit in chronic CHB and CHC.


Construction of deep learning-based disease detection model in plants.
Accurately detecting disease occurrences of crops in early stage is essential for quality and yield of crops through the decision of an appropriate treatments. However, detection of disease needs specialized knowledge and long-term experiences in plant pathology. Thus, an automated system for disease detecting in crops will play an important role in agriculture by constructing early detection system of disease. To develop this system, construction of a stepwise disease detection model using images of diseased-healthy plant pairs and a CNN algorithm consisting of five pre-trained models. The disease detection model consists of three step classification models, crop classification, disease detection, and disease classification. The 'unknown' is added into categories to generalize the model for wide application. In the validation test, the disease detection model classified crops and disease types with high accuracy (97.09%). The low accuracy of non-model crops was improved by adding these crops to the training dataset implicating expendability of the model. Our model has the potential to apply to smart farming of Solanaceae crops and will be widely used by adding more various crops as training dataset.


Impaired cholinergic vasodilation in the cholesterol-fed rabbit in vivo.
Endothelium-dependent cholinergic relaxation in vitro is impaired in large arteries of animals and man with atherosclerosis. To assess the physiological importance of this impairment, we compared vasodilator effects of acetylcholine and nitroprusside, an endothelium-independent agent, in control rabbits (n = 12) and rabbits fed a 1% cholesterol diet for 10 weeks (n = 8). The hindlimb of the rabbits was perfused via an extracorporal loop at a constant flow, and perfusion pressure was used as an index of total vascular resistance. The hindlimb vascular resistance was monitored during intraarterial bolus injections with graded concentrations of acetylcholine (0.01-1.000 ng) and nitroprusside (0.1-1.000 ng) which produced no change in systemic hemodynamics. Between 0.1 and 1.000 ng nitroprusside, resistance changes in control and cholesterol-fed rabbits were virtually identical. In contrast, the resistance change induced by acetylcholine was significantly suppressed in cholesterol-fed rabbits over a wide range of concentrations (1.0-1.000 ng; p less than 0.05). The results indicate that in a model of atherosclerosis there is a reduced vasodilatory responsiveness to the endothelium-dependent acetylcholine, whereas the effect of the endothelium-independent nitroprusside is fully preserved.


Onset of action between bupivacaine 0.5% and bupivacaine 0.5% plus fentanyl 75 mcg.
This study tested the hypothesis that the addition of fentanyl 75 mcg to bupivacaine 0.5% at the onset of epidural anesthesia for cesarean section reduces the onset time for T4 sensory blockade. The study was conducted in a randomized, double-blind fashion. The same observer performed sensory testing using pain to pinprick. Fourteen ASA I patients scheduled for elective cesarean section had epidural catheters placed. Group 1 (n = 7) received bupivacaine 0.5%, and group 2 (n = 7) received bupivacaine 0.5% plus fentanyl 75 mcg. Patients 5'0'' to 5'4'' in height received 15 ml, and patients 5'5'' to 5'9'' received 20 ml of bupivacaine. There were no adverse effects on the neonate or clinically important changes in maternal hemodynamics. The maternal age, height, weight, and bupivacaine dose did not differ between groups (p greater than 0.05). For group 1, the mean times for sensory loss at T7, T6, T5, and T4 were 13.1 +/- 3.8 minutes, 15.0 +/- 4.0 minutes, 16.9 +/- 4.3 minutes, and 19.3 +/- 4.9 minutes, respectively; for group 2, the mean times were 8.1 +/- 0.9 minutes, 9.9 +/- 1.1 minutes, 11.3 +/- 1.5 minutes, and 12.7 +/- 2.0 minutes, respectively. Two-factor analysis of variance between groups 1 and 2 showed a significant difference (p less than 0.0001), representing a 35% reduction of mean onset time. The coefficient of variation of the mean onset times for group 1 subjects was 26.6% +/- 1.7% and for group 2 subjects 12.7% +/- 2.2% (p less than 0.001), representing a 50% reduction in between-subject variation.(ABSTRACT TRUNCATED AT 250 WORDS)


Correction to: Probiotics' efficacy in paediatric diseases: which is the evidence? A critical review on behalf of the Italian Society of Pediatrics.
An amendment to this paper has been published and can be accessed via the original article.


Macrocyclic naphthalene diimides as G-quadruplex binders.
The synthesis, biological and molecular modeling evaluation of a series of macrocyclic naphthalene diimides is reported. The present investigation expands on the study of structure-activity relationships of prototype compound 2 by constraining the molecule into a macrocyclic structure with the aim of improving its G-quadruplex binding activity and selectivity. The new derivatives, compounds 4-7 carry spermidine- and spermine-like linkers while in compound 8 the inner basic nitrogen atoms of spermine have been replaced with oxygen atoms. The design strategy has led to potent compounds stabilizing both human telomeric (F21T) and c-KIT2 quadruplex sequences, and high selectivity for quadruplex in comparison to duplex DNA. Antiproliferative effects of the new derivatives 4-8 have been evaluated in a panel of cancer cell lines and all the tested compounds showed activity in the low micromolar or sub-micromolar range of concentrations. In order to rationalize the molecular basis of the DNA G-quadruplex versus duplex recognition preference, docking and molecular dynamics studies have been performed. The computational results support the observation that the main driving force in the recognition is due to electrostatic factors.


[Secondary spontaneous pneumothorax in tuberous sclerosis].
Secondary pneumothorax occurs as a symptom of an underlying pulmonary disease. We report the case of an 18-year-old woman with tuberous sclerosis (Bourneville's disease) and recurrent pneumothoraces. Clinical outcome was favorable 6 months after bilateral videothoracoscopic pleurectomy. The complete triad of tuberous sclerosis (TS) (mental retardation, seizures, adenoma sebacium) is not always present in those who develop pulmonary involvement. When TS involves the lung it is clinically and pathologically indistinguishable from lymphangioleiomyomatosis (LAM). The very rare pulmonary involvement of TS and LAM are problems primarily of women in childbearing age. A pneumothorax can be the first symptom of TS or LAM.


AM-111 protects against permanent hearing loss from impulse noise trauma.
The otoprotective peptide AM-111, a cell-permeable inhibitor of JNK mediated apoptosis, was tested for its efficacy as a rescue agent following impulse noise trauma. Single dose administrations of AM-111 at 1h or 4h post-impulse noise exposure (155 dB peak SPL) via systemic or local routes were evaluated with a total of 48 chinchillas. The animals received the compound either by IP injection or locally onto the round window membrane (hyaluronic acid gel formulation or osmotic mini-pump). Efficacy was determined by auditory brainstem responses (ABR) as well as cytocochleograms. Three weeks after impulse noise exposure, permanent threshold shifts (PTS) were significantly lower for AM-111 treated ears compared to controls, regardless of the drug administration route and the time point of drug delivery. Even the treatments which started 4h post-noise exposure, reduced hearing loss in the 2-8 kHz range compared to controls by up to 16-25 dB to a PTS as low as 6-17 dB, demonstrating significant protection against permanent hearing loss from impulse noise trauma. These findings suggest a key role for JNK mediated cochlear sensory cell death from oxidative stress.


Allergen profile of Protophormia terraenovae, other species of calliphoridae, and Lumbricus terrestris in anglers allergic to maggots in Cáceres, Spain.
Our group previously found that up to 7% of amateur anglers in Caceres, Spain may be allergic to the larvae of Protophormia terraenovae (order Diptera, family Calliphoridae) used as live bait for fishing. To identify the pattern of major allergens in P terraenovae and other species of Calliphoridae. Extracts of P terraenovae, Calliphora vomitoria, Lucilia sericata and Lumbricus terrestris were characterized using sodium dodecyl sulfate polyacrylamide gel electrophoresis and IgE-immunoblotting techniques in individual sera from 24 patients with a positive skin test result and/or specific IgE determination (enzyme-linked immunosorbent assay [ELISA]) to P terraenovae. ELISA and IgE-immunoblotting inhibition studies were also performed to identify potential cross-reactive allergens between these species. IgE-immunoblotting with P terraenovae showed a band of 15.3 kDa recognized by 15 patients, in addition to 2 further allergens of 22.8 kDa and 69 kDa. For C vomitoria, 5 bands of 73, 46, 40, 28, and 14 kDa were observed. For L sericata, 2 major allergens of 73 kDa and 14 kDa were observed. In the case of L terrestris, IgE from 13 patients recognized 1 allergen of around 15.5 kDa. IgE-immunoblotting and ELISA inhibition revealed the presence of cross-reactivity, mainly between L terrestris and P terraenovae. P terraenovae appears to have species-specific allergens and allergens shared with C vomitoria and L sericata. Striking immunological cross-reactivity was observed between P terraenovae and L terrestris. An allergen of 15-16 kDa could be involved in this phenomenon.


Zinc enhances the cell adhesion, migration, and self-renewal potential of human umbilical cord derived mesenchymal stem cells.
Zinc (Zn) is the second most abundant trace element after Fe, present in the human body. It is frequently reported in association with cell growth and proliferation, and its deficiency is considered to be a major disease contributing factor. To determine the effect of Zn on in vitro growth and proliferation of human umbilical cord (hUC)-derived mesenchymal stem cells (MSCs). hUC-MSCs were isolated from human umbilical cord tissue and characterized based on immunocytochemistry, immunophenotyping, and tri-lineage differentiation. The impact of Zn on cytotoxicity and proliferation was determined by MTT and Alamar blue assay. To determine the effect of Zn on population doubling time (PDT), hUC-MSCs were cultured in media with and without Zn for several passages. An in vitro scratch assay was performed to analyze the effect of Zn on the wound healing and migration capability of hUC-MSCs. A cell adhesion assay was used to test the surface adhesiveness of hUC-MSCs. Transcriptional analysis of genes involved in the cell cycle, proliferation, migration, and self-renewal of hUC-MSCs was performed by quantitative real-time polymerase chain reaction. The protein expression of Lin28, a pluripotency marker, was analyzed by immunocytochemistry. Zn at lower concentrations enhanced the rate of proliferation but at higher concentrations (> 100 µM), showed concentration dependent cytotoxicity in hUC-MSCs. hUC-MSCs treated with Zn exhibited a significantly greater healing and migration rate compared to untreated cells. Zn also increased the cell adhesion rate, and colony forming efficiency (CFE). In addition, Zn upregulated the expression of genes involved in the cell cycle (CDC20, CDK1, CCNA2, CDCA2), proliferation (transforming growth factor β1, GDF5, hypoxia-inducible factor 1α), migration (CXCR4, VCAM1, VEGF-A), and self-renewal (OCT4, SOX2, NANOG) of hUC-MSCs. Expression of Lin28 protein was significantly increased in cells treated with Zn. Our findings suggest that zinc enhances the proliferation rate of hUC-MSCs decreasing the PDT, and maintaining the CFE. Zn also enhances the cell adhesion, migration, and self-renewal of hUC-MSCs. These results highlight the essential role of Zn in cell growth and development.


Selection and characterization of nuclear mutations affecting mitochondria in Paramecium.
A screening method, based upon resistance to a tetrazolium salt (TTC), is described which permitted the isolation in Paramecium of 28 mutants resistant to TTC. These mutants displayed various defects in mitochondrial functions (cytochromic content cyanide insensitive respiration). Some mutations seemed to affect directly the respiration chain while others seemed to cause indirect modifications, possibly altering mitochondrial protein synthesis. Genetic analysis of four mutants showed in all that the resistance to TTC was of nuclear origin.


Population Pharmacokinetics of Boosted-Elvitegravir in HIV-Infected Patients.
Elvitegravir (EVG) is an HIV strand transfer integrase inhibitor approved for the treatment of HIV infection as a part of antiretroviral regimens containing cobicistat (COBI) or ritonavir (RTV) as a booster. The population pharmacokinetics of EVG in treatment-naive and -experienced HIV patients was determined, and the effects of demographic, biometric, and formulation covariates on EVG pharmacokinetics (PK) were evaluated. Data from 31 clinical studies (25 in healthy subjects, 6 phase 1b to phase 3 in HIV-1-infected patients) with COBI-boosted EVG studies (as EVG/co or EVG/COBI/FTC/TDF single-tablet regimen) or RTV-boosted EVG studies (EVG/r) were analyzed using NONMEM. The effect of the covariates age, sex, race, health status (healthy volunteers vs HIV patients), weight, body mass index (BMI), body surface area (BSA), creatinine clearance (estimated GFR), and formulation were evaluated. EVG PK, with COBI or RTV, was described by a 2-compartment model, with first-order absorption and elimination and an absorption lag time. A statistically significant, but not clinically relevant, effect of BSA on EVG clearance (CL) was observed. Coadministration of atazanavir or lopinavir with EVG/r had an effect on EVG CL consistent with the known interaction with these agents. No other covariate had a meaningful effect on EVG PK. EVG PK was well described in a population PK model with HIV-infected patients, with low PK variability and no relevant effect of demographic or biometric covariates.


Gentamicin serum concentrations in patients with gentamicin-PMMA beads for infected hip joints: a prospective observational cohort study.
Gentamicin-polymethylmethacrylate (PMMA) beads release gentamicin gradually, and high concentrations develop only locally. It is unclear how frequent and in which patients gentamicin serum concentrations are measurable and possibly lead to toxicity. The aim of this study was to investigate the measurability of gentamicin serum concentrations after the implantation of gentamicin-PMMA beads and to assess the nephrotoxicity of these beads. In this observational cohort study, gentamicin and creatinine concentrations were measured in 34 serum samples of 23 patients with implanted gentamicin-PMMA beads for infected hip joints with our regular immunoassay (lower limit of quantitation 0.4 mg/L). Samples were also analyzed with an adjusted immunoassay with a lower limit of quantitation of 0.05 mg/L. Gentamicin serum concentrations were >0.4 mg/L in 9 of 34 (26%) of all the samples measured (both after the first implantation and change of beads) and in 5 of 23 patients (22%) after the first implantation of gentamicin-PMMA beads. Gentamicin serum concentrations were >0.05 mg/L in 31 samples (91%). Nephrotoxicity (defined as increase in serum creatinine >44 μmole/L and/or a relative increase >25%) occurred more frequently in patients with measurable gentamicin serum concentrations than in those without measurable gentamicin serum levels (57% versus 43%, P = 0.02). Both nephrotoxicity and gentamicin serum concentration could not be associated with the number of implanted gentamicin-PMMA beads. Gentamicin serum concentrations >0.4 mg/L can be measured after the implantation of gentamicin-PMMA beads in certain patients with infected hip joints. Furthermore, elevated (>0.4 mg/L) gentamicin serum concentrations are associated with nephrotoxicity in patients with gentamicin-PMMA beads for infected hip joints.


Rapid recurrence of geographic atrophy after full macular translocation for nonexudative age-related macular degeneration.
To report the recurrence of geographic atrophy (GA) in a patient with nonexudative age-related macular degeneration (AMD) after full macular translocation. Observational case report. Review of the clinical, photographic, and angiographic records of a patient with GA who underwent full macular translocation. Progression of GA. A 73-year-old man with GA secondary to nonexudative AMD underwent a macular translocation with 360 peripheral retinectomy (MT 360) in his left eye. On postoperative month 4, fundus photography showed subtle alterations of the pigment underneath the translocated foveal region. On postoperative month 9, the visual acuity worsened to preoperative levels and there was frank retinal pigment epithelium atrophy involving the new macular region. The rapid recurrence and development of GA in the translocated fovea after MT 360 raise new questions regarding the pathogenesis of GA. They also raise concerns regarding the use of MT 360 in the management of nonexudative AMD.


Giant scrotal swelling in association with a congenital giant melanocytic nevus: A case report.
Scrotal lymphedema is a rare condition, with significant psychological and functional disability. To date, association with giant congenital melanocytic nevus has not been reported. We report a case of a 15-year-old male with a giant congenital nevus associated with giant scrotal lymphedema. Surgical debulking with penoscrotoplasty achieved satisfactory functional and esthetic results. Early diagnosis and surgical intervention should be advocated for congenital causes of large scrotal swelling.


Type I von Willebrand's disease presenting as recurrent corpus hemorrhagicum.
Female patients with undiagnosed von Willebrand's disease may present with heavy menorrhagia. This is a case report of a patient with undiagnosed von Willebrand's disease presenting with recurrent corpus hemorrhagicum. A nulliparous woman presented with her second episode of hemoperitoneum secondary to a ruptured corpus hemorrhagicum. Patients with recurrent corpus hemorrhagicum may be at risk for von Willebrand's disease even if no history of menorrhagia or bleeding disorder exists.


Obesity, stigma, and person-centered language: A serial cross-sectional analysis of scientific literature.
Language can influence societal perceptions of medical conditions. The employment of person-centered language (PCL) in health care is reflected in many scientific publications; however, the extent of this adaptation in reference to obesity is unknown. This cross-sectional analysis included a systematic search of PubMed obesity-related articles across four cohorts spanning January 2004 through December 2006; January 2008 through December 2010; January 2015 through December 2018; and January 2019 through May 2020, respectively. Approximately 1971 publications were screened and examined for prespecified, non-PCL terminology set forth by the American Medical Association Manual of Style and the International Committee of Medical Journal Editors, of which 991 were retained. Statistical analysis demonstrating PCL and non-PCL findings was then performed. Incidence rates and cohort classifications were reported. Of the 991 articles examined, it was found that 24.02% of publications adhered to PCL. Similar adherence was observed across obesity-specific, general medicine, and nutrition journals. PCL adherence increased over time. The most common non-PCL label was "obese," occurring in 75.48% of articles. This investigation showed that non-PCL in reference to obesity is widely evident in weight-focused journals despite recommendations for adherence to PCL guidelines. Continued use of non-PCL in reference to obesity in research may inadvertently perpetuate weight-based stigma and health disparities in future generations.


Time-Driven Activity-Based Cost Comparison of Thyroid Lobectomy and Radiofrequency Ablation.
Radiofrequency ablation (RFA) of benign thyroid nodules has gained traction for its therapeutic effectiveness, thyroid function preservation, and minimally invasive nature. While a growing body of evidence reports positive outcomes from thyroid RFA, financial comparisons between both procedures remain limited. This analysis aims to more accurately measure the direct cost of thyroid RFA in comparison to thyroid lobectomy. Bottom-up financial cost analysis. Tertiary endocrine head and neck surgery center. Time-driven activity-based costing was utilized to obtain unit-based cost estimates. The care cycles for thyroid lobectomy and RFA were defined, and process maps were developed comprising all personnel and work in the care cycle. Time estimates were calculated for all personnel involved, and public government data were used to obtain capacity cost rates for each component of the care cycle. Consumable supply and overhead costs were obtained for both procedures, and overall costs were compared. For thyroid lobectomy, total personnel costs were $1087.97, consumable supplies were $942.68, and overhead costs $17,199.10. For thyroid nodule RFA performed in an office setting, the total personnel cost calculated was $379.90, consumable supplies $1315.28, and overhead $7031.20. Overall, the total cost for thyroid lobectomy was $19,229.75 compared to $8726.38 for RFA. In-office thyroid nodule RFA is associated with lower direct costs than thyroid lobectomy, and overhead is the greatest cost driver for both procedures. If clinical and patient-centered outcomes are comparable, then RFA may provide higher value for appropriately selected patients.


Structural aspects of Plasmodium relevant to vaccination against malaria.
The extracellular stages of Plasmodium which can be inactivated with antibodies include the sporozoites, merozoites and microgametes. The surface of sporozoites and merozoites are known to bind antibodies which render them unable to invade host cells. Intra-erythrocytic merozoites, trophozoites and schizonts release antigens which are conveyed to the surface of the host cell, although they do not appear to be attacked by antibodies directly. The significance of these observations is discussed.


Soil aggregates indirectly influence litter carbon storage and release through soil pH in the highly alkaline soils of north China.
Soil aggregate-size classes, structural units of soil, are the important factors regulating soil organic carbon (SOC) turnover. However, the processes of litter C mineralization and storage in different aggregates-size classes are poorly understood, especially in the highly alkaline soils of north China. Here, we ask how four different aggregate sizes influence rates of C release (Cr) and SOC storage (Cs) in response to three types of plant litter added to an un-grazed natural grassland. Highly alkaline soil samples were separated into four dry aggregate classes of different sizes (2-4, 1-2, 0.25-1, and <0.25 mm). Three types of dry dead plant litter (leaf, stem, and all standing dead aboveground litter) of Leymus chinensis were added to each of the four aggregate class samples. Litter mass loss rate, Cr, and Cs were measured periodically during the 56-day incubation. The results showed that the mass loss in 1-2 mm aggregates was significantly greater than that in other size classes of soil aggregates on both day 28 and day 56. Macro-aggregates (1-2 mm) had the highest Cr of all treatments, whereas 0.25-1 mm aggregates had the lowest. In addition, a significant negative relationship was found between Cs/Cr and soil pH. After incubation for 28 and 56 days, the Cs was also highest in the 1-2 mm aggregates, which implied that the macro-aggregates had not only a higher CO2 release capacity, but also a greater litter C storage capacity than the micro-aggregates in the highly alkaline soils of north China.


Violence against women and the Millennium Development Goals: facilitating women's access to support.
Violence against women is a serious health and development concern, as well as a violation of women's human rights. Violence against women has a devastating effect on women's sexual and reproductive health, as well as the health of their children, and is rooted in gender inequality. Reducing violence against women is therefore a key strategy for the achievement of the Millennium Development Goals. Key lessons have emerged from more than two decades of experiences dealing with violence against women within the health sector. Interventions must go beyond training and curricula reform and utilize a system-wide approach, including changes in policies, procedures and attention to privacy and confidentiality. Providers must work together with other sectors, particularly at a community level, to strengthen local networks for support of survivors of violence. Prevention activities are critical, particularly those that seek to change cultural norms and laws that encourage violence and discriminate against women and girls.


Utilization of Bacillus Calmette-Guerin for Nonmuscle Invasive Bladder Cancer in an Era of Bacillus Calmette-Guerin Supply Shortages.
To study trends in Bacillus Calmette-Guerin (BCG) utilization for nonmuscle invasive bladder cancer (NMIBC) before and during national BCG shortages. The National Cancer Database was used to identify patients with localized NMIBC. Multivariate logistic regression was used to assess factors associated with BCG use. Temporal trends in BCG use were studied using segmented regression analysis. We identified 238,279 patients with NMIBC from 2004 to 2015. Overall, 33,660 (14.1%) patients with NMIBC received intravesical BCG during the study period. Segmented regression revealed a slower rate of rise of BCG utilization following major supply interruptions in 2011 and 2012 (2004-2012: +0.62% increase per year [P < .0001]; 2013-2015: +0.29% increase per year [P = .084]). This trend was most pronounced in Ta-low grade patients and least pronounced in T1-high grade patients. BCG utilization for NMIBC increased significantly over the study period, possibly representing increased adoption of national guidelines for BCG in NMIBC. In the years following interruptions in BCG supply, BCG use appears to have been rationed based on clinical risk, with the steepest declines in BCG use occurring in the lowest risk patients.


A multiple floating microelectrode for chronic implantation and longterm single unit recording in the cat.
This paper describes a multiple electrode, suitable for chronic implantation and single unit recording in the superficial cerebral cortex of the cat. The electrodes are fine wires, 5-8 per implant, not kept together in a bundle; a segment of them floats freely in saline in a closed chamber over the place of penetration. The electrode tips are not sharpened electrolytically, but cut at a bevel during surgery. Longevity of the implants is improved by slowing down the occasional rapid head shaking characteristic of cats, which tends to tear out implanted electrodes, by means of a small weight attached by a bar to the head.


Runx-dependent expression of PKC is critical for cell survival in the sea urchin embryo.
Runx transcription factors play critical roles in the developmental control of cell fate and contribute variously as oncoproteins and tumor suppressors to leukemia and other cancers. To discover fundamental Runx functions in the cell biology of animal development, we have employed morpholino antisense-mediated knockdown of the sea urchin Runx protein SpRunt-1. Previously we showed that embryos depleted of SpRunt-1 arrest development at early gastrula stage and underexpress the conventional protein kinase C SpPKC1. We report here that SpRunt-1 deficiency leads to ectopic cell proliferation and extensive apoptosis. Suppression of the apoptosis by pharmacological inhibition of caspase-3 prevents the ectopic proliferation and rescues gastrulation, indicating that many of the overt defects obtained by knockdown of SpRunt-1 are secondary to the apoptosis. Inhibition or knockdown of SpPKC1 also causes apoptosis, while cell survival is rescued in SpRunt-1 morphant embryos coinjected with SpPKC1 mRNA, suggesting that the apoptosis associated with SpRunt-1 deficiency is caused by the deficit in SpPKC1 expression. Chromatin immunoprecipitation indicates that SpRunt-1 interacts physically with SpPKC1 in vivo, and cis-regulatory analysis shows that this interaction activates SpPKC1 transcription. Our results show that Runx-dependent activation of SpPKC1 is essential for maintaining protein kinase C activity at levels conducive to cell survival during embryogenesis.


CD19 chimeric antigen receptor-T cells in B-cell leukemia and lymphoma: current status and perspectives.
The approval of tisagenlecleucel and axicabtagene ciloleucel represents a breakthrough in the field of immune and cellular therapy for hematologic malignancies. These anti-CD19 chimeric antigen receptor-T cells (CAR) proved to be highly effective in the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and specific histologic subtypes of B-cell non-Hodgkin lymphomas. This expert review aims to summarize the current available research evidence in this field, with a special focus on the different challenges faced by treating physicians, and we also provide future perspectives.


Psychosocial distress and quality of life in patients after radical cystectomy - one year follow-up in 842 German patients.
This study aims to report on psychosocial distress and QoL in bladder cancer patients after radical cystectomy (RC) and urinary diversion to obtain a better basis for patient counseling and postoperative care. The study relied on prospectively collected data for 842 patients, who underwent three weeks of inpatient rehabilitation after RC and creation of an ileal conduit (IC) or ileal neobladder (INB). Data on QoL and psychosocial distress were collected by validated questionnaires. Multivariate logistic regression was performed to identify predictors for high psychosocial distress. Four-hundred and forty-seven patients (326 male, 121 female) received an IC, while 395 patients (357 male, 38 female) received an INB. Health-related QoL improved steadily in the whole cohort during follow-up. Patients with an INB reported better physical function but suffered more from diarrhea and financial worries. Patients with an IC reported reduced satisfaction with their body image, increased worries about the future, and suffered more from constipation. Psychosocial distress increased significantly during follow-up. One year after surgery, 43.1% of patients suffered from high psychosocial distress. Multivariate regression analysis identified age ≤ 59 years (OR 1.731; CI 1.056-2.838; p = 0.030) and lymph node metastases (OR 2.073; CI 1.133-3.793; p = 0.018) as independent predictors for high psychosocial distress. QoL improves significantly in all patients one year after RC. However, psychosocial distress remains high in a substantial number of patients. To prevent chronic psychological disorders, easily accessible opportunities for psycho-oncological counseling are needed for patients following RC.


Maternal peripheral testosterone levels during the first half of pregnancy.
Peripheral serum testosterone levels were determined in 180 women during weeks 7 to 20 of pregnancy with a specific radioimmunoassay. After a normal pregnancy and delivery 90 serum samples were randomly selected from mothers of boys and 90 serum samples from mothers of girls. The testosterone concentrations were correlated with the sex of the fetuses. The mean testosterone level +/- S.D. in pregnant women with female fetuses was 597 +/- 167 pg. per milliliter. In pregnant women with male fetuses the testosterone concentrations were on the average significantly higher (p less than 0.01), with a mean value of 828 +/- 298 pg. per milliliter. The course of the testosterone concentrations in women with male fetuses showed an increase beginning in week 7, reaching a maximum during weeks 9 to 11, followed by a decrease until weeks 15 to 20. During weeks 9 to 11 of pregnancy fetal sex determination was possible in 28 per cent of the males and in 5 per cent of the females, with a probability of 95.5 per cent.


Smokers have less reductions in probing depth than non-smokers following nonsurgical periodontal therapy.
Studies were located using Medline, Embase and the Cochrane Central Register of Controlled Clinical Trials, as well as searching bibliographies of identified references, review articles and consensus statements by hand. As the habit of smoking cannot be randomised, studies included were both controlled clinical trials and arms of randomised controlled trials investigating the effects of nonsurgical periodontal treatment, which reported results separately for smokers and nonsmokers. Other inclusion criteria were that studies should assess otherwise healthy people who had been diagnosed with chronic or adult periodontitis and that the patient was the unit of analysis (rather than a tooth- or site-based analysis). Studies were not excluded on the basis of quality, only on whether they fulfilled the inclusion criteria for entry. General information about the paper, study characteristics, outcome measures, treatment characteristics and quality assessment was extracted independently, in duplicate. Where disagreement arose, this was resolved by discussion. Meta-analysis of data was performed and heterogeneity between studies was investigated using meta-analysis regression. Out of the 330 studies initially identified, 13 were considered eligible for inclusion. No studies reported data on tooth loss. For all sites, the reduction in probing depth (PD) was 0.13 mm greater in nonsmokers than in smokers (six studies) and there was no evidence to suggest that the studies were dissimilar in their estimates of this result (no evidence of heterogeneity; P>0.05). For sites with an initial PD of 5.00 mm (eight studies), a random-effects meta-analysis indicated a weighted mean difference in PD reduction of 0.43 mm favouring nonsmokers (95% confidence interval (CI), 0.24-0.63; P<0.001). Because of significant heterogeneity between studies, only a cautious observation can be made but, with one exception, all studies produced a summary estimate favouring nonsmokers. Meta-analysis of the two studies that compared the change in clinical attachment level between nonsmokers and ex-smokers, who had given up their habit, in sites with an initial PD of +/-5.00 mm, showed a difference in clinical attachment level gain of 1.34 mm favouring the nonsmokers (95% CI, 0.65-2.03; P<0.001; chi(2) test for heterogeneity, 7.47 with 1 degree of freedom; P=0.006). In both of these analyses, the degree of heterogeneity is a cause for concern. Bleeding was assessed after therapy in seven studies but meta-analysis was not performed because of great heterogeneity in the methods used to assess bleeding. No statistically significant differences in bleeding were found between smokers and nonsmokers either at baseline or after therapy in most of the studies. One study found significantly less bleeding in smokers than in nonsmokers at baseline and another found a reduced response in terms of bleeding in smokers than in nonsmokers. Two studies evaluating the change in bleeding in ex-smokers found no statistically significant difference after treatment. No data were reported for any of the included studies on patient-centred outcomes such as quality of life, ease of maintenance, changes in aesthetic appearance, or patient experience. Following nonsurgical periodontal therapy, people who smoke will experience less reduction in PD than nonsmokers. There is no evidence of a difference in gain in clinical attachment between smokers and nonsmokers or a reduction of bleeding on probing between smokers and nonsmokers. Differences in study design and lack of data precluded an adequate and complete pooling of data for a more comprehensive analysis. In short-term studies, it is unclear whether people who stop smoking will respond as favourably to nonsurgical therapy as those who have never been smokers. Progress in understanding the effects of smoking on periodontal therapy will require the evaluation of objective measures of smoking such as nicotine exposure and exhaled carbon monoxide in place of sole reliance on patient-reported information.


Antisense epidermal growth factor receptor RNA transfection in human glioblastoma cells down-regulates telomerase activity and telomere length.
Epidermal growth factor receptor is overexpressed and/or amplified in up to 50% of glioblastomas, suggesting an important role of this gene in glial tumorigenesis and progression. In the present study we demonstrated that epidermal growth factor receptor is involved in regulation of telomerase activity in glioblastoma. Antisense-epidermal growth factor receptor approach was used to inhibit epidermal growth factor receptor expression of glioblastoma U87MG cells. Telomerase activity in antisense-epidermal growth factor receptor cells decreased by up to 54 folds compared with control cells. Moreover, the telomere lengths of antisense-epidermal growth factor receptor cells were shortened. In addition, the tumorigenicity of antisense-epidermal growth factor receptor cells was significantly inhibited. Taken together, there were strong correlations between tumorigenicity and epidermal growth factor receptor expression levels, and between tumorigenicity and telomerase activity. These results provide evidence that epidermal growth factor receptor plays an important role in the regulation of telomerase activity of glioma cells. Our findings provide new insights into both the biological functions of epidermal growth factor receptor and the regulation of telomerase activity. The inhibition of telomerase activity triggered by antisense-epidermal growth factor receptor treatment may reflect yet another mechanism of antisense-epidermal growth factor receptor approach in tumour suppression.


Hb Lepore-Leiden: a new delta/beta rearrangement associated with a beta-thalassemia minor phenotype.
The Lepore hemoglobins (Hbs) are a group of structural defects resulting from different recombination events between the delta- and beta-globin genes. They may come with different beta-thalassemia (beta-thal) minor-like phenotypes in the carrier and with variably severe phenotypes in the rare homozygote, and in the common compound heterozygote with beta-thal. The most seriously affected patients are those of Yugoslavian origin presenting with severe transfusion-dependent hemolytic anemia, dyserythropoiesis, hepatosplenomegaly and skeletal malformations. Because of genetic risk, couples where both partners are carriers of these combinations may require prognosis and prenatal diagnosis. In these cases, recognition of the defect must be done with particular care. We report a case of Hb Lepore induced by a yet unknown crossover event found in a 24-year-old Turkish male and compare the novel mutation with those previously reported.


Heart failure is a risk factor for orthopedic fracture: a population-based analysis of 16,294 patients.
Heart failure (HF) is associated with factors that may contribute to accelerated bone loss and subsequent fractures. Whether it leads to an increased fracture risk is unknown. A population-based cohort of consecutive patients >/=65 years of age with cardiovascular disease presenting to all emergency rooms between 1998 and 2001 in Alberta, Canada (n=16294 patients), was used. The 2041 patients with a new diagnosis of HF were compared with a control group of 14 253 patients with non-HF cardiovascular diagnoses. The primary outcome was any orthopedic fracture requiring hospital admission in the year after the emergency room visit. Patients with HF had a median age of 78 years (interquartile range, 72 to 84 years), and 51.9% were female; control subjects had a median age of 73 years (interquartile range, 68 to 79 years), and 53.2% were female. In the first year after the emergency room visit, 4.6% of the HF cohort (n=93) and 1.0% of patients without HF (n=147) sustained an orthopedic fracture (P<0.001). Hip fractures occurred in 26 HF patients (1.3%) and 18 patients (0.1%) without HF (P<0.001). After multivariable adjustment, HF was independently associated with a greater risk of any orthopedic fracture (adjusted odds ratio, 4.0; 95% CI, 2.9 to 5.3) or hip fracture (adjusted odds ratio, 6.3; 95% CI, 3.4 to 11.8). HF is associated with an increased risk of subsequent orthopedic fracture, particularly hip fracture. This suggests that screening for and treatment of osteoporosis to reduce fracture risk need to be considered in those with HF.


TRICARE: changes included in the National Defense Authorization Act for Fiscal Year 2010; enhancement of transitional dental care for members of the Reserve Component on active duty for more than 30 days in support of a contingency operation. Final rule.
The Department is publishing this final rule to implement section 703 of the National Defense Authorization Act for Fiscal Year 2010 (NDAA for FY10). Specifically, that legislation amends the transitional health care dental benefits for Reserve Component members on active duty for more than 30 days in support of a contingency operation. The legislation entitles these Reserve Component members to dental care in the same manner as a member of the uniformed services on active duty for more than 30 days, thus providing care to the Reserve member in both military dental treatment facilities and authorized private sector dental care. This final rule does not eliminate any medical or dental care that is currently covered as transitional health care for the member.


Quantification of gastrointestinal sodium channelopathy.
Na(v)1.5 sodium channels, encoded by SCN5A, have been identified in human gastrointestinal interstitial cells of Cajal (ICC) and smooth muscle cells (SMC). A recent study found a novel, rare missense R76C mutation of the sodium channel interacting protein telethonin in a patient with primary intestinal pseudo-obstruction. The presence of a mutation in a patient with a motility disorder, however, does not automatically imply a cause-effect relationship between the two. Patch clamp experiments on HEK-293 cells previously established that the R76C mutation altered Na(v)1.5 channel function. Here the process through which these data were quantified to create stationary Markov state models of wild-type and R76C channel function is described. The resulting channel descriptions were included in whole cell ICC and SMC computational models and simulations were performed to assess the cellular effects of the R76C mutation. The simulated ICC slow wave was decreased in duration and the resting membrane potential in the SMC was depolarized. Thus, the R76C mutation was sufficient to alter ICC and SMC cell electrophysiology. However, the cause-effect relationship between R76C and intestinal pseudo-obstruction remains an open question.


Mapping CRISPR spaceromes reveals vast host-specific viromes of prokaryotes.
CRISPR arrays contain spacers, some of which are homologous to genome segments of viruses and other parasitic genetic elements and are employed as portion of guide RNAs to recognize and specifically inactivate the target genomes. However, the fraction of the spacers in sequenced CRISPR arrays that reliably match protospacer sequences in genomic databases is small, leaving the question of the origin(s) open for the great majority of the spacers. Here, we extend the spacer analysis by examining the distribution of partial matches (matching k-mers) between spacers and genomes of viruses infecting the given host as well as the host genomes themselves. The results indicate that most of the spacers originate from the host-specific viromes, whereas self-targeting is strongly selected against. However, we present evidence that the vast majority of the viruses comprising the viromes currently remain unknown although they are likely to be related to identified viruses.


Effects of deletion of the cytoplasmic domain upon surface expression and membrane stability of a viral envelope glycoprotein.
The envelope protein (gp52) of Friend spleen focus-forming virus (F-SFFV) is defective in its intracellular transport and accumulates in the rough endoplasmic reticulum of F-SFFV-infected cells. This defect in transport has been attributed to the lack of a cytoplasmic domain, and possible loss of signals required for transport to the cell surface. The mature form of gp52, designated gp65, is also reported to be secreted from SFFV-infected cells. To determine the specific changes in the envelope protein which may lead to its lack of transport and to its lack of stability in associating with membranes, the 3' end of the F-SFFV envelope gene, which encodes the transmembrane domain, was inserted in place of the normal 3' end of the Friend murine leukemia virus genome. This chimeric envelope gene was expressed using the vaccinia virus expression system. The chimeric gp70/p15E glycoprotein molecule lacks the cytoplasmic tail residues and as a consequence is about 3300 daltons smaller. The chimeric PrEnv molecule was found to be cleaved efficiently as indicated by pulse-chase experiments. Immunofluorescence studies demonstrate that the chimeric molecule is efficiently transported to the surface of cells, unlike the SFFV gp52 glycoprotein. The chimeric molecule was found to be unstable in its membrane association and is released into the culture medium. These results indicate that the changes in the membrane spanning region and the lack of a cytoplasmic tail do not determine the defective transport of gp52, but may determine the stability of its association with membranes.


Cultural change and mental health in Greenland: the association of childhood conditions, language, and urbanization with mental health and suicidal thoughts among the Inuit of Greenland.
In Greenland, the rapid sociocultural change of the last 50 years has been paralleled by an epidemiological transition characterized by a reduction in infectious diseases, an increase in cancer and cardiovascular diseases, and an increased prevalence of mental health problems. During 1993-94 and 1997-98, two health interview surveys were conducted among Inuit in Greenland and Inuit migrants in Denmark. The response rates were 71 and 55%. Information on mental health was obtained from 1388 and 1769 adults. As indicators of mental health, the prevalence of potential psychiatric cases according to the General Health Questionnaire (GHQ-12) and the prevalence of suicidal thoughts were studied in relation to childhood residence and father's occupation, current residence, and language. The statistical methods included logistic regression and graphical independence models. The results indicated a U-shaped association in Greenland of GHQ-cases with age and a high prevalence of suicidal thoughts among young people; a low prevalence of GHQ-cases among those who were bilingual or spoke only Danish; and a high prevalence of suicidal thoughts among migrants who grew up in Denmark and among residents of the capital of Greenland. In Greenland, women were more often GHQ-cases and had suicidal thoughts more often than men. The association between language and GHQ-cases is presumed to operate through socioeconomic factors. It is necessary to modify the common notion that rapid societal development is in itself a cause of poor mental health: as a result of successful integration into the modern Greenlandic society, some population groups have better mental health compared to other groups.


Auditory nerve-brain stem evoked potentials and EEG during severe hypoglycemia.
To investigate the effects of severe hypoglycemia on the ability of the brain to generate electrical activity, the EEG and auditory nerve-brain stem evoked potentials (ABP) were recorded before and during the development of insulin-induced hypoglycemia in rats (ABP only) and cats (ABP and EEG). No significant ABP changes were seen in rats in which the average blood glucose levels had reached 0.38 mmol/l (= 7 mg%). In cats, even though the EEG was depressed, no ABP latency changes and only slightly significant amplitude changes were seen in animals in which the average blood glucose level was 0.8 mmol/l. In both animals blood glucose levels were below 1.66 mmol/l for an average duration of 90 min. Therefore, even though it has been shown that the brain structures involved in generation of the ABP have higher metabolic rates, they seem to be resistant to deviations from homeostasis such as hypoglycemia.


Frequency variations in the methylated pattern of p73/p21 genes and chromosomal aberrations correlating with different grades of glioma among south Indian population.
Gliomas are the most common primary brain tumors in India. The main epigenetic modification in glioma is aberrant DNA methylation that is now renowned to be a common hallmark of brain tumors. This study was designed to determine the frequency of aberrant CpG island methylation in the promoter regions of p21 and p73 in different grades of glioma and to explore their respective chromosomal aberrations. Total of 160 patients with histologically confirmed grades of glioma (I, II, III, and IV) were included in the study. DNA samples from blood and brain tissues, including benign lesions were subjected to sodium bisulfite conversion and hypermethylation detection using methylation-specific PCR followed by RT-PCR. Western blotting was also carried out for p21 and its related protein, p53. A total of 124 of 160 glioma samples (77.5%) displayed CpG island hypermethylation of both p73, p21 genes associated with the loss of mRNA expression (P < 0.001) and the loss of protein expressions (p53 independent p21 expression). p73 gene showed increased methylation frequency in all grades, 40 of 60 (66%) glioblastomas and 16 of 30 (53.3%) anaplastic astrocytoma, 10 of 20(50%) oligodendrogliomas, 8 of 20 (40%) ependymoma, and low-grade glioma 6 of 20 (30%). The percentage of methylation significantly well correlated with the overall survival and also with chromosomal loss. Thus, the studied glioma patients among south Indians showed a high frequency of aberrant methylation with varied chromosomal signatures in different grades, playing a role in aggressiveness and characterization of a particular grade, the appreciation of which might help for designing a specific therapy.


Knotted and topologically complex proteins as models for studying folding and stability.
Among proteins of known three-dimensional structure, only a few possess complex topological features such as knotted or interlinked (catenated) protein backbones. Such unusual proteins offer potentially unique insights into folding pathways and stabilization mechanisms. They also present special challenges for both theorists and computational scientists interested in understanding and predicting protein-folding behavior. Here, we review complex topological features in proteins with a focus on recent progress on the identification and characterization of knotted and interlinked protein systems. Also, an approach is described for designing an expanded set of knotted proteins.


The prognostic role of serum uric acid level in patients with acute ST elevation myocardial infarction.
The role of uric acid as a prognostic factor in patients with acute ST elevation myocardial infarction is controversial. The purpose of this study was to demonstrate the relationship between serum uric acid level and mortality during admission period and 30-day period after admission. We assessed the relation between serum uric acid level and in-hospital and short-term mortality rates in 184 patients admitted with acute ST elevation myocardial infarction. We divided the patients according to their gender and uric acid level measured on admission into four groups: group A1: men with uric acid ⩽7 mg/dl versus group B1: men with uric acid >7 mg/dl and group A2: women with uric acid ⩽5.6 mg/dl versus group B2: women with uric acid >5.6 mg/dl. The patients were followed for 30 days after admission. In-hospital mortality rate in group B1 was higher than group A1 [P value: 0.011, Relative risk: 13.33 (95% confidence interval: 1.55-114.7)]. Short-term all-cause mortality was significantly higher in group B1 patients [P value: 0.037, Relative risk: 3.3 (95% confidence interval: 1.02-10.64)]. Multivariate logistic regression analysis of data showed an odds ratio of 15.23 for in-hospital mortality and odds ratio of 3.76 for short-term mortality in male hyperuricemic patients. Our data suggest that in the acute phase of ST elevation myocardial infarction, uric acid has a prognostic role for in-hospital and short-term (30-day) mortality in men.


Understanding intentionality in children with attention-deficit/hyperactivity disorder.
One of the main aspects of theory of mind is intentionality which refers to recognizing other people's intentions in their behaviors. The aim of this study was to investigate intentionality in children with attention-deficit/hyperactivity disorder (ADHD). Thirty children with ADHD were compared to thirty age- and IQ-matched normal children. All participants were assessed using the moving shapes paradigm task which contains one large red and one small blue triangle moving around a black screen. They were asked to describe what the movements mean and how the triangles interact with each other. The answers were rated based on the accuracy, type of descriptions applied, mental states, and length of phrases. With regard to intentionality score, children with ADHD performed significantly worse than normal children (P < .05). Based on appropriateness score, the accuracy of patients' answers was lower in comparison with the control group. Children with ADHD used longer phrases as compared to controls. Children with ADHD can have problems with comprehending others' intentionality. This leads to impairment in social relationship.


Flavonoid glycosides and ellagic acid cognates from defatted African mango (Irvingia gabonensis) seed kernel.
Seventeen compounds of diverse classes including four flavonoid glycosides, five ellagic acid derivatives, and eight other metabolites were isolated from the methanolic extract of the defatted seed kernel of Irvingia gabonensis. Among the isolates, quercetin 3-O-methyl-4'-[α-L-rhamnopyranosyl-(1→3)]-O-α-L-rhamnopyranoside (1) and 3,3'-di-O-methyl-4'-O-α-L-rhamnopyranosylellagic acid 4-sulfate ester (5) were found to be previously undescribed. Structure elucidation was mainly achieved by the interpretation of 1D and 2D NMR and HRESIMS spectral data. Though compound 6 was previously reported, its 13C NMR data is being reported herein for the first time. To the best of our literature search knowledge, this is the first phytochemical report on I. gabonensis seed kernels.